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The poor prognosis of arterial hypertension is mainly determined by its cardiac organ damages. Even borderline arterial hypertension significantly increases coronary morbidity and mortality, particularly in the presence of other risk factors such as hypercholesterolemia, diabetes, and cigarette smoking. Arterial hypertension causes myocardial hypertrophy and fibrosis, and affects coronary microcirculation by structural and functional changes of the small intramural resistance arteries, rarefiction of arterioles and capillaries and a distinct disturbance of endothelial vasomotion (i.e. "hypertensive remodeling"). Moreover, the presence of arterial hypertension predisposes to atherosclerotic coronary artery disease. Regarding the benefit-risk-ratio of antihypertensive therapy, benefit is much greater than risk: 1) An antihypertensive treatment with ACE-inhibitors, calcium channel blockers, beta-receptorblockers and anti-sympathicotonic substances leads to both reversal of LV hypertrophy and improvement of coronary flow reserve. Incidence of hypertensive heart failure has dropped considerably during the last 20 years. 3) Intervention studies have shown at least a clear tendency of a reduction in coronary morbidity and mortality. 4) In patients with coronary artery disease diastolic blood pressure should not be lowered under 85 mm Hg (J-curve). 5) An antihypertensive treatment should not adversely influence blood lipids when cholesterol is elevated. 6) Even in very elderly patients medical intervention to lower blood pressure is indicated from the cardiologic point of view (SHEP- and SHOP-studies).
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PMID:[Benefits and risks of hypertension therapy from the cardiac viewpoint]. 817 41

The clinical coincidence of hypertension, obesity and non insulin diabetes mellitus (NIDDM) has long been recognized. Increasing interest has also been recently focused on the possible role of insulin and insulin resistance in mediating this association. There is also evidence that hyperglycemia per se may have a role in the pathogenesis of hypertension and atherosclerosis in NIDDM patients. Glucose is a determinant to cellular ion homeostasis, promoting an increase of intracellular calcium and suppressing intracellular free magnesium and pH. Moreover, hyperglycemia promotes glycosilation of proteins and the consequent accumulation of advanced glycosilation end products in tissues. It has recently been suggested that iter is a cellular ionic basis for the clinical and epidemiological linkage of hypertension, left ventricular hypertrophy (LVH), obesity and non insulin dependent diabetes mellitus (NIDDM). These clinical conditions may be different expressions of a common underlying defect in ion handling, displayed by elevated cytosolic free calcium and suppressed free magnesium levels. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion specific agents, such as calcium channel blocker drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent cardiac, vascular and metabolic aspects of the hypertensive states.
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PMID:Diabetes, hypertension and atherosclerosis: pathophysiological role of intracellular ions. 820 15

Reduction of hypertension, whether systolic and diastolic or isolated systolic, is associated with significant reductions in mortality and morbidity rates even in older asymptomatic patients, particularly those less than 80 years old. The increased availability of antihypertensive preparations makes it possible to individualize the choice of therapy to meet the particular needs of the older patient. Although most presently available antihypertensive agents are effective, each one possesses different properties and none is free of side effects. We review the indications for and the action and side effects of diuretics, angiotensin converting enzyme inhibitors, calcium channel blockers, and adrenergic blocking drugs, and we offer treatment suggestions for hypertension associated with other diseases such as diabetes mellitus, heart failure, peripheral vascular insufficiency, depression, dementia, and urinary incontinence. Orthostatic hypotension is particularly serious in older patients because it may precipitate falls. It is also possible that the relationship between blood pressure levels and mortality and morbidity risks is not linear but J-shaped, both low and high levels increasing risks. Caution in treating hypertensive elderly patients will minimize the incidence of side effects.
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PMID:Management of hypertension in older patients. 821 49

Although many drugs effectively control hypertension in patients with diabetes mellitus, the risk of aggravating the diabetic process and inducing new complications can negate the benefits of reduced blood pressure. This article discusses the current status of antihypertensive therapy in diabetic patients and focuses on the use of calcium channel blockers that safely reduce blood pressure while having a neutral or beneficial effect on the diabetic state and related medical complications. While both calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors are suitable agents for the primary treatment of diabetic hypertension, the beneficial effects of calcium channel blockers on glucose homeostasis, lipid metabolism, and renal function support their routine use as alternatives to ACE inhibitors. Among the three classes of calcium channel blockers, second-generation dihydropyridines offer advantages over older calcium channel blockers because the second-generation drugs provide greater vascular selectivity and less direct myocardial depression.
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PMID:Treating hypertension in the diabetic patient: therapeutic goals and the role of calcium channel blockers. 822 13

Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an "aging process" on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of "muted" hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.
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PMID:Hypertension in the elderly: age- and disease-related complications and therapeutic implications. 824 Oct 7

The effect of three calcium antagonists (verapamil, diltiazem, and nifedipine) on insulin effects was investigated in isolated rat soleus muscles. Soleus muscles were incubated in the presence of insulin (100 microU/ml), a concentration that stimulates the rates of lactate formation and glycogen synthesis half-maximally and with and without a calcium antagonist. A decrease (48%; P < 0.001) was noted in the insulin-mediated rate of glycogen synthesis by verapamil at 100 microM; no effect was observed at lower concentrations of verapamil. Diltiazem decreased the insulin-mediated rates of glycogen synthesis by 36 (P < 0.001), 64 (P < 0.001), and 73% (P < 0.001) at 1, 10, and 100 microM, respectively. Nifedipine decreased the insulin-mediated rates of glycogen synthesis by 37% at 0.1 microM (P < 0.001), 36% at 1 microM (P < 0.001), 21% at 10 microM (P < 0.05), and 72% at 100 microM (P < 0.001). Verapamil at 100 microM decreased lactate formation by 48% (P < 0.001). However, diltiazem increased the rate of lactate formation by 22 (P < 0.01), 43 (P < 0.001), and 61% (P < 0.001) at 1, 10, and 100 microM, respectively. In contrast, nifedipine increased the insulin-mediated rate of lactate formation by 45% only at 100 microM (P < 0.01). The increased rate of lactate formation was probably caused by an increased rate of glycogenolysis, because high concentrations of all the calcium antagonists significantly decreased muscle glycogen content. The insulin-stimulated rate of 3-O-methyl-D-glucose transport or cAMP content was not affected by diltiazem at 1 or 10 microM. The results suggest that the calcium antagonists work by a mechanism, possibly by activating a calcium channel or an extracellular receptor, to influence markedly insulin-mediated intracellular glucose metabolism in skeletal muscle.
Diabetes 1994 Jan
PMID:Effects of calcium antagonists on insulin-mediated glucose metabolism in skeletal muscle. 826 20

Hypertension is the commonest cardiovascular disease in Africans occurring in more than 15% of the adult population in some studies. It occurs in the lower as much as in the higher socio-economic groups. Recent studies have confirmed earlier findings that essential hypertension in Africans is characterised by volume loading, low plasma renin activity, high salt taste threshold, high urinary sodium and low potassium excretion and high plasma aldosterone. The commonest complication of hypertension in Africans is congestive cardiac failure followed by cerebrovascular accidents. Coronary heart disease is rare. Even in the absence of overt heart failure and compounding factors like obesity, alcoholism, cigarette smoking, diabetes mellitus and myocarditis, evidence of abnormal left ventricular morphology and function is often present in newly diagnosed patients with moderate or severe hypertension. Response to monotherapy with beta-blockers or ACE inhibitors is usually poor but is good with thiazide diuretics or calcium channel blockers. The diuretics are an essential component of a two or three drug regime containing other classes of antihypertensive drugs. Cost of drugs is the most important determinant of compliance with drug treatment and consequently the likelihood of progression of the diseases to more severe forms in long term follow-up.
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PMID:Hypertension in Africa and effectiveness of its management with various classes of antihypertensive drugs and in different socio-economic and cultural environments. 826 3

Blood pressure (BP) was measured once every month during one year in 80 hypertensive outpatients. An orthostatic test was performed in winter and another during summer. The collective was aged 65 +/- 13 years (m +/- SD) and presented an elevated prevalence of diabetes mellitus, cardiac failure, and coronary, cerebral and arterial insufficiency. Diuretics, betablockers, converting enzyme inhibitors and calcium channel blockers were used by 31 patients as monotherapy and by 49 patients in association. During summer a significantly lower seated BP was found (144.1/79.4 mm Hg vs 150.8/82.9 mm Hg in winter, p < 0.001). One fourth of the patients did not show this diminution. On the basis of the WHO criteria of BP definition, 31% of the patients could be considered hypertensive in winter vs 16% in summer and 28% as normotensive in winter vs 43% in summer (p < 0.05). The summer reduction in BP depended on position. It was less marked in seated position (-5.3/-2.7 mm Hg) than in lying (-6/-5.1 mm Hg) or even in standing position (-10.8/-5.1 mm Hg). The orthostatic test induced a greater immediate fall in systolic BP in summer than in winter (-14.4 vs -9.6 mm Hg, p < 0.001), more orthostatic hypotensive episodes defined as a systolic BP fall of 20 mm Hg or more (34% of patients vs 20% in winter, p = 0.05) and more signs of reduced cerebral perfusion (14% vs 7.5% in winter, NS). Diabetic patients and patients treated by diuretic and vasodilator drugs are particularly exposed to orthostatic hypotension in summer. Betablockers can minimize this risk.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Seasonal variations in arterial pressure in hypertensive patients]. 827 12

Calcium channel blockers are used in the treatment of hypertension because of their ability to decrease peripheral vascular resistance. Recent research has suggested that these drugs also preserve or improve renal function in patients with essential hypertensive renal disease, diabetic renal disease, and in renal transplant recipients with or without cyclosporine therapy. In general, studies in both animal models and humans have demonstrated maintenance or reduction in renal vascular resistance, and preservation or enhancement of renal blood flow and glomerular filtration rate. In addition, calcium channel blockers appear to have a positive effect on renal haemodynamic function in the setting of diabetes mellitus; prospective trials have demonstrated reductions in urinary protein excretion in these patients. Current evidence suggests that calcium channel blockers are well suited for the treatment of patients with hypertensive disease even in the presence of renal impairment.
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PMID:Calcium channel blockers: do they offer renal protection? 834 86

The effect of calcium antagonists: nifedipine (corinfar, cordapheg), sensit, finoptin, foridon on carbohydrate and lipid metabolism was studied in intact and "alloxaned" rats as well as in non-insulin-dependent diabetes patients. It was found that the calcium channel blockers did not change glucose tolerance, normalized carbohydrate metabolism in some patients and decreased the level of triglycerides, B and pro-B lipoproteins. In some cases in intact and alloxane rats treated with finophin (isoptin), lactate decrease in blood and a tendency to insulin increase were often observed. The lipid metabolism was unchanged.
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PMID:[The effect of calcium antagonists on carbohydrate and lipid metabolism in diabetes mellitus]. 834 37


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