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Calcium antagonists are widely used in the treatment of hypertension. However, few endpoint studies with calcium antagonists have been done to prove reduction in hypertensive complications. Results of the STONE, SYST-EUR and SYST-CHINA studies show that long-acting calcium antagonists are effective compared to placebo, especially in patients with isolated systolic hypertension and diabetes. Ongoing prospective and randomized trials like STOP II, INSIGHT, NORDIL, ALLHAT and ASCOT will clarify whether calcium antagonists are more effective than well-proven diuretics and betablockers. ASCOT will test the hypothesis that amlodipine is more efficacious than atenolol in preventing cardiac complications in 18,000 hypertensive patients with high coronary risk including diabetes (among them, 2,000 in Norway). The study is also randomizing the patients in a factorial design to either atorvastatin or placebo, testing the so-called lipid hypothesis.
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PMID:[An overview of hypertension studies with calcium antagonists]. 1038 32

Several trials performed in elderly patients have demonstrated that antihypertensive drugs are effective in both systo-diastolic and isolated systolic hypertension, reducing the incidence of fatal and nonfatal cardiovascular events. However because of technical and design problems, the studies carried out to date have involved highly selected patients, almost always without any target organ damage, independent, cognitively normal and with low comorbidity. Therefore, trial results may be transferred to clinical practice only with some caution. Therapeutic behavior could be different in the presence of diseases associated with hypertension: a) in case of associated specific cardiovascular complications and/or diseases, such as diabetes or dyslipidemia, which could increase cardiovascular risk, treatment must be more aggressive; b) in case of associated diseases with fatal prognosis, treatment is aimed at preventing hypertensive emergencies; c) in case of associated diseases, which are not life-threatening but require chronic pharmacological intervention, drug interaction must be carefully considered. Finally, sudden and significant blood pressure drops due both to overdosage of antihypertensive drugs and/or to intercurrent illnesses must be prevented, because the reduction of blood flow may induce severe target organ ischemia.
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PMID:Treatment of hypertension in the elderly. 1038 46

The prevention and treatment of hypertension remain as major challenges for clinicians all over the world. The recently published Sixth Report of the Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) uses evidence-based medicine in providing guidelines to aid clinicians in the prevention, detection and treatment of high blood pressure, including pharmacological approaches. Calcium antagonists are used widely for the treatment of hypertension, and JNC-VI focuses on specific situations where calcium antagonists could be considered as preferred treatments. There are a large number of calcium antagonists available, with a variety of pharmacodynamic and pharmacokinetic actions. Several sustained-release formulations of these drugs are also available. In terms of blood pressure control, calcium antagonists are more effective as antihypertensive treatments than beta-blockers, ACE inhibitors and angiotensin II receptor blockers in Black patients. The dihydropyridine calcium antagonists have been shown to reduce morbidity and mortality in elderly patients with isolated systolic hypertension. The rate-lowering calcium antagonists can be used as alternatives to beta-blockers in patients with coronary artery disease and hypertension. Calcium antagonists can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus and/or renal disease. Some dihydropyridine calcium antagonists may be useful as alternatives to ACE inhibitors in patients with hypertension and systolic heart failure. Calcium antagonists appear to be extremely useful in patients with cyclosporin-induced hypertension, and in patients with hypertension and concomitant Raynaud's phenomenon and/or migraine. The rate-lowering agents can be used in patients with atrial tachyarrhythmias and hypertension. Clinicians should be aware of drug-drug interactions involving calcium antagonists, especially after the recent problems with mibefradil. Although retrospective studies have caused controversy regarding the safety of calcium antagonists in patients with hypertension, recent prospective studies have revealed no major safety concerns with these drugs.
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PMID:How to use calcium antagonists in hypertension: putting the JNC-VI guidelines into practice. Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 1055 31

It is clear that antihypertensive regimens based on a low dose thiazide diuretic are effective for the primary prevention of stroke, particularly in older patients. In patients with diabetes mellitus who are at a higher risk of stroke, low dose thiazide diuretics and ACE inhibitors are of benefit. In those with isolated systolic hypertension, long-acting dihydropyridine calcium antagonists, in addition tolow dose thiazide diuretics, have also been shown to significantly reduce stroke risk. However, to attain sufficient lowering of blood pressure (BP) to most effectively reduce the risk of stroke (i.e. to levels of 140-150/80-85 mm Hg or lower and perhaps to <140/<80 mm Hg in patients with diabetes mellitus) combination therapy will be required. Immediately following stroke BP tends to fall spontaneously and therapy is probably not required in the great majority of patients during the first few days poststroke. If treatment is required shortly after this period, agents with a slow and gentle onset of action appear to be preferable; some preliminary data suggest that ACE inhibitors, despite lowering systemic BP, have no significant effect on cerebral blood flow. However, there is little clinical outcome data to clearly define the role of antihypertensive treatment in the early poststroke period. Whether existing antihypertensive therapy should be continued following stroke is also unclear, but such decisions may be influenced by factors such as the actual BP level, other indications for treatment (e.g. angina pectoris or cardiac failure) or the presence of dysphagia. There is more evidence to suggest that, some weeks to months following stroke (particularly a minor stroke), lower rather than higher BP is favourable, and better control of high BP with therapy reduces stroke recurrence.
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PMID:Antihypertensive therapy in the prevention of stroke: what, when and for whom? 1055 36

The majority of patients with hypertension have one or more additional risk factors for cardiovascular disease. In planning an appropriate treatment program, it is useful to identify and stratify hypertensive patients according to their risk of developing cardiovascular, cerebrovascular, or renal disease. At particular risk are the elderly, patients with diabetes, and those with target-organ damage manifested by impaired renal function. Evidence supports increased risk in these patients, and clinical trial results demonstrate the considerable benefits realized through aggressive blood pressure (BP) control. The number of elderly individuals continues to increase in the United States and other industrialized countries. The prevalence of isolated systolic hypertension (ISH) is higher in the elderly than in younger individuals. ISH is associated with significant morbidity and mortality and should not be considered a physiologic manifestation of the normal aging process. Type 2 diabetes is also increasing in prevalence. Patients with diabetes are at increased risk for coronary heart disease, stroke, renal failure, and other cardiovascular complications. Aggressive treatment of elevated BP can produce dramatic decreases in the cardiovascular complications of diabetes. The incidence of end-stage renal disease has increased 2.5-fold in the past two decades, and poorly controlled BP is a major contributor to the increase. Lowering BP to levels well below the traditional goal of 140/90 mm Hg is needed to slow the progression of renal dysfunction and prevent renal failure in hypertensive patients with renal disease, whether related to diabetes or to another etiology. Aggressive treatment of hypertension in multiple-risk populations (to the goals of JNC VI and the recent WHO-ISH Guidelines for the Management of Hypertension) can be expected to produce significant reductions in the incidence and prevalence of stroke, heart failure, coronary heart disease, chronic renal failure, and total cardiovascular mortality.
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PMID:Treating multiple-risk hypertensive populations. 1059 63

Hypertension (HT) is a common disease in elderly. It has different pathophysiologic, clinical and therapeutic implications in this age group. Due to loss of arterial wall elasticity with age, major vessels including aorta become stiff and less distensible. As age advances, these stiff vessels also lose beta adrenergic responsiveness with unchanged alpha adrenergic responsiveness. These together raise peripheral vascular resistance and aortic impedance which needs a powerful systolic ejection of left ventricle to maintain cardiac output. Result is rise in systolic blood pressure (SBP) and increase in left ventricular (LV) mass with compromised cardiac output and renal blood flow. Participation of renin-angiotensin system and kidney in HT pathogenesis in elderly are minimum. Diagnosis of HT in elderly is made if SBP > 140 mm Hg and/or diastolic blood pressure (DBP) > 90 mm Hg or is taking antihypertensive medications. Isolated systolic hypertension (ISH) means SBP > 140 mm Hg with DBP < 90 mm Hg. Measurement of blood pressure (BP) is problematic, mainly due to pseudo HT, postural hypotension and white-coat HT. HT in absence of end organ changes suggest pseudo HT. Postural hypotension must be detected and treated. Systolodiastolic HT, carried over from middle age is the commonest type of HT in elderly. ISH is also common (10%). Atherosclerotic renovascular disease can cause secondary HT. Therapy is always needed in HT in elderly. Chance of coronary artery disease (CAD) and cerebrovascular accident (CVA) are quite high amongst elderly hypertensives. SBP is more dangerous than DBP. Benefits of therapy are more when compared to young. HT should be treated if SBP > 160 mm Hg and/or DBP > 90 mm Hg. ISH needs therapy if SBP > 160 mm Hg. The benefits of therapy becomes less after 80 years. Treatment goal should be to keep BP below 140/90 mm Hg. Therapy should be gradual and stepwise. Na-restriction should be modest. Diuretics (e.g., thiazide 25 mg/day) are the drug of choice unless contra-indicated. Beta blockers are inferior agents compared to diuretics unless angina or acute myocardial infarction (AMI) is present. Angiotensin converting enzyme (ACE) inhibitors are drug of choice only if congestive cardiac failure (CCF) and/or diabetes is present or other drugs are contra-indicated. Calcium entry blockers (CEB) are new but very good alternative to diuretics in elderly. Due to abnormal physiology, pharmacokinetics and drug interactions, side-effects are very common in elderly. They should be detected early and treated.
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PMID:Hypertension in elderly--an overview. 1065 9

Systolic blood pressure (SBP) is a more reliable predictor of cardiovascular disease (CVD) events than is diastolic blood pressure (DBP). Perhaps the reduction of SBP should be more of the imperative of treatment than the reduction of DBP. Although two recent guidelines (WHO/ISH and JNC-VI) have recommended treating SBP to goal, there seems to be a reluctance in the medical community to embrace this paradigm shift and revise treatment plans. The deleterious effects of ignoring these findings are especially damaging to those with isolated systolic hypertension (ISH), which affects approximately two-thirds of hypertensive patients between the ages of 65 and 89 years. Two large clinical trials, the Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe (Syst-EUR) trial have confirmed that reducing SBP in the elderly with stages 2 and 3 ISH (SBP > or = 160 mmHg with DBP < 90 mmHg in SHEP and SBP > 160 mmHg with DBP < 95 mmHg in Syst-EUR) reduced morbidity and mortality. Two SHEP sub-studies found that lowering SBP in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and those with a history of myocardial infarction (MI) reduced the incidence of stroke and heart failure, as well as several other endpoints. The beneficial effects were corroborated in Syst-EUR where stroke (fatal and nonfatal), CVD endpoints and mortality were all significantly reduced when SBP was lowered 20 mmHg in subjects > 60 years of age. Despite these findings, however, recent analysis suggests that most hypertension treatment decisions continue to be based on DBP measurements instead of SBP. To combat this treatment gap, we must disseminate this information and motivate physicians and other providers to include reduction of SBP in their treatment plans. We must also encourage the development of antihypertensive drugs that lower SBP more effectively than those that are currently available.
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PMID:Isolated systolic hypertension in the elderly: lessons from clinical trials and future directions. 1070 27

The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension (diastolic or isolated systolic) influences blood pressure (BP) response to treatment. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years. Dynamic randomization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors. Patients with isolated systolic hypertension were also separately randomized. Atenolol or enalapril was the mandatory second-line drug. In 5669 patients who completed the 18-week titration, BP fell from 172+/-15/99+/-9 mm Hg (mean+/-SD) while receiving placebo to 139+/-12/82+/-7 mm Hg. Twenty-six percent of patients required 2 drugs, and 4% required 3 drugs. Patients with diabetes were the most resistant to treatment, requiring second and third drugs 40% and 100% more frequently than patients without diabetes and achieving marginally the highest final BP, for any risk group, of 141+/-13/82+/-8 mm Hg. Age, smoking, gender, hypercholesterolemia, left ventricular hypertrophy, and existing atherosclerosis had little (<1 mm Hg) or no influence on BP at the end of titration, but all except smoking slightly reduced the initial response of either systolic or diastolic BP. Patients with isolated systolic hypertension were slightly more responsive than average to treatment. Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension, the risk factors themselves do not prevent the recommended BP targets from being achieved.
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PMID:Influence of diabetes and type of hypertension on response to antihypertensive treatment. 1081 61

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

Hypertension is one of the main risk factors for cerebrovascular disease (stroke), coronary artery disease (acute myocardial infarction), congestive heart failure (both systolic and diastolic dysfunction), and renal dysfunction. The risk is related to blood pressure level and to the presence of target organ damage. Together with hypertension, other cardiovascular risk factors, such as hyperlipidemia and/or diabetes, also contribute to the chain of events leading to atherosclerosis, vascular complications and death. Three-quarters of middle-aged, urban population show at least one cardiovascular risk factor and 91.3% of all hypertensives show at least one cardiovascular risk factor in addition to hypertension itself. In most populations, the risk of cardiovascular disease rises steeply with age. This powerful effect of age on disease risk has important consequences for the risk of cardiovascular disease related to blood pressure and other risk factors. At most ages the risk for cardiovascular diseases is higher in men than in women, although this difference declines with increasing age and is greater for coronary heart disease than for stroke; in the United States from age 34 to 74 the risk of death from coronary heart disease is 2- to 3-fold greater in men; the risk of death from stroke is 30% higher in men than in women; after age 75 the risk of death from stroke and from coronary heart disease is similar in men and women. Postmenopausal women share the same risk with men for cardiovascular disease. For many years the study and treatment of hypertension has been largely directed toward diastolic blood pressure; the importance of elevated systolic blood pressure in the management of cardiovascular disease is being largely underrecognized. Convincing evidence is presently available indicating that elevated systolic blood pressure is even a stronger predictor than diastolic blood pressure for progression of cardiovascular disease and adverse outcomes. The clinical and laboratory evaluation and drug treatment of the hypertension is related to age. The elderly benefit from treatment of elevated systolic blood pressure as much or even more than middle-aged hypertensive subjects. Two large clinical trials on treatment of isolated systolic hypertension, the Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe Study (Syst-Eur), have demonstrated that antihypertensive drug therapy in elderly patients with isolated systolic hypertension effectively reduces the risk of stroke and other major cardiovascular events.
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PMID:[Hypertension as a function of age]. 1090 25


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