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Heart Disease - Prevention Prevention and Behavior Prevention of CHD necessarily involves behavior change, since modification of risk factors for CHD is influenced primarily by individual choice and the decision to change one’s lifestyle. Although behavior change is fundamental to the prevention of CHD by reducing risk factors, differences in health care seeking behavior between blacks and whites may also contribute to racial differences in CHD mortality and morbidity. For example, blacks delay longer than whites in seeking care for general medical problems, as well as for acute CHD symptoms, including acute MI.Studies suggest that less tangible social support may be associated with stroke mortality and hypertension. The effects of diminished social supports on CHD in blacks appear to be particularly strong. Since it is likely that stress related to racial prejudice, economic disadvantage, and social disintegration is more common in blacks, understanding their relationship to CHD in blacks is likely to be helpful in elucidating strategies for lowering CHD rates. Studies also suggest that there may be differences between blacks and whites in symptom perception and symptom attribution. These factors may affect adherence to treatment recommendations and play a role in the utilization of cardiac procedures and ultimate health outcomes. Until the roles of access to care, knowledge and beliefs concerning CHD, coping styles and the social environment, as well as biological variables, such as cardiovascular reactivity, are clarified, understanding racial differences will be difficult. Culturally and ethnically appropriate techniques for individual and community behavior modification and lifestyle change, which would affect primary and secondary prevention of CHD, have not been developed specifically for blacks. Risk Factors The decline in CHD mortality and morbidity that began several decades ago, and continues to the present, has been coincident with widespread acceptance of the effectiveness of riskfactor reduction in preventing CHD. The significant change in lifestyle and secular trends in risk factors that has occurred in the majority population has been less dramatic in blacks. Because prevalence rates of modifiable CHD risk factors, such as hypertension, cigarette smoking, physical inactivity, and obesity, have been documented to be greater in blacks than in whites, the opportunities for prevention may be greater for blacks.Smoking rates in persons 18 years of age and older have declined in the general population, but remain higher in blacks. Studies of leisuretime physical activity suggest that blacks are more sedentary and less fit than whites, independent of income and education. Obesity, which is associated with hypertension, hyperlipidemia, hyperinsulinemia, and glucose intolerance, may be more common in blacks. The prevalence of obesity appears to be higher in black women than in white women or black men, but racial differences are less apparent between black and white men. Dietary patterns may differ slightly between blacks and whites, but foods selected by blacks and whites do not differ substantially in nutritional composition. Data in blacks are conflicting about the relationship of elevated levels of lipoprotein (a) [Lp(a)], a genetically determined lipoprotein associated with CHD, to CHD risk. Increased left ventricular (LV) wall thickness is more common in blacks, even in the absence of hypertension. The contribution of LVH to risk of sudden death and outofhospital death in blacks is not clear. Both individual and communitybased interventions have been successful in modifying CHD risk factors in blacks, although individual approaches may be less effective in blacks than in the general population. Local church and communitywide education programs have been particularly effective in the control of hypertension and smoking in some black communities. Genetics The recent, unprecedented progress over the past decade in genetics and molecular and vascular biology has enhanced understanding of the pathogenesis of human disease. Although initial progress was made in diseases resulting from mutations of a single gene, methods are now available that allow investigation of complex diseases, such as atherosclerosis, hypertension, and disorders of coagulation. One prerequisite for studying complex diseases is identification of aggregates of patients or families with relevant phenotypic characteristics.Family history comparisons between blacks and whites demonstrate a higher prevalence of positive family history of hypertension, stroke, diabetes, or obesity in black families. However, family history of CHD is similar among black and other populations. Black families also appear to be similar to other populations in having strong correlations for major CHD risk factors between biological relatives, but not with unrelated persons living in the same household. Complex diseases, such as atherosclerosis, are typified by etiological heterogeneity, in which a variety of physiological systems interact to produce a clinical disease entity. Identification of a gene that occurs frequently in a population with a specific disease may not establish linkage to the disease. For example, although Lp(a) is found more commonly in blacks, it has only been established as a risk factor for whites. Similarly, polymorphisms of the angiotensinogen gene have been associated with increased risk of hypertension and preeclampsia in selected populations, and there are some interesting new findings at the angiotensinogen locus that deserve further attention. Evidence suggests that pedigrees with a complex disease demonstrate genetic heterogeneity and that different individuals with a disease may be influenced by “nonoverlapping genetic components.” As differences in the distributions of alleles are identified between affected and unaffected pedigrees, more precise phenotypic characterization becomes essential, regardless of whether the investigative strategy primarily involves linkage analysis, identification of candidate genes, or detection of mutations of candidate genes. Vascular Biology Significant advances in understanding the mechanisms active in the development of atherosclerotic lesions and pathogenesis of macrovascular and microvascular disease now offer greater opportunities for acquiring knowledge on the clinical presentation, natural history, and outcomes of CHD in blacks. Studies of the biology of the arterial wall have led to significant advances in understanding endothelial function and structure, cellcell interaction, growth factors, connective tissue, and lipoprotein metabolism. There has been dramatic progress in understanding gene regulation of lipoprotein metabolism, biosynthesis, and mechanisms of action of lipoproteins. It is now possible to study the fibrous plaque and the fatty streak directly in the human artery using biopsy tissue, transplant tissue, and vascular rings or strips obtained during surgery or at autopsy. The growth in the clinical application of coronary atherectomy has provided an additional source of tissue for studying a wide array of pathogenetic mechanisms in atherosclerosis.Greater understanding has been gained of the interaction of the vascular endothelium and the vessel wall with specific cellular elements in blood; the function and composition of specific lipoproteins, enzymes, hormones, and receptors; the contribution of genetic and immunological factors; the impact of alterations in the autonomic nervous system; and the role of coagulation and thrombosis in atherogenesis and the coronary syndromes. It is not known, however, whether there are significant racial differences in the cellular and molecular mechanisms of atherogenesis. Left Ventricular Hypertrophy Research on CHD in blacks presents a unique challenge because of the increased prevalence of LVH and hypertension in the black population. In studying CHD in blacks, LVH and hypertension may be confounding factors, challenging investigators to identify the separate and common pathogenetic mechanisms of atherosclerosis, hypertension, and LVH and to explain their interaction. LVH has been shown to be an important risk factor for CHD, sudden death, and congestive heart failure, and it confers significant risk for future cardiovascular events, independent of atherosclerotic disease in the epicardial coronary vessels. Many of the pathogenetic features of LVH, such as endocrine, paracrine, and autocrine factors, can now be studied in humans.Because hypertension is common in blacks, the increased prevalence of LVH in blacks is often attributed to concurrent hypertension, but young blacks tend to have increased LV wall thickness, compared with whites, even in the absence of increased blood pressure. Cardiac myocytes constitute 75 percent of the heart mass, and the interstitium comprises 25 percent. Hypertension is the major stimulus to myocyte hypertrophy. Studies of the cellular response and remodeling of the interstitium in hypertension suggest that blacks have a tendency toward increased muscle cell mass. It is not clear whether there are racial differences in systolic and diastolic function in the ventricle with LVH alone, with CHD and LVH, or with isolated CHD. Selected pharmacological agents have now been widely shown to cause regression of LVH. The impact of LVH regression on the course of CHD, hypertension, congestive heart failure, and sudden death in blacks needs further exploration. Coronary Microvasculature Blacks demonstrate high rates of angiographically normal epicardial coronary arteries despite a higher prevalence of multiple CHD risk factors and disproportionate morbidity and mortality from CHD. This paradox has led investigators to seek explanations in the microvasculature of the heart. However, because of the small size of the vessels which compose the microvasculature, gross examination has been difficult and histological studies have been limited primarily to microscopic examination at autopsy.Still, much has been learned from studies of microvascular functional responses to physiological and pharmacological interventions. The microvasculature may respond differently to pharmacological agents than do large muscular arteries and veins. Endothelial dysfunction may play a role in microcirculatory disease and may occur in atherosclerosis, diabetes, lowrenin states, coronary vasospasm, and reperfusion injury. Increased sensitivity to the vasoconstrictive effects of catecholamines may also occur with endothelial dysfunction. Clinical diagnosis of abnormal microcirculation has been based largely on the demonstration of reduced coronary reserve. Abnormal coronary reserve is implicated if coronary blood flow does not increase when coronary resistance is lowered, usually in response to the administration of a potent coronary vasodilator, such as dipyridamole or papaverine, or to exercise. Numerous reports note the frequent occurrence of the syndrome in hypertensive patients with and without LVH or with hypercholesterolemia. Microvascular disease, or nonatherosclerotic CHD (the clinical syndrome of anginalike chest pain and angiographically normal coronary arteries), may occur in up to 20 percent of patients undergoing coronary angiography. In some studies of blacks, however, nearly half of those with anginalike chest pain have normal coronary angiograms. Black women, in particular, have a higher incidence of chest pain with normal coronary arteries. Abnormal coronary microvascular function may limit appropriate flow response to stress, possibly due to endothelial dysfunction. Pharmacological probes and provocative testing with agents such as acetylcholine may be helpful in determining whether there are physiological differences in the microvasculature between blacks and whites. The relative role of microvascular disease versus macrovascular disease in the pathogenesis of myocardial ischemia and vascular disease of the heart has not been studied extensively in blacks. Sudden Cardiac Death Death certificates and autopsy data indicate that more blacks than whites die out of the hospital or experience outofhospital cardiac arrest. Studies have not confirmed a relationship between race and access to emergency cardiac care or outcome of cardiac resuscitation. Outofhospital deaths may also be related to delay in the prehospital phase of acute MI care. LVH may be associated with increased atrial and ventricular arrhythmogenesis and, potentially, sudden death.It is not clear whether there are racial differences in the electrophysiological substrate in blacks related to the increased prevalence of LVH and hypertension. Diminished coronary reserve may also be more common in blacks and predispose to lifethreatening arrhythmias. The value of newer electrophysiological monitoring techniques in predicting risk of sudden death is also not clear, and the value of signalaveraged ECG in predicting arrhythmias has not been well studied in blacks. Smoking may also increase the risk of sudden death in some individuals, most likely through enhanced platelet adhesion and attendant thrombogenicity, increased vasomotor reactivity, and reduced threshold for sustained ventricular arrhythmias. The contribution of smoking to differences in sudden death and outofhospital deaths in blacks has not been studied extensively. Prevention and Behavior Although a reduction in traditional risk factors has been shown to be an effective prevention strategy for the general population, data on the efficacy of prevention efforts in blacks are minimal. Collection of prevention data in blacks has been limited by the lack of culturally validated instruments for data collection and reliable methods for establishing risk factor profiles in minority communities. Still, even though existing data are not sufficient for making generalizations about the impact of behavioral risk factors on CHD in blacks, effective strategies can be developed based on these data.New and improved tools for measuring risk factors in blacks, both in individuals and in populations, need to be developed and culturally validated. Data should be collected prospectively to allow assessment of the relative risk of factors that preferentially affect blacks as compared with those that have been studied most in whites. Identification and treatment of behavioral risk factors of special significance to black populations should be a high priority. Research on health care seeking behaviors is another priority area. These behaviors may be determined by a wide array of factors, most of which are functions of social and economic forces. Limited data are available on the impact of social supports, income, stress, acculturation, or personality on CHD risk in blacks. Studies are needed of the psychosocial predictors of CHD mortality and morbidity in blacks, interaction of psychosocial and biological factors and their effect on CHD outcomes, as well as the effectiveness of programs targeted to individuals and communities. Adherence to medical recommendations, acceptance of diagnostic testing procedures, and interactions with the health care system may be influenced by social and environmental forces. Educational strategies to improve adherence to prevention and treatment recommendations need to be developed, implemented, and evaluated. Innovative and effective research programs to increase longterm adherence to lifestyle modification programs are especially warranted. Risk Factors Prevention efforts in the general population have concentrated on identifying risk factors for CHD and treating specific risk factors in atrisk individuals. Differences in patterns of clinical CHD and short and longterm outcomes of CHD may be related to differential effects of traditional risk factors in blacks and whites and/or the presence of factors in blacks that may not confer similar risk in whites. Increased prevalence of CHD risk factors, such as hypertension, diabetes, increased LV wall thickness, cigarette smoking, and obesity have been documented in blacks. However, other features, also common in blacks, such as enhanced thrombogenicity, increased vascular reactivity, and greater potential for ventricular arrhythmias, may also be significant in explaining racial differences in CHD.If the mechanisms of CHD differ in blacks, the role of different risk factors may also vary. Smoking, for example, is more prevalent among blacks than whites. Yet, there are few data on the determinants of smoking habits in blacks. Valid and reliable instruments need to be developed for assessing the determinants of smoking topography and the contribution of smoking to the clinical manifestations and outcomes of CHD in blacks. Research also is needed to define the social, cultural, and environmental prerequisites for successful smoking cessation and to develop culturally relevant cessation programs. With regard to other risk factors, valid and culturally appropriate instruments need to be developed to assess nutrition, physical activity, and social supports. Genetics In order to demonstrate populationspecific genetic susceptibility, it will be necessary to show that there are differential frequencies of genes that condition risk in similar ways in both black and white populations. Studies of possible geneenvironment interactions are also recommended. A very large number of black sibships or families will have to be identified to study familyrisk syndromes and to understand the interaction of cultural and genetic heritability. This research includes identification of major gene segregation and detection of linkage and susceptibility loci.Trials of family prevention strategies will be important. Such trials should include identification of large numbers of highrisk families and longitudinal monitoring of the effect of risk factor reduction on CHD clinical expression and health outcomes. Detailed phenotypic data (e.g., on blood pressure, diabetes, obesity, insulin levels, LVH, and other variables) need to be collected and correlated with genetic data obtained from stored white cells from sibships and families. Studies that correlate genotype and phenotype should be given high priority. Studies of candidate genes and identification of specific genetic traits leading to pathophysiological processes and CHD are encouraged. Also recommended is research on the frequencies of gene variants in black populations and assessment of possible associations with features of CHD in other populations with CHD. Vascular Biology Basic research has enhanced understanding of the mechanisms of atherosclerotic CHD. In recent years, there has been an increase in the rate of progress in research on the endothelium, cellcell interaction, signal transduction, receptors, ion channels, growth factors, and vasoactive substances. Today, research on CHD in blacks should take advantage of modern techniques to study potential histopathological differences in coronary atheroma between blacks and whites. Investigations of necropsy, surgical, or explanted cardiac vascular tissue should be undertaken to define potential racial differences in lesion structure and the mechanism of transition from a stable lesion of chronic CHD to an active lesion of acute CHD. Studies of microvascular coronary artery function, using provocative pharmacological testing, are recommended for elucidating physiological differences between lesions in blacks and whites.Left Ventricular Hypertrophy The increased prevalence of LVH in blacks makes knowledge of its pathogenetic role critical to understanding CHD in blacks. Research on LVH will be greatly advanced by development of techniques that will yield better understanding of the cellular and biochemical basis of abnormal myocardial contraction and relaxation, and the role of the interstitium, in myocardial hypertrophy. The differential effects of hemodynamic loading conditions and of hormonal, dietary, and other nonhemodynamic factors in development of myocardial hypertrophy need to be clarified in blacks and whites.LVH may also predispose to ventricular arrhythmias in blacks. The role of intracellular ionic and metabolic changes in initiating and maintaining a reduced threshold for ventricular fibrillation and complex ventricular tachyarrhythmias needs to be determined, and studies of the racial differences in these factors are recommended. Researchers are encouraged to utilize human biopsy specimens to delineate subcellular changes in the sarcolemma, sarcoplasmic reticulum, and contractile apparatus which may account for changes in intracellular calcium handling and excitationcontraction coupling that occur in LVH. Valid and reliable noninvasive techniques should be developed for assessing the regression of LVH and its impact on the course of CHD in blacks. Experimental models are also needed for studying the role of hemodynamic, nonhemodynamic, and growth factors in development of LVH. Coronary Microvasculature Abnormalities of the coronary microvasculature have been proposed to explain the paradoxically high prevalence of normalappearing epicardial vessels on angiography in patients with anginalike chest pain. However, the nature and pathogenesis of coronary microvascular disease have not been studied extensively in humans, and data in animals are relatively sparse compared with research data on the macrovasculature.Investigations of the mechanisms that control microvascular function and structure, including endothelial function, intracellular ions, and vascular reactivity, are recommended. Interactions among endothelial, neural, and hormonal control of microvascular tone and coronary blood flow should be clarified using both animal and human vessels. The relative importance of the various control mechanisms in blacks and whites should be determined in in vitro microvascular reactivity profiles and how they are affected by CHD and hypertensive LVH. Studies of coronary vasodilator reserve in animal models (e.g., the pig model) using PET, NMR, or other imaging technologies may also be useful in assessing the determinants of microvascular function. New and improved techniques are needed for human studies of the microvasculature and measurement of coronary reserve and microcirculatory flow in blacks with atherosclerotic and nonatherosclerotic CHD. The influence of inflammation, vasculitis, or immune complex disease on abnormal coronary reserve, microvascular function, and chest pain syndromes in blacks should be assessed. Also needed are investigations of the impact of controlling CHD risk factors, such as hyperlipidemia, LVH, diabetes, and smoking, on chest pain and the natural history of microvascular disease. Further studies are recommended on the impact of microvascular disease on ventricular function and heart failure in blacks with anginalike chest pain and normal coronary arteries. Microvascular function should be compared in different vascular beds (i.e., forearm versus heart), and studies are needed on the relationship of abnormal microvasculature in different vascular beds to the signs and symptoms of CHD. Sudden Cardiac Death Although recent data suggest that outofhospital and sudden death rates are higher in blacks, much of these data are derived from local studies and have not been confirmed in broader populations. The incidence and prevalence of lifethreatening arrhythmias need to be determined in blacks with chest pain syndromes related to nonatherosclerotic and atherosclerotic CHD. The relationship of differences in cardiovascular reactivity to racial variations in sudden death and casefatality rates in blacks and whites also should be explored.Studies of diurnal variation in sudden death and other cardiac events are needed to identify the endocrine, paracrine, or autocrine factors that are most important in the pathogenesis of these events. Criteria for identifying individuals at high risk of arrhythmias and sudden death should be validated in blacks. Investigations are also needed on the relationship of traditional risk factors (e.g., LVH, hypertension, hyperlipidemia), and behavioral and environmental factors to the risk of sudden death and lifethreatening ventricular arrhythmias. |
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