Heart Disease and Diabetes

Excerpt

Heart disease remains a major cause of morbidity and mortality among individuals with type 2 diabetes. Meta-analyses have demonstrated a pooled relative risk for incident coronary heart disease (CHD) that is approximately twofold higher overall in adults with diabetes compared to those without diabetes. In studies that further stratify results by sex, the relative risk of CHD is higher in women than men in the presence of diabetes. Nonetheless, the age-standardized prevalence for all categories of heart disease remains higher in men with diabetes than women with diabetes in the United States. Although the rates of diabetes are higher in Hispanic and non-White individuals compared to non-Hispanic White adults, it should be noted that non-Hispanic White adults with diabetes generally report heart disease rates up to twice as high as Hispanic persons with diabetes, with an intermediate prevalence of any heart condition in non-Hispanic Black individuals. Despite a more than twofold increase in type 2 diabetes prevalence from the 1970s to the 2020s, the prevalence of heart disease has increased modestly in both men with diabetes and women with diabetes, while in contrast, it has remained stable or decreased for men and women without diabetes.

Classic heart disease risk markers have been clearly demonstrated to be important determinants of heart disease in diabetes, including elevated low-density lipoprotein cholesterol, elevated blood pressure, smoking, and elevated triglycerides and low high-density lipoprotein cholesterol. Obesity is an important risk factor for type 2 diabetes but has not consistently been shown to have an independent association with heart disease, possibly because obesity is in the causal pathway between these risk factors and heart disease development. However, several studies indicate that the excess prevalence of heart disease in diabetes is not fully accounted for by measured classic cardiovascular disease risk factors. In addition, novel biomarkers have been found to either add no or only modest incremental significance in the prediction of heart disease. The association between fasting glucose and heart disease displays a J-shaped curve in several studies. Glycosylated hemoglobin also has a graded association with heart disease. The association between insulin resistance and heart disease is inconsistent, at least in part because of methodologic differences among studies. Other important risk factors include lifestyle factors, such as physical activity, smoking, diet, and social determinants of health, such as food insecurity, access to health care, or poverty.

Clinical trials involving modification of cardiovascular risk factors in diabetes have helped to clarify their roles in heart disease development. Clinical trials focusing on weight reduction through an intensive lifestyle intervention specifically in people with diabetes have not demonstrated benefit in cardiovascular events despite improvement in risk factors. Whether improvement of glycemic control reduces heart disease has long been a central question, since older trials had not consistently demonstrated benefit. By contrast, lipid-lowering clinical trials have shown that statin treatment, in both secondary as well as primary prevention trials, significantly reduces atherosclerotic heart disease with a similar risk reduction to that seen in people without diabetes. Large randomized trials have demonstrated that highly purified eicosapentaenoic acid ethyl ester significantly reduces risk of ischemic events. Trials of more intensive compared to standard blood pressure control in people with diabetes did not generally find that achieving a lower goal leads to a reduction in cardiovascular events overall. The benefits of aspirin in reducing serious vascular events have been demonstrated in trials of people with diabetes, but these benefits are largely counterbalanced by an increase in major bleeding events.

Post-marketing cardiovascular outcome trials have been required by the U.S. Food and Drug Administration to demonstrate safety for all antihyperglycemic agents newly approved since 2008. All agents in the glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor classes have demonstrated safety, while some agents within these classes of medication have further demonstrated superiority in reducing major adverse cardiovascular events, hospitalization for heart failure, and kidney failure in specific populations.

In conclusion, despite intensive management of cardiovascular risk factors, the high risk for heart disease among people with diabetes remains a major health concern. Importantly, over the past few years, an increasing number of therapies have become available to reduce cardiovascular risk in people with type 2 diabetes.