Heart in Diabetes: Not Only a Macrovascular Disease

EPIDEMIOLOGY—The importance of diabetes as a cause of mortality and morbidity is well known. The number of patients increases alongside aging of the population, raising the prevalence of obesity and a sedentary lifestyle. As a disease that is strongly associated with both microand macrovascular complications, diabetes results in organ and tissue damage. Cardiovascular disease (CVD) causes up to 70% of all deaths in people with diabetes. The epidemic of diabeteswill thus be followed by an epidemic of diabetesrelated vascular diseases. Almost two of three patients who present with symptomatic chronic heart disease have abnormal glucose homeostasis. Although the mortality from coronary artery disease (CAD) in patients without diabetes has declined over the past 20 years, the mortality in men with type 2 diabetes has not changed significantly. Moreover, diabetes is an independent risk factor for heart failure, and there are a substantial number of patients with diabetes and heart failure. The main macrovascular complications, for which diabetes has been a well-established risk factor throughout the cardiovascular system, are CAD, peripheral vascular disease, increased intima-media thickness, and stroke. Ischemic heart disease and stroke account for the highest proportion of comorbid diseases associated with diabetes. The joint guidelines of the European Society of Cardiology and the European Association of Diabetes take into account the close reciprocal relationship between diagnostics and therapeutics in cardiology and diabetology. Patients with diabetes and CVD have an unfavorable prognosis (1). Mortality rates due to heart disease are two to four times higher among people with diabetes compared with those without diabetes after correction for traditional risk factors for CVD such as age, obesity, smoking, dyslipidemia, and hypertension. It appears, however, that the presence of even one of these risk factors leads to poorer outcomes among people with diabetes compared with those without diabetes. People with diabetes have an up to fivefold-higher risk for a first myocardial infarction (MI) and a twofold-greater risk for a recurrent MI than people who previously had an MI but do not suffer from diabetes. Patients with diabetes with prior MI have the worst prognosis (2). Furthermore, people with diabetes have a poorer long-term prognosis after MI, including an increased risk for congestive heart failure and death. People with diabetes are two to four times more likely to develop stroke than people without diabetes. Diabetes accounted for a significant percentage of patients with a diagnosis of heart failure in numerous epidemiologic studies such as The Framingham Study, UK Prospective Diabetes Study (UKPDS), Cardiovascular Health Study, and Euro Heart Failure Surveys. Data from UKPDS regarding the adjusted rate of heart failure demonstrate a rise from 2.3 events per 100 person-years in people with HbA1c levels,6% to 11.9 events per 100 personyears in those presenting with HbA1c levels .10% (3). An increase in HbA1c of 1% correlates to an increment of 8% in heart failure (3,4). Diabetes is a powerful predictor of cardiovascular morbidity and mortality and is an independent risk factor for death in patients with established heart failure. In addition, the prevalence of heart failure in elderly diabetic patients was up to 30% (5). Diabetic women are more likely to develop heart failure than men if compared with age-matched control subjects (5.1-fold vs. 2.1-fold increase) (6). The reason for this difference is not yet fully understood, but may be in part due to a worse comorbid risk factor profile, and the permissive effect upon outcome, particularly in diabetic women (7). The combination of hyperglycemia, insulin resistance, dyslipidemia, hypertension, and chronic inflammation injures the vascular endothelium, resulting in microvascular damage (alterations in capillary density and vascular permeability), macrovasculopathy, and CVD. Most importantly, more than 70% of people with diabetes have high blood pressure or are being treated with medications for hypertension. Because prediabetic subjects often present with multiple CVD risk factors such as insulin resistance, obesity, central obesity, elevated blood pressure, elevated total triglycerides, and low HDL cholesterol, the onset of cardiovascular damage is not closely related to hyperglycemia alone, but has to be seen in the concert of metabolic derangement (8). The cardiac risk in diabetic patients is not only with respect to type 1 or type 2 diabetic patients, but also to several pathophysiological mechanisms and features such as CAD, heart failure, and autonomic neuropathy.