The leading cause of death worldwide is CHD (WHO, 2008). Although atherosclerosis, the preclinical antecedent of CHD, begins in childhood, the clinical manifestations of CHD occur in adulthood and include angina pectoris, MI, heart failure, and sudden death. Major cardiovascular risk factors are those that independently influence the development of atherosclerosis and CHD. More than a half century ago the Framingham Heart Study identified cigarette smoking, elevated serum cholesterol, hypertension, and advancing age as major risk factors (Dawber et al, 1951). Since then, conventional wisdom has come to accept that four modifiable traditional cardiovascular risk factors (i.e., smoking, hypertension, hypercholesterolemia, type 2 diabetes mellitus) account for "only 50%" of the risk for CHD (Braunwald, 1997; Hennekens, 1998). However, some investigators have contended that the 50% figure is a myth and that traditional risk factors account for far more than half the prevalence of CHD (Canto and Iskandrian, 2003). In fact, given what we now know about modifiable risk factors, it appears that they account for almost all CHD mortality. INTERHEART was a standardized case-control study of acute MI in 52 countries representing every inhabited continent (Yusuf et al, 2004). As might be expected in a study whose age distribution is determined by MI, the median age in years for men was in the 50 s and for women in the 60 s although there was a variation related to geographic region and ethnic origin. The 15,152 cases and 14,820 controls were compared in terms of self-reported smoking, history of hypertension, history of diabetes, dietary patterns, physical activity, consumption of alcohol, and psychosocial factors as well as by tape measurements for adiposity and blood measurement for apolipoproteins (Apo). Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, and psychosocial stressors were found to be associated with increased risk, whereas daily consumption of fruits or vegetables, moderate or strenuous exercise, and consumption of alcohol were protective. INTERHEART found that the major risk factors having odds ratios (OR) of 2 or greater in univariate analyses included smoking, abnormal lipids, psychosocial factors, hypertension, diabetes, and abdominal obesity. They were qualitatively similar and consistently adverse in all regions of the world and in all ethnic groups.
INTERHEART (Yusuf et al, 2004) made an important contribution to our knowledge of cardiovascular risk by documenting the generaliz-ability of modifiable risk factors across diverse regions and ethnicities. In order to accomplish this monumental task, the investigators made a number of important compromises. Thus, rather than using fasting blood to evaluate triglycerides, HDL-, and LDL-cholesterol, they used the ratio of ApoB/ApoA1 from non-fasting blood as an index of abnormal lipids. Neither blood pressure, blood glucose nor plasma insulin were assessed directly. Similarly, psychosocial stress was examined by four simple questions about stress at work and at home, financial stress, and major life events in the past year (Rosengren et al, 2004). Depression was evaluated by a modified version of the short form of the composite international diagnostic interview questionnaire (Patten, 1997). Interestingly, all of these psychosocial variables were associated with increased risk of MI. For severe global stress, the size of the effect appeared to be less than that for smoking, but comparable with that for hypertension and abdominal obesity.
The measurement deficiencies in INTERHEART, essential as they may have been in order to meet study objectives, suggest that some of the methods used may have led to variations in estimated risk that could be improved by more sensitive measurement (e.g., blood pressure, fasting lipids, impaired glucose tolerance, psychosocial distress). This would be particularly important for planning secondary prevention in CHD patients who, although usually offered pharmacological treatment for traditional risk factors, may have 5-7 times the relative risk of recurrent MI when compared with the general population of same age adults (National Cholesterol Education Program, 1994). Thus, in such patients it is important that both psychosocial behavioral and pharmacological treatment should be guided by an understanding of the variables likely to be mediating the associations between traditional risk factors and cardiovascular mortality including inflammation, insulin resistance, oxidative stress, and platelet coagulation. The design of such rehabilitation programs for post-MI patients should consider behavioral variables including medication adherence and lifestyle modification, reduction of sympathetic nervous system arousal and glucocorticoid dysregula-tion, and the bidirectional interaction between behavior and stress. There is also need to assess the role of moderating variables such as low socioeconomic status (e.g., Marmot et al, 1984) (see Chapter 22), whose adverse effects upon cardiovascular mortality may operate through behavioral, biological, psychosocial, and environmental (including access to health care, fresh fruits and vegetables, and safe neighborhoods) risk factors (Albert et al, 2006; Steptoe and Marmot, 2002).
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