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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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... 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
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.
... 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.
... 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. ...
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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.
... 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.
... 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. ...
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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.
... 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. ...
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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] . ...
... 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.
... 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. ...
... [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. ...
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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.
... 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. ...
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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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Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed DNA methylation of ∼480,000 sites in human adipose tissue from 96 males and 94 females, and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1,050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of ageing in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2,825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with methylation of 711 sites, annotated to e.g. RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for metabolic diseases and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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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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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: 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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Diabetes is associated with increased mortality following acute myocardial infarction compared to the general population. Elevated glycated haemoglobin (HbA1c) in diabetic patients is also associated with increased mortality following acute myocardial infarction, while mild elevation in HbA1c are associated with impaired glucose tolerance. The aim of this study was to determine the influence of HbA1c on outcome of acute myocardial infarction in 253 non-diabetic patients, 46 of whom died in one year. In univariate analysis, risk factors for death included smoking, glucose, cholesterol and HbA1c. In logistic regression analysis HbA1c was an independent risk factor for death. Over one-third of the fatality group had an HbA1c in the highest quartile, compared to one-fifth of the surviving group (p = 0.02). Elevated HbA1c is a risk marker for short-term mortality following acute myocardial infarction in non-diabetic subjects.
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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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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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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.
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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 &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.
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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 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.
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.
Article
In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear. To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons. Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease. Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease. Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria. Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1-percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43]). This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results. Pending confirmation from large, ongoing clinical trials, this analysis shows that observational studies are consistent with limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.
Article
Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease (CHD), but the extent to which hemoglobin A(1c) (HbA(1c)) level, a marker of long-term glycemic control, is independently related to CHD risk is uncertain. We conducted a prospective case-cohort study of 1321 adults without diabetes and a cohort study of 1626 adults with diabetes from the Atherosclerosis Risk in Communities Study. Using proportional hazards models, we assessed the relation between HbA(1c) level and incident CHD during 8 to 10 years of follow-up. In adults with diabetes, the relative risk (RR) of CHD was 2.37 (95% confidence interval [CI], 1.50-3.72) for the highest quintile of HbA(1c) level compared with the lowest after adjustment for CHD risk factors. In persons without diabetes, the adjusted RR of CHD in the highest quintile of HbA(1c) level was 1.41 (95% CI, 0.90-2.30); however, there was evidence of a nonlinear relationship in this group. In nondiabetic adults, HbA(1c) level was not related to CHD risk below a level of 4.6% but was significantly related to risk above that level (P<.001). In diabetic adults, the risk of CHD increased throughout the range of HbA(1c) levels. In the adjusted model, the RR of CHD for a 1-percentage point increase in HbA(1c) level was 2.36 (95% CI, 1.43-3.90) in persons without diabetes but with an HbA(1c) level greater than 4.6%. In diabetic adults, the RR was 1.14 (95% CI, 1.07-1.21) per 1-percentage point increase in HbA(1c) across the full range of HbA(1c) values. Elevated HbA(1c) level is an independent risk factor for CHD in persons with and without diabetes.
Article
Glycohemoglobin (hemoglobin A1c [HbA1c]) and high-sensitivity C-reactive protein (hsCRP) are risk indicators for atherosclerosis. Limited information exists regarding the combined effects of inflammation and hyperglycemia. We investigated the joint effects of both parameters on early carotid atherosclerosis progression and major vascular events in diabetic and nondiabetic subjects. We analyzed the data of INVADE (Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria), a prospective, population-based study conducted in 3534 subjects (mean age, 69 years). In addition to common risk factors, measurements of carotid intima-media thickness (IMT), hsCRP, and HbA1c were performed at baseline and after 2 years of follow-up. For the entire population, IMT progression was significantly related to HbA1c (P=0.003) but not to hsCRP (P=0.06) after risk factor adjustment. The interaction hsCRPxHbA1c was highly significant (P=0.001), and the most pronounced IMT progression was seen in subjects with both parameters in the fourth quartiles compared with subjects with both parameters in the first quartiles (0.028 [0.025, 0.031] versus 0.012 mm/year [0.007, 0.019]; P=0.0013). We observed a significant joint effect of HbA1c and hsCRP on IMT progression in the diabetic (n=882) as well as the nondiabetic subgroup (n=2652). Subjects with HbA1c and hsCRP in the upper 2 quartiles had an increased risk for new vascular events (adjusted hazard ratio in diabetics: 4.3 [1.8, 7.3]; P=0.001; nondiabetics: 2.9 [1.6, 4.7]; P=0.001). The combination of hyperglycemia and inflammation is associated with an advanced early carotid atherosclerosis progression and an increased risk of new vascular events in diabetic as well as nondiabetic subjects.
Article
Hemoglobin A1c (HbA1c) is a marker of cumulative glycemic exposure over the preceding 2- to 3-month period. Whether mild elevations of this biomarker provide prognostic information for development of clinically evident type 2 diabetes and cardiovascular disease among individuals at usual risk for these disorders is uncertain. We examined baseline HbA1c levels as a predictor of incident clinical diabetes and cardiovascular disease (nonfatal myocardial infarction, coronary revascularization procedure, ischemic stroke, or death from cardiovascular causes) in a prospective cohort study beginning in 1992 of 26,563 US female health professionals aged 45 years or more without diagnosed diabetes or vascular disease (median follow-up 10.1 years). During follow-up, 1238 cases of diabetes and 684 cardiovascular events occurred. In age-adjusted analyses using quintiles of HbA1c, a risk gradient was observed for both incident diabetes and cardiovascular disease. After multivariable adjustment, HbA1c remained a strong predictor of diabetes but was no longer significantly associated with incident cardiovascular disease. In analyses of threshold effects, adjusted relative risks for incident diabetes in HbA1c categories of less than 5.0%, 5.0% to 5.4%, 5.5% to 5.9%, 6.0% to 6.4%, 6.5% to 6.9%, and 7.0% or more were 1.0, 2.9, 12.1, 29.3, 28.2, and 81.2, respectively. Risk associations persisted after additional adjustment for C-reactive protein and after excluding individuals developing diabetes within 2 and 5 years of follow-up. These prospective findings suggest that HbA1c levels are elevated well in advance of the clinical development of type 2 diabetes, supporting recent recommendations for lowering of diagnostic thresholds for glucose metabolic disorders. In contrast, the association of HbA1c with incident cardiovascular events is modest and largely attributable to coexistent traditional risk factors.
Article
Epidemiologic data indicate that a postprandial state characterized by abnormally increased levels of glucose and lipids (also referred to as postprandial dysmetabolism) is an independent predictor of future cardiovascular events, even in nondiabetic subjects. The cardiovascular toxicity of postprandial dysmetabolism is mediated by oxidant stress, which is directly proportional to the increase in glucose after a meal. This transient increase in free radicals acutely triggers inflammation, endothelial dysfunction, hypercoagulability, sympathetic hyperactivity, and a cascade of other atherogenic changes. The postprandial dysmetabolism hypothesis has been bolstered by interventional studies that have demonstrated that blunting the postprandial spikes in glucose and lipids improves inflammation and endothelial function immediately. Early randomized controlled trials indicate that reducing postprandial dysmetabolism appears to significantly slow atherosclerotic progression and may improve cardiovascular prognosis. In conclusion, postprandial dysmetabolism appears to be an important proximate cause of adverse cardiovascular events. Addressing this fundamental and largely unrecognized condition will require specific screening and treatment strategies. Diet, exercise, and various pharmacologic agents can improve postprandial dysmetabolism. Using these strategies may help improve the prognosis for patients with diabetes mellitus and/or coronary heart disease.
Diagnosis and classification of diabetes mellitus.
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
  • Stratton I.M.
  • Adler A.I.
  • Neil H.A.