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The epidemiologic approach to investigation of atherosclerotic cardiovascular disease has provided many insights into the preclinical and clinical spectrum of the disease. The hazard of developing atherosclerotic cardiovascular disease is substantial with coronary heart disease (CHD), the most common and most lethal feature. The outlook in those who manage to survive the initial episode is also serious, with a 10-year mortality rate of 37% for persons with angina and a 55% rate for those sustaining a myocardial infarction. Fifteen percent of persons developing CHD present with a fatal event, and 38% of infarctions go unrecognized. The presence of atherosclerosis in one vascular territory imposes an increased risk of its appearing in another area at two to six times the general population rate. The major cardiovascular risk factors adversely affect all arterial vascular territories so that correction of risk factors targeted at one particular atherosclerotic outcome may also favorably influence the other risk factors. Coronary disease is the most prevalent lethal hazard of hypertension, dyslipidemia, glucose intolerance, and cigarette smoking. These risk factors cluster and optimal therapy must improve the whole risk profile. Women share the same risk factors for CHD as men. Although women have a lower absolute risk for most risk factors, a high total/HDL cholesterol ratio, left ventricular hypertrophy, and diabetes each tend to eliminate the female advantage. Menopause also promptly escalates risk threefold. Although women tend to have a lower incidence than men, the initial attack is just as highly lethal in women, and their subsequent outlook as survivors is at least as serious as for men. Sudden death is a pre-eminent feature of coronary disease and cardiac failure. Coronary disease increases sudden death risk 3.3-fold and cardiac failure 4.8-fold. Sudden death incidence varies in relation to the same cardiovascular risk factors as coronary heart disease, with no unique risk factors identified. However, multivariate combinations of these in a profile can identify high-risk candidates for sudden death as well as coronary attacks in general. The key to prevention of sudden death is to prevent coronary attacks and cardiac failure. Despite aggressive cardiac revascularization and treatment of hypertension, congestive heart failure (CHF) has not decreased in prevalence, and innovations in the treatments of overt failure have not substantially improved survival. Median survival is only 1.7 years for men and 3.2 years for women. The conditional probability of developing CHF can be estimated using a logistic function comprised of age, systolic pressure, vital capacity, heart rate, ECG-left ventricular hypertrophy (LVH), glucose intolerance, x-ray enlargement, and presence of CHD and heart murmurs. Eighty percent of CHF events occur in persons in the upper quintile of multivariate risk. Continued clinical, metabolic, and epidemiologic research have expanded and refined atherosclerosis risk factors. The lipid connection is now concerned with the apoprotein makeup of the lipids, subfractions of lipids, and Lp(a). The diabetic influence is now focused on insulin resistance. Ambulatory monitoring is being used to evaluate blood pressure and silent ischemia. Fibrinogen and leukocyte counts have emerged as possible indicators of unstable lesions. Prospects for primary and secondary prevention are good if public health measures, health education, and preventive medicine are implemented based on existing knowledge of correctable or avoidable risk factors. The potential for more effective prevention continues to expand, and great advances have already been made in countries where aggressive preventive measures have been implemented to correct the major established risk factors.
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PMID:Hazards, risks, and threats of heart disease from the early stages to symptomatic coronary heart disease and cardiac failure. 921 Oct 12

HYPERTENSION-ASSOCIATED ABNORMALITIES THAT PROMOTE CORONARY DISEASE: Although antihypertensive treatment has been effective in reducing premature cardiovascular mortality, the effect on various organ-specific morbid events has been unequal; the effect is much more impressive on stroke reduction than on reduction of coronary events. A student of pathophysiology would have anticipated such an outcome since blood pressure elevation is only one of multiple abnormalities in hypertension. Even in its mildest form hypertension is associated with the metabolic syndrome of dyslipidemia/insulin resistance which is conducive to early atherosclerosis. A large proportion of patients also have increased sympathetic and decreased parasympathetic tone, a constellation conducive to arrhythmias and, ultimately, to sudden death. An elevated hematocrit is also found in a substantial proportion of male patients and excessive platelet aggregability has also been described in hypertension. These hematologic abnormalities are conducive to coronary thrombosis. Angiotensin II and norepinephrine, two of the most potent trophic hormones, are frequently elevated in hypertension. The effect of these hormones on the cardiac and vascular structure further increases the predilection for negative outcomes. Left ventricular hypertrophy is a potent risk factor of coronary mortality, congestive heart failure and sudden death. Vascular hypertrophy reduces the coronary reserve and at the level of skeletal muscles contributes to the evolution of the metabolic syndrome. ORGAN-SPECIFIC HYPERTENSION TREATMENT: Because of these abnormalities we are entering a new era of treatment in hypertension. Whereas an effective fall in blood pressure remains the main goal of treatment, differential effects of various antihypertensive agents on organ-specific morbidity are being actively explored. If this research proves that certain drugs have a specific advantage in defined subgroups of patients, clinical practice will change. It is reasonable to expect that in the next century we will witness a further improvement in the impact of antihypertensive treatment on public health.
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PMID:Coronary disease in hypertension: a new mosaic. 921 91

A direct, continuous, and independent association between blood pressure values and incidence of coronary artery disease has been well documented. However, the evidence that the reduction of blood pressure alone is not able to completely reverse the increase in the risk of coronary artery disease associated with essential hypertension suggests that the link between hypertension and coronary artery disease is a complex process including other factors beside the increase in blood pressure values. In this regard, the main determinant of coronary artery disease in hypertensive patients seems to be the development of left ventricular hypertrophy (LVH). In fact, hypertensive patients who died from sudden cardiac death showed a lesser degree of coronary atherosclerosis compared with normotensives, but a higher incidence of LVH. Several mechanisms can account for the increased coronary risk with LVH, including (1) an increase in left ventricular (LV) mass, which by itself requires more oxygen for tissue perfusion; (2) impairment of coronary flow reserve; (3) perivascular fibrosis, which then impairs oxygen supply to the myocardium; and (4) deterioration of LV diastolic function, which hampers myocardial perfusion. Recently, a study reported an impairment of endothelial function and abnormal control of the sympathetic tone in hypertensive patients, which may contribute to the risk of coronary artery disease. In particular, the impaired endothelial function resulting in a prevalence of vasoconstrictive, thrombogenic, and proliferative factors may account for the enhanced ischemic susceptibility of these patients. Furthermore, the cardiac adrenergic system plays an important role in regulating myocardial blood flow. On one hand, hypertensive patients show an exaggerated sympathetic response to physiologic stimuli, whereas on the other hand, the beta-adrenergic receptor-mediated vasodilating component of the sympathetic response is blunted in hypertension. Finally, excess body weight, dyslipidemia, glucose intolerance, and hyperinsulinemia, which are frequently interrelated, represent independent predictors of both coronary artery disease and hypertension.
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PMID:Systemic hypertension and coronary artery disease: the link. 971 15

Approximately 80% of all patients with diabetes die of cardiovascular disease. The traditional management of type 2 diabetes has been ineffective in altering this dismal prognosis. Insulin resistance is the fundamental defect of type 2 diabetes. Insulin resistance often leads to hyperinsulinemia, which is associated with hypertension, atherogenic dyslipidemia, left ventricular hypertrophy, impaired fibrinolysis, visceral obesity, and sedentary lifestyle. Although all these conditions are associated with atherosclerosis and adverse cardiovascular events, the therapeutic efforts in patients with diabetes have focused predominantly on normalizing glucose levels. Improved insulin sensitivity through lifestyle modifications or pharmacologic therapy (troglitazone and metformin) will lower both insulin and glucose levels as well as diminish dyslipidemia and hypertension. In contrast, sulfonylurea agents lower glucose by increasing insulin levels and may increase the risk of cardiovascular events. Therapy including aspirin, lipid agents (for example, statins), angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, postmenopausal estrogen replacement, and vitamin E should be considered for patients with type 2 diabetes. In most patients with diabetes who have multivessel coronary artery disease, coronary artery bypass grafting is superior to coronary angioplasty for improving long-term cardiovascular prognosis. This superiority is mediated in part by the use of a left internal mammary graft to the left anterior descending coronary artery. Urgent coronary angioplasty or thrombolytic therapy should be considered for all patients with diabetes who have acute myocardial infarction.
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PMID:Improving the adverse cardiovascular prognosis of type 2 diabetes. 1006 57

The recent decrease of cardiovascular mortality in the USA is less pronounced than it has been in the preceding three decades. Elsewhere, cardiovascular mortality decreased and in some countries it increased. Cerebrovascular disease and ischemic heart disease were responsible for 21% of deaths recorded by the World Health Organization in 1990 and 1997, of which hypertension was estimated to be directly responsible for half of these deaths. Apart from blood pressure (BP) elevation, essential hypertension is frequently associated with factors that increase the risk of poor cardiovascular outcomes: insulin resistance/dyslipidemia, elevated angiotensin and norepinephrine, a tendency for hypercoagulability, platelet overactivity, tachycardia, vulnerability to arrhythmias, vascular hypertrophy, endothelial dysfunction, and left ventricular hypertrophy. Excess activation of the renin-angiotensin system, independent of BP elevation, contributes to these abnormalities. To achieve better results in the future, focus must be shifted from BP lowering to recognition of specific effects of drugs on these diverse pathophysiologic aspects of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which is evaluating the effect of valsartan (Diovan((R))) vs. amlodipine, is a milestone in the effort to test whether newer compounds offer a better reduction of the cardiovascular consequences of hypertension, as well as good BP control. The hypothesis is that valsartan by antagonizing the negative effects of angiotensin on smooth muscle cell growth, endothelial function, sympathetic overactivity, and coagulation, may have for the same degree of BP lowering, better protective effects than the leading calcium antagonist amlodipine.
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PMID:Long-term potential of angiotensin receptor blockade for cardiovascular protection in hypertension: the VALUE trial. Valsartan Antihypertensive Long-term Use Evaluation. 1044 89

Norwegian renal transplant recipients have a high prevalence of cardiovascular disease. In this group of patients cardiovascular disease causes three out of four deaths. Well-known risk factors such as hypertension, dyslipidemia, impaired glucose tolerance and diabetes mellitus are common in renal transplant recipients, but these factors cannot fully explain the high cardiovascular morbidity and mortality. Atherosclerotic disease and left ventricular hypertrophy are highly prevalent in uremic patients before transplantation. Hyperhomocysteinemia, elevated levels of advanced glycosylated end products, and immunosuppressive medication may also accelerate the atherosclerotic process. Until results from controlled trials on the effect of lipid-lowering therapy in renal transplant recipients are available, treatment decisions must be based on studies in non-transplanted patients. Every patient should be treated individually with the overall risk pattern taken into account.
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PMID:[Cardiovascular disease after kidney transplantation]. 1057 45

Cardiovascular disease remains a frequent cause of morbidity and mortality in industrialized countries, particularly in subjects with hypertension, diabetes mellitus, and dyslipidemia, conditions frequently associated with central obesity. Identification of early morphological and/or functional alterations of the cardiovascular system may help target individuals most likely to benefit from preventive measures. The literature data and our own experience suggest that parameters that are direct expressions of cardiovascular damage, can be identified at an early stage. For example, diastolic dysfunction may precede the clinical expression of several cardiac diseases, left ventricular hypertrophy is one of the first manifestations of cardiac involvement in hypertension, central obesity and diabetes mellitus, and a carotid plaque may point to concomitant coronary artery disease. Other early manifestations of cardiovascular involvement are microalbuminuria and endothelial dysfunction. Insulin resistance and alterations of the renin-angiotensin-aldosterone system play an important physiopathogenic role in the development of cardiovascular damage in obese subjects, and their association with risk and cardiovascular disease has been confirmed in numerous studies. Since all these changes generally precede overt clinical manifestations and are closely related to cardiovascular morbidity, they may help identify individuals at the highest risk of cardiovascular events.
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PMID:Early markers of cardiovascular damage in obese subjects. 1072 13

Both type 2 diabetes mellitus (DM2) and left ventricular hypertrophy are associated with an increased risk of cardiovascular diseases (CVD). A strong association between hyperinsulinemia, which is the hallmark of DM2 and of insulin resistance syndrome (a cohort of metabolic abnormalities such as DM2, dyslipidemia, hyperuricemia, obesity, hypertension, hyperfibrinogenemia), and left ventricular (LV) hypertrophy was found in several studies. We studied 140 consecutive (both normo- and hypertensive) DM2 patients to determine a possible link between metabolic features and the degree of LV mass, calculated by the ECG method of Cornell voltage. The Cornell voltage value was 12.9+/-0.5 mm in the DM2 population as a whole, and 13.6+/-0.7 vs 11.7+/-0.9 mm (p=NS) in hypertensive and normotensive DM2 subgroups, respectively. Among all the metabolic parameters taken into account, the multivariate analysis shows that the fasting plasma insulin level is the strongest independent predictor of LV mass, both in the whole population (p=0.0005) and in the normo (p=0.0460) and hypertensive DM2 (p=0.0184) subgroups.
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PMID:Left ventricular mass in type 2 diabetes mellitus. A study employing a simple ECG index: the Cornell voltage. 1080 69

The Framingham Study was initiated in 1948 to investigate an epidemic of coronary disease in the USA, using a prospective epidemiological approach. Insights were provided into the prevalence, incidence, full clinical spectrum and predisposing factors. The major "risk factors" (a term coined by the Framingham Study) for coronary disease, stroke, peripheral artery disease and heart failure were identified and clinical misconceptions dispelled about isolated systolic hypertension, left ventricular hypertrophy, dyslipidemia, atrial fibrillation and glucose intolerance. Average values for blood lipids, blood pressure, body weight, glucose and fibrinogen were shown to be dangerously suboptimal and to have a continuous graded relationship to cardiovascular disease without critical values. Dyslipidemia, glucose intolerance and elevated fibrinogen were shown to have smaller hazard ratios in the elderly, but this was offset by a higher absolute risk. Diabetes was shown to operate more strongly in women, eliminating their advantage over men. Serum total cholesterol was shown to derive its atherogenic potential from its LDL component and also to reflect cholesterol being removed in the HDL fraction. The total/HDL-cholesterol ratio was demonstrated to be the most efficient lipid profile for predicting coronary disease. LDL was shown to be correlated with hemostatic factors, suggesting that there would be additional benefits to lowering LDL. High triglyceride associated with reduced HDL, indicating insulin resistance and small dense LDL, was shown to be associated with excess coronary disease. All the risk factors tended to cluster, and this was shown to be promoted by insulin resistance induced by weight gain. Multivariate risk profiles were produced to facilitate risk stratification of candidates for coronary disease, stroke, peripheral artery disease and heart failure. The Framingham Study is now engaged in quantifying the independent contributions of homocysteine Lp(a), insulin resistance, small dense LDL, C reactive protein, clotting factors and genetic determinants of cardiovascular disease. We are now able to estimate the lifetime risk of all the atherosclerotic cardiovascular disease outcomes.
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PMID:The Framingham Study: ITS 50-year legacy and future promise. 1087 16

Rilmenidine is an antihypertensive agent with selectivity for I1 imidazoline receptors that acts both centrally by reducing sympathetic overactivity and in the kidney by inhibiting the Na+/H+ antiport. Rilmenidine provides antihypertensive efficacy comparable with that of diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Experience from trials and clinical practice highlights rilmenidine's clinical and metabolic acceptability in hypertensive populations, including those at special risk because of old age, renal impairment, diabetes mellitus, or dyslipidemia. In the at-risk hypertensive, rilmenidine reduces left ventricular hypertrophy to a similar degree to other reference agents. New studies show a significant improvement in glucose metabolism in metabolic syndrome patients treated with rilmenidine, and a significant reduction in microalbuminuria during rilmenidine treatment of hypertensive type 2 diabetics. Thus the efficacy/tolerance ratio of rilmenidine supports its role as a first-line antihypertensive option for all groups of hypertensive patient, with specific advantages in some at-risk populations.
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PMID:Rilmenidine: a clinical overview. 1092 29


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