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Left ventricular hypertrophy with diffuse intermyocardiocytic fibrosis is a feature of uremia. The role of blood pressure and/or other cardiovascular uremic risk factors in cardiac remodeling is still uncertain. To determine the extent to which improvement of kidney function and the control of uremia-related risk factors are associated with a reduction of myocardial injury, we evaluated the effect of dietary protein restriction or the angiotensin-converting enzyme inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after subtotal nephrectomy, Wistar rats were allocated to receive drinking water solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet (6%) (group 3) for 12 weeks. Group 2 and 3 showed a comparable efficacy in preventing the expected rise in creatininemia, urinary protein excretion, and glomerulosclerosis. However, hypertension development was prevented only in group 2. Groups 1 and 3 developed a significant (P < .01) increase in left ventricular weight (2.45 +/- 0.1 and 2.5 +/- 0.5 mg/g body wt, respectively) compared with group 2 (1.9 +/- 0.06 mg/g body wt). Cardiac hydroxyporline concentration was also lower in group 2 compared with group 1 (2.07 +/- 0.16 versus 2.73 +/- 0.17 mg/g left ventricular weight, P < .05) but not compared with group 3 (2.59 +/- 0.19 mg/g left ventricular weight). The effect of angiotensin-converting enzyme inhibition on left ventricular mass and intracardiac collagen content appeared to be dissociated from anemia, sympathetic activity, and hyperlipidemia. There was a close relationship between systolic pressure and left ventricular mass; however, no relationship between the degree of cardiac fibrosis and systolic pressure could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of systemic blood pressure to myocardial remodeling in uremic rats. 763 42

Hypertension is a major contributor to cardiovascular disease, which imparts a threefold increased risk over that of normotensive persons the same age. It accelerates atherogenesis-promoting premature coronary disease, now its most common sequela. The effect of elevated blood pressure on cardiovascular disease morbidity and mortality in general and on coronary disease incidence in particular is independent of the influence of other predisposing atherogenic cofactors but is greatly affected by them. Elevated blood pressure is more often than usual associated with hyperlipidemia, hyperglycemia, hyperuricemia, excessive weight, elevated fibrinogen, and electrocardiogram (ECG) abnormalities, which enhance its impact. Hypertensive coronary candidates usually have an increased low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, impaired glucose tolerance. ECG abnormalities, or a cigarette smoking habit. These coexisting risk factors exert a greater influence than the character of the blood pressure elevation. Those at risk for hypertensive stroke have left ventricular hypertrophy (LVH), atrial fibrillation, cardiac failure, coronary disease, diabetes, or a cigarette habit. Cardiovascular risk ratios for hypertension diminish with advancing age, but this is offset by a higher absolute risk, making hypertension an important precursor of cardiovascular disease in the elderly.
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PMID:Hypertension as a risk factor for cardiac events--epidemiologic results of long-term studies. 769 48

A high rate of cardiovascular death in renal patients, particularly patients with endstage renal failure, has not been well appreciated in the past. It is obvious that cardiovascular lesions are more severe than can be explained by the classical risk factors of elevated blood pressure and dyslipidemia. In renal failure, a number of pathomechanisms are operative which may be paradigms of more general relevance, e.g. activation of the renin and sympathetic system, inhibition of the vasoconstrictor NO system, left ventricular hypertrophy in excess of what is expected for high blood pressure. A paradox inverse relation between lipid concentrations and cardiovascular death, i.e. a protective effect of hyperlipidemia, in dialysed patients, presumably results from the confounding effect of malnutrition, high lipid levels being a substitute marker of adequate nutrition.
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PMID:Excess cardiovascular mortality in the uremic patient--what does it teach for other risk factors in the non-renal patient? 773 91

Patients with diabetes mellitus have a two- to fourfold increase in clinical manifestations of atherosclerotic cardiovascular disease (ASCVD). Traditional risk factors such as age, hypertension, left ventricular hypertrophy, hyperlipidemia and smoking are still operative in diabetes but do not account for the total increase in ASCVD risk associated with diabetes. The most common lipid abnormalities in noninsulin-dependent diabetes mellitus and poorly controlled insulin-dependent diabetes mellitus are hypertriglyceridemia and low high density lipoprotein cholesterol. Evidence is presented to support the hypothesis that these lipid abnormalities are atherogenic in diabetes. Treatment of diabetic dyslipidemia with conservative measures (diet, weight loss, aerobic exercise, improved glycemic control) and pharmacological management have been shown to be highly effective in normalizing the lipid abnormalities. However, few trials of lipid lowering therapy have included patients with known diabetes mellitus and, to date, there have been no well-controlled prospective trials of lipid lowering therapy in diabetes. There is therefore no definitive proof regarding the benefit of lipid lowering therapy in diabetes mellitus. There are also no data regarding the cost effectiveness of lipid lowering therapy in reducing ASCVD complications in diabetes. There are data, however, showing that complications of ASCVD in patients with diabetes account for a large percentage of total health care expenditures. The overwhelming evidence that patients with diabetes have a high rate of ASCVD, that traditional risk factors for ASCVD are operative in diabetes and that the dyslipidemia of diabetes is highly prevalent and proatherogenic, predicts that the treatment of ASVD risk factors, including dyslipidemia, will be associated with a substantial reduction in ASCVD complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetic dyslipidemia: a case for aggressive intervention in the absence of clinical trial and cost effectiveness data. 775 45

The burden of cardiac disease is high in chronic uremia. Cardiomyopathy results from a combination of cardiac disorders, particularly dilated cardiomyopathy, left ventricular hypertrophy with normal systolic function, and ischemic heart disease. The prognosis for these cardiac disorders is poor. Known potentially reversible risk factors include uremia, anemia, hypertension, smoking, coronary artery disease, hyperparathyroidism, hyperlipoproteinemia, and left ventricular hypertrophy. Randomized controlled clinical trials of interventions that may prevent or ameliorate cardiac disease in dialysis patients are required. These interventions include normalization of hematocrit with erythropoietin compared with partial correction of anemia, increased amount of dialysis compared with that provided by a dialysis prescription of KT/V of 1., control of blood pressure using angiotensin-converting enzyme inhibitors compared with other antihypertensive agents, control of hyperlipidemia, and treatment of diabetes with agents that prevent collagen cross-linking.
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PMID:The management of cardiac disease in chronic uremia. 784 64

The hyperlipidemia associated with the nephrotic syndrome is well characterized. There is, however, a paucity of data in humans on the risk factors for atherosclerotic heart disease and the role of hyperlipidemia on the risk of progression of renal disease in this population. In our study, we retrospectively evaluated a large uniform population of patients (mean creatinine, 1.78 mg/dL; mean 24-hour proteinuria, 7.1 g) with idiopathic nephrotic syndrome for the presence of risk factors for coronary artery disease. One hundred patients with either focal segmental glomerulosclerosis (n = 56) or membranous nephropathy (n = 44) were assessed for the following cardiovascular risk factors: male sex or postmenopausal female, hyperlipidemia, hypertension, smoking history, and left ventricular hypertrophy. Sixty-six percent of the patients were either male or postmenopausal females; 35% were smokers. Hypertension and left ventricular hypertrophy were present in 53% and 13% of patients, respectively. Eighty-seven percent, 53%, and 25% of patients had a total cholesterol of more than 200 mg/dL, more than 300 mg/dL, and more than 400 mg/dL, respectively. Low-density lipoprotein cholesterol was greater than 130 mg/dL and greater than 160 mg/dL in 77.2% and 64.9% of patients, respectively. Virtually all patients (99%) had at least one risk factor for cardiovascular disease; over two thirds (68%) had two risk factors and over one quarter (26%) had three risk factors. In comparing the group that progressed to renal failure with the groups that did not, the initial mean serum cholesterol was lower in the group that progressed (292 mg/dL v 388 mg/dL, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The nephrotic syndrome, lipids, and risk factors for cardiovascular disease. 832 76

Atherosclerotic cardiovascular disease is a complex problem involving lipid deposition, pressure, rheologic forces, carbohydrate tolerance and thrombogenesis. The major contributors identified through epidemiologic research include atherogenic personal attributes, living habits which promote them, signs of a compromised coronary circulation and host susceptibility to these risk factors. Of the atherogenic risk attributes, such as blood lipids, blood pressure, glucose tolerance and fibrinogen, each independently contributes to risk, and the risk associated with any one is compounded by the presence of the others. The risk associated with hypertension, hyperlipidemia or diabetes varies widely depending on the level of associated risk factors. Also, at a given level of total cholesterol, risk is greatly affected by the total/HDL cholesterol ratio, which provides a practical means for assessing the two-way traffic of cholesterol. In addition, living habits, such as cigarette smoking or lack of exercise, can independently affect the risk associated with any of the atherogenic traits. These living habits, obesity and diet can also affect the level of atherogenic risk factors and must be taken into account in assessing risk and implementing preventive measures. Finally, preclinical indicators of silent myocardial ischemia greatly augment the risk associated with a poor cardiovascular risk profile. Hence, ECG left ventricular hypertrophy, blocked intraventricular conduction, repolarization abnormalities and abnormal response to exercise on monitoring must be taken into consideration. Optimal risk predictions require a quantitative synthesis of risk factors into a composite estimate. Handbooks, hand calculators and PC software have been devised for office use based on multiple logistic risk formulations. These have been shown to accurately predict disease risk in a variety of American population samples, in elderly as well as young coronary candidates. Preventive management as well as risk estimation should be multifactorial if optimal results are to be achieved. Preventive strategies should include public health measures to alter the ecology so as to shift the distribution of risk factors to a more favorable level, health education to enable people to protect their own health and preventive medicine for high-risk candidates. Greater skill must be developed to carry out such interventions. In selecting drugs to correct hypertension, diabetes and lipid disorders, it is important to choose agents which do not adversely affect the composite risk profile.
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PMID:Long-term epidemiologic prediction of coronary disease. The Framingham experience. 832 76

High blood pressure (BP) in the elderly must not be ignored as a normal consequence of aging. The criteria for the diagnosis of hypertension and the necessity to treat it are the same in elderly and younger patients. The aim of treatment of elderly hypertensive patients is to decrease BP safely and to reduce risk factors associated with cerebrovascular, cardiovascular and renal morbidity and mortality. The treatment of elderly hypertensive patients should be adjusted according to the needs of the individual, based upon age, race, severity of hypertension, co-existing medical problems, other cardiovascular risk factors, target-organ damage, risk-benefit considerations and costs. In addition to the elevated BP, other cardiovascular risk factors include smoking, glucose intolerance, hyperinsulinaemia, dyslipidaemia, hypercreatininaemia, peripheral vascular disease, left ventricular hypertrophy, and microalbuminuria (or albuminuria). Thus, the choice of initial antihypertensive therapy in elderly hypertensive patients should be based not only on the expected response, but also on the effects of therapy on lipid, potassium, glucose and uric acid levels, and left ventricular anatomy and function. Co-existing medical conditions (such as asthma, diabetes mellitus, heart failure, renal failure, gout, coronary artery disease, hyperlipidaemia and peripheral vascular disease) are major determinants for the selection of antihypertensive medications. With previous therapies (diuretics, beta-blockers, etc.), good BP control in the elderly was associated with clear and statistically significant reductions in stroke-related morbidity and mortality, but the overall effects on cardiovascular and renal complications of hypertension was either more variable or less obvious. Angiotensin converting enzyme (ACE) inhibitors are not only efficacious antihypertensive agents in the elderly, but also appear promising in counteracting some of the cardiovascular and renal consequences of hypertension. They are well tolerated and have a relatively low incidence of adverse effects. ACE inhibitors possess ancillary characteristics that are potentially beneficial for many elderly patients, including reduction of left ventricular mass, lack of metabolic and lipid disturbances, no adverse CNS effects, no risk of induction of heart failure, and a low risk of orthostatic hypotension. Since ACE inhibitors may improve perfusion to the heart, kidney and brain, they are well worth considering for the treatment of elderly patients with hypertensive target organ damage, especially in patients with heart failure, and diabetic patients with early nephropathy.
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PMID:ACE inhibitors. Differential use in elderly patients with hypertension. 857 91

Numerous studies have shown that effective control of elevated blood pressure has greatly reduced the risk of stroke and, to a lesser extent, the risk of coronary artery disease. Although the relationship between diastolic blood pressure and both stroke and coronary disease is significant, systolic blood pressure correlates more strongly with stroke, congestive heart failure, coronary artery disease, declining renal function, and left ventricular hypertrophy. Studies have also shown that the presence of a wide pulse pressure (>/=60-70 mm Hg) also has an independent and major impact on coronary disease mortality and is strongly correlated with increased risk for cardiovascular disease. Because many hypertensives have end-organ damage (cardiac, central nervous system, renal), and the majority also have a comorbid condition such as diabetes and hyperlipidemia, which also increases cardiovascular risk, it is necessary to view the risks and comorbidity of hypertension and antihypertensive therapy in light of these problems. Despite evidence that antihypertensive therapy reduces the risk of stroke and coronary events, and despite the availability of effective agents, roughly half of the hypertensives in the United States remain untreated and only 24% have blood pressure <140 mm Hg systolic and 90 mm Hg diastolic. To ensure that hypertensive patients receive adequate therapy, physicians should treat patients aggressively and appropriately, avoiding antihypertensive drugs that adversely affect comorbid conditions and selecting those that also exert favorable therapeutic effects on these conditions.
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PMID:Blood pressure control. 890 Mar 37

The results of longitudinal studies in geriatric medicine were reviewed by referring to relatively recent publications. "Longidufinal studies" comprised not only cohort studies but also prospective case-control studies in the broad sense. Poor self-rated health, weight loss hypoalbuminemia, inability to perform activities of daily living, low levels of physical activity, and cognitive dysfunction, all of which could be manifestations of chronic diseases, might shorten longevity. Cardiomegaly or left ventricular hypertrophy on ECG were again found to be important risk factors for cardiovascular disease in the aged, because of their relation to atherosclerosis. There is no evidence regarding the contribution of hyperlipidemia to the risk of cardiovascular disease in the aged, although insulin resistance can increase serum triglyceride levels and reduced level of high-density lipoprotein cholesterol even in the aged. Mortality due to stroke and heart disease have been decreasing in most developed countries, and several recent community-based studies have also shown decreases in the incidence of cerebral stroke. Large-scale case-control studies on the pharmacological treatment of hyperlipidemia have resulted in both primary and secondary prevention of coronary heart disease. However, information concerning the effects of treatment for hyperlipidemia on coronary heart disease in the aged is limited. Results of large-scale case-control studies indicate that pharmacological treatment of elderly hypertensive patients can reduce cardiovascular morbidity and mortality, and angiotensin-converting enzyme inhibitors have recently been shown ot be useful.
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PMID:[Longitudinal studies in geriatric medicine]. 971 Oct 88


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