Diabetic and Hypertensive Heart Disease

Diabetes mellitus and hypertensiontwo disorders that frequently coexist in the same patientlead to structural and functional cardiac impairments that accelerate progression to cardiovascular illness and death from cardiovascular causes [1, 2]. Clinical and experimental studies suggest that the presence of diabetes and hypertension in the same patient results in more severe cardiomyopathy than would be expected with either condition alone [3, 4]. We summarize the features of heart disease in patients with diabetes and hypertension. Methods We searched the MEDLINE database for English-language articles published between 1980 and January 1996; we used the terms diabetes mellitus, hypertension or blood pressure, and heart. We also reviewed pertinent articles cited in the identified papers. The term diabetes mellitus included insulin-dependent and noninsulin-dependent diabetes mellitus; however, in some studies, the type of diabetes was not specified. We indicate the type of diabetes if this information was available. We divided the articles into those that addressed coronary artery disease or myocardial ischemia and those that addressed nonischemic cardiomyopathy and its sequelae. Articles about cardiac complications that result from the combination of diabetes mellitus and hypertension were emphasized. Results Diabetic Heart Disease Long-standing diabetes has been documented to cause structural and functional cardiac impairment and to lead to ischemic heart disease, cardiomyopathy, and congestive heart failure. Ischemic Heart Disease Diabetes mellitus is an independent risk factor for the development of coronary artery disease [5, 6]. At coronary angiography or autopsy, diabetic patients have a higher incidence of double- and triple-vessel disease and a lower incidence of single-vessel disease than do their nondiabetic counterparts [5, 7]. In one large study [8], 83% of patients with noninsulin-dependent diabetes mellitus had severe two- or three-vessel involvement at autopsy. Of patients who had no known coronary artery disease, 31% had severe narrowing of at least one major coronary artery. The presence of diabetes mellitus reduces survival after myocardial infarction. The 5-year mortality rate after acute myocardial infarction can be as great as 55% in diabetic patients but only reaches 30% in patients without diabetes, and the rate of reinfarction may be as much as 60% higher in diabetic than in nondiabetic patients [9]. In a recent study of Mexican-American and non-Hispanic white persons, Orlander and coworkers [10] found higher short-term and long-term mortality rates and a higher rate of pump failure in persons with diabetes mellitus than in persons without the disease. The effect of noninsulin-dependent diabetes mellitus on mortality and morbidity in coronary heart disease is more marked in women than in men [11]. Accelerated atherosclerosis in patients with diabetes mellitus may be related to lipid disorders, hyperinsulinemia, and poor glycemic control. Hyperinsulinemia, particularly from exogenous insulin, may exert both a beneficial effect (by reducing hypoglycemia) and an adverse effect (by directly promoting atherogenesis, thrombogenesis, or both) [12, 13]. In addition to accelerating atherosclerosis, diabetes mellitus is associated with abnormal platelet function, coagulation, fibrinolysis, and endothelial function that may favor coronary thrombosis [14]. Autonomic neuropathy related to diabetes mellitus also contributes to the occurrence of ischemic myocardial events. Diabetic autonomic neuropathy initially involves the parasympathetic nerve fibers, leading to a relative increase in sympathetic tone with tachycardia at rest and exaggerated coronary vasoconstriction and, later (in advanced diabetic autonomic neuropathy), to sympathetic dysfunction with postural hypotension [15]. Autonomic neuropathy in patients with diabetes is also associated with an increased rate of sudden death caused by ventricular arrhythmia [16]. Ventricular arrhythmia may be secondary to silent myocardial ischemia or to the combination of a prolonged QT interval and increased sympathetic tone [16-18]. Diabetic patients have a decreased perception of ischemic pain, which contributes to a high prevalence of silent ischemia. Nesto and colleagues [19] showed that during ischemia on thallium exercise testing, angina is less common in diabetic patients than in nondiabetic patients. The time interval from the onset of ST-segment depression to the occurrence of angina is longer in diabetic than in nondiabetic patients and correlates with the extent of autonomic nervous dysfunction [20]. Asymptomatic infarction is almost twice as common in diabetic patients as in nondiabetic patients [21, 22]. These data are consistent with autopsy results showing that myocardial scars, in the absence of a history of infarction, are three times more common in diabetic patients than in nondiabetic patients [23]. Diabetic Cardiomyopathy Several clinical and experimental studies [2, 24-33] have indicated that diabetes mellitus is associated with cardiomyopathy that is independent of atherosclerotic coronary artery disease. Macroscopic changes include muscular hypertrophy with pale appearance and firmness to palpation. Microscopic changes include thickening of the capillary basement membranes, intimal proliferation of small myocardial arterioles and capillary microaneurysms, and focal myocardial fibrosis with an accumulation of interstitial glycoprotein and collagen [34]. Electron microscopy shows perivascular damage with loss of contractile myocardial elements and deposition of either glycoprotein or material that is positive on periodic acid-Schiff stain [31]. Various metabolic derangements [35-53] that can contribute to the development of diabetic cardiomyopathy are beyond the scope of this review. Microvascular Disease Small-vessel coronary artery disease frequently occurs in patients with diabetes [34]. On the basis of necropsy findings, Hamby and associates [28] suggested that changes in small vessels of the myocardium are responsible for diabetic cardiomyopathy. Fein and Sonnenblick [51] reported that patients with diabetes have increased sensitivity to catecholamines, which may cause myocardial ischemia through the focal vasoconstriction of small coronary arteries. Altered Cardiac Function Structural changes in patients with diabetes are associated. with impaired ventricular performance. Using echocardiography, Shapiro [54] found abnormal diastolic function in patients with diabetes mellitus who did not have heart disease. Diabetes mellitus seems to have less effect on systolic function, as was shown in a study by Borow and colleagues [55] in which indices of contractility and contractile reserve after stimulation with dobutamine were normal. Structural changes suggestive of cardiomyopathy can be detected with echocardiography on the basis of quantitative backscatter imaging, even before ventricular function is impaired [56]. Mustonen and coworkers [57] found similar resting ejection fractions in diabetic patients and controls. However, during 4 years of follow-up, the left ventricular ejection fraction at rest markedly decreased only in the patients with noninsulin-dependent diabetes mellitus. Several studies have shown that ejection fractions after myocardial infarction are lower in diabetic than in nondiabetic patients [10, 58, 59]. Contractile abnormalities are more pronounced in postmenopausal diabetic women than in diabetic men [58]. Not surprisingly, congestive heart failure is a common and serious complication of diabetes mellitus. Data from the Framingham study showed that men with diabetes had a 2.4-fold greater risk for heart failure than did men without diabetes [2]. Hypertensive Heart Disease Sustained hypertension can cause structural and functional cardiac abnormalities that lead to myocardial ischemia, congestive heart failure, and sudden cardiac death. Ischemic Heart Disease in Patients with Hypertension Myocardial ischemia is common in patients with hypertension [60, 61]. Pathogenic mechanisms that may lead to myocardial ischemia include the following. First, long-standing hypertension accelerates arteriosclerosis in systemic and coronary arteries [62]. Second, an increase in arterial pressure increases left ventricular wall stress, wall tension, and stroke work. Third, resistance of the coronary microvasculature (microvascular angina) is abnormally elevated in hypertensive patients even in the absence of left ventricular hypertrophy [63]. Fourth, long-standing hypertension causes left ventricular hypertrophy, which is associated with an increase in the diameter of myocardial cells without a proportional proliferation of the capillary vasculature; this leads to an increased diffusion distance [64]. Fifth, vasodilator reserve appears to be compromised in the coronary circulation of hearts in patients with left ventricular hypertrophy [65, 66]. Finally, left ventricular hypertrophy itself (that is, the increased myocardial muscle mass seen with this condition) requires an enhanced supply of oxygen to the myocardium. It should be noted that hypertensive patients, especially those with left ventricular hypertrophy, are as susceptible to silent myocardial ischemia as patients with diabetes [67-69]. Hypertensive Cardiomyopathy The classic cardiac adaptation to a sustained pressure overload is concentric left ventricular hypertrophy. Hemodynamic factors offer a reasonable explanation for increased left ventricular mass; however, in several groups of patients with uncomplicated essential hypertension, physicians' measurements of blood pressure have been only weakly related to left ventricular mass on echocardiography [70]. Therefore, such nonhemodynamic factors as sodium intake, activity of growth-promoting hormones (such as insulin and thyroxine), activity of the sympathetic nervous system, renin angiotensin systems, whole-blood visco