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Abstract

Objective: To examine the association between hemoglobin A(1c) (HbA(1c)) and the presence, severity, and complexity of angiographically proven coronary artery disease (CAD) in nondiabetic patients. Patients and methods: We performed a single-center, observational, cross-sectional study of 1141 consecutive nondiabetic patients who underwent coronary angiography from January 1, 2011, through December 31, 2011. The study population was divided into 4 interquartiles according to HbA(1c) levels (<5.5%, 5.5%-5.7%, 5.8%-6.1%, and >6.1%). Results: Patients with higher HbA(1c) levels tended to be older, overweight, and hypertensive, had higher blood glucose levels, and had lower glomerular filtration rates. Higher HbA(1c) levels were associated in a graded fashion with the presence of CAD, disease severity (higher number of diseased vessels and presence of left main and/or triple vessel disease), and disease complexity (higher SYNTAX score, higher number of patients in intermediate or high SYNTAX tertiles, coronary calcium, and chronic total occlusions). After adjustment for major conventional cardiovascular risk factors, compared with patients with HbA(1c) levels less than 5.5%, the odds ratios of occurrence of CAD in the HbA(1c) quartiles of 5.5% to 5.7%, 5.8% to 6.1%, and greater than 6.1% were 1.8 (95% CI, 1.2-2.7), 3.5 (95% CI, 2.3-5.3), and 4.9 (95% CI, 3.0-8.1), respectively. Conclusion: The HbA(1c) level has a linear incremental association with CAD in nondiabetic individuals. The HbA(1c) level is also independently correlated with disease severity and higher SYNTAX scores. Thus, HbA(1c) measurement could be used to improve cardiovascular risk assessment in nondiabetic individuals.

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... In addition, as a traditional risk factor for CAD, chronic hyperglycemia can adversely impact inflammation, cellular injury, apoptosis, ischemic myocardial metabolism, endothelial function, the coagulation cascade, and platelet aggregation [32]. As CAD progresses is a chronic condition, HbA1c serves as a sensitive indicator of chronic dysglycemia and is strongly correlated with the SYNTAX score [13,33,34]. In summary, the interplay between ACS and acute and chronic hyperglycemia is complex. ...
... An SHR < 0.68 indicates a combination of chronic hyperglycemia (high HbA1c) and currently lower blood glucose (low acute blood glucose). Previous studies have extensively established chronic hyperglycemia as a risk factor for CAD severity [12,13,15,33,34], and additional studies have shown that oscillating glucose can have more detrimental effects than constant high glucose on endothelial function and oxidative stress, suggesting that recurrent low acute blood glucose also contributes to CAD progression [42,43]. Therefore, in all scenarios where the linear correlation between ABG and HbA1c deviates, the OR of the mid/ high SYNTAX score increases through different mechanisms. ...
... However, this study seemingly did not further explore its potential nonlinear trends. Additionally, several studies have demonstrated a substantial correlation between HbA1c levels and the SYNTAX score, even among individuals without DM [12,13,15,33,34]. For example, Garg N et al. found that the HbA1c level had a linear incremental association with CAD in 1141 nondiabetic individuals, and the HbA1c level was also independently correlated with disease severity and higher SYNTAX scores. ...
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Background Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. Methods A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. Results Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). Conclusions There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.
... The Atherosclerosis Risk in Communities trial showed that, among the non-diabetic adults, higher HbA1c levels lead to higher ASCVD and death [5]. A tremendous amount of work has been done to show the linear relationship between HbA1c and ASCVD in non-diabetics in past years [6][7][8][9][10][11]. Yet, few studies have shown that HbA1c is not related to the severity of coronary artery disease (CAD) in nondiabetic patients [12,13]. ...
... Our study was designed to find out the possible association between HbA1c and the severity of CAD in non-diabetic patients with ACS. Most of the published data claimed HbA1c, even in the normal range, as a predictor of severity of CAD in non-diabetics [6][7][8][9][10][11][22][23][24]. However, Xinhong and some authors claimed that HbA1c was not related to the severity of CAD in either diabetic or nondiabetic patients [12,13]. ...
... Garg et al. and Ayhan et al. concluded a cut-off HbA1c level of 5.7% and 6.52%, respectively, as an independent predictor of the severity of CAD in non-diabetic patients [11,28]. So, the best clinical threshold of HbA1c for the prediction of CAD needs to be reevaluated in non-diabetic patients with ACS. ...
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In the present study, we aimed to evaluate the association of glycosylated hemoglobin A1c (HbA1C) and cardiac troponin I levels (cTn1) with the 30-day mortality and severity of myocardial infarction in patients presenting with ACS. The present cross-sectional study was done over two years in the medical centers of Zabol University of Medical Sciences. All patients who were referred to the cardiovascular emergency department between 2017 and 2019 presenting with acute coronary syndrome were included. Serum cTn1 and HbA1C concentration were measured between 12 and 48 h after the onset of chest pain, and the mortality rate of these patients was studied by the census method. All statistical analysis was done using SPSS software. There was a significant difference in the cTn1 level between patients with SYNTAX scores higher than 22 and the rest of patients (96 ± 11.3 versus 71 ± 17.8). The patients who were diagnosed with acute MI showed significantly higher levels of HbA1C compared to unstable angina cases (6.9 ± 1.2 versus 5.2 ± 0.8). The results of pearson correlation showed a positive correlation between HbA1C levels and cTn1 levels (correlation coefficient: 0.80, p < 0.001) (Fig. 1). In addition, there was a positive correlation between HbA1C and SYNTAX score (correlation coefficient: 0.45, p < 0.001). The HbA1C level was significantly higher among the deceasesd patients compared to the survived cases (7.8 ± 0.7 versus 6.0 ± 1.3). In conclusion, our study underscores the prognostic importance of HbA1C and cTnI, especially in the STEMI subset within the larger ACS cohort. The association of these markers with a heightened 30-day mortality rate in STEMI patients stands out. Yet, it is paramount to emphasize that these observations are predominantly tailored to the STEMI subset and may not universally apply to all ACS patients. The null mortality in our NSTEMI cohort punctuates the need for more refined research to discern the implications of HbA1C and cTnI across diverse ACS subgroups.
... There are lots of researches elaborating the effects of glycemic metabolism on CAD. [2][3][4][5][6][7][8][9][10] These studies show that HbA1C were correlated positively with the Severity of CAD in different groups of people, such as older patients with diabetes mellitus, 8 Type 2 Diabetes Mellitus, 7 Non-Diabetic Subjects, 4,6 Diabetic and Non-Diabetic Subjects, 3,9 PCI Patients With HbA1c 5.7% to 6.4 10 and Non-diabetic Patients with Acute Coronary Syndrome 5 . However, previous studies regarding the relationship between HbA1c and SYNTAX score just adjusted some conventional risk factor, not adjusted conventional cardiovascular drugs. ...
... There are lots of researches elaborating the effects of glycemic metabolism on CAD. [2][3][4][5][6][7][8][9][10] These studies show that HbA1C were correlated positively with the Severity of CAD in different groups of people, such as older patients with diabetes mellitus, 8 Type 2 Diabetes Mellitus, 7 Non-Diabetic Subjects, 4,6 Diabetic and Non-Diabetic Subjects, 3,9 PCI Patients With HbA1c 5.7% to 6.4 10 and Non-diabetic Patients with Acute Coronary Syndrome 5 . However, previous studies regarding the relationship between HbA1c and SYNTAX score just adjusted some conventional risk factor, not adjusted conventional cardiovascular drugs. ...
... With increasing HbA1c levels, a marked increase in SYNTAX score was noted in the patients without a history of taking Epidemiologic studies show that HbA1c is a cardiovascular risk factor in all kinds of individuals. [3][4][5][6][7][8][9][10] Our findings are in accordance with prior studies that demonstrated that HbA1c levels are independently associated with SYNTAX score which represents the degree of coronary atherosclerosis in non-diabetic and diabetic individuals. This association is graded, continuous, and independent of conventional major cardiovascular risk factors and history of taking cardiovascular related drugs. ...
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Background Many studies have shown that glycated hemoglobin (HbA1c) is associated with coronary artery disease (CAD). HbA1c was independently related to angiographic severity in Chinese patients with CAD after adjusting for other covariates. Some traditional cardiovascular drugs may have an impact on this relationship. Methods This retrospective study enrolled a total of 572 CAD patients who underwent their coronary angiography and had their HbA1c levels measured at the Chinese Hospital. The complexity of the coronary artery lesions was evaluated using the Syntax score, and the subjects were divided into 4 inter quartiles according to HbA1c levels. Covariates included history of traditional cardiovascular drugs. Results The average age of selected participants was 61.00 ± 9.15 years old, and about 54.72% of them were male. Result of fully adjusted linear regression showed that HbA1c was positively associated with Syntax score after adjusting confounders (β = 1.09, 95% CI: 0.27, 1.91, P = 0.0096). By interaction and stratified analyses, the interactions were observed based on our specification including with the medication history of statins and angiotensin receptor blockers (ARBs) (P values for interaction <0.05). Conclusion In this study, we found a positive correlation between the HbA1c levels and the SYNTAX score among CAD individuals, and oral statins and ARBs medication could affect the correlation. Thus, HbA1c measurement could be used for the evaluation of the severity and complexity of coronary lesions among CAD patients.
... The Atherosclerosis Risk in Communities trial showed that, among the non-diabetic adults, higher HbA1c levels lead to higher ASCVD and death [5]. A tremendous amount of work has been done to show the linear relationship between HbA1c and ASCVD in non-diabetics in past years [6][7][8][9][10][11]. Yet, few studies have shown that HbA1c is not related to the severity of coronary artery disease (CAD) in nondiabetic patients [12,13]. ...
... Our study was designed to find out the possible association between HbA1c and the severity of CAD in non-diabetic patients with ACS. Most of the published data claimed HbA1c, even in the normal range, as a predictor of severity of CAD in non-diabetics [6][7][8][9][10][11][22][23][24]. However, Xinhong and some authors claimed that HbA1c was not related to the severity of CAD in either diabetic or nondiabetic patients [12,13]. ...
... Garg et al. and Ayhan et al. concluded a cut-off HbA1c level of 5.7% and 6.52%, respectively, as an independent predictor of the severity of CAD in non-diabetic patients [11,28]. So, the best clinical threshold of HbA1c for the prediction of CAD needs to be reevaluated in non-diabetic patients with ACS. ...
Article
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Introduction The relationship between the severity of coronary artery disease (CAD) with hemoglobin A1c (HbA1c) levels in diabetic patients is well-understood. However, the association between HbA1c and the severity of CAD in non-diabetics is still controversial. We wanted to find out if HbA1c of the non-diabetic adult population, presenting with an acute coronary syndrome (ACS), had any correlation with the severity of CAD. Methods We selected 119 non-diabetic adults who underwent coronary intervention for clinical reasons during the period of July 2015 to February 2017. The mean age of the patients was 54 ± 10.2 years. All patients were labeled as ‘acute coronary syndrome’, which included unstable angina, non-ST elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). We obtained blood samples of patients for laboratory investigations, including HbA1c. We used the SYNTAX score as a tool to classify the severity of CAD, and patients having a SYNTAX score of >22 were considered to be having severe CAD. Results In order to find out the association between HbA1c and CAD, a linear regression analysis of HbA1c with the SYNTAX score was performed, which showed no statistically significant correlation between the SYNTAX score and HbA1c (correlation co-efficient = 0.142; p-value = 0.124). To compare the median value of HbA1c in groups with SYNTAX scores of ≤22 and those with SYNTAX scores of >22, we analyzed the data with the Mann-Whitney U test, which showed no significant difference in HbA1c between the two groups (p-value = 0.771). We determined the independent predictors of the severity of CAD by analyzing all variables with logistic regression, considering a SYNTAX score of >22 as a dependent variable. None of the variables, including HbA1c, proved to be statistically significant in multivariate logistic regression analysis. The unadjusted and adjusted odds ratio (OR) of HbA1c with 95% confidence intervals (CI) were 1.71 (0.47-2.92), p-value = 0.735 and 0.87 (0.33-2.29), and 0.78, respectively. Conclusion In conclusion, we find that HbA1c is not an independent predictor of the severity of CAD in non-diabetic adult patients.
... The problems with estimating the prevalence of diabetes, prediabetes and dysglycemia in the present study raise important questions about the comparability of accepted methods for estimating diabetes prevalence from different types of samples using different assays, 12,15 even when there are population-specific recommendations for each. 16 A series of prior reports have identified similar challenges 17,18,16,19 although the extent of the problem we observed has not been identified previously. 20,21 The criteria used for the diagnosis of diabetes, prediabetes, and dysglycemia based on different assay techniques in Indian populations are inconsistent and further work is required to clarify the cut-off points at which the correct prevalence estimates would be achieved. ...
... The problems with estimating the prevalence of diabetes, prediabetes and dysglycemia in the present study raise important questions about the comparability of accepted methods for estimating diabetes prevalence from different types of samples using different assays, 12,15 even when there are population-specific recommendations for each. 16 A series of prior reports have identified similar challenges 17,18,16,19 although the extent of the problem we observed has not been identified previously. 20,21 The criteria used for the diagnosis of diabetes, prediabetes, and dysglycemia based on different assay techniques in Indian populations are inconsistent and further work is required to clarify the cut-off points at which the correct prevalence estimates would be achieved. ...
... 25 Diabetes and prediabetes are responsible for considerable morbidity and mortality caused by macro-and microvascular disease complications. 11,16,19 Progressive urbanization of the Indian population, 11,26 increases in life expectancy, 27 and unhealthy lifestyles are likely to further compound the consequences of dysglycemia, 28 as is a likely genetic predisposition to type 2 diabetes and serious complications among South Asians. 28,29 Our data shine a further spotlight on the huge issue of diabetes in the Indian population. ...
Article
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Background: Communities in rural Andhra Pradesh may be at increasing risk of diabetes. We analysed three cross-sectional studies over nine years to estimate the changing prevalence of dysglycaemia (diabetes and prediabetes). Methods: The 2005 study sampled 4535 individuals from 20 villages. The 2010 study sampled 4024 individuals from 14 villages. The 2014 project of 62 254 individuals sought to include all adults 40 to 85 years old from 54 villages. Blood glucose levels were estimated using a hand-held device in 2005 and 2014 and using glycosylated haemoglobin dried blood spots in 2010. Results: In primary analyses restricted to assays based upon fasting samples (2005 n = 3243; 2014 n = 749) the prevalence estimates for dysglycaemia were 53 · 7% (51 · 8-55 · 7) in 2005 and 62 · 0% (58 · 5-65 · 4) in 2014 (p < 0 · 001). Mean BMI rose from 22 · 2 kg/m(2) to 24 · 3 kg/m(2) over the same period (mean difference 2.1 95% CI 2.0-2.2, p < 0 · 001). In the secondary analyses using data from all participants (2005 n = 4535; 2010 n = 4024; 2014 n = 62 254) regardless of measurement technique, the estimated prevalence of dysglycaemia was 53 · 9% (52 · 0-55 · 9) in 2005, 50 · 5% (46 · 1-54 · 9) in 2010, and 41 · 3% (40 · 9-41 · 7) in 2014 (p < 0 ·001). Conclusions: The prevalence of dysglycaemia was high at every assessment using every measurement method. Dysglycaemia in this population is most likely to have risen with the rise in BMI. The decline in prevalence suggested by the secondary analyses was likely due to confounding from the different assessment methods.
... For example, Silbernagel et al. reported that HbA1c significantly and independently of fasting blood glucose predicted all-cause of cardiovascular death in white population without diabetes [7]. Garg N and colleagues showed that in non-diabetics, HbA1c level has a linear incremental association with ASCVD [11]. Nonetheless, data from the Emerging Risk Factors Collaboration revealed that HbA1c merely added little incremental benefit for ASCVD risk prediction in patients without known ASCVD and diabetes [12]. ...
... Consistent with previous some epidemiological studies [11,18,19,27], data from our study also revealed that after adjusted for traditional risk factors including age, smoking, TC, HDL-C, HbA1c remained strongly associated with the severity of CAD. Notably, even after adjusted for fasting blood glucose, an independent risk factor for ASCVD and diabetes, there was still significant relationship between HbA1c and the severity of CAD, further supporting previous findings that HbA1c might be superior to fasting blood glucose in the respects of CVD risk discrimination. ...
... Notably, even after adjusted for fasting blood glucose, an independent risk factor for ASCVD and diabetes, there was still significant relationship between HbA1c and the severity of CAD, further supporting previous findings that HbA1c might be superior to fasting blood glucose in the respects of CVD risk discrimination. However, there was one distinctive discrepancy between our research and previous studies [11,18,19,27] were that we concomitantly evaluated the relationship between HbA1c level and CAD severity including clinical scenario severity and the number of coronary artery stenosis. ...
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To investigate relationship between glycated hemoglobin (HbA1c) level and coronary artery disease (CAD) severity METHODS: Observational study was conducted and 573 participants were enrolled and baseline characteristics were collected. Clinical presentations in terms of stable angina, unstable angina or acute myocardial infarction were diagnosed. All participants were performed coronary angiography to figure out the numbers of coronary artery stenosis in terms of none-stenosis (< 50% stenosis), single or multiple vessels stenoses (>= 50% stenosis). All participants were divided into subgroups according to two categories in terms of severity of clinical presentation (stable angina, unstable angina, or acute myocardial infarction) and the number of coronary artery stenosis (none, single, and multiple vessels). Primary endpoint was to evaluate relationship between baseline HbA1c value and CAD severity. Consistent to previous studies, participants with CAD had more risk factors such as elderly, smoking, low HDL-C and high CRP levels. Notably, HbA1c level was more prominent in CAD group than that without CAD. As compared to stable angina subgroup, HbA1c levels were gradually increased in unstable angina and acute myocardial infarction groups. Similar trend was identified in another category in terms of higher HbA1c level corresponding to more vessels stenoses. Multivariate regression analyses showed that after adjusted for traditional risk factors as well as fasting blood glucose, HbA1c remained strongly associated with the severity of CAD. Nonetheless, there was no significant association when CRP was accounted for. HbA1c may be a useful indicator for CAD risk evaluation in non-diabetic adults.
... In the present study, we found that prediabetic group had higher number of diseased vessel, higher multivessel disease and more total occlusions than non-diabetic group. These results are in concordant with Garg et al. (17) who found that patients with impaired glucose tolerance (i.e, HbA1c 5.7 -6.4 %) had markedly higher risk of CAD, higher mean number of diseased vessels, higher left main and/or triple vessel disease, more chronic total occlusions compared to patients with HbA1C < 5.7%. Our findings are in consistent with the study done by Kurihara et al. (18) , who reported that both the degree of coronary atherosclerosis and the plaque vulnerability were more advanced in patients with prediabetes than in those without diabetes. ...
... Our findings are concordant with the study done by Garg et al. (17) , their results implied that HbA1C not only was a marker of chronic dysglycemia but also could be used as an independent predictor of CAD and its severity even in nondiabetic individuals. Measurements of HbA1C levels might improve risk assessment in non-diabetic patients. ...
... Yet other large trials have shown that patients with type 2 diabetes benefited from more intensive therapy, with a significant risk reduction for myocardial infarction and death [4]. Furthermore, in the diabetic population, hemoglobin A1c (HbA 1c ) may be a predictor of CAD [5,6]. ...
... HbA 1c is known to be an independent predictor for the severity of CAD. It has been suggested that high-normal glucose and HbA 1c level in patients without diabetes are associated with a higher risk of CAD [5,6]. Studies have also shown that in the patients with diabetes, HbA 1c is an independent risk factor for CAD [5,27]. ...
Article
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Background The association between coronary artery disease (CAD) and diabetes mellitus (DM) is strong but the physiologic mechanisms responsible for this association remain unclear. Patients with DM exhibit high circulating levels of glycated proteins and lipoproteins called advanced glycation end products (AGEs) which have been implicated in the development of oxidative damage to vascular endothelium. We examined the relationships between the presence and extent of CAD and AGEs in patients undergoing elective coronary artery catheterization in an urban teaching hospital. Methods Patients with possible CAD (n= 364) were recruited prior to elective cardiac catheterization (52% male, 48% diabetic). Regression and correlation analyses were used to examine the relationship between serum AGE concentrations, soluble AGE receptor (sRAGE) concentration, HbA1c, LDL and the presence of obstructive CAD along with the burden of CAD measured by SYNTAX and SYNTAX II scores. Results AGE and sRAGE levels did not significantly correlate with any of the studied coronary artery disease parameters. HbA1c showed positive correlation with both SYNTAX and SYNTAX II scores in patients with and without diabetes. Conclusion In this cross-sectional study of patients with possible CAD, serum AGEs and sRAGE concentrations did not correlate with SYNTAX or SYNTAX II scores regardless of diabetic status. HbA1C correlated positively with the SYNTAX and SYNTAX II scores in both diabetic and non-diabetic populations.
... Studies have shown significant associations between HbA1c and subclinical atherosclerosis factors, such as carotid atherosclerosis [4] and arterial stiffness [5] in patients with diabetes. Epidemiological studies have reported a positive association between HbA1c and increased risk of CVDs in individuals without diabetes [6,7], whereas other studies have not observed such an association [8,9]. Moreover, it is unclear whether HbA1c is associated with subclinical atherosclerotic parameters in the population without diabetes. ...
... Epidemiological studies have shown that increased HbA1c is associated with CVD in patients with diabetes [2,3] and in individuals without diabetes [6,7]. However, little is known about the underlying mechanisms for the association between HbA1c and CVD. ...
Article
Objectives: We examined the associations between HbA1c levels and various atherosclerotic vascular parameters among adults without diabetes from the general population. Methods: A total of 6500 community-dwelling adults, who were free of type 2 diabetes and ≥50 years of age, were included. High-resolution B-mode ultrasound was used to evaluate carotid artery structure, including intima-media thickness (IMT), plaque, and luminal diameter. Brachial-ankle pulse wave velocity (baPWV), which is a useful indicator of systemic arterial stiffness, was determined using an automatic waveform analysis device. Results: No significant associations were observed between HbA1c, carotid IMT, plaque, or luminal diameter in a fully adjusted model. However, the odds ratio (95% confidence interval) for high baPWV (defined as the highest quartile) increased by 1.43 (1.19-1.71) per 1% HbA1c increase after adjusting for conventional risk factors in a multivariate logistic regression analysis. In addition, HbA1c was independently associated with baPWV in a multivariate linear regression analysis. Conclusions: High-normal HbA1c level was independently associated with arterial stiffness, but not with carotid atherosclerotic parameters, in the general population without diabetes. Our results suggest that the functional atherosclerotic process may already be accelerated according to HbA1c level, even at a level below the diagnostic threshold for diabetes.
... There was also a significant difference between those with intermediate and high SYNTAX score and those with low score regarding the number of VD, with 50% of those with intermediate and high SYNTAX score had 4 VD versus 2.7% of those with low score, P less than 0.001. In this context, in similar study by Garg et al. [26] who found mean SYNTAX score was significantly increased with increasing HbA1c level 9.9% ± 12.2%, 12.9% ± 12.7%, 15.4% ± 15.2%, 19 ± 15.5% in patients with HbA1c levels less than 5.5%, 5e5.7%, 5.8e6.1%, and greater than 6.1%, respectively, with P trend less than 0.001. ...
... [3,20] An observational cohort study showed that HbA1c added to traditional cardiovascular risk factors better identifies individuals with subclinical atherosclerosis. [21] Albashir et al [22] collected coronary angiography results and baseline HbA1c data from 85 ACS patients, assessed the severity of coronary artery disease using the Gensini score, and found that HbA1c levels were associated with the severity of coronary artery disease in ACS patients with diabetes. The potential mechanisms by which abnormal glucose metabolism contributes to increased cardiovascular risk in ACS patients may be as follows: on the one hand, oxidative stress from elevated blood glucose and insulin resistance leads to decreased antioxidant capacity, aggravates vascular endothelial injury, and stimulates vascular smooth muscle cell proliferation, resulting in unstable plaque formation; on the other hand, patients with abnormal glucose metabolism have increased coagulation factor levels, increased platelet aggregation, impaired plasma fibrinolytic activity, and increased risk of thrombosis. ...
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The objective of the current study is to assess the usefulness of HbA1cAp ratio in predicting in-hospital major adverse cardiac events (MACEs) among acute ST-segment elevation myocardial infarction (STEMI) patients that have undergone percutaneous coronary intervention (PCI). Further, the study aims to construct a ratio nomogram for prediction with this ratio. The training cohort comprised of 511 STEMI patients who underwent emergency PCI at the Huaibei Miners’ General Hospital between January 2019 and May 2023. Simultaneously, 384 patients treated with the same strategy in First People’s Hospital of Hefei formed the validation cohort during the study period. LASSO regression was used to screen predictors of nonzero coefficients, multivariate logistic regression was used to analyze the independent factors of in-hospital MACE in STEMI patients after PCI, and nomogram models and validation were established. The LASSO regression analysis demonstrated that systolic blood pressure, diastolic blood pressure, D-dimer, urea, and glycosylated hemoglobin A1c (HbA1c)/apolipoprotein A1 (ApoA1) were significant predictors with nonzero coefficients. Multivariate logistic regression analysis was further conducted to identify systolic blood pressure, D-dimer, urea, and HbA1c/ApoA1 as independent factors associated with in-hospital MACE after PCI in STEMI patients. Based on these findings, a nomogram model was developed and validated, with the C-index in the training set at 0.77 (95% CI: 0.723–0.817), and the C-index in the validation set at 0.788 (95% CI: 0.734–0.841), indicating excellent discrimination accuracy. The calibration curves and clinical decision curves also demonstrated the good performance of the nomogram models. In patients with STEMI who underwent PCI, it was noted that a higher HbA1c of the ApoA1 ratio is significantly associated with in-hospital MACE. In addition, a nomogram is constructed having considered the above-mentioned risk factors to provide predictive information on in-hospital MACE occurrence in these patients. In particular, this tool is of great value to the clinical practitioners in determination of patients with a high risk.
... Under these conditions, the patient is exposed to a high risk of becoming diabetic (5-10% every year) and this is associated with complications of diabetes, including cardiovascular complications (19). Our study findings are supported by previous observations reporting that based on both the SYNTAX and Gensini criteria, the percentage of glycosylated hemoglobin is associated with the severity of cardiovascular involvement (18,27). Moreover, a similar recent study conducted by Mirza et al. in the Middle East supports our findings about the population living in this region (28). ...
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Background The current study was carried out aiming at investigating the relationship between glycosylated hemoglobin level and coronary atherosclerosis in patients with the first episode of acute coronary syndrome. Methods This case-control study evaluated 450 patients with the first episode of acute coronary syndrome in Ayatollah Rouhani Hospital in Babol (Iran) from 2011 to 2018. Based on glycosylated hemoglobin, patients were divided into three groups of non-diabetic, pre-diabetic, and diabetic (n=150 in each group). Since SYNTAX score and Gensini score are employed to evaluate the extent of cardiovascular disease and predict CVD in patients with CAD over long-term follow-up, we calculated SYNTAX score and Gensini score based on angiographic results. Results Concerning the factors related to the severity of cardiovascular involvement, the results revealed no significant difference between the diabetic and pre-diabetic groups in terms of the frequency of patients in terms of SYNTAX score, Gensini score, and the number of vessels involved (0.142 and 87, respectively, and P=0.102). However, this difference between the diabetic and non-diabetic groups, as well as between the pre-diabetic and non-diabetic groups was statistically significant (respectively for SYNTAX score, p< 0.001 and P=0.001; for Gensini score, P=0.013 and P=0.019; and for the number of vessels involved P=0.001and p<0.001). Conclusion According to the findings of the current study, since there was no significant difference between diabetic and pre-diabetic patients in terms of the components indicating the severity of cardiovascular involvement, pre-diabetes itself may be associated with the severity of cardiovascular involvement as a predisposing factor.
... Current consensus guidelines define a target range of 70-180 mg/dL (9,10), which still falls far from healthy norms (11). Maintaining blood sugar levels as close to normal as possible is essential (12)(13)(14)(15)(16)(17)(18)(19). Lowering blood sugar levels is associated with reduced risks of complications and mortality in T1D (20-22). ...
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Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.
... (which approximately translates to 37-39 mmol mol −1 ) were almost twice as likely to be diagnosed with coronary artery disease compared to individuals with less than 5.5% (ref. 33). Thus, it is likely that a reduction of 0.85 mmol mol −1 is meaningful at the population level. ...
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Diabetes is a leading cause of morbidity, mortality and cost of illness1,2. Health behaviours, particularly those related to nutrition and physical activity, play a key role in the development of type 2 diabetes mellitus³. Whereas behaviour change programmes (also known as lifestyle interventions or similar) have been found efficacious in controlled clinical trials4,5, there remains controversy about whether targeting health behaviours at the individual level is an effective preventive strategy for type 2 diabetes mellitus⁶ and doubt among clinicians that lifestyle advice and counselling provided in the routine health system can achieve improvements in health7–9. Here we show that being referred to the largest behaviour change programme for prediabetes globally (the English Diabetes Prevention Programme) is effective in improving key cardiovascular risk factors, including glycated haemoglobin (HbA1c), excess body weight and serum lipid levels. We do so by using a regression discontinuity design¹⁰, which uses the eligibility threshold in HbA1c for referral to the behaviour change programme, in electronic health data from about one-fifth of all primary care practices in England. We confirm our main finding, the improvement of HbA1c, using two other quasi-experimental approaches: difference-in-differences analysis exploiting the phased roll-out of the programme and instrumental variable estimation exploiting regional variation in programme coverage. This analysis provides causal, rather than associational, evidence that lifestyle advice and counselling implemented at scale in a national health system can achieve important health improvements.
... Garg et al., [10] Ayhan et al., [11] and Kis and Guzel [12] found the cut-off values of HbA1c as 5.7, 6.52, and 5.5, respectively, and concluded that it was an independent predictor of the severity of CAD in nondiabetic patients. In our study, the HbA1c cut-off value was determined as 5.66 as a predictor of a severe coronary artery lesion in coronary CTA. ...
Article
Objectives: In this study, we aimed to investigate whether there is a relationship between coronary artery lesion severity detected on coronary computed tomography angiography (CTA) and the hemoglobin A1c (HbA1c) value in nondiabetic patients with chronic coronary syndrome (CCS). Patients and methods: The retrospective observational study included 125 patients (64 males, 61 females; median age: 55 years; IQR, 46.5-63.0) who underwent coronary CTA with the diagnosis of CCS and applied between March 2020 and July 2022. Two groups were formed according to the severity of coronary artery lesion by coronary CTA: Group 1 (n=71), with <70% coronary lesion severity, and Group 2 (n=54), with >70% coronary lesion severity. Results: The two groups were similar in terms of median age, (p=0.09) and male sex ratios (47% vs. 55%, p=0.47). The HbA1c value in Group 2 was statistically significantly higher than in Group 1 [5.89 (5.43-6.15) vs. 5.42 (5.1-5.8), p=0.001]. The HbA1c cut-off value was determined as 5.66. The ideal HbA1c cut-off value, calculated by the Youden index, had a sensitivity of 64% and a specificity of 63% in predicting the severity of coronary artery lesions in nondiabetic patients with CCS. Conclusion: In nondiabetic patients with CCS, HbA1c is associated with the presence of severe CAD lesions detected in coronary CTA.
... The correlation of HbA1c with CAD has mixed results, with some reporting significant association while others showed contradictory results. [12] We have not found a significant association between HbA1C and CAD, whereas age, gender and hypertension are independent risk factors in our study. A few studies, including the Framingham cohort study, have also reported gender differences in this correlation wherein HbA1c is an independent risk factor in females whereas, in males, it is not. ...
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Objective: This study was done to analyse the demographic profile and presentation of diabetes in Central India. Design: Data was collected for this cross-sectional study from an electronic diabetes registry from 2014 to 2019. Demographic details, patient history and presence or absence of co-morbid conditions, duration of diabetes, age of onset of diabetes, drug history, personal history, presence of micro and/or macrovascular complications and investigations done were obtained. Statistical analysis: The association between each factor and the outcome was studied in terms of prevalence ratio (PR) using the R-3.0.0 programming (R Foundation for Statistical Computing, Vienna, Austria) language. Statistical significance was evaluated at a 5% level. Results: Among 12,434 patients, 54.95% were below 50 years and 45.05% were above 50 years. 50.21% were females and 49.79% were males. The mean age was 47.49 ± 14.78 years and the mean body mass index (BMI) was 26.85 ± 5.19 kg/m2 with 62.29% of obese patients (>25 kg/m2). The mean overall duration of diabetes was 7.64 ± 7.63 years. Mean Glycosylated Haemoglobin (HbA1c) in patients <=50 years was 8.60 ± 2.63 and 8.90 ± 1.91 for over 50. 65.59% had uncontrolled blood sugars. 25.19% of patients had hypertension and 18.1% had dyslipidaemia. Coronary artery disease (CAD), nephropathy, neuropathy and retinopathy were observed in 21.49%, 9.60%, 33.65% and 14.65%, respectively. The adjusted PR of cardiovascular disease (CVD) was 5.374 times higher for patients over 50 (P < 0.0001); 3.775 times higher for males (P < 0.0001), 1.64 times higher for patients with BMI >25 kg/m2 (P < 0.0001) and 3.643 times higher in hypertensive cases (P < 0.0001). Similar associations were observed with nephropathy, neuropathy and retinopathy. Conclusion: From a large population study on diabetes, it was found a majority of the type 2 diabetes mellitus (T2DM) cases (65%) are sub-optimally controlled with HbA1c levels. Also, microvascular complications were related to the sub-optimal glycaemic control, but not the macro-vascular complications.
... For example, Garg et al used grammar scores to assess the severity of CHD and concluded that HbA1c levels increased significantly in patients with increased CHD severity. 38 In this study, LDL-C was a risk factor for CHD in T2DM patients and was positively correlated with the probability of CHD. When the level of LDL-C in the blood increases, LDL-C is deposited in the artery wall and gradually forms atherosclerotic plaques to block the corresponding blood vessels. ...
Article
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Introduction This study aimed to study risk factors for coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) patients and establish a clinical prediction model. Research Design and Methods A total of 3402 T2DM patients were diagnosed by clinical doctors and recorded in the electronic medical record system (EMRS) of six Community Health Center Hospitals from 2015 to 2017, including the communities of Huamu, Jinyang, Yinhang, Siping, Sanlin and Daqiao. From September 2018 to September 2019, 3361 patients (41 patients were missing) were investigated using a questionnaire, physical examination, and biochemical index test. After excluding the uncompleted data, 3214 participants were included in the study and randomly divided into a training set (n = 2252) and a validation set (n = 962) at a ratio of 3:1. Through lead absolute shrinkage and selection operator (LASSO) regression analysis and logistic regression analysis of the training set, risk factors were determined and included in a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were used to validate the distinction, calibration and clinical practicality of the model. Results Age, T2DM duration, hypertension (HTN), hyperuricaemia (HUA), body mass index (BMI), glycosylated haemoglobin A1c (HbA1c), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were significant factors in this study. The C-index was 0.750 (0.724–0.776) based on the training set and 0.767 (0.726–0.808) based on the validation set. Through ROC analysis, the set area was 0.750 for the training set and 0.755 for the validation set. The calibration test indicated that the S:P of the prediction model was 0.982 in the training set and 0.499 in the validation set. The decision curve analysis showed that the threshold probability of the model was 16–69% in the training set and 16–73% in the validation set. Conclusion Based on community surveys and data analysis, a prediction model of CHD in T2DM patients was established.
... Similar results were reported by other authors. [21][22][23] Correlation of hemoglobin A1c with coronary flow velocity Although many studies have analyzed the association between CAD and HbA1c, there are very few studies comparing the association of HbA1c with CFV. We examined the relationship between HbA1c and SCF. ...
Article
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Introduction: Increasing hemoglobin A1c (HbA1c) levels in individuals with and without diabetes mellitus are risk factors for cardiovascular events and atherosclerosis. Aims and Objectives: The aim and objective was to study the association of HbA1c with coronary flow velocity (CFV). Materials and Methods: This was a single-center, hospital-based, nonrandomized, prospective observational study. All consecutive patients admitted in the department of cardiology with the diagnosis of chronic stable angina who underwent coronary angiography from April 1, 2017, to October 31, 2018, were subjected to the eligibility criteria. The patients were divided into the four HbA1c quartiles based on the HbA1c at hospital admission: Group A (HbA1c < 5.2%), Group B (HbA1c: 5.2–5.6), Group C (HbA1c: 5.7–6.4), and Group D (HbA1c: ≥6.5%). Corrected TIMI frame count (TFC) was used to assess the CFV. The severity of coronary artery disease (CAD) was studied by Gensini score. Results: A total of 263 consecutive patients with a mean age of 56.71 ± 10.59 years were included. Nearly 70% (n = 184) of the patients were males. The mean HbA1c was statistically significantly higher in obstructive CAD versus nonobstructive versus no CAD (6.06 vs. 5.63 vs. 5.23) (P < 0.001). Increasing HbA1c among all quartiles was statistically significantly associated with increasing TFC in all coronary arteries (left anterior descending artery [LAD] 30.32 vs. 34.05 vs. 36.72 vs. 36.94; left circumflex artery [LCX] 19.89 vs. 22.41 vs. 24.05 vs. 23.76; right coronary artery [RCA] 19.42 vs. 22.02 vs. 23.24 vs. 23.50, respectively, for the four HbA1c quartiles; P < 0.001). HbA1c had a significant linear correlation with TFC of LAD, LCX, and RCA (r = 0.6, 0.54, and 0.51, respectively). Among the various quartiles of HbA1c, CAD was significantly more common in patients with higher HbA1c values (P < 0.0001) (1.03% vs. 33.89% vs. 73.33% vs. 82.35%, respectively). The mean Gensini score increased with increasing HbA1c quartiles (0.40 vs. 4.68 vs. 21.63 vs. 30.52, respectively, P < 0.001). Conclusion: HbA1c has a significant association with CFV even in subdiabetic range. However, the therapeutic strategies and benefit of lower HbA1c in nondiabetic patients are still uncertain. Large randomized trials are needed to address this issue.
... HbA1c was more strongly associated with the risks of ASCVD and mortality from any causes [5,6] . In non-diabetics, HbA1c level has a linear incremental association with CVD [7] . ...
... [23] HbA1C had an impact on the severity of coronary disease, as is also seen with RDW, and a potential linking mechanism could therefore exist. [24][25][26] In our study, there was no statistically significant correlation between CRP and RDW. However, a significant and graded correlation between RDW and Table 3 Overview of logistic regression models showing that elevated RDW remains associated with the parameters of systolic and diastolic dysfunction after adjustments for potential confounders. ...
Article
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Multiple studies have demonstrated the association of red cell distribution width (RDW) with the ultrasound parameters of both systolic and diastolic heart dysfunction. We aimed to further investigate the clinical associations of RDW in the setting of ST-elevation myocardial infarction (STEMI) and to comparatively evaluate its predictive properties regarding systolic and diastolic dysfunction. A total of 89 patients with STEMI were prospectively analyzed. RDW was obtained at the time of STEMI and compared to the parameters of systolic and diastolic dysfunction obtained by transthoracic heart ultrasound on the 5th through 7th day post-STEMI. The median RDW was 13.9%, and among other factors, RDW was significantly associated with older age (P < .001), arterial hypertension (P = .017), hyperlipoproteinemia 2, nonsmoking (P = .027), increased thrombolysis in myocardial infarction score (P = .004), and multivessel disease (P = .007). A higher RDW was observed in patients with parameters that indicated systolic and diastolic dysfunction (ejection fraction of the left ventricle < 50% [P = .009], early/late diastolic filling wave ratio [E/A] < 1 [P = .001], ratio of peak early transmitral velocity and early diastolic annular velocity [E/E′] >10 [P < .001], and combined E/A < 1 and E/E′ > 10 [P < .001]). The best discriminatory properties were observed for combined E/A < 1 and E/E′ > 10. RDW remained significantly associated with the aforementioned parameters in a series of multivariate regression models. Elevated RDW is significantly associated with the parameters of systolic and diastolic dysfunction even after adjusting for several confounding factors in the setting of STEMI and subsequent percutaneous coronary intervention. RDW seems to be better at discriminating patients with diastolic rather than systolic dysfunction.
... This method is now routinely used to assess glycemic control in the large majority of health care settings 38 . All major clinical trials including diabetes control and complications trials (DCCT) in T1D and the UKPDS in T2D have used it as a tool to monitor glycemic control 39,40 . Alltogether, they have demonstrated the benefits of intensive treatment in reference to the development/ progression of micro and macrovascular complications. ...
... It was found to be an important determinant of subclinical atherosclerosis, such as carotid atherosclerosis in T2DM [11]. Although it is widely used in diabetic patients, some epidemiological studies suggested an association between HBA1c and CVD in non-diabetic populations [12,13], but other studies failed to reach this conclusion [14,15]. Thus, there is uncertainty if HBA1c is correlated with subclinical atherosclerosis in non-diabetic patients or if it can be used to predict the cIMT. ...
Article
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Background: The carotid intima media thickness (cIMT) and carotid plaque score (cPS) are respective markers of early and late stage subclinical atherosclerosis. Relationships between some laboratory parameters and subclinical atherosclerosis are not yet clear in community dwelling individuals and non-diabetic subjects, so we try to elucidate these relationships and find a model to predict early and late stage subclinical atherosclerosis. Methods: We examined relationships of the cIMT and cPS with different laboratory and demographic data of 331 subjects from a community-based prospective cohort study, using univariate and multivariate analyses. Results: In regression models and after multiple adjustments, only systolic blood pressure (SBP), age, glycated hemoglobin (HBA1c), and waist circumference (WC) were determinants of the cIMT, and only age, SBP, HBA1c, and blood urea nitrogen (BUN) were determinants of a cPS of > 2 in all individuals. Only HBA1c lost its association with regard to predicting the cIMT in non-diabetic subjects. Conclusions: HBA1c at > 5.9% can determine early and late stage subclinical atherosclerosis in community dwelling individuals, but only late stage subclinical atherosclerosis in non-diabetic subjects.
... 9,10 In addition, recent epidemiological studies have shown that elevated HbA1c concentrations are associated with atherosclerosis and cardiovascular disease, even in individuals without DM. [11][12][13] To date, any association between snoring and HbA1c levels in individuals without DM has received little attention. Polysomnography, the gold standard for diagnosis of obstructive sleep apnea, is expensive, labor-intensive, and time-consuming. ...
Article
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Purpose We explored whether a gender difference was evident in terms of the associations of snoring with hemoglobin A1c (HbA1c) and homeostatic model assessment-insulin resistance (HOMA-IR) levels in a healthy population without type 2 diabetes mellitus (DM). Materials and Methods We analyzed 2706 males and 4080 females who participated in the baseline survey of the Namwon Study. In terms of self-reported snoring frequency, participants were classified as non-snorers or occasional (1–3 days/week), frequent (4–6 days/week), or constant (7 days/week) snorers. Participants with DM, defined as a fasting blood glucose level ≥126 mg/dL and/or use of insulin or hypoglycemic medication, were excluded from the analysis. Results In females, the fully adjusted mean (95% confidence interval) HbA1c levels in non-snorers and in occasional, frequent, and constant snorers were 5.53% (5.47–5.59%), 5.53% (5.47–5.59%), 5.57% (5.49–5.64%), and 5.57% (5.51–5.64%), respectively, reflecting a dose-response relationship (p trend=0.004). Compared with female non-snorers, the risk of an elevated HbA1c level (top quintile, ≥5.9%) in constant snorers remained significant (odds ratio 1.30, 95% confidence interval 1.02–1.66) after full adjustment. In addition, in females, a significant linear trend in HbA1c level odds ratio by increased snoring frequency was apparent (p trend=0.019 in model 3). In contrast, no significant association between snoring frequency and HbA1c level was identified in males. No significant association between snoring frequency and HOMA-IR was detected in either gender. Conclusion We discovered a gender-specific association between snoring and HbA1c level in a healthy, community-dwelling population free of DM.
... In particular, the group of biomarkers of interest includes: transforming growth factor beta (TGF-β1) [50]; cellular adhesion molecules (CAMs) [51,52]; monocyte chemoattractant protein-1 (MCP-1) [53][54][55]; stromal cell-derived factor-1α (SDF-1α) [56][57][58]; lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) [59][60][61]; pentraxin 3 (PTX3) [62][63][64]; bilirubin [65][66][67] and haemoglobin A1c (HbA1c) [68,69], whose serum and/or plasmatic levels were associated with the presence and severity of CHD. ...
Article
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The major issue in coronary heart disease (CHD) diagnosis and management is that symptoms onset in an advanced state of disease. Despite the availability of several clinical risk scores, the prediction of cardiovascular events is lacking, and many patients at risk are not well stratified according to the canonical risk factors alone. Therefore, adequate risk assessment remains the most challenging issue. Recently, the integration of imaging data with biochemical markers in a radiogenomic framework has been proposed in many fields of medicine as well as in cardiology. Multimodal imaging and advanced processing techniques can provide both direct (e.g., remodeling index, calcium score, total plaque volume, plaque burden) and indirect (e.g., myocardial perfusion index, coronary flow reserve) imaging features of CHD. Furthermore, the identification of novel non-invasive biochemical markers, mainly focused on plasma and/or serum samples, has increased the specificity of findings, reflecting several pathophysiological pathways of atherosclerosis, the principal actor in CHD. In this context, a multifaced approach, derived from the strengths of all these modalities, appears promising for finer risk stratification and treatment strategies, facilitating the decision-making and clinical management of patients. This review underlines the role of different imaging modalities in the quantification of coronary atherosclerosis and describes novel blood-based markers that could improve diagnosis and have a better predictive value in CHD.
... Further, the continuous relationship between A1c and CVD is not unique to the USA. Consistent findings have been reported in the United Kingdom [46], Australia [42], India [47], and in meta-analyses spanning a wide range of ethnic groups [27••, 43, 48]. ...
Article
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Purpose of review: We reviewed published literature to determine the relationship between A1c and cardiovascular disease (CVD) and summarize the need and implications for CVD risk reduction with interventions, focusing in the prediabetic A1c range (<6.5%). Recent findings: Strong evidence supports a continuous relationship between A1c and CVD-even below the current levels of A1c-defined prediabetes and after adjustment for known risk factors for CVD. Clinical trials have demonstrated a reduction in CV morbidity and/or mortality when interventions are invoked in the prediabetic A1c range. Guidelines advocating CV risk factor management in prediabetes have not been widely adopted, subsequently leading to comparable coronary heart disease risk between people with prediabetes (HR = 1.9, 95% CI 1.7-2.1 vs normoglycemia) and diabetes itself (HR=2.0, 95% CI 1.8-2.2 vs no diabetes). This review highlights the missed opportunity to utilize multiple risk factor interventions to reduce CVD in high-risk people with prediabetes.
... Garg N and colleagues showed that in nondiabetics, HbA1c level has a linear incremental association with ASCVD. [3] Nonetheless, data from the Emerging Risk Factors Collaboration revealed that HbA1c merely added little incremental benefit for ASCVD risk prediction inpatients without known ASCVD and diabetes. [4] One case-control study suggested that HbA1c is associated with coronary heart disease risk among apparently healthy, non-diabetic women and men and may be an important early clinical marker of disease risk. ...
... Another study on non- diabetic patients was conducted by Garg et al. In that study, they used the syntax scores to assess the severity of CAD and concluded that HbA1c levels were significantly elevated in patients with increased severity of CAD (19) . ...
Article
Introduction: Diabetes mellitus (DM) has long been recognized as a major risk factor for coronary artery diseases (CAD). Although Hemoglobin A1c (HbA1c) has been widely used as a marker for predicting the severity of DM, there are controversial reports in the literature regarding its association with the severity of CAD. The aim of our study was to determine the association between HbA1c levels and severity of CAD in both diagnosed and undiagnosed diabetic patients with admission hyperglycemia. Materials and methods: The files of the patients who were admitted to the emergency department of a regional training and research hospital from 2014 to 2015 due to acute coronary syndrome and whose diagnosis was confirmed by coronary angiography and HbA1c levels were analyzed were reviewed retrospectively. Those patients whose HbA1c levels were measured were divided into two groups: diagnosed diabetes (DD) or undiagnosed diabetes (UDD). Gensini score was measured for all patients and the correlation between elevated HbA1c levels and severity of coronary artery disease was subjected to statistical analysis. Results: Out of 168 patients who met the inclusion criteria, 85.1% (n=143) were male, while 14.9% (n=25) were female. The mean age was 46.6±6.5 years. HbA1c was found to have a significantly positive correlation with the Gensini score in DD group (n=77), whereas no significant correlation was found between HbA1c and the Gensini score in UDD group (n=91) (p < 0.001; correlation coefficient: 0.656, p=0.207; correlation coefficient: 0.251, respectively). Linear regression analysis revealed that HbA1c was a significant predictor for gensini score (p < 0.001; ß: 0.632). Conclusion: HbA1c can be used as a predictor for the evaluation of diabetic patients with CAD. Moreover, HbA1c was not found to have a significant association with the severity of CAD in undiagnosed diabetic CAD patients with admission hyperglycemia.
... Even in the absence of DM, higher blood glucose levels, higher hemoglobin A1c levels, and insulin resistance (IR) have been shown to be associated with an increased risk of ASCVDs (87)(88)(89). IR plays crucial roles in atherosclerosis (90), and it has been clarified that IR was positively associated with coronary severity (91), the coronary calcium score (92), and a remodeling index (93). Various past studies in basic research have supported the results of these clinical trials. ...
Article
The prevalence of atherosclerotic cardiovascular diseases (ASCVDs) is increasing globally and they have become the leading cause of death in most countries. Numerous experimental and clinical studies have been conducted to identify major risk factors and effective control strategies for ASCVDs. The development of imaging modalities with the ability to determine the plaque composition enables us to further identify high-risk plaque and evaluate the effectiveness of different treatment strategies. While intensive lipid-lowering by statins can stabilize or even regress plaque by various mechanisms, such as the reduction of lipid accumulation in a necrotic lipid core, the reduction of inflammation, and improvement of endothelial function, there are still considerable residual risks that need to be understood. We reviewed important findings regarding plaque vulnerability and some encouraging emerging approaches for plaque stabilization.
... 15 Indeed, glycated hemoglobin (HbA1c), which is the parameter of glycemic control, has been reported as a predictor and risk factor of MACE, acute coronary syndrome, and CHD in both diabetic and non-diabetic patients. [17][18][19][20][21][22] Also, it is well established that low high density lipoprotein (HDL) cholesterol level is a cardiovascular risk factor, negatively correlated with blood viscosity. 23 Previous studies have reported correlations between hemorheological abnormalities, poor glycemic control, and low HDL cholesterol. ...
Article
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Background: Hemorheological and glycemic parameters and high density lipoprotein (HDL) cholesterol are used as biomarkers of atherosclerosis and thrombosis. Objective: To investigate the association and clinical relevance of erythrocyte sedimentation rate (ESR), fibrinogen, fasting glucose, glycated hemoglobin (HbA1c), and HDL cholesterol in the prediction of major adverse cardiovascular events (MACE) and coronary heart disease (CHD) in an outpatient population. Methods: 708 stable patients who visited the outpatient department were enrolled and followed for a mean period of 28.5 months. Patients were divided into two groups, patients without MACE and patients with MACE, which included cardiac death, acute myocardial infarction, newly diagnosed CHD, and cerebral vascular accident. We compared hemorheological and glycemic parameters and lipid profiles between the groups. Results: Patients with MACE had significantly higher ESR, fibrinogen, fasting glucose, and HbA1c, while lower HDL cholesterol compared with patients without MACE. High ESR and fibrinogen and low HDL cholesterol significantly increased the risk of MACE in multivariate regression analysis. In patients with MACE, high fibrinogen and HbA1c levels increased the risk of multivessel CHD. Furthermore, ESR and fibrinogen were significantly positively correlated with HbA1c and negatively correlated with HDL cholesterol, however not correlated with fasting glucose. Conclusion: Hemorheological abnormalities, poor glycemic control, and low HDL cholesterol are correlated with each other and could serve as simple and useful surrogate markers and predictors for MACE and CHD in outpatients.
... Additional studies have noted an increased prevalence of diabetes complications such as nephropathy and cardiovascular disease in patients with diabetes and elevated RDW levels [103,104]. Garg et al. demonstrated that HbA 1C levels had an impact on CAD severity in patients without diabetes; therefore, these levels may be considered a mechanism linking RDW values to impaired glucose metabolism [105]. ...
Article
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Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization.
... In contrast, macrovascular complications or deaths from atherosclerotic CVD have not been specifically and rigorously addressed [288], perhaps since most adults with CF have been thought to have few risk factors for CVD and have not lived long enough to develop CVD [293]. Finally there is recent concern that prediabetics without overt diabetes may be susceptible to an increased incidence of CVD [295], which could be of concern to older CF patients without overt CFRD. ...
Article
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Cystic Fibrosis (CF) represents one of a number of localized lung and non-lung diseases with an intense chronic inflammatory component associated with evidence of systemic oxidative stress. Many of these chronic inflammatory diseases are accompanied by an array of atherosclerotic processes and cardiovascular disease (CVD), another condition strongly related to inflammation and oxidative stress. As a consequence of a dramatic increase in long lived patients with CF in recent decades, the specter of CVD must be considered in these patients who are now reaching middle age and beyond. Buttressed by recent data documenting that CF patients exhibit evidence of endothelial dysfunction, a recognized precursor of atherosclerosis and CVD, the spectrum of risk factors for CVD in CF are reviewed here. Epidemiological data further characterizing the presence and extent of atherogenic processes in CF patients would seem important to interrogate. Such studies should further inform and offer mechanistic insights into how other chronic inflammatory diseases potentiate the processes leading to CVDs.
Article
Objectives This study aims to investigate the relationship between erythrocyte sedimentation rate (ESR), glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL), triglycerides, and their potential ability to predict major adverse cardiovascular events (MACE) in diabetic patients. Methods This study uses a cross-sectional analysis of 453 diabetic patients to investigate associations between MACE and sociodemographic, clinical, and laboratory characteristics. The study defined MACE as the presence of myocardial infarction (MI), coronary heart disease (CHD), or both. It likewise characterized dyslipidemia as high levels of cholesterol or triglycerides based on the Adult Treatment Panel III guidelines. The data collected from medical records were analyzed using SPSS. Results from Chi-square and Fisher's exact tests and univariate and multivariate logistic regression models indicated significant associations between ESR, HbA1c, triglycerides, HDL, and MACE in diabetic patients. Multicollinearity was assessed using the variance inflation factor method, with statistical significance determined by a p-value of less than 0.05 and a 95% confidence interval. Results The study found a positive correlation between MACE and several factors, including age, triglyceride levels, ESR, HbA1c, fasting blood glucose, and body mass index (BMI). In addition, the study found a negative correlation between MACE and HDL levels. The results of the univariate analysis revealed that an increased risk of MACE corresponded significantly with higher levels of HbA1c, ESR, triglycerides, total cholesterol, LDL, fasting blood glucose, and BMI. Moreover, the multivariate analysis indicated that several factors—triglycerides, HbA1c, HDL, ESR, and age—were significantly associated with an increased risk of MACE. Thus, an increase in triglycerides, HbA1c age, and ESR corresponded to an increase in MACE likelihood, while an increase in HDL corresponded to a decrease in MACE likelihood. Conclusions This study's results show a correlation between levels of ESR, HbA1c, HDL, triglycerides, and the likelihood of MACE, suggesting that these biomarkers may serve as effective indicators and predictors for MACE among patients with diabetes mellitus (DM).
Article
Background: Long-term ambient particulate matter (PM) exposure exerts detrimental effects on cardiovascular health. Evidence on the relation of chronically exposed ambient PM10 and PM2.5 with coronary stenosis remains lacking. Our aim was to investigate the association of PM10 and PM2.5 with coronary stenosis in patients undergoing coronary angiography. Methods: We performed a retrospective cohort study consisting of 7513 individuals who underwent coronary angiography in Fujian Province, China, from January 2019 to December 2021. We calculated a modified Gensini score (GS) to represent the degree of stenosis in coronary arteries by selective coronary angiography. We fitted linear regressions and logistic models to assess the association of PM10 and PM2.5 with coronary stenosis. We employed restricted cubic splines to describe the exposure-response curves. We performed mediation analyses to assess the potential mediators. Results: Long-term ambient PM10 and PM2.5 (prior three years average) exposure was significantly associated with the GS, with a breakpoint concentration of 47.5 μg/m3 and 25.8 μg/m3 for PM10 and PM2.5, respectively, above which we found a linear positive exposure-response relationship of ambient PM with GS. Each 10 µg /m3 increase in PM10 exposure (β: 4.81, 95 % CI: 0.44-9.19) and PM2.5 exposure [β: 10.50, 95 % CI: 3.14-17.86] were positively related to the GS. The adjusted odds ratio (OR) for each 10 µg/m3 increment in PM10 exposure on severe coronary stenosis was 1.33 (95 % CI: 1.04-1.76). Correspondingly, the adjusted OR for PM2.5 was 1.87 (95 % CI: 1.24-2.99). The mediation analysis indicated that the effect of PM10 on coronary stenosis may be partially mediated through total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum creatinine and blood urea nitrogen, and the effect of PM2.5 may be mediated in part by hemoglobin A1c. Conclusion: Our study provides the first evidence that chronic ambient PM10 and PM2.5 exposure was associated with coronary stenosis assessed by GS in patients with suspected coronary artery disease and reveals its potential mediators.
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One hundred years after its discovery, insulin remains the life-saving therapy for many patients with diabetes. It has been a 100-years-old success story thanks to the fact that insulin therapy has continuously integrated the knowledge developed over a century. In 1982, insulin becomes the first therapeutic protein to be produced using recombinant DNA technology. The first “mini” insulin pump and the first insulin pen become available in 1983 and 1985, respectively. In 1996, the first generation of insulin analogues were produced. In 1999, the first continuous glucose-monitoring device for reading interstitial glucose was approved by the FDA. In 2010s, the ultra-long action insulins were introduced. An equally exciting story developed in parallel. In 1966. Kelly et al. performed the first clinical pancreas transplant at the University of Minnesota, and now it is a well-established clinical option. First successful islet transplantations in humans were obtained in the late 1980s and 1990s. Their ability to consistently re-establish the endogenous insulin secretion was obtained in 2000s. More recently, the possibility to generate large numbers of functional human β cells from pluripotent stem cells was demonstrated, and the first clinical trial using stem cell-derived insulin producing cell was started in 2014. This year, the discovery of this life-saving hormone turns 100 years. This provides a unique opportunity not only to celebrate this extraordinary success story, but also to reflect on the limits of insulin therapy and renew the commitment of the scientific community to an insulin free world for our patients.
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Purpose: The study aimed to identify diseases that exhibit significant differences between hyperuricaemia (HUA) and non-hyperuricaemia (NHUA) groups and analyse the risk factors for HUA based on the related diseases in type 2 diabetes mellitus (T2DM). Methods: A total of 3264 T2DM patients were investigated from 2013 to 2017 in the Jinyang and Sanlin communities by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 3000 patients (264 patients were missing during follow-up) were investigated with questionnaires, physical examinations and biochemical index tests. After removing missing values, 2899 patients were divided into HUA and NHUA groups. The chi-square test was used to identify diseases with differences. Using Lasso analysis and logistic regression analysis, risk factors for HUA based on the related diseases were obtained. The C-index, receiver operating characteristic (ROC) curve and calibration plot were used to validate the discrimination and accuracy of the factors. Results: The chi-square test showed that there were significant differences in coronary heart disease (CHD) and diabetic nephropathy (DN) between the HUA group and the NHUA group. Through Lasso regression, glycosylated haemoglobin A1c (HbA1c), triglyceride (TG), blood urea nitrogen (BUN) and serum creatinine (SCR) were screened in the CHD group. Body mass index (BMI), HbA1c, total cholesterol (TC), TG, BUN, SCR and urine microalbumin (UMA) were screened in the DN group. The P-value of all the variables was less than 0.05. Through the C-index, calibration, and ROC curve analyses, these risk factors had medium accuracy. Conclusion: HUA was significantly related to CHD and DN. The level of UA was correlated with HbA1c, TG, BUN, and SCR based on CHD. The level of UA was associated with BMI, HbA1c, TC, TG, BUN, SCR, and UMA based on DN.
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Introduction: Previous studies have predicted an independent relationship between red cell distribution width (RDW) and the risk of death and cardiovascular events in patients with coronary artery disease (CAD). The aim of this study was to investigate the relationship between RDW and extensiveness of CAD in patients with diabetes mellitus (DM). Methods: Two hundred and thirty-three diabetic patients who underwent coronary angiographies at our centre in 2010 were included in the study. All of the angiograms were re-evaluated and Gensini scores were calculated. Triple-vessel disease was diagnosed in the presence of stenosis > 50% in all three coronary artery systems. Result: RDW was significantly higher in diabetic CAD patients (p < 0.001). Patients with CAD who had a RDW value above the cut-off point also had higher Gensini scores, higher percentages of obstructive CAD and triple-vessel disease (p ≤ 0.001 for all). According to the cut-off values calculated using ROC analysis, RDW > 13.25% had a high diagnostic accuracy for predicting CAD. RDW was also positively correlated with Gensini score, obstructive CAD and triple-vessel disease (r < 0.468 and p < 0.001 for all). Conclusion: RDW values were found to be increased in the diabetic CAD population. Higher RDW values were related to more extensive and complex coronary lesions in patients with DM.
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Introduction: Glycated Hemoglobin (HbA1c) levels are predictive of cardiovascular disease and mortality in patients with diabetes mellitus, however, association of HbA1c with Coronary Artery Disease (CAD) in non-diabetics is inconsistent. Aim: To evaluate the correlation between HbA1c level and severity of CAD in non-diabetic patients using SYNTAX score in a cohort of proven CAD on angiography at Gauhati Medical College, Guwahati, Assam, India, which is a major tertiary care hospital of North-Eastern India. Materials and methods: We prospectively collected data of non-diabetic patients with proven CAD on angiography from June 2014 to June 2015. Patients were divided into four groups (interquartiles) according to HbA1c levels, less than 4.8%, 4.8% to 5.1%, 5.1% to 5.6%, and 5.6% to 6.5%. Severity of CAD was assessed using SYNTAX score and the number of coronary vessels diseased. We compared different quartiles of HbA1c with regard to SYNTAX score and number of diseased vessels. Results: A total of 346 patients were included in the study. Mean age was 58.1±10.4 years. Of the total 91.9% (318) were males, 44.8% (155) were hypertensives, 29.2% (101) were smokers and 34.7% (120) were dyslipidemic. We found that CAD severity by SYNTAX score as well as number of vessels involved was significantly different among quartiles (p-values <0.001 and <0.001 respectively). Increase in HbA1c level was strongly correlated with disease severity and higher SYNTAX score. A significant increase was noted in the mean number of diseased vessels (p-value <0.001) as HbA1c level increases. Age, gender, hypertension and dyslipidemia did not show significant difference among quartiles however smoking was found to be an independent predictor of severity of CAD by SYNTAX score (p <0.05). Conclusion: From this clinical study, we can conclude that a significant correlation exists between HbA1c and severity of CAD by SYNTAX score as well as number of vessels involved in non- diabetes.
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Background: Vascular complications of diabetes mellitus (DM) are associated with 5% of deaths globally every year. Early diagnosis and treatment could reduce this figure. The aim of this project was to investigate the frequency of undiagnosed DM among blood donors and the possibility of blood banks participating in DM screening. Methods: Of the approximate 5,600 candidates for blood donation who were evaluated, 4,601 were considered suitable. Candidates with any type of DM, hypertension, thyroid disease, and/or continuous use of any drugs were excluded, resulting in the participation of 635 donors aged 18 - 69 years. Glycated hemoglobin (HbA1c) levels were used to classify the donors: HbA1c < 5.7% (low risk of DM), HbA1c 5.7 - 6.4% (pre-diabetes), and HbA1c ≥ 6.5% (diabetes). Another subsample (n = 576) that excluded donors with HbA1c levels < 5.0% or > 6.5% were classified according to the risk of developing DM in 5 years: HbA1c 5 - 5.5% (low risk, < 9%), HbA1c 5.6 - 6.0% (moderate risk, 9 - 25%), and HbA1c 6.1 - 6.5% (high risk, 26 - 50%). Results: Three donors (0.5%) had HbA1c levels suggestive of DM, and 57 donors (9.0%) had levels associated with pre-DM. Regarding the risk of developing DM in 5 years, 111 donors (19.3%) were classified at moderate risk, and 10 donors (1.7%) were classified at high risk. Conclusions: DM screening in blood banks using HbA1c can identify new cases of DM and individuals at an increased risk of DM. In summary, blood banks could participate in DM screening, benefitting the general public and public health care system in Brazil.
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This article summarizes the main developments reported in 2014 on ischemic heart disease, together with the most important innovations in intensive cardiac care.
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This article summarizes the main developments reported in 2014 on ischemic heart disease, together with the most important innovations in intensive cardiac care. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
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The degree of glycaemia has been shown to be associated with all-cause and cardiovascular mortality in diabetic subjects. Whether this association also exists in the general population is still controversial. We studied the predictive value of fasting plasma glucose, 2-hour post-load glucose and HbA1c in a population-based cohort of 2363 older (50-75 years) subjects, without known diabetes. Relative risks (RR) of all-cause and cardiovascular mortality were estimated by Cox proportional hazards model, adjusting for age and sex, and additionally for known cardiovascular risk factors. During 8 years of follow-up, 185 subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.1 mmol/l. Post-load glucose and HbA1c values were, even within the non-diabetic range, associated with an increased risk (p for linear trend < 0.05). These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors. After exclusion of subjects with newly diagnosed diabetes or with pre-existent cardiovascular disease (n = 551), a 5.8 mmol/l increase of post-load glucose (corresponding to two standard deviations of the population distribution) was associated with a higher age-adjusted and sex-adjusted risk of all-cause (RR 2.24) and cardiovascular mortality (RR 3.40) (p < 0.05). After additional adjustment for known cardiovascular risk factors, these relative risks were still statistically significant, with values of 2.20 and 3.00 respectively (p < 0.05). High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA1c values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes.
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To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis of diabetes. The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point. In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).
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The purpose of this study was to compare national estimates from the National Health Interview Survey (NHIS) and the Behavioral Risk Factor Surveillance System (BRFSS). The authors compared data from the 2 surveys on smoking, height, weight, body mass index, diabetes, hypertension, immunization, lack of insurance coverage, cost as a barrier to medical care, and health status. Overall national estimates were similar for 13 of the 14 measures examined. Small differences according to demographic characteristics were found for height and body mass index, with larger differences for health status. Although estimates differed within subgroups, the BRFSS provided national estimates comparable to those of the NHIS. BRFSS national data could provide rapidly available information to guide national policy and program decisions.
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Increasing evidence suggests a continuous relationship between blood glucose concentrations and cardiovascular risk, even below diagnostic threshold levels for diabetes. To examine the relationship between hemoglobin A1c, cardiovascular disease, and total mortality. Prospective population study. Norfolk, United Kingdom. 4662 men and 5570 women who were 45 to 79 years of age and were residents of Norfolk. Hemoglobin A1c and cardiovascular disease risk factors were assessed from 1995 to 1997, and cardiovascular disease events and mortality were assessed during the follow-up period to 2003. In men and women, the relationship between hemoglobin A1c and cardiovascular disease (806 events) and between hemoglobin A1c and all-cause mortality (521 deaths) was continuous and significant throughout the whole distribution. The relationship was apparent in persons without known diabetes. Persons with hemoglobin A1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality. An increase in hemoglobin A1c of 1 percentage point was associated with a relative risk for death from any cause of 1.24 (95% CI, 1.14 to 1.34; P < 0.001) in men and with a relative risk of 1.28 (CI, 1.06 to 1.32; P < 0.001) in women. These relative risks were independent of age, body mass index, waist-to-hip ratio, systolic blood pressure, serum cholesterol concentration, cigarette smoking, and history of cardiovascular disease. When persons with known diabetes, hemoglobin A(1c) concentrations of 7% or greater, or a history of cardiovascular disease were excluded, the result was similar (adjusted relative risk, 1.26 [CI, 1.04 to 1.52]; P = 0.02). Fifteen percent (68 of 521) of the deaths in the sample occurred in persons with diabetes (4% of the sample), but 72% (375 of 521) occurred in persons with HbA1c concentrations between 5% and 6.9%. Whether HbA1c concentrations and cardiovascular disease are causally related cannot be concluded from an observational study; intervention studies are needed to determine whether decreasing HbA1c concentrations would reduce cardiovascular disease. The risk for cardiovascular disease and total mortality associated with hemoglobin A1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes.
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Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances.
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OBJECTIVE—To assess the relation between fasting plasma glucose (FPG) or 2-h plasma glucose (2hPG) and mortality from all causes, cardiovascular disease (CVD), and non-CVD and to determine whether the relationship is graded or threshold. RESEARCH DESIGN AND METHODS—Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe (DECODE) is a collaborative prospective study of 22 cohorts in Europe with baseline glucose measurements for 29,714 subjects aged 30–89 years who were followed-up for 11 years (329,050 person-years). Hazard ratio (HR) for death was estimated using Cox regression analysis. RESULTS—High glucose concentrations as well as very low glucose levels were associated with increased risk of death. Compared with an FPG of 4.50–6.09 mmol/l, the multivariate-adjusted HR (95% CI) for FPG <4.50 mmol/l was 1.2 (1.0–1.4) for all-cause, 1.3 (1.0–1.8) for CVD, and 1.1 (0.9–1.4) for non-CVD mortality; the corresponding HRs for diabetes (FPG ≥7.0 mmol/l) were 1.6 (1.4–1.8), 1.6 (1.3–1.9), and 1.6 (1.4–1.9), respectively. For a 2hPG of 3.01–4.50 mmol/l, as compared with a 2hPG of 4.51–5.50 mmol/l, the HRs were 1.1 (1.0–1.2), 1.1 (0.9–1.3), and 1.1 (1.0–1.3), respectively; the corresponding HRs for diabetes (2hPG ≥11.1 mmol/l) were 2.0 (1.7–2.3), 1.9 (1.5–2.4), and 2.1 (1.7–2.5), respectively. The HR for previously undetected diabetes defined by 2hPG was not significantly different from that for known diabetes, which was significantly higher than that for undetected diabetes based on FPG. Subjects with a 2hPG of 10.01–11.09 mmol/l had mortality risks similar to those diabetic subjects defined by an FPG ≥7.0 mmol/l. CONCLUSIONS—The relation between mortality and glucose was J shaped rather than showing threshold effect at high glucose levels, except for CVD mortality and 2hPG, where the relation was graded and increasing.
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Background: Increasing evidence suggests a continuous relationship between blood glucose concentrations and cardiovascular risk, even below diagnostic threshold levels for diabetes. Objective: To examine the relationship between hemoglobin A 1c , cardiovascular disease, and total mortality. Design: Prospective population study. Setting: Norfolk, United Kingdom. Participants: 4662 men and 5570 women who were 45 to 79 years of age and were residents of Norfolk. Measurements: Hemoglobin A 1c and cardiovascular disease risk factors were assessed from 1995 to 1997, and cardiovascular disease events and mortality were assessed during the follow-up period to 2003. Results: In men and women, the relationship between hemoglobin A 1c and cardiovascular disease (806 events) and between hemoglobin A 1c and all-cause mortality (521 deaths) was continuous and significant throughout the whole distribution. The relationship was apparent in persons without known diabetes. Persons with hemoglobin A 1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality. An increase in hemoglobin A 1c of 1 percentage point was associated with a relative risk for death from any cause of 1.24 (95% Cl, 1.14 to 1.34; P < 0.001) in men and with a relative risk of 1.28 (Cl, 1.06 to 1.32; P < 0.001) in women. These relative risks were independent of age, body mass index, waist-to-hip ratio, systolic blood pressure, serum cholesterol concentration, cigarette smoking, and history of cardiovascular disease. When persons with known diabetes, hemoglobin A 1c concentrations of 7% or greater, or a history of cardiovascular disease were excluded, the result was similar (adjusted relative risk, 1.26 [Cl, 1.04 to 1.52]; P = 0.02). Fifteen percent (68 of 521) of the deaths in the sample occurred in persons with diabetes (4% of the sample), but 72% (375 of 521) occurred in persons with HbA 1c concentrations between 5% and 6.9%. Limitations: Whether HbA 1c concentrations and cardiovascular disease are causally related cannot be concluded from an observational study; intervention studies are needed to determine whether decreasing HbA 1c concentrations would reduce cardiovascular disease. Conclusions: The risk for cardiovascular disease and total mortality associated with hemoglobin A 1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA 1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A 1c concentrations in persons without diabetes.
Article
OBJECTIVE - To assess the relation between fasting plasma glucose (FPG) or 2-h plasma glucose (2hPG) and mortality from all causes, cardiovascular disease (CVD), and non-CVD and to determine whether the relationship is graded or threshold. RESEARCH DESIGN AND METHODS - Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe (DECODE) is a collaborative prospective study of 22 cohorts in Europe with baseline glucose measurements for 29,714 subjects aged 30-89 years who were followed-up for 11 years (329,050 person-years). Hazard ratio (HR) for death was estimated using Cox regression analysis. RESULTS - High glucose concentrations as well as very low glucose levels were associated with increased risk of death. Compared with an FPG of 4.50-6.09 mmol/l, the multivariate-adjusted HR (95% CI) for FPG <4.50 mmol/l was 1.2 (1.0-1.4) for all-cause, 1.3 (1.0-1.8) for CVD,and 1.1 (0.9-1.4) for non-CVD mortality; the corresponding HRs for diabetes (FPG &GE;7.0 mmol/l) were 1.6 (1.4-1.8), 1.6 (1.3-1.9), and 1.6 (1.4-1.9), respectively. For a 2hPG of 3.01-4.50 mmol/l, as compared wit a 2hPG of 4.51-5.50 mmol/l, the HRs were 1.1 (1.0-12), 1.1 (0.9-1.3), and 1.1 (1.0-1.3), respectively; the corresponding HRs for diabetes (2hPG &GE;11.1 mmol/l) were 2.0 (1.7-2.3), 1.9 (1.5-2.4), and 2.1 (1.7-2.5), respectively. The HR for previously undetected diabetes defined by 2hPG was not significantly different from that for known diabetes, which was significantly higher than that for undetected diabetes based on FPG. Subjects with a 2hPG of 10.01-11.09 mmol/l had mortality risks similar to those diabetic subjects defined by an FPG &GE;7.0 mmol/l. CONCLUSIONS - The relation between mortality and glucose was J shaped rather than showing threshold effect at high glucose levels, except for CVD mortality and 2hPG, where the relation was graded and increasing.
Article
Background: Increasing evidence suggests a continuous relationship between blood glucose concentrations and cardiovascular risk, even below diagnostic threshold levels for diabetes. Objective: To examine the relationship between hemoglobin A1c, cardiovascular disease, and total mortality. Design: Prospective population study. Setting: Norfolk, United Kingdom. Participants: 4662 men and 5570 women who were 45 to 79 years of age and were residents of Norfolk. Measurements: Hemoglobin A1c and cardiovascular disease risk factors were assessed from 1995 to 1997, and cardiovascular disease events and mortality were assessed during the follow-up period to 2003. Results: In men and women, the relationship between hemoglobin A1c and cardiovascular disease (806 events) and between hemoglobin A1c and all-cause mortality (521 deaths) was continuous and significant throughout the whole distribution. The relationship was apparent in persons without known diabetes. Persons with hemoglobin A1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality. An increase in hemoglobin A1c of 1 percentage point was associated with a relative risk for death from any cause of 1.24 (95% CI, 1.14 to 1.34; P < 0.001) in men and with a relative risk of 1.28 (CI, 1.06 to 1.32; P < 0.001) in women. These relative risks were independent of age, body mass index, waist-to-hip ratio, systolic blood pressure, serum cholesterol concentration, cigarette smoking, and history of cardiovascular disease. When persons with known diabetes, hemoglobin A1c concentrations of 7% or greater, or a history of cardiovascular disease were excluded, the result was similar (adjusted relative risk, 1.26 [CI, 1.04 to 1.52]; P = 0.02). Fifteen percent (68 of 521) of the deaths in the sample occurred in persons with diabetes (4% of the sample), but 72% (375 of 521) occurred in persons with HbA1c concentrations between 5% and 6.9%. Limitations: Whether HbA1c concentrations and cardiovascular disease are causally related cannot be concluded from an observational study; intervention studies are needed to determine whether decreasing HbA1c concentrations would reduce cardiovascular disease. Conclusions: The risk for cardiovascular disease and total mortality associated with hemoglobin A 1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes.
Article
Objective To examine the value of glycated haemoglobin (HbA1c) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. Design Prospective population study. Setting Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Subjects 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999. Main outcome measures Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. Results Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA1c concentration. HbA1c was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA1c concentrations below 5%. An increase of 1% in HbA1c was associated with a 28% (P<0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P=0.05 adjusted for age and risk factors) after men with known diabetes, a HbA1c concentration ≥7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA1c concentration ≥5% occurred in men with diabetes, but 82% occurred in men with concentrations of 5%-6.9% (the majority of the population). Conclusions Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA1c through behavioural means.
Article
Background: Studies from the balloon angioplasty and bare metal stent eras have demonstrated that coronary artery bypass grafting (CABG) is cost-effective compared with percutaneous coronary intervention (PCI) for patients undergoing multivessel coronary revascularization-particularly among patients with complex coronary artery disease or diabetes mellitus. Whether these results apply in the drug-eluting stent (DES) era is unknown. Methods and results: Between 2005 and 2010, 1900 patients with diabetes mellitus and multivessel coronary artery disease were randomized to PCI with DES (DES-PCI; n=953) or CABG (n=947). Costs were assessed from the perspective of the U.S. health care system. Health state utilities were assessed using the EuroQOL 5 dimension 3 level questionnaire. A patient-level microsimulation model based on U.S. life-tables and in-trial results was used to estimate lifetime cost-effectiveness. Although initial procedural costs were lower for CABG, total costs for the index hospitalization were $8622 higher per patient. Over the next 5 years, follow-up costs were higher with PCI, owing to more frequent repeat revascularization and higher outpatient medication costs. Nonetheless, cumulative 5-year costs remained $3641 higher per patient with CABG. Although there were only modest gains in survival with CABG during the trial period, when the in-trial results were extended to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with substantial gains in both life expectancy and quality-adjusted life expectancy and incremental cost-effectiveness ratios <$10 000 per life-year or quality-adjusted life-year gained across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. Conclusions: Despite higher initial costs, CABG is a highly cost-effective revascularization strategy compared with DES-PCI for patients with diabetes mellitus and multivessel coronary artery disease. Clinical trial registration: URL: http://www.clinical-trials.gov. Unique identifier: NCT00086450.
Article
Background: Due to the negative prognostic impact, it is important to accurately detect undiagnosed glucose perturbations in patients with acute coronary syndromes (ACS). Design: This study compares oral glucose tolerance test (OGTT) to fasting plasma glucose (FPG) and HbA1c as screening tools. Methods: Patients hospitalized for ACS had an OGTT, FPG, and HbA1c measured 4-21 (median 6) days after admission as a screening process for an intervention study. Results: Out of 174 patients, 75 (43%) had a normal glucose tolerance, 63 (36%) impaired glucose tolerance (IGT), and 36 (21%) diabetes type 2 (T2DM). Of these, 20 were non-eligible, and of the remaining 79 patients, 52 had IGT and 27 T2DM according to the OGTT. In patients with IGT, the median FPG was 6.0 mmol/l and the median HbA1c was 39 mmol/mol. The corresponding levels in patients with T2DM were 6.3 mmol/l and 41 mmol/mol, respectively. Seventeen of the 27 patients with T2DM according to OGTT had not been disclosed if the screening had been based on FPG. HbA1c identified two patients. Conclusions: Compared to OGTT, the use of FPG or HbA1c alone leaves a majority of patients with IGT or T2DM undetected when screening for unknown glucose perturbations as a part of total risk assessment of patients with ACS.
Article
The purpose of this study was to examine the association between hyperglycemia and subclinical myocardial injury in persons without clinically evident coronary heart disease (CHD). Hyperglycemia is associated with an increased risk of cardiac events, but limited information is available on its relationship to subclinical myocardial damage. Elevated cardiac troponin T even below traditional detection levels can be detected by a novel high-sensitivity assay. We examined the association between baseline glycated hemoglobin (HbA1c) and high-sensitivity cardiac troponin T (hs-cTnT) in 9,661 participants free of CHD and heart failure in the ARIC (Atherosclerosis Risk in Communities) study. Multivariable logistic regression models characterized the association between clinical categories of HbA1c (<5.7%, 5.7% to 6.4%, and ≥6.5%) and our primary outcome of elevated hs-cTnT (≥14 ng/l). Higher baseline values of HbA1c were associated in a graded fashion with elevated hs-cTnT (p for trend < 0.001). After adjusting for traditional risk factors, compared to persons with HbA1c <5.7%, the odds ratios of elevated hs-cTnT for persons with HbA1c 5.7% to 6.4% and ≥6.5% were 1.26 (95% confidence interval: 1.01 to 1.56) and 1.97 (95% confidence interval: 1.44 to 2.70), respectively. Higher HbA1c is associated with elevated hs-cTnT among persons without clinically evident CHD, suggesting that hyperglycemia contributes to myocardial injury beyond its effects on development of clinical atherosclerotic coronary disease.
Article
Current guidelines for treating patients with type 2 diabetes mellitus are based on glycemic standards derived from epidemiologic data; however, the course of the disease, from prediabetes to end-stage complications, is not the same in all patients. Microvascular complications, including nephropathy, retinopathy, and neuropathy, are strongly related to hemoglobin A1c (HbA1c). However, vascular complications may progress in patients who have HbA1c <7.0% and may appear even in undiagnosed patients owing to transient increases in plasma glucose concentrations. Concomitant atherosclerosis and occult macrovascular disease may follow an accelerated course in type 2 diabetes. Macrovascular complications may develop early, and, like microvascular complications, do not correlate linearly with HbA1c. Managing hyperglycemia in the later stages of type 2 diabetes does not appear to be associated with improved cardiovascular outcomes. The glucotoxicity and lipotoxicity that may precede prolonged hyperglycemia and beta-cell dysfunction are early, reversible pathophysiologic events. This suggests that prompt management may modify the course of hyperglycemia and prevent or delay long-term complications. The challenge remains to identify patients with early type 2 diabetes who are at risk for rapid progression of beta-cell decline and premature development of microvascular complications. Ongoing research into the mechanisms responsible for diabetic complications may provide new markers to help identify patients with type 2 diabetes who can benefit from earlier antidiabetes treatments.
Article
The increase in the incidence of diabetes and prediabetes, the association with cardiovascular disease and the accompanying high morbidity and mortality make glucose perturbations a serious public health issue. The poor prognosis among patients with type 2 diabetes and cardiovascular disease may relate to several factors. There seems to be a misconception among cardiologists that diabetes is a nonfrequent, almost unexciting disease and if it exists, it is labelled as 'mild' and/or 'easy to treat.' If screened with an oral glucose tolerance test approximately two-thirds of patients with coronary artery disease, stable and unstable, and earlier unknown glucometabolic perturbations indeed have impaired glucose tolerance or newly detected diabetes. Both conditions are related to an increase in cardiovascular mortality and morbidity. The European guidelines for diabetes, prediabetes and cardiovascular disease recommend that all patients with cardiovascular disease manifestations are screened with an oral glucose tolerance test. Many cardiologists seem more focused on the manifestation of the cardiac condition, not fully understanding the need for simultaneous and aggressive interactions directed towards the underlying metabolic disorder and the frequently existing concomitant risk factors. Treatment must be multifactorial and target driven. Treatment targets are stricter for patients with diabetes than those without diabetes. Patient management according to such standards is highly rewarding but necessitates transprofessional collaboration between cardiologists and diabetologists to be successfully accomplished.
Article
Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose. We compared the prognostic value of glycated hemoglobin and fasting glucose for identifying adults at risk for diabetes or cardiovascular disease. We measured glycated hemoglobin in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990-1992 period) of the Atherosclerosis Risk in Communities (ARIC) study. The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios (with 95% confidence intervals) for diagnosed diabetes were 0.52 (0.40 to 0.69), 1.00 (reference), 1.86 (1.67 to 2.08), 4.48 (3.92 to 5.13), and 16.47 (14.22 to 19.08), respectively. For coronary heart disease, the hazard ratios were 0.96 (0.74 to 1.24), 1.00 (reference), 1.23 (1.07 to 1.41), 1.78 (1.48 to 2.15), and 1.95 (1.53 to 2.48), respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose. In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.
Article
The Modification of Diet in Renal Disease Study is randomized, multicenter, clinical trial designed to determine the effects of three levels of dietary control of protein and phosphorus and two levels of blood pressure control on the rate of decline of kidney function among persons with chronic renal disease. Study participants were assigned to one of two studies, Study A or Study B, depending on their GFR just before randomization. Within each study, participants were randomly allocated to one of two levels of blood pressure control and to one of two dietary interventions according to separate 2 x 2 factorial designs. A total of 840 men and women aged 18 to 70 were randomized. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized participants at the time of entry into the trail, overviews the protocol and purposes of the baseline period before randomization, and evaluates the balance among the treatment intervention groups within Studies A and B at the time of randomization. Major indicators of renal function were found to be well balanced among the treatment groups. Selected baseline characteristics of participants in the Modification of Diet in Renal Disease Study are compared with those of other renal clinical trials and with those of new cases of treated ESRD reported in the United States Renal Data System.
Article
Glycated hemoglobin measures average blood glucose over the preceding 2 to 3 months. The authors examined the tracking of the major glycated hemoglobin A1c (HbA1c), over a period of 4 to 6 years. Two HbA1c measurements were obtained between 1986 and 1993 from 639 elderly, presumptively nondiabetic members of the original cohort of the Framingham Heart Study, Framingham, Massachusetts. Mean +/- standard deviation (SD) baseline and follow-up HbA1c were 5.43% +/- 0.7 and 5.71% +/- 0.9, respectively. Intraclass correlation of 0.59 between baseline and follow-up measurements indicated good reliability of a single HbA1c measurement. Ninety-one percent of follow-up measurements were within +/- 20% of baseline value; HbA1c values tended to move 15% closer to the baseline mean over time. There was a modest tendency for HbA1c values to increase with time; the mean difference between measurements was 0.28% +/- 0.7 SD (p < 0.0001). Change in HbA1c was positively associated with age and body mass index at baseline examination, and negatively associated with cigarette smoking, even after controlling for age and body mass index. These effects were very small, however. We conclude that glycated hemoglobin reliably categorizes the glucose control of nondiabetic subjects over a period of 4 to 6 years, confirming its value as an epidemiological measure.
Article
To examine the relation between GHb, fasting plasma glucose (FPG), postchallenge plasma glucose (PCPG), and mortality from cardiovascular disease (CVD) and ischemic heart disease (IHD) in older adults. A community-based study of 1,239 nondiabetic older adults followed for an average of 8 years, from baseline (1984-1987) to 1993. GHb, but not FPG or PCPG, was significantly related to CVD and IHD mortality in women but not men. The age-adjusted relative hazard for those in the highest quintile of GHb (> or = 6.7%) compared with women with lower levels was 2.37 for fatal CVD (95% CI = 1.30-4.31, P = 0.005) and 2.43 for IHD (95% CI = 1.12-5.25, P = 0.024). This association persisted after adjustment for all covariates (age, systolic blood pressure, BMI, LDL, HDL, triglycerides, cigarette smoking, antihypertensive medication use, and estrogen use). GHb was significantly associated with LDL and HDL levels in women, but the association between GHb and CVD or IHD persisted after adjustment for these lipoproteins. We concluded that GHb is a better predictor of CVD and IHD mortality than FPG or PCPG in women without diabetes; no single measure of glycemia was predictive in men. The reason for the sex difference is unexplained.
Article
People with diabetes are at increased risk for cardiovascular events. However, questions remain about what role, if any, homeostatic glucose control plays in the development of cardiovascular disease among nondiabetic individuals. We investigated the relationship between HbA1c level and carotid intimal-medial thickening in normoglycemic individuals. We conducted a case-control study among 208 normoglycemic individuals (fasting glucose < or = 6.4 mmol/l and no history of diabetes) who had carotid initial-medial thickening (case subjects) and 208 normoglycemic control subjects individually matched for age, sex, race, field center, and date of exam. Subjects were free-living men and women, aged 45-64 years at baseline, who participated in the Atherosclerosis Risk in Communities (ARIC) Study. HbA1c levels, expressed as percent of total hemoglobin, ranged from 4 to 7% and correlated only modestly with single measurements of fasting glucose (r = 0.16) and fasting insulin (r = 0.14). The mean level of HbA1c was 5.18% among case subjects and 5.07% among control subjects (P = 0.004, paired t test). As compared with the first quartile of HbA1c the matched relative odds of being a case were 1.15, 1.33, and 2.30 for the second, third, and fourth quartiles, respectively (P = 0.005 for linear trend). After multivariate adjustment for age, fasting glucose, fasting insulin, BMI, smoking status, hypertension, LDL cholesterol, HDL cholesterol, fibrinogen, and education level, the respective relative odds estimates were 0.98, 1.07, and 1.88 (P = 0.16 for linear trend). When modeled linearly as a continuous variable and after adjustment for the above-mentioned covariates, a 1% point increment in HbA1c level was associated with 1.77 greater odds of being a case (95% CI, 0.9-3.5). These data provide some support to the hypothesis that in the absence of diabetes, homeostatic glycemic control is a risk factor for atherosclerosis.
Article
To examine the value of glycated haemoglobin (HbA(1c)) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. Prospective population study. Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999. Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA(1c) concentration. HbA(1c) was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA(1c) concentrations below 5%. An increase of 1% in HbA(1c) was associated with a 28% (P<0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P=0.05 adjusted for age and risk factors) after men with known diabetes, a HbA(1c) concentration >/=7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA(1c) concentration >/=5% occurred in men with diabetes, but 82% occurred in men with concentrations of 5%-6.9% (the majority of the population). Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA(1c) through behavioural means.
Article
The roles of transforming growth factor (TGF)-β1 in vascular proliferation, atherosclerosis, and plaque still remain controversial. TGF-β1 has been previously reported to inhibit the proliferation and migration of vascular smooth muscle cells and endothelial cells, in vitro. On the other hand, administration or transgenic overexpression of TGF-β1 enhances extracellular matrix synthesis and cellular hyperplasia of the intima and media in the normal artery and injured artery in vivo. We evaluated the correlation of arterial proliferation with plasma levels of TGF-β1 and TGF-β receptor type II, respectively, in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new strain of spontaneous non-insulin-dependant diabetes mellitus (NIDDM) models. OLETF rats (n=30) were divided into three groups aged 5,15, and 30 weeks. Long-Evans Tokushima Otsuka (LETO) rats (n=30) were used as age-matched non-diabetic controls. Plasma TGF-β1 and insulin were determined by enzyme-linked immunosorbent assay. Immunoreactive TGF-β receptor type II antigen was detected by immunohistochemistry on the thoracic artery. Arterial media area was measured microscopically. Oral glucose tolerance test was performed to examine the stage of diabetes mellitus. The thoracic aorta wall section area increased significantly from the age of 15 weeks in OLETF rats, versus LETO rats. In both OLETF and LETO rats, plasma TGF-β1 increased significantly from the age of 15 weeks. In OLETF rats, plasma TGF-β1 increased significantly over that in LETO rats (P
Article
To test the hypothesis that fasting hyperglycemia (FHG) and 2-h postchallenge glycemia (2hPG) independently increase the risk for cardiovascular disease (CVD). During 1991-1995, we examined 3,370 subjects from the Framingham Offspring Study who were free from clinical CVD (coronary heart disease, stroke, or intermittent claudication) or medication-treated diabetes, and we followed them for 4 years for incident CVD events. We used proportional-hazards regression to assess the risk associated with FHG (fasting plasma glucose > or =7.0 mmol/l) and 2hPG, independent of the risk predicted by standard CVD risk factors. Mean subject age was 54 years, 54% were women, and previously undiagnosed diabetes was present in 3.2% by FHG and 4.9% (164) by FHG or a 2hPG > or =11.1 mmol/l. Of these 164 subjects, 55 (33.5%) had 2hPG > or =11.1 without FHG, but these 55 subjects represented only 1.7% of the 3,261 subjects without FHG. During 12,242 person-years of follow-up, there were 118 CVD events. In separate sex- and CVD risk-adjusted models, relative risk (RR) for CVD with fasting plasma glucose > or =7.0 mmol/l was 2.8 (95% CI 1.6-5.0); RR for CVD per 2.1 mmol/l increase in 2hPG was 1.2 (1.1-1.3). When modeled together, the RR for FHG decreased to 1.5 (0.7-3.6), whereas the RR for 2hPG remained significant (1.1, 1.02-1.3). The c-statistic for a model including CVD risk factors alone was 0.744; with addition of FHG, it was 0.746, and with FHG and 2hPG, it was 0.752. Postchallenge hyperglycemia is an independent risk factor for CVD, but the marginal predictive value of 2hPG beyond knowledge of standard CVD risk factors is small.
Article
The National High Blood Pressure Education Program (NHBPEP), coordinated by the National Heart, Lung, and Blood Institute (NHLBI), has released its long-awaited Joint National Committee (JNC) 7 report.1 The report will be made available in 2 forms: the “Express” or short version and a longer version that will be published in Hypertension and will provide more detail regarding the recommendations. On its surface, it resembles the 6 predecessors, but to fully appreciate this new landmark document, one must recognize the process and context from which it is derived and what it is about to do. You cannot direct the winds; you can adjust the sails. Approximately 35 years ago, clinicians were busy managing severe and malignant hypertension. Hospitals filled their beds with stroke patients and stroke wards were commonplace. Coronary heart disease and stroke prevalence and accompanying mortality rates were the highest ever recorded. During the next generation, different classes of antihypertensive agents were developed and tested in a variety of settings and among different patients. The studies independently and collectively contributed to a universal finding: lowering arterial pressure can remarkably reduce cardiovascular morbidity and mortality rates as well as slow the progression of renal disease, retinopathy, and all-cause deaths. When these findings first became available, the NHLBI formed the NHBPEP, designed to translate this information through public and professional education programs. …
Article
High levels of HbA1c have been associated with increased mortality and an increased risk of atherosclerosis assessed as carotid intima-media thickness or plaque prevalence. In the present population-based study, we examined the association between HbA1c and plaque prevalence with emphasis on plaque echogenicity in subjects not diagnosed with diabetes. HbA1c measurements and ultrasonography of the carotid artery were performed in 5960 subjects (3026 women, 2934 men) 25 to 84 years of age. Plaque morphology was categorized into 4 groups from low echogenicity (soft plaque) to strong echogenicity (hard plaque). HbA1c was categorized into 5 groups: <5.0%, 5.0% to 5.4%, 5.5% to 5.9%, 6.0% to 6.4% and >6.4%. Carotid plaque prevalence increased with increasing HbA1c level (P for linear trend=0.002). The OR for hard plaques versus no plaques was 5.8 in the highest HbA1c group (>6.4%) compared with subjects in the lowest group (<5.0%) after adjustment for several possible confounders. The risk of predominantly hard plaques was also significantly associated with HbA1c levels, although the ORs at each level were somewhat lower than for hard plaques. With respect to the risk of soft plaques versus no plaques, no statistically significant relationship with HbA1c levels was found. Metabolic changes reflected by HbA1c levels may contribute to the development of hard carotid artery plaques, even at modestly elevated levels.