ArticleLiterature Review

Type 2 diabetes mellitus and the risk of sudden cardiac arrest in the community

February 2010
Reviews in Endocrine and Metabolic Disorders 11(1):53-9

February 2010
11(1):53-9

DOI:10.1007/s11154-010-9133-5

Source
PubMed

Authors:

Thomas Rea

University of Washington Seattle

Trivellore Raghunathan

University of Michigan

Show all 6 authorsHide

The reduction of mortality from sudden cardiac arrest (SCA) in the setting of coronary heart disease (CHD) remains a major challenge, especially among patients with type 2 diabetes. Diabetes is associated with an increased risk of SCA, at least in part, from an increased presence and extent of coronary atherosclerosis (macrovascular disease). Diabetes also is associated with microvascular disease and autonomic neuropathy; and, these non-coronary atherosclerotic pathophysiologic processes also have the potential to increase the risk of SCA. In this report, we review the absolute and relative risk of SCA associated with diabetes. We summarize recent evidence that suggests that the increase in risk in patients with diabetes is not specific for SCA, as diabetes also is associated with a similar increase in risk for non-SCA CHD death and non-fatal myocardial infarction. These data are consistent with prior observations that coronary atherosclerosis is a major contributor to the increased SCA risk associated with diabetes. We also present previously published and unpublished data that demonstrates that both clinically-recognized microvascular and autonomic neuropathy also are associated with the risk of SCA among treated patients with diabetes, after taking into account prior clinically-recognized heart disease and other risk factors for SCA. We then discuss how these data might inform research and clinical efforts to prevent SCA. Although the prediction of SCA in this "high" risk population is likely to remain a challenge, as it is in other "high" risk clinical populations, we suggest that current recommendations for the prevention of SCA in the community, related to both lifestyle prescriptions and risk factor reduction, are likely to reduce mortality from SCA among patients with diabetes.

Using routine primary care data to assess Sudden Cardiac Arrest risk in people with type 2 diabetes: a proof-of-concept case-control study

Preprint

Full-text available

Jan 2024

Background Approximately 50% of out-of-hospital Sudden Cardiac Arrest (SCA) occurs in people with unrecognized SCA-risk and no preceding cardiologic care records. General practitioner (GP) records include these people, specifically people with type 2 diabetes (T2D) with increased SCA-risk. We aimed to provide a proof-of-concept for using routine primary care data to study SCA-risk in people with T2D. Methods This case-control study, identified SCA cases through the AmsteRdam REsuscitation STudies (ARREST) registry of out-of-hospital SCA in the Dutch region of Noord-Holland (2005-2019). We included cases with presumed cardiac cause and T2D registered at participating GP practices from the PHARMO Data Network and the academic network of general practice Amsterdam UMC (ANHA). Cases were matched (age, sex, T2D, GP-practice) with up to five non-SCA controls. From their GP files, we collected clinical measurements, medication use and medical history. Associations with SCA were analysed using univariable and multivariable conditional logistic regression (Odds Ratios, 95% confidence intervals). Results We included 247 cases and 1,143 controls. In the multivariable model, high fasting glucose (1.08 (1.01-1.16) per 1 mmol/L), high cholesterol ratio (1.17 (1.03-1.34)), moderate albuminuria (2.77 (1.84-4.16)), severe albuminuria (2.96 (1.44-6.08)), dyslipidaemia (0.53 (0.33-0.86)) and a history of cardiovascular disease (1.72 (1.23-2.17)) were significantly associated with SCA. Current smoking behaviour, decreased eGFR, insulin use, hypertension and microvascular complications were close to significantly associated with SCA. Conclusions The relatively strong associations in our small sample are consistent with those found in cardiologic care populations, indicating that GP file data can be useful to study SCA-risk.

Sulfonylurea Is Associated With Higher Risks of Ventricular Arrhythmia or Sudden Cardiac Death Compared With Metformin: A Population-Based Cohort Study

Article

Full-text available

Sep 2022

BACKGROUND: Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. METHODS AND RESULTS: Patients aged ≥40years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16596 metformin users (47.70% men; age, 68±11years; mean follow-up, 4.92±2.55years) and 16596 sulfonylurea users (49.80% men; age, 70±11years; mean follow-up, 4.93±2.55years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. CONCLUSIONS: Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes.

Diagnostic and therapeutic characteristics of diabetes mellitus and risk of out-of-hospital cardiac arrest

Article

Full-text available

Jan 2022

This study aimed to evaluate the risks of diabetes mellitus (DM) on out-of-hospital cardiac arrest (OHCA) and to investigate whether the risks of DM on OHCA varied according to the diagnostic and therapeutic characteristics of diabetes. We conducted a multicenter prospective case–control study in 17 University hospitals in Korea from September 2017 to December 2020. Cases were EMS-treated OHCA patients aged 20 to 79 with a presumed cardiac etiology. Community-based controls were recruited at a 1:2 ratio after matching for age, sex, and urbanization level of residence. A structured questionnaire and laboratory findings were collected from cases and controls. Multivariable conditional logistic regression analyses were conducted to estimate the risk of DM on OHCA by characteristics. A total of 772 OHCA cases and 1544 community-based controls were analyzed. A total of 242 (31.3%) OHCAs and 292 (18.9%) controls were previously diagnosed with DM. The proportions of type I DM (10.7% vs. 2.1%) and insulin therapy (15.3% vs. 6.5%) were higher in OHCAs with DM than in controls with DM. The duration of DM was longer in OHCAs than in controls (median 12 vs. 7 years). DM was associated with an increased risk of OHCA (aOR (95% CI), 2.13 (1.64–2.75)). Compared to the no diabetes group, the risks of OHCA increased in the diabetes patients with type I DM (5.26 (1.72–16.08)) and type II DM group (1.63 (1.18–2.27)), a long duration of DM prevalence (1.04 (1.02–1.06) per 1-year prevalence duration), and a high HbA1c level (1.38 (1.19–1.60) per 1% increase). By treatment modality, the aOR (95% CI) was lowest in the oral hypoglycemic agent (1.47 (1.08–2.01)) and highest in the insulin (6.63 (3.04–14.44)) groups. DM was associated with an increased risk of OHCA, and the risk magnitudes varied according to the diagnostic and therapeutic characteristics.

Sulfonylurea antidiabetics are associated with lower risk of out‐of‐hospital cardiac arrest: Real‐world data from a population‐based study

Article

Full-text available

Apr 2021
BRIT J CLIN PHARMACO

Aims Out‐of‐hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP‐regulated K⁺ channels (KATP channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes. Methods We conducted a population‐based case–control study in 219 VT/VF‐documented OHCA cases with diabetes and 697 non‐OHCA controls with diabetes. We studied the association of SU drugs (alone or in combination with metformin) with OHCA risk compared to metformin monotherapy, and of individual SU drugs compared to glimepiride, using multivariable logistic regression analysis. We studied the effects of these drugs on APD during simulated ischaemia using patch‐clamp studies in human induced pluripotent stem cell‐derived cardiomyocytes. Results Compared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (ORSUdrugs‐alone 0.6 [95% CI 0.4–0.9], ORSUdrugs + metformin 0.6 [95% CI 0.4–0.9]). We found no differences in OHCA risk between SU drug users who suffered OHCA inside or outside the context of AMI. Reduction of OHCA risk compared to glimepiride was found with gliclazide (ORadj 0.5 [95% CI 0.3–0.9]), but not glibenclamide (ORadj 1.3 [95% CI 0.6–2.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (ORadj 0.6 [95% CI 0.3–1.002]). Glibenclamide attenuated simulated ischaemia‐induced APD shortening, while the other SU drugs had no effect. Conclusions SU drugs were associated with reduced OHCA risk compared to metformin monotherapy, with gliclazide having a lower risk than glimepiride. The differential effects of SU drugs are not explained by differential effects on APD.

SGLT2 Inhibitors and Their Antiarrhythmic Properties

Article

Full-text available

Jan 2022
INT J MOL SCI

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are gaining ground as standard therapy for heart failure with a class-I recommendation in the recently updated heart failure guidelines from the European Society of Cardiology. Different gliflozins have shown impressive beneficial effects in patients with and without diabetes mellitus type 2, especially in reducing the rates for hospitalization for heart failure, yet little is known on their antiarrhythmic properties. Atrial and ventricular arrhythmias were reported by clinical outcome trials with SGLT2 inhibitors as adverse events, and SGLT2 inhibitors seemed to reduce the rate of arrhythmias compared to placebo treatment in those trials. Mechanistical links are mainly unrevealed, since hardly any experiments investigated their impact on arrhythmias. Prospective trials are currently ongoing, but no results have been published so far. Arrhythmias are common in the heart failure population, therefore the understanding of possible interactions with SGLT2 inhibitors is crucial. This review summarizes evidence from clinical data as well as the sparse experimental data of SGLT2 inhibitors and their effects on arrhythmias.

EFECTIVIDAD DEL CURSO FAMILIARES Y AMIGOS RCP EN EL APRENDIZAJE DE LA REANIMACIÓN CARDIOPULMONAR EN FAMILIARES DE PACIENTES CON ALTO RIESGO CARDIOVASCULAR O QUE HAN PRESENTADO UN EVENTO CARDIOVASCULAR

Thesis

Full-text available

Mar 2021

ntecedentes: La reanimación cardiopulmonar (RCP) temprana y de alta calidad aumenta la supervivencia en el paro cardíaco. Si bien la mayoría de casos ocurre en el hogar y son presenciados por testigos, en pocos casos se inicia RCP. Por ello, resulta importante su enseñanza y especialmente en familiares de pacientes con alto riesgo cardiovascular. Objetivo: Demostrar la efectividad de la enseñanza del curso Familiares y Amigos RCP en el aprendizaje teórico y práctico de la reanimación cardiopulmonar en familiares de pacientes con alto riesgo cardiovascular o que han presentado un evento cardiovascular. Materiales y métodos: Estudio de tipo analítico, cuasi experimental, prospectivo, de intervención antes y después. Se utilizó un cuestionario de conocimientos teóricos y una lista de cotejo sobre RCP en adultos para evaluar el nivel de conocimiento teórico y práctico, respectivamente. La parte teórica fue medida en tres momentos (antes, inmediatamente después y un mes después) y la parte práctica en dos momentos (inmediatamente después y un mes después). Resultados: El nivel de conocimiento teórico fue malo (8.64 +/- 2.47) antes de la intervención, logrando un nivel de conocimiento bueno inmediatamente después (17.33 +/- 2.02) y un mes después (16.5 +/- 1.91). Además, las medianas del nivel de conocimiento práctico fueron de 15 inmediatamente después y un mes después, mostrando que mantuvieron un nivel de conocimiento práctico bueno. Conclusiones: El curso Familiares y Amigos RCP fue efectivo en el aprendizaje teórico y práctico sobre RCP en la población estudiada, y se mantuvo un mes posterior a la intervención.

Association between sodium-glucose cotransporter-2 inhibitors and risk of sudden cardiac death or ventricular arrhythmias: a meta-analysis of randomized controlled trials

Article

Full-text available

Aug 2021
EUROPACE

Aims Sudden cardiac death (SCD) and ventricular arrhythmias (VAs) are important causes of mortality in patients with type 2 diabetes mellitus (T2DM), heart failure (HF), or chronic kidney disease (CKD). We evaluated the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors on SCD and VAs in these patients. Methods and results We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with T2DM and/or HF and/or CKD comparing SGLT2i and placebo or active control. PubMed and ClinicalTrials.gov were systematically searched until November 2020. A total of 19 RCTs with 55 ,590 participants were included. Sudden cardiac death events were reported in 9 RCTs (48 patients receiving SGLT2i and 57 placebo subjects). There was no significant association between SGLT2i therapy and SCD [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.50–1.08; P = 0.12]. Ventricular arrhythmias were reported in 17 RCTs (126 patients receiving SGLT2i and 134 controls). SGLT2i therapy was not associated with a lower risk of VAs (RR 0.84, 95% CI 0.66–1.06; P = 0.14). Besides the subgroup of low-dosage SGLT2i therapy that demonstrated decreased VAs compared to control (RR 0.45, 95% CI 0.25–0.82; P = 0.009), or to placebo (RR 0.46, 95% CI 0.25–0.85; P = 0.01), further subgroup analysis did not demonstrate any significant differences. Conclusion SGLT2i therapy was not associated with an overall lower risk of SCD or VAs in patients with T2DM and/or HF and/or CKD. However, further research is needed since the number of SCD and VA events were relatively few leading to wide confidence intervals, and the point estimates suggested potential benefits.

Risk of sudden cardiac arrest and ventricular arrhythmia with sulfonylureas: An experience with conceptual replication in two independent populations

Article

Full-text available

Jun 2020

Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardiac arrest (SCA) or ventricular arrhythmia (VA). We assessed the comparative real-world risk of SCA/VA among users of second-generation sulfonylureas: glimepiride, glyburide, and glipizide. We conducted two incident user cohort studies using five-state Medicaid claims (1999–2012) and Optum Clinformatics commercial claims (2000–2016). Outcomes were SCA/VA events precipitating hospital presentation. We used Cox proportional hazards models, adjusted for high-dimensional propensity scores, to generate adjusted hazard ratios (aHR). We identified 624,406 and 491,940 sulfonylurea users, and 714 and 385 SCA/VA events, in Medicaid and Optum, respectively. Dataset-specific associations with SCA/VA for both glimepiride and glyburide (vs. glipizide) were on opposite sides of and could not exclude the null (glimepiride: aHRMedicaid 1.17, 95% CI 0.96–1.42; aHROptum 0.84, 0.65–1.08; glyburide: aHRMedicaid 0.87, 0.74–1.03; aHROptum 1.11, 0.86–1.42). Database differences in data availability, populations, and documentation completeness may have contributed to the incongruous results. Emphasis should be placed on assessing potential causes of discrepancies between conflicting studies evaluating the same research question.

The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: Real-world evidence on thiazolidinedione safety

Article

Full-text available

Feb 2020
CARDIOVASC DIABETOL

Background: The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA). Methods: We conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999-2012) and a commercial health insurance plan (Optum Clinformatics | 2000-2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset. Results: The adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75-1.10) in Medicaid and 0.88 (0.61-1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54-0.93] and 1.16 [0.89-1.52] in men and women respectively, interaction term p-value = 0.01). Conclusions: Rosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.

Pollution de l'air et arrêts cardiaques hors hôpital en Nord-Pas-de-Calais, France : approche principale en étude de cas-croisé stratifiée sur le temps

Thesis

Sep 2018

Marie Albert Thananayagam

L'arrêt cardiaque est un problème majeur de santé publique. Il se caractérise par une perte subite des fonctions cardiaques, de la respiration et de l’état de conscience et est habituellement causé par une perturbation électrique au niveau du coeur. Les arrêts cardiaques hors hôpital (ACHH) concernent plus de 85% des arrêts cardiaques. Les taux de survie, tout en restant bas, varient largement à travers le monde, de 2 à 20%. Dans la population générale, l'incidence de la mort subite par arrêt cardiaque serait estimée à 4-5 millions de cas par an. La pollution de l'air est un problème environnemental majeur pour la santé. En 2013, elle était le quatrième facteur de risque de mortalité globale et était estimée être à l'origine de 5,5 millions de décès par an à travers le monde. Dans la littérature, l'exposition à court terme à la pollution de l'air, notamment en ce qui concerne les particules en suspension, est retrouvée en association avec la morbidité et la mortalité cardiovasculaire. Plusieurs études trouvent une association positive entre les particules fines notées PM2,5 (de diamètre aérodynamique inférieur à 2,5 μm) et les arrêts cardiaques hors hôpital (ACHH) bien que l'association soit non significative dans d'autres études. En ce qui concerne les particules en suspension notées PM10 (de diamètre aérodynamique inférieur à 10 μm), le dioxyde d'azote (NO2), l'ozone (O3) et le dioxyde de soufre (SO2), l'évaluation du risque d'ACHH conduit à des résultats discordants. Les mécanismes impliqués dans la relation entre la pollution de l'air et les ACHH ne sont pas clairement connus. Ils pourraient mettre en jeu des perturbations électriques et des réactions inflammatoires. Le but de notre travail est d'étudier l'effet de l'exposition à ces différents polluants à des échelles de temps horaire et journalière sur la survenue d'ACHH dans la région Nord-Pasde- Calais, France. De plus, nous nous sommes intéressés plus spécifiquement aux ACHH survenant en période scolaire avec des analyses en sous-groupes notamment par sexe, âge, cause de l'arrêt, statut diabétique, afin de pouvoir révéler des sous-groupes potentiellement plus vulnérables. L'étude a collecté les ACHH qui sont survenus dans la région Nord-Pas-de-Calais, France, en 2015. Une étude de cas-croisé stratifiée sur le temps couplée à une régression logistique conditionnelle a été principalement utilisée pour évaluer l'association entre les ACHH et les polluants de l'air (PM2,5, PM10, NO2, O3, SO2) mesurés dans l'heure de l'arrêt jusqu'à 5 jours avant l'arrêt. 1039 cas ont été inclus dans l'étude. La plupart des associations positives significatives ont été observées pour les expositions aux PM2,5 et PM10 et pour les ACHH en période scolaire. Pour la plus petite p-value, le plus grand OR était : pour l'ensemble des ACHH et dans le sous-groupe des hommes, pour la moyenne cumulée sur 12 heures avant l'arrêt des PM10 (OR=1,33, p<0,001 et OR=1,34, p=0,001 respectivement) ; dans le sous-groupe des âges de 50 à 75 ans, pour la moyenne le jour de l'arrêt des PM2,5 (OR=1,27, p<0,001) ; dans le sous-groupe des arrêts de cause cardiaque, pour la moyenne quatre jours avant l'arrêt des PM2,5 (OR=1,26, p<0,001) ; dans le sous-groupe des cas avec diabète, pour la moyenne cumulée sur quatre heures avant l'arrêt des PM2,5 (OR=1,55, p=0,002). Les résultats montrent des associations significatives entre les particules en suspension et les ACHH en période scolaire, avec des sous-groupes de susceptibilité (hommes, âge de 50 à 75 ans, ACHH de cause cardiaque, et les diabétiques). L'exploration de sous-groupes de vulnérabilité est d'autant plus importante dans les études épidémiologiques des polluants de l'air du fait des risques peu élevés à l'échelle de la population habituellement observés. L'ensemble de ces informations pourraient encourager les autorités publiques à émettre des politiques de recommandations spécifiques ciblées pour les sous-groupes de susceptibilité.

Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia

Article

Feb 2018
DIABETES CARE

Objective: To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA). Research design and methods: We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model. Results: Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null. Conclusions: Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.

Computational Modeling of Sodium Ion Channel-Based Glucose Sensing Biophysics to Study Cardiac Atrial Cell Electrophysiology

Preprint

Full-text available

May 2024

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding the internal mechanisms has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing biophysics mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, computational model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our mathematical model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

In Silico Exploration of Sodium Ion Channel-Mediated Glucose Sensing Biophysics to Study Cardiac Atrial Cells Electrophysiology

Preprint

Full-text available

Apr 2024

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding this link has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, in-silico model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

Computational Modeling of Sodium Ion Channel-Based Glucose Sensing Biophysics to Study Abnormal Electrical Activities in Cardiac Atrial Cell

Preprint

Full-text available

Apr 2024

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding this link has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, in-silico model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

Exploration of Medicine Type 2 diabetes mellitus and coronary artery stenosis: a risk pattern association study

Article

Jan 2024

Dharmsheel Shrivastav

Cardiovascular diseases (CVD) are the leading cause of death globally. In the condition of type 2 diabetes mellitus (T2DM), the prevalence of CVD increase parallel with the rise of metabolic complication and higher incidence of coronary artery stenosis. The aim of this study was to compare the level of percent stenosis in coronary arteries in patients with coronary artery disease (CAD) with and without T2DM, and to measure the severity of CVD using Gensini score (GS) through angiographic data. Methods: The current study was conducted in tertiary care specialized hospital in Delhi, India. The level of percent stenosis in coronary arteries was compared in patients with CAD with and without T2DM. The patients were divided into two groups: group I included 100 patients with T2DM, and group II included 100 non-diabetic CAD patients who underwent coronary angiography by Judkin's technique. The severity of CVD was measured by GS through angiographic data. The serum levels of glycated haemoglobin (HbA1c) ≥ 6.5% were considered diabetic. Results: Significant difference was observed in serum HbA1c, and random blood sugar levels between group I and group II were also observed (P ≤ 0.001). Serum HbA1c shows a significant positive association with GS (r = 0.36, P = 0.007). Conclusions: The study shows a significant level of stenosis in coronary arteries of CAD diabetic patients. However, further prospective analysis of a larger population size will be needed to strengthen the findings and the significant association.

Green synthesis of copper oxide nanoparticles using Amaranthus dubius leaf extract for sensor and photocatalytic applications

Article

Nov 2023

Copper oxide nanoparticles (CuO NPs) were produced through an environmentally friendly green synthesis. The characteristics of these green synthesized CuO NPs, including their structural, optical, morphological, and electrochemical properties, were examined using various characterization techniques. X-ray diffraction analysis revealed that the CuO NPs have a monoclinic structure with a C2/c space group. Electrochemical detection of glucose was carried out using cyclic voltammetry. The green synthesized CuO NPs exhibited excellent catalytic properties for both electrochemical sensing and photocatalysis. Significantly, these CuO NPs exhibited excellent selectivity and sensitivity in glucose detection, with a sensitivity of 370 μA mM-1 cm-2 and a detection limit of 1.0 μM. Furthermore, the CuO NPs demonstrated a substantial 84% degradation of dyes within 150 minutes. These results underscore the potential of the green synthesized CuO NPs as a promising material for applications in both sensing and dye degradation. 2

The Role of Noncommunicable Disease Clinics in Improving Control of Hypertension and Diabetes Among Adults Residing in Rural Ballabgarh, Haryana

Article

Full-text available

Apr 2023

Introduction High systolic blood pressure (SBP) and raised plasma glucose are major attributable and preventable causes of death worldwide. The objective of this study was to estimate the control rates and identify determinants of control of hypertension and diabetes among adults. Methods A longitudinal follow-up study was conducted among all the adults registered at the noncommunicable disease (NCD) clinics under the national program at two primary health centers in Faridabad, Haryana. Data were collected every month from the individual booklet generated for registered adults. Two monthly visits in three months and four in six months were considered adequate follow-ups at the NCD clinic. Results In the study, 495 (82.2%) adults had hypertension, and 242 (40.2%) had diabetes. The control rates at the third and sixth months were 37.1% (95% confidence interval (CI): 31.4-42.7) and 53.6% (95% CI: 43.4-59.8) among hypertensives and 28.7% (95% CI: 21.7-35.7) and 35.9% (95% CI: 27.5-44.4) among diabetics. Among hypertensives, six-month control status was associated with adequate follow-up at the NCD clinic (adjusted odds ratio (AOR) 2.3; 95% CI: 1.4-4.0; p-value: 0.002), male sex (AOR 0.5; 95% CI: 0.3-0.9; p-value: 0.02) and high SBP (AOR 0.5; 95% CI: 0.3-0.9; p-value: 0.017). Conclusions Control status was achieved in half of the adults with hypertension and one-third of adults with diabetes after six months of regular follow-up. Adequate follow-up at the NCD clinic, male sex, and raised SBP emerged as determinants of control among hypertensives.

Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: a systematic review and meta-analysis of randomized controlled trials

Article

Full-text available

Dec 2022

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been highly recommended for glycemic control and weight reduction. However, evidence has accumulated that GLP-1 RAs treatment is related to an increase in heart rate, which could potentially induce cardiac arrhythmias. This study aims to investigate the association of GLP-1 RAs therapy with incident arrhythmias in diabetic and obese patients. Methods MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception up to May 25, 2022. Randomized controlled trials (RCTs) comparing GLP-1 RAs with placebo or active control for adults with type 2 diabetes or obesity were included. The outcomes of interest were prespecified as incident atrial fibrillation (AF), atrial flutter (AFL), ventricular arrhythmias (VAs), and sudden cardiac death (SCD). Mantel-Haenszel relative risk (MH-RR) with a corresponding 95% confidence interval (95% CI) was estimated using a fixed-effects model. Results A total of 56 RCTs involving 79,720 participants (44,028 GLP-1 RAs vs 35,692 control: mean age 57.3 years) were included from 7692 citations. GLP-1 RAs use overall did not significantly increase the risk of AF (RR 0.97, 95% CI 0.83–1.12), AFL (RR 0.83, 95% CI 0.59–1.17), VAs (RR 1.24, 95% CI 0.92–1.67), and SCD (RR 0.89, 95% CI 0.67–1.19), compared with controls. In further subgroup analyses, we observed an increasing trend toward incident AF with dulaglutide (RR 1.40, 95% CI 1.03–1.90) while an inverse trend with oral semaglutide (RR 0.43, 95% CI 0.21–0.87). Additionally, higher doses of GLP-1 RAs (RR 1.63, 95% CI 1.11–2.40) and higher baseline BMI (RR 1.60, 95% CI 1.04–2.48) might significantly increase the risk of VAs. No significant differences were identified in other subgroup analyses. Conclusions GLP-1 RAs therapy was not associated with an overall higher risk of arrhythmias, demonstrating an assuring cardiovascular safety profile. Further studies are required to determine whether the potential antiarrhythmic or arrhythmogenic effect of GLP-1 RAs is drug-specific and varies from doses or baseline BMI. Trial registration : PROSPERO Identifier: CRD42022339389.

Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives

Article

Full-text available

Jul 2022

The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.

Cardiac Arrest during Interventional Radiology Procedures: A 7-Year Single-Center Retrospective Study

Article

Full-text available

Jan 2022

An intervention radiology (IR) unit collected cardiac arrest data between January 2014 and July 2020. Of 344,600 procedures, there were 23 cardiac arrest patients (0.0067%). The patient data was compared to a representative sample (N = 400) of the IR unit to evaluate the incidence and factors associated with cardiac arrest during IR procedures. Age, procedure urgency, American Society of Anesthesiologists (ASA) physical status, procedure type, and underlying medical conditions were identified as valuable predictors of a patient’s susceptibility to cardiac arrest during an IR procedure. The proportion of pediatrics was higher for cardiac arrest patients, and most required immediate procedures. The distribution of high ASA physical status (III or greater) was skewed compared to that of the non-cardiac arrest patients. Vascular procedures were associated with higher risk than non-vascular procedures. The patients who underwent non-transarterial chemoembolization arterial procedures demonstrated relative risks of 4.4 and 11.7 for cardiac arrest compared to biliary procedures and percutaneous catheter drainage, respectively. In addition, the six patients (26.1%) who died before discharge all underwent vascular procedures. Relative to patients with acute kidney injury, patients with malignancy, hypertension, and diabetes mellitus demonstrated relative risks of 3.3, 3.4, and 4.8 for cardiac arrest, respectively.

The role of metabolic syndrome in sudden cardiac death risk: Recent evidence and future directions

Article

Full-text available

Oct 2021

Metabolic syndrome (MetS) is a frequent condition whose deleterious effects on the cardiovascular system are often underestimated. MetS is nowadays considered a real pandemic with an estimated prevalence of 25% in general population. Individuals with MetS are at high risk of sudden cardiac death (SCD) as this condition accounts for 50% of all cardiac deaths in such a population. Of interest, recent studies demonstrated that individuals with MetS show 70% increased risk of SCD even without previous history of coronary heart disease (CHD). However, little is known about the interplay between the two conditions. MetS is a complex disease determined by genetic predisposition, unhealthy lifestyle, and aging with deleterious effects on different organs. MetS components trigger a systemic chronic low-grade pro-inflammatory state, associated with excess of sympathetic activity, cardiac hypertrophy, arrhythmias, and atherosclerosis. Thus, MetS has an important burden on the cardiovascular system as demonstrated by both preclinical and clinical evidence. The aim of this review is to summarize recent evidence concerning the association between MetS and SCD, showing possible common etiological processes, and to indicate prospective for future studies and therapeutic targets.

Effectiveness of the Family and Friends CPR course in learning cardiopulmonary resuscitation in relatives of patients with high cardiovascular risk or who have suffered a cardiovascular event

Article

Full-text available

Oct 2021

Introduction: Early, high-quality cardiopulmonary resuscitation (CPR) increases survival rates in cardiac arrest. Although most cases occur at home and are witnessed, CPR is performed in few of these cases. For this reason, teaching CPR is especially important in relatives of patients with high cardiovascular risk. Therefore, the aim of this study was to demonstrate the effectiveness of the Family and Friends CPR course in the theoretical and practical learning of cardiopulmonary resuscitation in relatives of patients with high cardiovascular risk or who have suffered a cardiovascular event. Materials and methods: We carried out an analytical, quasi-experimental, prospective, before-and-after study. We selected 20 participants during outpatient consultation at the Cardiology Department of the Cayetano Heredia Hospital in Lima, Peru. A theoretical knowledge questionnaire and an adult CPR checklist were used to assess the level of theoretical and practical knowledge, respectively. The theoretical knowledge was measured at three points in time (before, immediately after and one month after the intervention) and the practical skills at two points in time (immediately after and a month after the intervention). Results: The level of theoretical knowledge was low (8.64 ± 2.47) before the intervention, achieving a good level of knowledge immediately after (17.33 ± 2.02) and one month later (16.5 ± 1.91). Furthermore, the medians of the level of practical knowledge were 15 immediately after and one month later, showing that they maintained a good level of practical knowledge. Conclusions: The Family and Friends CPR course was effective in the theoretical and practical learning of CPR in the studied population, and was sustained one month after the intervention.

Weight reduction ameliorates inflammatory cytokines, adipocytokines and endothelial dysfunction biomarkers among Saudi patients with type 2 diabetes

Article

Full-text available

Oct 2020
Afr Health Sci

Background: Type 2 diabetes mellitus (T2DM) considered as one of the cardiovascular disorders (CVD) principle risk factor as diabetes is associated with abnormal levels of endothelial function, inflammatory and adipocytokines. Objective: The aim of this study was to measure the impact of weight reducing on inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients. Methods: One-hundred T2DM patients enrolled in the present study; the age range was 35-55 year. Participants shared in this study were enrolled in group (A) received diet control and aerobic exercise on treadmill, while, group (B) had no intervention for 3 months. Results: The mean values of body mass index (BMI), tumor necrosis factor -alpha (TNF-α), interleukin-6 (IL-6), leptin, inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), E-selectin and plasminogen activator inhibitor-1 activity (PAI-1 activity) were significantly decreased and adiponectin was increased significantly in the training group, however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. Conclusion: Weight reducing program modulates inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients.

Placebo-Controlled, Double-Blind Study of Empagliflozin (EMPA) and Implantable Cardioverter-Defibrillator (EMPA-ICD) in Patients with Type 2 Diabetes (T2DM): Rationale and Design

Article

Full-text available

Sep 2020

Introduction: Type 2 diabetes (T2DM) is associated with cardiovascular death, including sudden cardiac death due to arrhythmias. Patients with an implantable cardioverter-defibrillator (ICD) are also at high risk of developing a clinically significant ventricular arrhythmia. It has been reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular deaths; however, the physiological mechanisms of this remain unclear. It is, however, well known that SGLT2 inhibitors increase blood ketone bodies, which have been suggested to have sympatho-suppressive effects. Empagliflozin (EMPA) is an SGLT2 inhibitor. The current clinical trial titled "Placebo-controlled, double-blind study of empagliflozin (EMPA) and implantable cardioverter-defibrillator (EMPA-ICD) in patients with type 2 diabetes (T2DM)" was designed to investigate the antiarrhythmic effects of EMPA. Methods: The EMPA-ICD study is a prospective, multicenter, placebo-controlled, double-blind, randomized, investigator-initiated clinical trial currently in progress. A total of 210 patients with T2DM (hemoglobin A1c 6.5-10.0%) will be randomized (1:1) to receive once-daily placebo or EMPA, 10 mg, for 24 weeks. The primary endpoint is the number of clinically significant ventricular arrhythmias for 24 weeks before and 24 weeks after study drug administration, as documented by the ICD. The secondary endpoints of the study are the change from baseline concentrations in blood ketone and catecholamine 24 weeks after drug treatment. Conclusion: The EMPA-ICD study is the first clinical trial to assess the effect of an SGLT2 inhibitor on clinically significant ventricular arrhythmias in patients with T2DM and an ICD. Trial registration: Unique trial number, jRCTs031180120 ( https://jrct.niph.go.jp/latest-detail/jRCTs031180120 ).

Potassium Disturbances and Risk of Ventricular Fibrillation Among Patients With ST‐Segment–Elevation Myocardial Infarction

Article

Full-text available

Feb 2020

Background Potassium disturbances per se increase the risk of ventricular fibrillation ( VF ). Whether potassium disturbances in the acute phase of ST ‐segment–elevation myocardial infarction ( STEMI ) are associated with VF before primary percutaneous coronary intervention ( PPCI ) is uncertain. Methods and Results All consecutive STEMI patients were identified in the Eastern Danish Heart Registry from 1999 to 2016. Comorbidities and medication use were assessed from Danish nationwide registries. Potassium levels were collected immediately before PPCI start. Multivariate logistic models were performed to determine the association between potassium and VF . The main analysis included 8624 STEMI patients of whom 822 (9.5%) had VF before PPCI . Compared with 6693 (77.6%) patients with normokalemia (3.5–5.0 mmol/L), 1797 (20.8%) patients with hypokalemia (<3.5 mmol/L) were often women with fewer comorbidities, whereas 134 (1.6%) patients with hyperkalemia (>5.0 mmol/L) were older with more comorbidities. After adjustment, patients with hypokalemia and hyperkalemia had a higher risk of VF before PPCI (odds ratio 1.90, 95% CI 1.57–2.30, P <0.001) and (odds ratio 3.36, 95% CI 1.95–5.77, P <0.001) compared with normokalemia, respectively. Since the association may reflect a post‐resuscitation phenomenon, a sensitivity analysis was performed including 7929 STEMI patients without VF before PPCI of whom 127 (1.6%) had VF during PPCI . Compared with normokalemia, patients with hypokalemia had a significant association with VF during PPCI (odds ratio 1.68, 95% CI 1.01–2.77, P =0.045) after adjustment. Conclusions Hypokalemia and hyperkalemia are associated with increased risk of VF before PPCI during STEMI . For hypokalemia, the association may be independent of the measurement of potassium before or after VF .

Is type 2 diabetes mellitus a coronary heart disease equivalent or not? Do not just enjoy the debate and forget the patient!

Article

Full-text available

Sep 2019

In last several years there have been a large debate whether patients with type 2 diabetes (DMT2) should be treated as those with high or very high cardiovascular risk, and whether DMT2 should be considered as coronary heart disease (CHD) equivalent of CHD. All started in 2001 in National Cholesterol Education Program-Adult Treatment Panel III recommendations and the knowledge has changed on this issue at least several times. But the main problem is that due to these inconsistencies and different approach to the cardiovascular risk of DMT2 patients, we have more and more patients with DMT2 not effectively treated, and diabetologists mostly focus on glucose (glucocentric approach), often forgetting about the overall cardiovascular risk of those patients. In this review we discuss the above-mentioned topic, try to give some practical suggestions, and rise the issue whether we should not start the discussion on treating all patients with DMT2 as those at very high cardiovascular risk, or to at least to try to unify the definition and find such variables/risk factors which are easy to measure to help physicians to treat those patients optimally. We have obviously discussed these issues in the context of new European Society of Cardiology (ESC) / European Association for the Study of Diabetes (EASD) Guidelines 2019.

Decision tree model for predicting in‐hospital cardiac arrest among patients admitted with acute coronary syndrome

Article

Full-text available

Sep 2019
CLIN CARDIOL

Background: In-hospital cardiac arrest (IHCA) may be preventable, with patients often showing signs of physiological deterioration before an event. Our objective was to develop and validate a simple clinical prediction model to identify the IHCA risk among cardiac arrest (CA) patients hospitalized with acute coronary syndrome (ACS). Hypothesis: A predicting model could help to identify the risk of IHCA among patients admitted with ACS. Methods: We conducted a case-control study and analyzed 21 337 adult ACS patients, of whom 164 had experienced CA. Vital signs, demographic, and laboratory data were extracted from the electronic health record. Decision tree analysis was applied with 10-fold cross-validation to predict the risk of IHCA. Results: The decision tree analysis detected seven explanatory variables, and the variables' importance is as follows: VitalPAC Early Warning Score (ViEWS), fatal arrhythmia, Killip class, cardiac troponin I, blood urea nitrogen, age, and diabetes. The development decision tree model demonstrated a sensitivity of 0.762, a specificity of 0.882, and an area under the receiver operating characteristic curve (AUC) of 0.844 (95% CI, 0.805 to 0.849). A 10-fold cross-validated risk estimate was 0.198, while the optimism-corrected AUC was 0.823 (95% CI, 0.786 to 0.860). Conclusions: We have developed and internally validated a good discrimination decision tree model to predict the risk of IHCA. This simple prediction model may provide healthcare workers with a practical bedside tool and could positively impact decision-making with regard to deteriorating patients with ACS.

MCP-1 Promotes Detrimental Cardiac Physiology, Pulmonary Edema and Death in the cpk model of Polycystic Kidney Disease

Article

Full-text available

May 2019

Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity

Article

Full-text available

Oct 2018

A rapid growth in the incidence of diabetes and obesity has transpired to a major heath issue and economic burden in the postindustrial world, with more than 29 million patients affected in the United States alone. Cardiovascular defects have been established as the leading cause of mortality and morbidity of diabetic patients. Over the last decade, significant progress has been made in delineating mechanisms responsible for the diminished cardiac contractile function and enhanced propensity for malignant cardiac arrhythmias characteristic of diabetic disease. Rhythmic cardiac contractility relies upon the precise interplay between several cellular Ca2+ transport protein complexes including plasmalemmal L-type Ca2+ channels (LTCC), Na+-Ca2+ exchanger (NCX1), Sarco/endoplasmic Reticulum (SR) Ca2+-ATPase (SERCa2a) and ryanodine receptors (RyR2s), the SR Ca2+ release channels. Here we provide an overview of changes in Ca2+ homeostasis in diabetic ventricular myocytes and discuss the therapeutic potential of targeting Ca2+ handling proteins in the prevention of diabetes-associated cardiomyopathy and arrhythmogenesis.

Reevaluating the Evidence for Blood Pressure Targets in Type 2 Diabetes

Article

Jun 2018
DIABETES CARE

There is general consensus that treating adults with type 2 diabetesmellitus (T2DM) and hypertension to a target blood pressure (BP) of <140/90 mmHg helps prevent cardiovascular disease (CVD).Whether more intensive BP control should be routinely targeted remains a matter of debate. While the American Diabetes Association (ADA) BP guidelines recommend an individualized assessment to consider different treatment goals, the American College of Cardiology/American Heart Association BP guidelines recommend a BP target of ,130/80mmHg formost individualswith hypertension, including those with T2DM (1-3).

Effect of body mass index on survival after sudden cardiac arrest

Article

Full-text available

Jan 2018

Background Although elevated body mass index (BMI) is a risk factor for cardiac disease, patients with elevated BMI have better survival in the context of severe illness, a phenomenon termed the “obesity paradox.” Hypothesis Higher BMI is associated with lower mortality in sudden cardiac arrest (SCA) survivors. Methods Data were collected on 1433 post-SCA patients, discharged alive from the hospitals of the University of Pittsburgh Medical Center between 2002 and 2012. Of those, 1298 patients with documented BMI during the index hospitalization and follow-up data constituted the study cohort. Results In the overall cohort, 30 patients were underweight (BMI <18.5 kg/m2), 312 had normal weight (BMI 18.5–24.9 kg/m2), 417 were overweight (BMI 25.0–29.9 kg/m2), and 539 were obese (BMI ≥30 kg/m2). As expected, the prevalence of coronary artery disease, myocardial infarction, diabetes mellitus, and hypertension increased significantly with increasing BMI. Over a median follow-up of 3.6 years, 602 (46%) patients died. Despite higher prevalence of cardiovascular comorbidities in more obese patients, a higher BMI was associated with lower all-cause mortality on univariate analysis (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.78-0.94, P = 0.002) and multivariate analysis after adjusting for unbalanced baseline comorbidities (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.77-0.96, P = 0.009). Conclusions Higher BMI is associated with lower all-cause mortality in survivors of SCA, suggesting that the obesity paradox applies to the post-arrest population. Further investigation into its mechanisms may inform the management of post-SCA patients.

Inhibition of aldose-reductase-2 by a benzofuroxane derivative BF-5m increases the expression of KCNE1, KCNQ1 in high glucose cultured H9c2 cardiac cells and sudden cardiac death

Article

Full-text available

Jul 2015

Long QT syndrome (LQTS) is characterized by prolonged QT interval, leading to sudden cardiac death. Hyperglycemia is an important risk factor for LQTS, inhibiting the cardiac rapid component delayed rectifier K+ current (Iks), responsible for QT interval. We previously showed that the new ALR2 inhibitor BF-5m supplies cardioprotection from QT prolongation induced by high glucose concentration in the medium, reducing QT interval prolongation and preserving morphology. Here we investigated the effects of BF-5m on cell cytotoxicity and viability in H9c2 cells, and on cellular potassium ion channels expression. H9c2 cells were grown in medium with high glucose and high glucose plus the BF-5m by assessing the cytotoxic effects and the cell survival rate. In addition, KCNE1 and KCNQ1 expression in plasma and mitochondrial membranes were monitored. Also, the expression levels of miR-1 proved to suppress KCNQ1 and KCNE1, were analyzed. BF-5m treatment reduced the cytotoxic effects of high glucose on H9c2 cells by increasing cell survival rate and improving H9c2 morphology. Plasmatic KCNE1 and KCNQ1 expression levels were restored by BF-5m in H9c2 exposed to high glucose, down-regulating miR-1. These results suggest that BF-5m exerts cardioprotection from high glucose in rat heart ventricle H9c2 cells exposed to high glucose.

The efficacy of black cumin seed (Nigella sativa) oil and hypoglycemic drug combination to reduce HbA1c level in patients with metabolic syndrome risk

Conference Paper

Full-text available

Dec 2017

Metabolic syndrome is a conditions caused by metabolic abnormalities include central obesity, atherogenic dyslipidemia, hypertension, and insulin resistance. HbA1c examination is required to study the long-term glycemic status and to prevent diabetic complications of metabolic syndrome. The purpose of this study is to determine the efficacy of black cumin seed (Nigella sativa) oil and hypoglycemic drug combination to reduce HbA1c level in patients with metabolic syndrome risk. This research performed using an experimental randomized single - blind controlled trial design. A total of 99 outpatients at the Jetis I Public Health Center, Yogyakarta, Indonesia with metabolic syndrome risk were divided into three groups: The control group received placebo and two treatment groups received black seed oil orally at dose of 1.5 mL/day and 3 mL/day, respectively, for 20 days. The clinical conditions such as blood pressure, pulse rate, BMI, blood glucose serum and HbA1c levels were examined on day 0 and 21. The results obtained were analyzed with one-way ANOVA test. The mean of HbA1c levels of all groups before treatment was higher than the normal values and there was no significant difference in HbA1c value on day 0. Administration of 1.5 and 3 mL/day of black seed oil for 20 days decreased (p<0.05) HbA1c levels. It can be concluded that administration of black cumin seed oil and hypoglycemic drug combination for 20 days in patients at risk of metabolic syndrome may reduce to HbA1c levels

The efficacy of black cumin seed ( Nigella sativa ) oil and hypoglycemic drug combination to reduce HbA1c level in patients with metabolic syndrome risk

Article

Full-text available

Nov 2017

Severity and multiplicity of microvascular complications are associated with QT interval prolongation in patients with type 2 diabetes

Article

Full-text available

Nov 2017

Aims/introduction: A prolonged QT interval plays a causal role in life-threatening arrhythmia and becomes a risk factor for sudden cardiac death. Here, we assessed the association between microvascular complications and the QT interval in patients with type 2 diabetes. Materials and methods: Patients with type 2 diabetes (n = 219) admitted to our hospital for glycemic control were enrolled. QT interval was measured manually in lead II on the electrocardiogram and corrected for heart rate using Bazett's formula (QTc). Diabetic neuropathy, retinopathy, and nephropathy were assessed by neuropathic symptoms or Achilles tendon reflex, ophthalmoscopy, and urinary albumin excretion, respectively. Results: In univariate analyses, female gender (P = 0.025), duration of type 2 diabetes (P = 0.041), BMI (P = 0.0008), systolic blood pressure (P = 0.0011), and receiving insulin therapy (P < 0.0001) were positively associated with QTc. Patients with each of the three microvascular complications had longer QTc than those without; neuropathy (P = 0.0005), retinopathy (P = 0.0019), and nephropathy (P = 0.0001). As retinopathy or nephropathy progressed, QTc became longer (P < 0.001 and P < 0.001 for trend in retinopathy and nephropathy, respectively). Furthermore, QTc was prolonged with the multiplicity of the microvascular complications (P < 0.001 for trend). Multiple regression analyses revealed that neuropathy, nephropathy, and the multiplicity of the microvascular complications were independently associated with QTc. Conclusions: Patients with type 2 diabetes with severe microvascular complications may be at high risk for life-threatening arrhythmia associated with QT interval prolongation. This article is protected by copyright. All rights reserved.

Dysglycemia and arrhythmias

Article

Full-text available

Aug 2023

Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.

Role of Noncommunicable Disease Clinic in Improving Control of Hypertension and Diabetes among Adults Residing in Rural Ballabgarh, Haryana

Poster

Full-text available

Apr 2023

Premature death can be prevented when blood pressure (BP) and plasma glucose levels are within a certain limit defined as the 'controlled' status (2,3). The NCD clinic under the NPCDCS is operational from and above the CHC level and thus affects the early diagnosis and initiation of treatment among adults with poor accessibility to these centers. Hypertension and diabetes are chronic diseases that need regular follow-up. A longitudinal follow-up study was conducted among all the adults registered at the NCD clinics at two primary health centers in Faridabad, Haryana. The study showed the use of data collected in programmatic settings for the generation of local scientific evidence. Such data strengthen initiatives under the national health program and help to make public health gains at the community level.

Copper(II)-Incorporated Porphyrin-Based Porous Organic Polymer for a Nonenzymatic Electrochemical Glucose Sensor

Article

Mar 2023
INORG CHEM

To date, the fabrication of multifunctional nanoplatforms based on a porous organic polymer for electrochemical sensing of biorelevant molecules has received considerable attention in the search for a more active, robust, and sensitive electrocatalyst. Here, in this report, we have developed a new porous organic polymer based on porphyrin (TEG-POR) from a polycondensation reaction between a triethylene glycol-linked dialdehyde and pyrrole. The Cu(II) complex of the polymer Cu-TEG-POR shows high sensitivity and a low detection limit for glucose electro-oxidation in an alkaline medium. The characterization of the as-synthesized polymer was done by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and 13C CP-MAS solid-state NMR. The N2 adsorption/desorption isotherm was carried out at 77 K to analyze the porous property. TEG-POR and Cu-TEG-POR both show excellent thermal stability. The Cu-TEG-POR-modified GC electrode shows a low detection limit (LOD) value of 0.9 μM and a wide linear range (0.001-1.3 mM) with a sensitivity of 415.8 μA mM-1 cm-2 toward electrochemical glucose sensing. The interference of the modified electrode from ascorbic acid, dopamine, NaCl, uric acid, fructose, sucrose, and cysteine was insignificant. Cu-TEG-POR exhibits acceptable recovery for blood glucose detection (97.25-104%), suggesting its scope in the future for selective and sensitive nonenzymatic glucose detection in human blood.

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared to metformin: a population-based cohort study

Preprint

Full-text available

Jan 2022

Background: Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD) between metformin and sulfonylurea in patients with type 2 diabetes. Methods: Patients aged 40 years or older who were diagnosed with type-2 diabetes mellitus or prescribed anti-diabetic agents in Hong Kong between 1st January 2009 and 31st December 2009 were included and followed up till 31st December 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of VA/SCD. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. Results: The study cohort consisted of 5756 metformin users (48.00% male, age 68±11 years, mean follow-up 5.04±2.57 years) and 5756 sulfonylurea users (50.30% male, age 69±11 years, mean follow-up 5.04±2.54 years). Sulfonylurea was associated with higher risk of VA/SCD than metformin (hazard ratio 1.84 [1.56 - 2.16], p<0.001). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusion: Sulfonylurea use is associated with higher risk of VA/SCD than metformin in patients with type 2 diabetes.

Nano- and Microstructured Copper/Copper Oxide Composites on Laser-Induced Carbon for Enzyme-Free Glucose Sensors

Article

Full-text available

Dec 2021

Low-cost enzyme-free glucose sensors with partial flexibility adaptable for wearable Internet of Things devices that can be envisioned as personalized point-of-care devices were produced by electroplating copper on locally carbonized flexible meta-polyaramid (Nomex) sheets using laser radiation. Freestanding films were annealed in nitrogen and nitrogen/air working environments, leading to the formation of Cu microspheroids and CuO urchins dispersed on the substrate film. The aggregation mechanism, crystallographic properties, surface chemistry, and electrochemical properties of the films were studied using scanning electron microscopy, X-ray diffractometry, transmission electron microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry. Cu microspheroids and CuO urchins attained activity for glucose detection and showed improvement of amperometric sensitivity to 0.25 and 0.32 mA cm–2 mM–1, respectively. The CuO urchin film retained its chemical composition after amperometric testing, and, by rinsing, allowed multiple repetitions with reproducible results. This study opens the possibility for the fabrication of durable composite biosensors with tailored shape, capable of implementation in flexible carriers, and microfluidic systems.

National guidelines for risk estimation and prevention of sudden cardiac death (2nd edition)

Book

Full-text available

Jan 2018

Mortality from cardiovascular diseases in the Russian Federation is one of the highest globally and amounts to 614 per 100,000 people per year. The leading causes of death associated with cardiovascular diseases are the progression of chronic heart failure (about half of all deaths) and sudden cardiac death (SCD) (the other half). According to the Federal State Statistics Service, about 899,000 people died from cardiovascular diseases in the Russian Federation in 2016. Thus, we can assume that our country had at least 300,000 sudden cardiac deaths in 2016 was. Accordingly, SCD is a highly relevant issue for the national health care system. The interest in this topic is also heightened by potential effective preventive measures which could improve the situation. The presented National Recommendations continue to use the principles of decision-making algorithms in various clinical situations set out in the first edition in 2012. The group of experts that developed this edition of the Guidelines accounted for the latest developments in predicting and preventing SCD in various patient populations and social groups, described in the recently published Russian, European, and American guidelines. In contrast to the other recently published documents, our group of experts considered it appropriate to thoroughly review risk stratification and prevention of SCD in such categories as the elderly and patients with heart transplants. These Guidelines will allow a wide range of doctors (therapists, cardiologists, cardiac surgeons, X-ray surgeons, resuscitators) to identify risk factors for SCD in everyday clinical practice and develop an optimal program for its prevention in each patient. These Guidelines continue our efforts to create and implement an effective SCD prevention program in our country, which began in 2012. The Guidelines are based on the concept of the primary and secondary risk factors for SCD, just like the first edition. If the patient has the primary risk factors, we suggest choosing more aggressive methods of SCD prevention (interventional and/or surgical treatment). If the patient has the secondary risk factors for SCD, we propose a milder strategy, which means modifying risk factors for the underlying disease in a particular patient (for example, quitting smoking, losing weight) and optimizing the drug treatment.

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors and Sudden Cardiac Arrest and Ventricular Arrhythmia: Population-Based Cohort Studies

Article

Jul 2021

In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase‐4 inhibitors, but evidence from population‐based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high‐dimensional propensity score (hdPS) matched, new‐user cohort studies. We analyzed Medicaid and Optum Clinformatics separately. We identified new users of saxagliptin, sitagliptin (both databases), and linagliptin (Optum only). We defined SCA/VA outcomes using emergency department and inpatient diagnoses. We identified and then controlled for confounders via a data‐adaptive, hdPS approach. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar year. We identified the following matched comparisons: saxagliptin vs. sitagliptin (23,895 vs. 96,972) in Medicaid, saxagliptin vs. sitagliptin (48,388 vs. 117,383) in Optum, and linagliptin vs. sitagliptin (36,820 vs. 78,701) in Optum. In Medicaid, use of saxagliptin (vs. sitagliptin) was associated with an increased rate of SCA/VA (adjusted HR [aHR], 2.01; 95% confidence interval 1.24–3.25). However, in Optum data, this finding was not present (aHR, 0.79; 0.41–1.51). Further, we found no association between linagliptin (vs. sitagliptin) and SCA/VA (aHR, 0.65; 0.36–1.17). We found discordant results regarding the association between SCA/VA with saxagliptin compared to sitagliptin in two independent datasets. It remains unclear whether these findings are due to heterogeneity of treatment effect in the different populations, chance, or unmeasured confounding.

Kode Biru pada Pasien Sepsis di RSUP Prof. Dr. R. D. Kandou selang Juni 2018 sampai Juli 2019

Article

Jul 2019

Code blue is an emergency code used by hospitals throughout the world for handling emergency cases such as cardiac and pulmonary arrest. The code blue has to be announced immediately whenever someone is diagnosed as heart or respiratory attack; therefore, the hospital prepares a special team for implementation of this code. Sepsis is an inflammatory response of severe infection that can cause organ damage and even death. This study was aimed to determine the code blue in septic patients at Prof. Dr. R. D. Kandou Hospital Manado. This was a retrospective and observational study conducted at the Medical Record Installation of Prof. Dr. R. D. Kandou Hospital Manado. Samples were code blue patients diagnosed as sepsis during the period of June 2018 to July 2019. There were 34 septic patients as samples. The highest number/percentages of the samples were, as follows: ages of >50 years in 29 patients (72.5%), female sex in 22 patients (55%), response time <5 minutes in 33 patients (97%), and death <24 hours after the code blue in 34 patients (100%). In conclusion, with response time less than 5 minutes, the code blue mortality rate among septic patients was still high which was 100% within the first 24 hours.Keywords: code blue, sepsis Abstrak: Kode biru adalah suatu kode darurat yang digunakan rumah sakit di seluruh dunia untuk penanganan kasus darurat seperti henti jantung dan paru. Kode biru harus segera dimulai kapan saja seseorang ditemukan dengan serangan jantung atau pernapasan sehingga dibentuk tim khusus oleh rumah sakit. Sepsis merupakan respon inflamasi dari infeksi berat yang dapat menyebabkan kerusakan organ hingga kematian. Penelitian ini bertujuan untuk mengetahui kode biru pada pasien sepsis di RSUP Prof. Dr. R.D. Kandou Manado. Penelitian dilakukan di Instalasi Rekam Medik RSUP Prof. Dr. R. D. Kandou Manado. Jenis penelitian ialah observasional retrospektif. Sampel penelitian ialah pasien kode biru di RSUP Prof. Dr. R. D. Kandou Manado dengan diagnosis sepsis yang memenuhi kriteria inklusi pada data rekam medik periode Juni 2018 sampai Juli 2019. Hasil penelitian mendapatkan jumlah total 34 pasien. Jumlah/persentase tertinggi dari pasien setelah dilakukan tindakan kode biru didapatkan pada usia >50 tahun yaitu 29 orang (72,5%); jenis kelamin perempuan yaitu 22 orang (55%); response time <5 menit yaitu 33 orang (97%); dan pasien yang meninggal dunia <24 jam yaitu 34 orang (100%). Simpulan penelitian ini ialah dengan response time <5 menit, angka kematian pasien sepsis dengan kode biru masih tetap tinggi yaitu mencapai 100% dalam waktu <24 jam.Kata kunci: kode biru, sepsis

Triggers of Cardiovascular Diseases in Rheumatoid Arthritis

Article

Apr 2021
CURR PROB CARDIOLOGY

The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than that in patients without RA, and it is even higher than that in patients with diabetes. Autoimmune-mediated inflammation is observed in patients with RA, resulting in endothelial dysfunction, oxidative stress and activation, and vascular migration of white blood cells. Traditionally, RA-associated CVD was assumed to be mediated by disease-related inflammation, resulting in atherosclerosis (AS). However, this concept has been challenged because treatment with anti-rheumatic drugs, such as methotrexate or proinflammatory cytokine antagonists, such as tumor necrosis factor-alpha (TNF-α) inhibitors, did not reduce the risk of CVD in patients with RA. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in patients with RA but without clear biomarkers and treatment goals. There is no scientific basis for establishing therapeutic targets for cardiovascular risk factors in RA. Numerous studies have shown that the mechanism of early cardiac dysfunction in patients with RA may occur prior to AS. Therefore, it is crucial to explore the related mechanisms to prevent early cardiac dysfunction in patients with RA.

Uma Avaliação Recente da Repolarização Ventricular em Pacientes Diabéticos

Article

Full-text available

Jan 2013

Kode Biru pada Pasien Sepsis di RSUP Prof. Dr. R. D. Kandou selang Juni 2018 sampai Juli 2019

Article

Jul 2019

Presence of fragmented QRS may be associated with complex ventricular arrhythmias in patients with type-2 diabetes mellitus

Article

Nov 2019
ACTA CARDIOL

Background: Ventricular arrhythmias (VAs) are frequent in diabetes mellitus (DM) patients. Myocardial fibrosis is one of the components of diabetic cardiomyopathy secondary to DM. Fragmented QRS (fQRS) on electrocardiography (ECG) has been shown to be a marker of myocardial fibrosis. In this study, we aimed to investigate the association between fQRS and complex VAs in patients with DM. Methods: Three hundred and thirty-six consecutive patients who were diagnosed with DM were included in the study. The control group consisted of 275 age- and sex-matched healthy individuals. ECG and transthoracic echocardiography were performed in all the patients. fQRS was defined as additional R’ wave or notching/splitting of S wave in two contiguous ECG leads. All the patients underwent 24-h Holter monitoring and VAs were classified using Lown’s scoring system. Lown class ≥ 3 VAs were considered as complex VAs. Results: As compared to the healthy individuals, prevalence of fQRS (37.5% vs. 6.9%, p < .001) and complex VAs (14% vs. 0%, p < .001) were significantly higher in patients with DM. Furthermore, complex VAs (28.4% vs. 6.4%, p < .001) were significantly higher in DM patients with fQRS. In multiple logistic regression analysis, DM duration (OR: 1.510, 95% CI:1.343 to 1.698; p < .001) and presence of fQRS (OR: 3.262, 95% CI: 1.443 to 7.376; p = .004) were independent predictors for complex VAs. Conclusions: The presence of fQRS may be associated with complex VAs in patients with DM. Therefore, fQRS may be used as a predictor of complex VAs and the risk of sudden death in patients with DM.

Association between diabetes mellitus and poor patient outcomes after out-of-hospital cardiac arrest: A systematic review and meta-analysis

Article

Full-text available

Dec 2018

Diabetes mellitus (DM) serves as an important prognostic indicator in patients with cardiac-related illness. Our objective is to compare survival and neurological outcomes among diabetic and non-diabetic patients who were admitted to the hospital after an out-of-hospital cardiac arrest (OHCA). We searched MEDLINE and EMBASE for relevant articles from database inception to July 2018 without any language restriction. Studies were included if they evaluated patients who presented with OHCA, included mortality and neurological outcome data separately for DM patients and Non-DM patients and reported crude data, odds ratio (OR), relative risk (RR) or hazard ratio (HR). Two investigators independently reviewed the retrieved citations and assessed eligibility. The quality of included studies was evaluated using Newcastle-Ottawa quality assessment scale for cohort studies. Random-effect models using the generic variance method were used to create pooled odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I² value. Survival and neurological outcomes (using modified rankin scale and cerebral performance category scale) after OHCA in hospitalized patients with DM compared with patients without DM. Out of 57 studies identified, six cohort studies met the inclusion criteria. In an analysis of unadjusted data, patients with DM had lower odds of survival, pooled OR 0.64; 95% CI, 0.52–0.78, [I² = 90%]. When adjusted ORs were pooled, the association between DM and survival after OHCA was still significantly reduced, pooled OR 0.78, 95% CI, 0.68–0.89 [I² = 55%]. Unadjusted pooled OR revealed poor neurological outcomes in patients with DM, pooled OR 0.55, 95% CI, 0.38–0.80 [I² = 90%]. The result demonstrates significant poor outcomes of in-hospital survival and neurological outcomes among DM patients after OHCA.

Autonominė širdies ritmo reguliacija bei jos pokyčiai sergant miokardo infarktu ir cukriniu diabetu

Article

Full-text available

Mar 2010
MED LITH

Išeminė širdies liga ir cukrinis diabetas yra dvi glaudžiai susijusios ligos. Sunkiausia išeminės širdies ligos forma – miokardo infarktas. Ūminio miokardo infarkto eiga ir prognozė cukriniu diabetu sergantiems ligoniams yra daug blogesnė nei to paties amžiaus ir lyties cukriniu diabetu nesergantiems ligoniams. Jau seniai ieškoma, kaip pagerinti tokių ligonių būklės vertinimą ir rizikos patvirtinimą. Daug žadanti sritis – autonominės širdies ir kraujagyslių sistemos bei jos pokyčių, sergant šiomis ligomis, tyrimai. Parasimpatinė ir simpatinė širdies dažnio moduliacija jau daug metų tiriama įvairiuose lygmenyse, tačiau mechanizmai yra sudėtingi ir iki šiol nepakankamai ištirti. Straipsnyje pateikiama literatūros apžvalga apie autonominės širdies ir kraujagyslių sistemos reguliacijos mechanizmų tyrimus bei jų pokyčius sergant miokardo infarktu ir cukriniu diabetu, taip pat apie šiuolaikinius autonominės širdies reguliacijos tyrimo metodus bei galimus intervencinius ir medikamentinius autonominio tonuso keitimo būdus. Norint geriau suprasti patologinių pokyčių atsiradimą ir eigą sergant miokardo infarktu ir cukriniu diabetu, straipsnyje pateikiama ir trumpa širdies ritmo vedlio funkcijos bei normalios autonominės širdies inervacijos bei širdies dažnio reguliacijos apžvalga.

Optimization of sudden cardiac death prevention in type 2 diabetes in France : a public health simulation study on a realistic virtual population

Thesis

Oct 2017

Hai-Ha LE

Type 2 diabetes (T2D) has increasingly become a common metabolic condition, associated with numerous micro and macro-vascular complications. Diabetic patients are at about two-time higher risk of sudden cardiac death (SCD), compared to non-diabetic ones. Pharmacologic intervention (anti-platelet, anti-hypertensive, lipid lowering, and to a lesser extent, anti-diabetic agents) appear to be the most efficient and economic candidate to prevent this event at long term, yet treatment effects have not well addressed. We aimed to optimize their use and estimate their impact on public health via analysis, synthesis and modeling studies.This work engaged three phases: First, to construct a risk score to predict SCD risk in T2D from the INDANA database. Second, to perform the meta-analyses/systematic reviews of different therapeutic strategies in order to estimate their effects on SCD risk. Finally, to simulate therapeutic strategies on a generated French diabetic realistic virtual population (RVP) of T2D, by estimating the occurrence of SCD with and without treatments, thus their absolute benefits, through the Number of Events Prevented (NEP) due to treatment, and the Number of patients Needed to be Treated to prevent one SCD (NNT).We built a 7-risk factor to predict 5-year risk of SCD in patients with hypertension (+/-diabetes) and collected the best evidence on drugs’ effects. Integrating and simulating altogether on a generated French diabetic RVP suggested that for every 57 individuals of the 10% highest predicted SCD risk, the co-prescription of angiotensin converting enzyme inhibitor-aspirin-empagliflozin could prevent one SCD in 5 years. For the whole population, the corresponding number was 135. In perspectives, this approach could help better transposing clinical trial results into practice and facilitating clinical decision at both public health and individual levels

Rimonabant as an adjunct therapy in overweight/obese patients with type 2 diabetes: reply

Article

Full-text available

Jun 2007

Diabetes and the risk of sudden cardiac death, the Atherosclerosis Risk in Communities study

Article

Full-text available

Oct 2009
ACTA DIABETOL

Studies suggest that diabetes may specifically elevate the risk of sudden cardiac death in excess of other heart disease outcomes. In this study, we examined the association of type 2 diabetes with the incidence of sudden cardiac death when compared to the incidence of non-sudden cardiac death and non-fatal myocardial infarction (MI). We used data from the Atherosclerosis Risk in Communities (ARIC) study to examine the incidence of sudden and non-sudden cardiac death and non-fatal MI among persons with and without diabetes in follow-up from the baseline data collection (1987-1989) through December 31, 2001. There were 209 cases of sudden cardiac death, 119 of non-sudden cardiac death, and 739 of non-fatal MI identified in this cohort over an average 12.4 years of follow-up. In analyses adjusted for age, race/ARIC center, gender, and smoking, the Cox proportional hazard ratio of the association of baseline diabetes was 3.77 (95% CI 2.82, 5.05) for sudden cardiac death, 3.78 (95% CI 2.57, 5.53) for non-sudden cardiac death, and 3.20 (95% CI 2.71, 3.78) for non-fatal MI. Elevated risk for each of the three outcomes associated with diabetes was independent of adjustment for measures of blood pressure, lipids, inflammation, hemostasis, and renal function. Among those with diabetes, the risk of cardiac death, but not of non-fatal MI, was similar for men and women. Findings from this prospective, population-based cohort investigation indicate that diabetes does not confer a specific excess risk of sudden cardiac death. Our results suggest that diabetes attenuates gender differences in the risk of fatal cardiac events.

Prolonged QT period in diabetic autonomic neuropathy: A possible role in sudden cardiac death?

Article

Full-text available

Apr 1988
Br Heart J

Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy.

The impact of diabetes mellitus and prior myocardial infarction on mortality from all causes and from coronary heart disease in men

Article

Full-text available

Sep 2002
J AM COLL CARDIOL

The goal of this study was to examine the impact of diabetes and prior myocardial infarction (MI) on mortality in men. Previous studies have suggested that a history of diabetes and a prior MI confer similar risk for subsequent fatal coronary heart disease (CHD). Few studies have examined duration of diabetes in relation to mortality. We examined type 2 diabetes and prior MI in relation to mortality among 51,316 men aged 40 to 75 years in the Health Professionals Follow-up Study. During 10 years of follow-up, we documented 4,150 deaths from all causes, including 1,124 deaths from CHD. Compared with men without diabetes or prior MI at baseline, the multivariate relative risks (RRs) for fatal CHD were 3.84 (95% confidence interval [CI], 3.12 to 4.71) for those with diabetes only, 7.88 (95% CI, 6.86 to 9.05) for those with MI only, and 13.41 (95% CI, 10.49 to 17.16) for those with both diabetes and MI. The corresponding RRs for total mortality were 1.91 (95% CI, 1.70 to 2.15), 2.23 (95% CI, 2.03 to 2.45), and 3.13 (95% CI, 2.56 to 3.84), respectively. Duration of diabetes was an independent risk factor for total as well as CHD mortality; the multivariate RRs of CHD mortality for increasing duration of diabetes (< or = 5 years, 6 to 10 years, 11 to 15 years, 16 to 25 years, 26+ years) were 1.63, 1.93, 2.35, 2.31, and 3.87, respectively (p for trend <0.001), compared with nondiabetic participants. These findings support that both diabetes and MI are associated with elevated total and CHD mortality, and having both conditions is particularly hazardous. Longer duration of diabetes is a strong predictor of death among diabetic men.

Trends in Cardiovascular Complications of Diabetes

Article

Full-text available

Dec 2004
J Am Med Assoc

Despite reductions in cardiovascular disease (CVD) mortality over the past few decades, it is unclear whether adults with and without diabetes have experienced similar declines in CVD risk. To determine whether adults with and without diabetes experienced similar declines in incident CVD in 1950-1995. Participants aged 45-64 years from the Framingham Heart Study original and offspring cohorts who attended examinations in 1950-1966 ("earlier" time period; 4118 participants, 113 with diabetes) and 1977-1995 ("later" time period; 4063 participants, 317 with diabetes). Incidence rates of CVD among those with and without diabetes were compared between the earlier and later periods. Myocardial infarction, coronary heart disease death, and stroke. Among participants with diabetes, the age- and sex-adjusted CVD incidence rate was 286.4 per 10,000 person-years in the earlier period and 146.9 per 10,000 in the later period, a 49.3% (95% confidence interval [CI], 16.7%-69.4%) decline. Among participants without diabetes, the age- and sex-adjusted incidence rate was 84.6 per 10,000 person-years in the earlier period and 54.3 per 10,000 person-years in the later period, a 35.4% (95% CI, 25.3%-45.4%) decline. Hazard ratios for diabetes as a predictor of incident CVD were not different in the earlier vs later periods. We report a 50% reduction in the rate of incident CVD events among adults with diabetes, although the absolute risk of CVD is 2-fold greater than among persons without diabetes. Adults with and without diabetes have benefited similarly during the decline in CVD rates over the last several decades. More aggressive treatment of CVD risk factors and further research on diabetes-specific factors contributing to CVD risk are needed to further reduce the high absolute risk of CVD still experienced by persons with diabetes.

Sudden cardiac death in diabetes mellitus: Risk factors in the Rochester diabetic neuropathy study

Article

Full-text available

Mar 2005

To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS). Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death. 21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p<0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease. Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

Diabetes, Glucose, Insulin, and Heart Rate Variability The Atherosclerosis Risk in Communities (ARIC) study

Article

Full-text available

Apr 2005
DIABETES CARE

To describe the progression of autonomic impairment among individuals with diabetes and pre-diabetic metabolic impairments. We investigated the consequence of diabetes and pre-diabetic metabolic impairments on the 9-year change in heart rate variability (HRV) in a population-based cohort of 6,245 individuals aged 45-64 years at baseline and cross-sectional associations among 9,940 individuals. Diabetic subjects had a more rapid temporal decrease in HRV conditional on baseline HRV than nondiabetic subjects. Adjusted mean annual changes (95% CI) (ms/year) in the SD of all normal-to-normal R-R intervals were -0.65 (-0.69 to -0.61) for those with normal fasting glucose vs. -0.95 (-1.09 to -0.81) for diabetic subjects, in root mean square of successive differences in normal-to-normal R-R intervals -0.35 (-0.39 to -0.30) vs. -0.66 (-0.82 to -0.51), and in R-R interval 6.70 (6.37-7.04) vs. 3.89 (2.72-5.05). While we found cross-sectional associations between decreased HRV and diabetes and nondiabetic hyperinsulinemia and a weak inverse association with fasting glucose, neither impaired fasting glucose nor nondiabetic hyperinsulimenia was associated with a measurably more rapid decline in HRV than normal. Cardiac autonomic impairment appears to be present at early stages of diabetic metabolic impairment, and progressive worsening of autonomic cardiac function over 9 years was observed in diabetic subjects. The degree to which pre-diabetic metabolic impairments in insulin and glucose metabolism contribute to decreases in cardiac autonomic function remains to be determined.

Electrocardiographic QT Interval Prolongation and Risk of Primary Cardiac Arrest in Diabetic Patients

Article

Full-text available

Sep 2005
DIABETES CARE

Sudden cardiac death, also known as primary cardiac arrest (PCA), is a major cause of mortality among diabetic patients and typically occurs in the setting of coronary heart disease. Because it can occur as the first clinical manifestation of coronary heart disease, identifying diabetic patients at risk of PCA remains challenging. Interrelated sequelae of diabetes, including QT prolongation and autonomic failure (1, 2), have been repeatedly implicated in the pathophysiology of PCA (3–6). However, it remains unknown whether the QT interval on a 12-lead electrocardiogram (ECG) has potential utility in risk stratification of diabetic patients without prior physician-diagnosed heart disease for PCA (7–12). We therefore conducted a case-control study of PCA in a large prepaid health plan, Group Health Cooperative of Puget Sound. We included patients age 18–79 years who were enrolled for ≥1 year or had four or more clinic visits in the prior year, had physician-diagnosed diabetes noted in their ambulatory care medical record or were treated with oral hypoglycemics or insulin, and had an ECG recorded before their index date (see below). We excluded enrollees with prior physician-diagnosed heart disease (Table 1). Patients were diabetic enrollees who experienced out-of-hospital PCA (a sudden, pulseless condition without a known noncardiac cause) between …

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD)

Article

Full-text available

Feb 2007

Cardiometabolic Risk in Impaired Fasting Glucose and Impaired Glucose Tolerance The Atherosclerosis Risk in Communities Study

Article

Full-text available

Mar 2007
DIABETES CARE

We compared and contrasted cardiovascular disease (CVD) risk factors, subclinical manifestations of CVD, incident coronary heart disease (CHD), and all-cause mortality by categories of impaired glucose regulation in nondiabetic individuals. The study included 6,888 participants aged 52-75 years who had no history of diabetes or CVD. All-cause mortality and incident CHD were ascertained over a median of 6.3 years of follow-up. Agreement between fasting and postchallenge glucose impairment was poor: 3,048 subjects (44%) had neither impaired fasting glucose (IFG) nor impaired glucose tolerance (IGT), 1,690 (25%) had isolated IFG, 1,000 (14%) had isolated IGT, and 1,149 (17%) had both IFG and IGT. After adjustment for age, sex, race, and center, subjects with isolated IFG were more likely to smoke, consume alcohol, and had higher mean BMI, waist circumference, LDL cholesterol, and fasting insulin and lower HDL cholesterol than those with isolated IGT, while subjects with isolated IGT had higher mean triglycerides, systolic blood pressure, and white cell counts. Measures of subclinical CVD and rates of all-cause mortality and incident CHD were similar in isolated IFG and isolated IGT. Neither isolated IFG nor isolated IGT was associated with a more adverse CVD risk profile.

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus: A Scientific Statement From the American Heart Association and the American Diabetes Association Response to Buse et al.

Article

Full-text available

Jul 2007

The recent American Diabetes Association/American Heart Association statement recommends the use of low doses of aspirin as a strategy for primary prevention of cardiovascular diseases in all individuals with diabetes aged >40 years or who have additional risk factors (1). Like in previous recommendations (2), only selected pieces of evidence are mentioned to support this statement. The data used to sustain the efficacy of aspirin come from the Early Treatment Diabetic Retinopathy Study, the only study specifically conducted in diabetic patients with and without previous cardiovascular disease (3). In this trial, treatment with 650 mg aspirin for 5 years was associated with a nonsignificant 9% reduction in the primary end …

Diabetic retinopathy is associated with an increased incidence of cardiovascular events in Type 2 diabetic patients - Reply

Article

Jul 2008

Giovanni Targher

Diabetes mellitus and mortality from all-causes and coronary heart disease in women: 20 years of follow up

Article

May 2000
DIABETES

Guidelines on Diabetes, Pre-Diabetes, and Cardiovascular Diseases: Executive Summary The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD).

Article

Jan 2007
Rev Esp Cardiol

Trends in Cardiovascular Complications of Diabetes--Reply

Article

Jan 2005

Caroline S Fox

Context Despite reductions in cardiovascular disease (CVD) mortality over the past few decades, it is unclear whether adults with and without diabetes have experienced similar declines in CVD risk.Objective To determine whether adults with and without diabetes experienced similar declines in incident CVD in 1950-1995.Design, Setting, and Participants Participants aged 45-64 years from the Framingham Heart Study original and offspring cohorts who attended examinations in 1950-1966 (“earlier” time period; 4118 participants, 113 with diabetes) and 1977-1995 (“later” time period; 4063 participants, 317 with diabetes). Incidence rates of CVD among those with and without diabetes were compared between the earlier and later periods.Main Outcome Measures Myocardial infarction, coronary heart disease death, and stroke.Results Among participants with diabetes, the age- and sex-adjusted CVD incidence rate was 286.4 per 10 000 person-years in the earlier period and 146.9 per 10 000 in the later period, a 49.3% (95% confidence interval [CI], 16.7%-69.4%) decline. Among participants without diabetes, the age- and sex-adjusted incidence rate was 84.6 per 10 000 person-years in the earlier period and 54.3 per 10 000 person-years in the later period, a 35.4% (95% CI, 25.3%-45.4%) decline. Hazard ratios for diabetes as a predictor of incident CVD were not different in the earlier vs later periods.Conclusions We report a 50% reduction in the rate of incident CVD events among adults with diabetes, although the absolute risk of CVD is 2-fold greater than among persons without diabetes. Adults with and without diabetes have benefited similarly during the decline in CVD rates over the last several decades. More aggressive treatment of CVD risk factors and further research on diabetes-specific factors contributing to CVD risk are needed to further reduce the high absolute risk of CVD still experienced by persons with diabetes.

Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients

Article

Apr 1991

QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group. Thirty-two male diabetic subjects with varying degrees of autonomic dysfunction had repeat QT measurements 3 (range 2-6) years later. QT and QTC lengthened significantly at the second visit, unrelated to age or time between recordings, but which corresponded with changes in autonomic function. Of 71 male diabetic subjects under 60 years followed for 3 years, 13 had died, 8 unexpectedly. Of those with autonomic neuropathy. QT and QTC were significantly longer in those who subsequently died, despite similar ages and duration of diabetes. We conclude that QT/RR interval relationships are altered in diabetic autonomic neuropathy, and that changes in QT length with time parallel changes in autonomic function. There may be an association between QT interval prolongation and the risk of dying unexpectedly in diabetic autonomic neuropathy.

QT Interval Prolongation and Sudden Cardiac Death in Diabetic Autonomic Neuropathy*

Article

May 1987

Alterations in cardiac sympathetic innervation may result in QT interval prolongation and predispose to sudden arrhythmias and death. Sudden cardiac death occurs in diabetic patients who have autonomic neuropathy, but the cause is uncertain. In 30 patients with insulin-dependent diabetes mellitus who had no evidence of ischemic heart disease, cardiac autonomic neuropathy, determined by clinical tests, was found in 17. The corrected QT interval (QTc), measured using Bazett's formula at rest and peak exercise, was prolonged (greater than 440 msec) in 12 of these patients at rest and in 15 at peak exercise. Prolonged QTc intervals were found only in patients who had definite cardiac autonomic neuropathy. As a group, the QTc interval (mean +/- SD) in the diabetic patients with cardiac autonomic neuropathy was prolonged compared to that in patients without cardiac autonomic neuropathy at rest (447 +/- 28 vs. 405 +/- 9 ms; P less than 0.0001) and peak exercise (468 +/- 23 vs. 402 +/- 23 ms; P less than 0.0001). There was a direct linear relationship between the extent of cardiac autonomic neuropathy and the QTc interval (r = 0.71; P less than 0.001). One of the patients with cardiac autonomic neuropathy and prolonged QTc intervals had a nonuniform loss of adrenergic neurons in his heart demonstrated by meta-iodobenzyl-guanidine scintigraphy, indicating sympathetic imbalance; he subsequently died unexpectedly. These data suggest that diabetic cardiac autonomic neuropathy may result in sympathetic imbalance and QTc interval prolongation, predisposing these patients to sudden arrhythmias and death.

The natural history of diabetic autonomic neuropathy

Article

Feb 1980
QJM

Seventy-three diabetics (62 males and 11 females) who complained of symptoms suggestive of autonomic neuropathy were followed prospectively for up to five years. Thirty patients presented with impotence alone, while the other 43 presented with one or more of the following: postural hypotension, intermittent diarrhoea, hypoglycaemic unawareness, sweating abnormalities and gastric fullness. Most subjects with impotence alone had normal autonomic function tests (responses to the Valsalva manoeuvre and sustained handgrip) whereas the majority with other symptoms had abnormal tests. Twenty-six subjects (20 males and six females) died during the follow-up period. Of the 33 with initially normal autonomic function tests, five (15 per cent) died, whereas of the 40 with initially abnormal tests, 21 (53 per cent) died. Diabetics with symptoms of autonomic neuropathy and abnormal autonomic function tests, had a calculated mortality rate after two-and-a-half years of 44 per cent and after five years of 56 per cent. Half the deaths in those with abnormal tests were from renal failure, and the remainder were either sudden and unexpected, or from other causes which may have been associated with the autonomic neuropathy. Autonomic function testing repeated during the follow-up period showed that some normal tests later became abnormal, but once tests were abnormal, they usually remained abnormal. A number of subjects with impotence alone developed other features of autonomic neuropathy and abnormal tests during the follow up period. Symptoms of autonomic neuropathy, particularly postural hypotension, gastric symptoms and hypoglycaemic unawareness, together with abnormal autonomic function tests, carry a very poor prognosis. Diarrhoea and importence, on their own, cannot be relied on as symptoms of autonomic neuropathy. Autonomic function testing using simple cardiovascular reflexes give a good guide to the prognosis of diabetic autonomic neuropathy.

Sudden Death, Impaired Glucose Tolerance, and Diabetes in Japanese American Men

Article

May 1995

Diabetes and glucose intolerance have been shown to increase the risk of cardiovascular mortality in a number of different populations. Most studies have been based on short follow-up periods, and few have had sufficient numbers to allow researchers to look at sudden death as an outcome. The relation of sudden death, defined as unexpected death occurring within either 1 or 24 hours of first symptoms, to glucose intolerance measured by a nonfasting 1-hour postload measurement made in 1965 or history of diabetes was examined by use of 23 years of follow-up on the 8006 participants enrolled in the Honolulu Heart Program. After adjustment for baseline body mass index, hypertension, cholesterol, triglycerides, smoking, alcohol consumption, and left ventricular hypertrophy or strain, the relative risks for sudden death within 24 hours in individuals with high-normal (151 to 224 mg/dL), asymptomatic high glucose values (> or = 225 mg/dL), and diabetes compared with those with lower glucose values (< 151 mg/dL) were 1.59, 2.22, and 2.76, respectively. All these relative risks were statistically significant (P < or = .05). Trends for sudden death in 1 hour were similar. Among men with sudden death < 1 hour after onset of symptoms, the strength of the association between diabetes and sudden death was stronger among those classified as having died of unknown causes who thus were more likely to have died of an arrhythmia than among those classified as having died of coronary heart disease. The relations seen in these analyses indicate that individuals with glucose intolerance or diagnosed diabetes are at increased risk for sudden death.

Epidemiology of sudden coronary death: An overview

Article

Jul 1994
PROG CARDIOVASC DIS

Mortality in Diabetic Patients with Cardiovascular Autonomic Neuropathy

Article

Dec 1993

Cardiovascular autonomic diabetic neuropathy (CADN) may carry an increased risk of mortality. However, in previous studies the prognosis of patients with CADN seemed to be influenced by life-threatening macro- and microvascular complications which had already been present at the start of the study period. Between 1981 and 1983, 1015 diabetic patients have been examined for CADN (abnormal heart rate variation at rest and during deep respiration) at the Diabetes Research Institute, Düsseldorf. Thirty-five patients (28 with Type 1 diabetes, 7 with Type 2 diabetes) with CADN have been retrospectively recruited and reviewed 8 years later and compared with 35 patients without CADN who were matched for sex, age, and duration of diabetes. Exclusion criteria for entry into the study included severe micro- or macrovascular complications, such as proliferative retinopathy, proteinuria or symptomatic coronary artery disease. During the 8-year observation period, 8 patients with CADN and 1 patient without CADN died. The survival rate estimates steadily declined in patients with CADN over the whole period studied. The 8-year survival rate estimate in patients with CADN was 77% compared with 97% in those with normal autonomic function (p < 0.05). Deaths were mainly due to macrovascular diseases (n = 3) and sudden unexpected deaths (n = 3). One patient with CADN died after an episode of severe hypoglycaemia. Among the decreased patients, coefficient of variation of R-R intervals during deep breathing was significantly reduced when compared with those who survived (1.04 +/- 0.5% vs 1.87 +/- 1.0%; p < 0.05), and symptoms of autonomic neuropathy (orthostatic hypotension, gastroparesis, gustatory sweating) were more frequent (7/8 vs 10/27 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden coronary death in women

Article

Aug 1998
AM HEART J

The objective of this study was to examine prospectively the incidence, predisposing cardiovascular conditions, and risk factors for sudden death in women compared with men. The study design was a prospective general population examination of a cohort of 2873 women for development of sudden coronary death in relation to antecedent overt coronary heart disease (CHD), cardiac failure, and risk factors for coronary heart disease. Participants were women aged 30 to 62 years participating in the Framingham Study, receiving routine biennial examinations for risk factors and cardiovascular conditions. Among women monitored over a period of 38 years, there were 750 initial coronary events, of which 94 (12%) were sudden cardiac deaths. Of the 292 CHD fatalities in women, 32% were sudden cardiac deaths and 37% of the women had a history of prior CHD. Sudden death incidence in women logged behind that in men by >10 years. However, above age 75 years, 17% of all CHD events in women were sudden deaths. Sudden death risk in women with CHD was half as high as in men if they had CHD. In both sexes, a myocardial infarction conferred twice the risk of angina. Cardiac failure escalated sudden death risk of women 5-fold but was only one fourth that of men with failure or CHD. Ventricular ectopy increased sudden death risk only in women without prior overt CHD. Except for diabetes, CHD risk factors imposed a lower sudden death risk in women than men. However, even in women, sudden death risk increased over a 17-fold range in relation to their burden of CHD risk factors. Sudden death is a prominent feature of CHD in women as well as men, particularly in advanced age. A higher fraction of sudden deaths in women than men is unexpected occurring in the absence of prior overt CHD. It is subject to the same risk factors and as predictable in women as in men. However, at any level of multivariate risk, women are less vulnerable to sudden death than men.

Diabetes as a risk factor for sudden death

Article

Jan 2000

Although a family history of sudden death was a risk factor for sudden death in the Paris Prospective Study I, diabetes was also a strong risk factor, with a similar risk after accounting for other cardiovascular risk factors. Diabetes, however, was not a risk factor for death by myocardial infarction.

Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study)

Article

Aug 2000
AM J CARDIOL

This study was designed to examine the association of heart rate variability (HRV) with blood glucose levels in a large community-based population. Previous reports have shown HRV to be reduced in diabetics, suggesting the presence of abnormalities in neural regulatory mechanisms. There is scant information about HRV across the spectrum of blood glucose levels in a population-based cohort. One thousand nine hundred nineteen men and women from the Framingham Offspring Study, who underwent ambulatory electrocardiographic recordings at a routine examination, were eligible. HRV variables included the SD of normal RR intervals (SDNN), high-frequency (HF, 0.15 to 0.40 Hz) and low-frequency (LF, 0.04 to 0.15 Hz) power, and LF/HF ratio. Fasting plasma glucose levels were used to classify subjects as normal (<110 mg/dl; n = 1, 779), as having impaired fasting glucose levels (110 to 125 mg/dl; n = 56), and as having diabetes mellitus (DM >/=126 mg/dl or receiving therapy; n = 84). SDNN, LF and HF power, and LF/HF ratio were inversely related to plasma glucose levels (p <0.0001). SDNN and LF and HF powers were reduced in DM subjects (4.28 +/- 0.03, 6.03 +/- 0. 08, and 4.95 +/- 0.09) and in subjects with impaired fasting glucose levels (4.37 +/- 0.04, 6.26 +/- 0.10, and 5.06 +/- 0.11) compared with those with normal fasting glucose (4.51 +/- 0.01, 6.77 +/- 0.02, and 5.55 +/- 0.02, all p <0.005), respectively. After adjusting for covariates (age, sex, heart rate, body mass index, antihypertensive and cardiac medications, systolic and diastolic blood pressures, smoking, and alcohol and coffee consumption), LF power and LF/HF ratio were lower in DM subjects than in those with normal fasting glucose (p <0.005). HRV is inversely associated with plasma glucose levels and is reduced in diabetics as well as in subjects with impaired fasting glucose levels. Additional research is needed to determine if low HRV contributes to the increased cardiovascular morbidity and mortality described in subjects with hyperglycemia.

Diabetes and All-Cause and Coronary Heart Disease Mortality Among US Male Physicians

Article

Feb 2001
ARCH INTERN MED

While diabetes has long been associated with increased risk of coronary heart disease (CHD), the magnitude of risk of diabetes-related CHD is uncertain. To evaluate the impact of diabetes and prior CHD on all-cause and CHD mortality. In a prospective cohort study of 91 285 US male physicians aged 40 to 84 years, participants were divided into 4 groups: (1) a reference group of 82 247 men free of both diabetes and CHD (previous myocardial infarction and/or angina) at baseline, (2) 2317 men with a history of diabetes but not CHD, (3) 5906 men with a history of CHD but not diabetes, and (4) 815 men with a history of both diabetes and CHD. Rates of all-cause and CHD mortality were compared in these groups. Over 5 years (49 7952 person-years of follow-up), 3627 deaths from all causes were documented, including 1242 deaths from CHD. Compared with men with no diabetes or CHD, the age-adjusted relative risk of death from any cause was 2.3 (95% confidence interval [CI], 2.0-2.6) among men with diabetes and without CHD, 2.2 (95% CI, 2.0-2.4) among men with CHD and without diabetes, and 4.7 (95% CI, 4.0-5.4) among men with both diabetes and CHD. The relative risk of CHD death was 3.3 (95% CI, 2.6-4.1) among men with diabetes and without CHD, 5.6 (95% CI, 4.9-6.3) among men with CHD and without diabetes, and 12.0 (95% CI, 9.9-14.6) among men with both diabetes and CHD. Multivariate adjustment for body mass index, smoking status, alcohol intake, and physical activity as well as stratification by these variables did not materially alter these associations. These prospective data indicate that diabetes is associated with a substantial increase in all-cause and CHD mortality. For all-cause mortality, the magnitude of excess risk conferred by diabetes is similar to that conferred by a history of CHD; for mortality from CHD, a history of CHD is a more potent predictor of death. The presence of both diabetes and CHD, however, identifies a particularly high-risk group.

Reducing mortality from sudden cardiac death in the community: Lessons from epidemiology and clinical applications research

Article

Jun 2001

The reduction of mortality from sudden cardiac death (SCD) in the community remains a challenge. Clinical-epidemiologic studies have identified a range of factors that are associated with an increased risk of SCD. While of potential etiologic and prognostic importance, these factors have limited sensitivity and a low positive predictive value for SCD. On the other hand, clinical trials have suggested that a variety of interventions, including risk factor reduction, nutritional interventions, drug therapies, cardiac procedures, and new technologies, have the potential to reduce mortality from SCD. In this review, we examine what is known about the epidemiology and clinical application of interventions to reduce mortality from SCD; and, we consider the impact of both prevention and clinical interventions on mortality from SCD from a community perspective. There is mounting evidence that supports both public health and clinical efforts to prevent the occurrence of SCD. There also is evidence suggesting that new technologies, such as automated external defibrillators, have the potential to reduce case-fatality from SCD. Further progress will depend on improved methods to identify persons-at-risk, reduction of risk factors, and application of techniques -- both simple and advanced -- to improve survival in victims of SCD.

The Impact of Diabetes Mellitus on Mortality From All Causes and Coronary Heart Disease in Women

Article

Aug 2001
ARCH INTERN MED

Few data are available on the long-term impact of type 2 diabetes mellitus on total mortality and fatal coronary heart disease (CHD) in women. We examined prospectively the impact of type 2 diabetes and history of prior CHD on mortality from all causes and CHD among 121 046 women aged 30 to 55 years with type 2 diabetes in the Nurses' Health Study who were followed up for 20 years from 1976 to 1996. During 20 years of follow-up, we documented 8464 deaths from all causes, including 1239 fatal CHD events. Compared with women with no diabetes or CHD at baseline, age-adjusted relative risks (RRs) of overall mortality were 3.39 (95% confidence interval [CI], 3.08-3.73) for women with a history of diabetes and no CHD at baseline, 3.00 (95% CI, 2.50-3.60) for women with a history of CHD and no diabetes at baseline, and 6.84 (95% CI, 4.71-9.95) for women with both conditions at baseline. The corresponding age-adjusted RRs of fatal CHD across these 4 groups were 1.0, 8.70, 10.6, and 25.8, respectively. Multivariate adjustment for body mass index and other coronary risk factors only modestly attenuated the RRs. Compared with nondiabetic persons, the multivariate RRs of fatal CHD across categories of diabetes duration (< or =5, 6-10, 11-15, 16-25, >25 years) were 2.75, 3.63, 5.51, 6.38, and 11.9 (P< .001 for trend), respectively. The combination of prior CHD and a long duration of clinical diabetes (ie, >15 years) was associated with a 30-fold (95% CI, 20.7-43.5) increased risk of fatal CHD. Our data indicate that among women, history of diabetes is associated with dramatically increased risks of death from all causes and fatal CHD. The combination of diabetes and prior CHD identifies particularly high-risk women.

Sudden Cardiac Death in the United States, 1989 to 1998

Article

Oct 2001
CIRCULATION

Sudden cardiac death (SCD) is a major clinical and public health problem. United States (US) vital statistics mortality data from 1989 to 1998 were analyzed. SCD is defined as deaths occurring out of the hospital or in the emergency room or as "dead on arrival" with an underlying cause of death reported as a cardiac disease (ICD-9 code 390 to 398, 402, or 404 to 429). Death rates were calculated for residents of the US aged >/=35 years and standardized to the 2000 US population. Of 719 456 cardiac deaths among adults aged >/=35 years in 1998, 456 076 (63%) were defined as SCD. Among decedents aged 35 to 44 years, 74% of cardiac deaths were SCD. Of all SCDs in 1998, coronary heart disease (ICD-9 codes 410 to 414) was the underlying cause on 62% of death certificates. Death rates for SCD increased with age and were higher in men than women, although there was no difference at age >/=85 years. The black population had higher death rates for SCD than white, American Indian/Alaska Native, or Asian/Pacific Islander populations. The Hispanic population had lower death rates for SCD than the non-Hispanic population. From 1989 to 1998, SCD, as the proportion of all cardiac deaths, increased 12.4% (56.3% to 63.9%), and age-adjusted SCD rates declined 11.7% in men and 5.8% in women. During the same time, age-specific death rates for SCD increased 21% among women aged 35 to 44 years. SCD remains an important public health problem in the US. The increase in death rates for SCD among younger women warrants additional investigation.

Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes

Article

Dec 2002
DIABETES RES CLIN PR

The objective of this study is to evaluate whether autonomic neuropathy predicts short term all-cause mortality in an elderly cohort of veteran patients with diabetes. All of the diabetic patients receiving primary care at one VA medical center were eligible for participation, between 1990 and 1997. One thousand and fifteen patients were identified, of whom 14% declined to participate, so that a total of 843 diabetic patients were enrolled. Autonomic neuropathy was evaluated by heart rate response to timed deep breathing. One hundred and fifty one patients have died since the onset of the study. Mean follow-up was 42.4 months. Subjects who died had greater diabetes duration compared with survivors (13.1 vs. 11.4 years, P=0.04) but were comparable with regards to type of diabetes and mean glycosylated hemoglobin level. The Cox proportional hazards analysis, adjusting for age, smoking status, creatinine, pack-years of cigarettes smoked, diabetes duration, race, history of ischemic heart disease and hypertension showed that those patients with the lowest quintile of heart rate variability had a significantly increased risk of mortality (hazard ratio=1.49, 95% confidence limits 1.01-2.19). This study supports the hypothesis that decreased heart rate variability is an independent risk factor for mortality in diabetic patients followed in a primary care setting.

Prospective Study of Sudden Cardiac Death Among Women in the United States

Article

May 2003
CIRCULATION

There are few data regarding the determinants of sudden cardiac death (SCD) in women, primarily because of their markedly lower rate of SCD compared with men. Nonetheless, existing data, although sparse, suggest possible gender differences in risk factors for SCD. In this prospective cohort of 121 701 women aged 30 to 55 years at baseline, SCD was defined as death within 1 hour of symptom onset. From 1976 to 1998, 244 SCDs were identified. Although the risk of SCD increased markedly with age, the percentage of cardiac deaths that were sudden decreased. Most (69%) women who suffered a SCD had no history of cardiac disease before their death. However, almost all of the women who died suddenly (94%) had reported at least 1 coronary heart disease risk factor. Smoking, hypertension, and diabetes conferred markedly elevated (2.5- to 4.0-fold) risk of SCD, similar to that conferred by a history of nonfatal myocardial infarction (relative risk, 4.1; 95% confidence interval, 2.9 to 6.7). Family history of myocardial infarction before age 60 years and obesity were associated with moderate (1.6-fold) elevations in risk. With regard to mechanism, 88% of SCDs were classified as arrhythmic. In 76% of these, the first rhythm documented was ventricular tachycardia or ventricular fibrillation. These prospective data suggest that, as in men, coronary heart disease risk factors predict risk of SCD in women and that SCD is usually an arrhythmic death. Therefore, prevention of atherosclerosis or ventricular arrhythmias may reduce the incidence of SCD in women.

Cardiovascular Events in Diabetic and Nondiabetic Adults With or Without History of Myocardial Infarction

Article

Feb 2004
CIRCULATION

Whether diabetic patients without a history of myocardial infarction (MI) have the same risk of coronary heart disease (CHD) events as nondiabetic patients with a history of MI remains controversial. We compared risks of CHD and stroke events and mortality from cardiovascular disease (CVD) in diabetic and nondiabetic men and women with and without a history of MI. We followed a total of 13 790 African American and white men and women ages 45 to 64 years who participated in the Atherosclerosis Risk in Communities study, beginning in 1987 to 1989. There were 634 fatal CHD or nonfatal MI events, 312 fatal or nonfatal strokes, and 358 deaths from CVD during an average of 9 years of follow-up (125 998 person-years). After adjustment for age, sex, race, Atherosclerosis Risk in Communities field center, and multiple baseline risk factors, patients who had a history of MI without diabetes at baseline had 1.9 times the risk of fatal CHD or nonfatal MI (95% CI, 1.35 to 2.56; P<0.001) compared with diabetic patients without a prior history of MI. The nondiabetic patients with MI also had 1.8 times the risk of CVD mortality compared with diabetic patients without MI (95% CI, 1.22 to 2.72; P=0.003). However, stroke risk was similar between diabetic patients without MI and nondiabetic patients with MI (RR, 1.05; 95% CI, 0.61 to 1.79; P=0.87). We also observed that nondiabetic patients with MI had a carotid artery wall thickness similar to diabetic patients without MI (P=0.77). Diabetic patients without MI had lower risk of CHD events and mortality from CVD compared with nondiabetic patients with MI, but stroke risk was similar between these 2 groups.

Sudden cardiac death in patients with diabetes

Article

Jul 2004

Sudden cardiac death (SCD) affects over 450,000 people in the United States annually. The mechanisms involved are poorly understood. The predictors currently known include traditional coronary heart disease risk factors, electrocardiographic abnormalities, cardiac autonomic neuropathy, left ventricular hypertrophy, cardiomyopathy, and conduction abnormalities. Diabetes mellitus and impaired glucose tolerance are of special importance due to their increased prevalence reaching epidemic proportions and the elevated risk of SCD in people with these disorders. This article reviews the current predictors of SCD with a focus on people with diabetes, hoping to offer physicians and researchers a better understanding of and a solid ground for further needed research on this important cause of premature death.

Incidence of Out-of-Hospital cardiac arrest

Article

Jul 2004
AM J CARDIOL

Estimates of the incidence of out-of-hospital primary cardiac arrest (CA) have typically relied solely upon emergency medical service or death certificate records and have not investigated incidence in clinical subgroups. Overall and temporal patterns of CA incidence were investigated in clinically defined groups using systematic methods to ascertain CA. Estimates of incidence were derived from a population-based case-control study in a large health plan from 1986 to 1994. Subjects were enrollees aged 50 to 79 years who had had CA (n = 1,275). A stratified random sample of enrollees who had not had CA was used to estimate the population at risk with various clinical characteristics (n = 2,323). Poisson's regression was used to estimate incidence overall and for 3-year time periods (1986 to 1988, 1989 to 1991, and 1992 to 1994). The overall CA incidence was 1.89/1,000 subject-years and varied up to 30-fold across clinical subgroups. For example, incidence was 5.98/1,000 subject-years in subjects with any clinically recognized heart disease compared with 0.82/1,000 subject-years in subjects without heart disease. In subgroups with heart disease, incidence was 13.69/1,000 subject-years in subjects with prior myocardial infarction and 21.87/1,000 subject-years in subjects with heart failure. Risk decreased by 20% from the initial to the final time period, with a greater decrease observed in those with (25%) compared with those without (12%) clinical heart disease. Thus, CA incidence varied considerably across clinical groups. The results provide insights regarding absolute and population-attributable risk in clinically defined subgroups, information that may aid strategies aimed at reducing mortality from CA.

Diabetes, glucose level, and risk of sudden cardiac death

Article

Oct 2005

The prevalence of diabetes mellitus in industrialized countries is rapidly increasing, and diabetes is suspected to carry a particular high risk for sudden cardiac death (SCD). We conducted a population-based case-control study at Group Health Cooperative. Cases (n=2040) experienced out-of-hospital cardiac arrest due to heart disease between 1980 and 1994. Controls (n=3800) were a stratified random sample of enrollees. Diabetes status was classified into four exclusive groups: (i) no diabetes, (ii) borderline, (iii) diabetes without microvascular disease (retinopathy or proteinuria), and (iv) diabetes with microvascular disease. When compared with no diabetes, we observed progressively higher risk of SCD associated with borderline diabetes [Odds ratio (OR)=1.24 (0.98-1.57)], diabetes without microvascular disease [OR=1.73 (1.28-2.34)], and diabetes with microvascular disease [OR=2.66 (1.84-3.85)], after adjustment for potential confounders (P-value for trend <0.001). Higher glucose levels were also associated with the risk of SCD both in the absence and in the presence of microvascular disease. However, subjects with microvascular complications but with glucose level <7.7 mmol/L were not at significant increased risk of SCD. These results emphasize the role of diabetes as a strong risk factor for SCD and outline the importance of glucose level at every stage of diabetes severity.

ACC/AHA/HRS 2006 Key Data Elements and Definitions for Electrophysiological Studies and Procedures A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology)

Article

Jan 2007
CIRCULATION

ACC/AHA/HRS 2006 Key Data Elements and Definitions for Electrophysiological Studies and Procedures. A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology)

Article

Jan 2007

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus A Scientific Statement From the American Heart Association and the American Diabetes Association

Article

Feb 2007
CIRCULATION

The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: The ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Sudden cardiac death: Influence of diabetes

Article

Aug 2008
DIABETES OBES METAB

Peter M Spooner

This article reviews current thinking on the problem of sudden cardiac death (SCD) within community settings, highlighting progress in understanding risks and mechanisms. Information available on the influence of diabetes as a risk factor for SCD and the question of whether this disease enhances susceptibility to ventricular arrhythmias is summarized as are central strategies in risk stratification and mortality prevention.

Diabetic retinopathy of cardiovascular events in Type 2 diabetic patients

Article

Jan 2008
DIABETIC MED

We investigated the association of diabetic retinopathy with the risk of incident cardiovascular disease (CVD) events in a large cohort of Type 2 diabetic adults. Our study cohort comprised 2103 Type 2 diabetic outpatients who were free of diagnosed CVD at baseline. Retinal findings were classified based on fundoscopy (by a single ophthalmologist) to categories of no retinopathy, non-proliferative retinopathy and proliferative/laser-treated retinopathy. Outcomes measures were incident CVD events (i.e. non-fatal myocardial infarction, non-fatal ischaemic stroke, coronary revascularization procedures or cardiovascular death). During approximately 7 years of follow-up, 406 participants subsequently developed incident CVD events, whereas 1697 participants remained free of diagnosed CVD. After adjustment for age, body mass index, waist circumference, smoking, lipids, glycated haemoglobin, diabetes duration and medications use, patients with non-proliferative or proliferative/laser-treated retinopathy had a greater risk (P < 0.001 for all) of incident CVD events than those without retinopathy [hazard ratio 1.61 (95% confidence interval 1.2-2.6) and 3.75 (2.0-7.4) for men, and 1.67 (1.3-2.8) and 3.81 (2.2-7.3) for women, respectively]. After additional adjustment for hypertension and advanced nephropathy (defined as overt proteinuria and/or estimated glomerular filtration rate < or = 60 ml/min/1.73 m(2)), the risk of incident CVD remained markedly increased in those with proliferative/laser-treated retinopathy [hazard ratio 2.08 (1.02-3.7) for men and 2.41 (1.05-3.9) for women], but not in those with non-proliferative retinopathy. Diabetic retinopathy (especially in its more advanced stages) is associated with an increased CVD incidence independent of other known cardiovascular risk factors.

Overview of sudden cardiac arrest and sudden cardiac death

D S Siscovick
P J Podrid

key data elements and definitions for electrophysiological studies and procedures: a report of the American College of Cardiology

Jan 2006
2534-70

Ae Buxton
H Calkins
Dj Callans
Jp Dimarco
Jd Fisher
Hl Greene

Buxton AE, Calkins H, Callans DJ, DiMarco JP, Fisher JD, Greene HL, et al. ACC/AHA/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/ HRS Writing Committee to Develop Data Standards on Electrophysiology ). Circulation. 2006; 114(23):2534–70. [PubMed: 17130345]

The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up

Jan 2001
1717

F B Hu
M J Stampfer
C G Solomon
S Liu
W C Willett
F E Speizer
FB Hu

Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the

Jan 2007
114

J B Buse
H N Ginsberg
G L Bakris
N G Clark
F Costa
R Eckel
JB Buse

ACC/AHA/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology)

Jan 2006
2534

A E Buxton
H Calkins
D J Callans
J P Dimarco
J D Fisher
H L Greene
AE Buxton

Type 2 diabetes mellitus and the risk of sudden cardiac arrest in the community

Abstract

No full-text available

Recommended publications

Mild hypothermia preserves myocardial conduction during ischemia by maintaining gap junction intrace...

The D allele of the ACE I/D common gene variant is associated with Type 2 diabetes mellitus in Cauca...

Epidemiología de la enfermedad coronaria

QoS aware platform for dependable sensory environments