Coronary Heart Disease In Diabetic Patients Research Articles

Coronary heart disease in Type 2 diabetes: mechanisms and comprehensive prevention strategies

Individuals with Type 2 diabetes mellitus suffer from a higher incidence of coronary heart disease (CHD) compared with those without diabetes. The mechanisms for the increased CHD in diabetic patients are multifactorial, including endothelial dysfunction, vessel wall modification, hyperglycemic toxicity, oxidative stress and inflammation, and insulin resistance. Moreover, multifactorial intervention, other than glycemic control alone, is recognized as the promising strategy for diabetic patients with CHD. In this review, the roles of the major contributors to the development of CHD and the comprehensive management strategies dealing with diabetes mellitus are focused upon.

Genetic Susceptibility to Coronary Heart Disease in Type 2 Diabetes: 3 Independent Studies

The aim of this study was to evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes. No study has examined the effects of these genetic variants on CHD in diabetic patients. We genotyped 15 genetic markers of 12 loci in 3 studies of diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544 control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451 control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and 435 control subjects). Five single-nucleotide polymorphisms, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the 5 significantly associated loci. The OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p < 0.0001). Individuals with GRS ≥8 (19% of diabetic subjects) had almost a 2-fold increase in CHD risk (OR: 1.94, 95% confidence interval: 1.60 to 2.35) as compared with individuals with GRS ≤5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p < 0.001) when the GRS was added to a model including clinical predictors in the combined samples. Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.

Diabetes and Cardiovascular Disease

The prevalence of obesity and diabetes continues to increase rapidly in the U.S. and all over the world (1–3). Obesity and diabetes are major risk factors for cardiovascular diseases (CVDs), but despite the increase in their prevalence, there seems to be a continuous steady decline in death rates from coronary heart disease (CHD) and stroke (4). Moreover, cause-specific excess death associated with obesity has been declining despite the increase in obesity rates (5). The reason behind this apparent paradox is probably a better control of other risk factors for CVD, such as cholesterol levels, hypertension, and smoking. Several trials demonstrated that more than half the decline in deaths from CHD in the last decades may be attributable to reductions in major risk factors (6). Of all risk factors, treating high cholesterol levels had the highest impact on the decline in CHD mortality (7). This is hardly surprising because the LDL cholesterol level is the strongest determinant of CHD risk, even in diabetic patients (8). ### Prevention of CHD in diabetic patients and the question of residual risk Statins are the most effective agents in reducing the risk of CHD in diabetic patients, reducing the relative risk by about one-third (9,10). An analysis based on the UK Prospective Diabetes Study (UKPDS) risk engine demonstrated that even in the Steno-2 study, in which multifactorial intervention was used for the treatment of diabetes with an impressive reduction of both cardiovascular morbidity and mortality, lipid-lowering therapy accounted for more than 70% of CVD risk reduction (11). Actually, many more patients in the intensive therapy group achieved their cholesterol goal compared with the conventional therapy group (70 vs. 20%), while there was no difference between the groups in the attainment of their triglyceride goal (11). The main difference between the intensive and conventional treatment groups was in the use of statins (12 …

Screening Guidelines for Coronary Heart Disease in Diabetes: Current Recommendations

Diabetes and cardiovascular disease are so intertwined with one another that the presence of one prompts a search for the other. Diabetes has been considered to be equivalent to coronary heart disease (CHD), and conversely many patients with known CHD have concomitant diabetes or its pre-states. This review has been compiled based on the guidelines of the American Diabetes Association, the Third Report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III), the European Society of Cardiology, and the European Association for the Study of Diabetes. A systematic approach was developed by the European Society of Cardiology and the European Association for the Study of Diabetes recently to help detect CHD in patients with diabetes and to detect metabolic diseases in patients with CHD.This article is intended for the clinician in everyday practice focusing on the impact of recent advances in the prevention and management of CHD in diabetic patients and the background behind it.

Prevention of Macrovascular Disease in Type 2 Diabetic Patients: Blockade of the Renin-Angiotensin-Aldosterone System

Type 2 diabetes is reaching epidemic proportions throughout the world, which has major health implications as such patients have considerably increased risk of coronary heart disease (CHD). The renin-angiotensin-aldosterone system (RAAS) is involved in a wide range of adverse effects that contribute to the pathogenesis of CHD in diabetic patients, including vascular haemodynamic regulation, oxidative stress and hypertrophy of vascular cells. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. In diabetic patients ACE inhibitors and ARBs both effectively lower blood pressure, particularly in combination with low-dose thiazide diuretics, and may be considered first line therapies in the treatment of diabetic hypertension. Additionally they have important renoprotective actions independent of their blood pressure-lowering action, which is of particular benefit in diabetic patients, who are at increased risk of developing nephropathy. ARBs are generally well tolerated, but ACE inhibitor therapy is associated with some side effects such as cough and both may result in hyperkalaemia. Blockade of the RAAS with these agents appears to play an important role not only in protecting from renal disease, but it may also help to reduce morbidity and mortality from certain vascular diseases in diabetic patients.

Von Willebrand factor, endothelial dysfunction, and cardiovascular disease.

von Willebrand factor (VWF), a glycoprotein involved in arterial thrombus formation, is released into the circulation by secretion from endothelial cells. Plasma VWF levels are determined by genetic factors including ABO blood groups and VWF mutations, and by non-genetic factors including aging, impaired nitric oxide production, inflammation, free radical production and diabetes. Plasma VWF levels have been proposed as a risk factor for cardiovascular events. Although they are only weakly associated with the risk of coronary heart disease (CHD) in the general population, they are a more promising CHD risk factor in high-risk populations with previous cardiovascular events, diabetes or old age. However, is it still unclear whether VWF levels directly determine the rate and severity of arterial thrombus formation or whether they merely reflect alteration in other endothelial functions. The future status of VWF levels as a cardiovascular risk factor depends on additional studies on the genetic determinants of both VWF levels and cardiovascular outcomes. Further studies on VWF levels as a predictor of the risk of stroke (rather than CHD) in elderly or other high-risk population are also promising. Such studies could lead to the clinical use of plasma VWF levels to refine the estimation of the cardiovascular risk and of the expected benefit of antithrombotic agents.

Analysis of quantitative lipid traits in the genetics of NIDDM (GENNID) study.

Coronary heart disease (CHD) is the leading cause of death among individuals with type 2 diabetes. Dyslipidemia contributes significantly to CHD in diabetic patients, in whom lipid abnormalities include hypertriglyceridemia, low HDL cholesterol, and increased levels of small, dense LDL particles. To identify genes for lipid-related traits, we performed genome-wide linkage analyses for levels of triglycerides and HDL, LDL, and total cholesterol in Caucasian, Hispanic, and African-American families from the Genetics of NIDDM (GENNID) study. Most lipid traits showed significant estimates of heritability (P < 0.001) with the exception of triglycerides and the triglyceride/HDL ratio in African Americans. Variance components analysis identified linkage on chromosome 3p12.1-3q13.31 for the triglyceride/HDL ratio (logarithm of odds [LOD] = 3.36) and triglyceride (LOD = 3.27) in Caucasian families. Statistically significant evidence for linkage was identified for the triglyceride/HDL ratio (LOD = 2.45) on 11p in Hispanic families in a region that showed suggestive evidence for linkage (LOD = 2.26) for triglycerides in this population. In African Americans, the strongest evidence for linkage (LOD = 2.26) was found on 19p13.2-19q13.42 for total cholesterol. Our findings provide strong support for previous reports of linkage for lipid-related traits, suggesting the presence of genes on 3p12.1-3q13.31, 11p15.4-11p11.3, and 19p13.2-19q13.42 that may influence traits underlying lipid abnormalities associated with type 2 diabetes.

Reducing coronary heart disease associated with type 2 diabetes: lifestyle intervention and treatment of dyslipidaemia

Efforts to reduce the burden of coronary heart disease (CHD) associated with type 2 diabetes should include increased emphasis on preventing progression to diabetes in individuals with impaired glucose tolerance. Recent large-scale studies have shown that lifestyle intervention can reduce progression to diabetes by nearly 60%. Dyslipidaemia is a risk factor for CHD in diabetic patients. Accumulation of evidence indicating significant reductions in CHD risk with statin treatment to lower low-density lipoprotein (LDL)–cholesterol has led to the recommendation that reduction of LDL-cholesterol be considered the highest priority in treating diabetic dyslipidaemia; additional aims of treatment include raising high-density lipoprotein (HDL)–cholesterol and reducing triglyceride levels. In a recent trial of rosuvastatin alone or combined with fenofibrate in diabetic patients with combined hyperlipidaemia, rosuvastatin 40 mg monotherapy produced marked beneficial changes in LDL-cholesterol (−47%), HDL-cholesterol (+6%) and triglycerides (−30%), with the combination of lower-dose rosuvastatin (10 mg) and fenofibrate producing a significantly greater triglyceride reduction (−47%) and comparable changes in other lipid measures. Combination therapies for dyslipidaemia may be the key to optimizing CHD risk reduction in type 2 diabetes.