Outcomes of treating hypertension in the elderly: a short commentary on current issues

Because treating hypertension in the elderly so effectively reduces major cardiovascular events, it is vital to diagnose this very common condition early. Much of the hypertension that occurs with aging results from stiffening of the major capacitance arteries, typically marked by high systolic and low diastolic blood pressures. Pulse pressure, derived by subtracting diastolic from systolic values, is a useful index of stiffness, but new noninvasive techniques for measurement of arterial compliance have shown that blood pressures cannot reliably predict the state of the arteries in older people. The Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe (Syst-Eur) trial demonstrated that treating hypertension in the elderly with diuretics or calcium channel blockers reduces strokes and cardiac events; these results are also clearly evident in high-risk groups like diabetics. Further analysis of Syst-Eur has suggested that a calcium channel blocker reduces new-onset dementia, while follow-up data from SHEP indicate that a diuretic provides survival and stroke benefits in obese or overweight elderly hypertensives, but not in the lean. In general, comparisons of antihypertensive agents, including diuretics, βblockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers have found similar clinical end point effects. But recently, the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study, performed in patients (average age, 67) with left ventricular hypertrophy and predominant systolic hypertension, showed that the angiotensin receptor blocker losartan was significantly more effective than the β blocker atenolol in reducing such key outcomes as strokes and new-onset diabetes. Even so, careful but effective control of blood pressure in elderly patients, including those over age 80, still remains a critical factor in preventing major cardiovascular events.     

Calcium channel inhibitors and ventricular filling]

Abnormalities of ventricular relaxation and compliance often precede changes in systolic function in ischemic and hypertrophic or hypertensive heart disease. Several studies using non-invasive methods have confirmed the beneficial effects of calcium channel blockers on left ventricular diastolic function in ischemic and primary hypertrophic cardiomyopathies. Their usefulness remains controversial in secondary cardiac hypertrophy such as in hypertensive heart disease. Improved left ventricular isovolumic relaxation and filling results more from the coronary and peripheral vasodilatory effects of calcium channel blockers than from a direct action on the cardiac muscle.     

Risk Reduction Following Regression of Cardiac Hypertrophy

Cardiac hypertrophy in essential hypertension is documented to be an independent risk factor for congestive heart failure, coronary heart disease and cardiac sudden death. Reduction of left ventricular hypertrophy therefore emerged as a new challenge of antihypertensive treatment. Sympatholytic agents, calcium entry blockers, and angiotensin converting enzyme inhibitors have been found to reduce left ventricular hypertrophy, whereas vasodilators (and most likely also diuretics) are unable to reduce left ventricular mass despite good control of arterial hypertension. Several studies indicated that reduction of left ventricular hypertrophy is not detrimental to cardiac pump function: systolic and diastolic function were found to be maintained at rest and during exposure to increased pressure load. In hypertensive patients with left ventricular hypertrophy ventricular arrythmias have been reported to be increased and to be the pathophysiological link for the increased risk of cardiac sudden death. Reduction of cardiac hypertrophy was found to be accompanied by a reduction of prevalence and severity of ventricular arrhythmias if treated with betablockers, calcium entry blockers or converting enzyme inhibitors. Whether reduction of cardiac hypertrophy indeed decreases the cardiovascular risk attributed to left ventricular hypertrophy is unknown at present, although clinical studies support such a viewpoint.     

Nicardipine, a new calcium channel blocker: role for vascular selectivity

Calcium channel blockers are important drugs for the treatment of chronic stable angina. However, negative inotropic and dromotropic effects may limit their usefulness in patients with atrioventricular conduction abnormalities or left ventricular dysfunction. A new generation of calcium channel blockers will soon be available that have a more vascular selective action than currently available agents. Of the new agents, nicardipine has been most extensively studied. In experimental studies, nicardipine is more specific for vascular smooth muscle than for cardiac smooth muscle and for coronary than peripheral vasculature. In controlled trials, nicardipine exhibited efficacy and safety that was comparable to older calcium blockers or beta blockers. However, nicardipine was associated with minimal negative inotropic or dromotropic effects even in patients with existing left ventricular dysfunction. Thus, nicardipine may have an advantage over existing calcium channel blockers, especially in patients with underlying cardiac disease.     

Management of hypertension in liver transplant patients

Hypertension is a common co-morbidity and a frequent complication in liver transplant patients. The aim of this paper is to concisely review available clinical data and propose a hypertension treatment algorithm in liver transplant patients. Calcium channel blockers are mainstay of the treatment due to their potent vasodilatory effects. Dihydropyridine calcium channel blockers are preferable due to their least interaction with cytochrome P450 enzyme system and, therefore, minimal risk of potential disruption of immunosuppressive drug levels. Beta-blockers may be considered first line drugs in patients with resting tachycardia and in those with high cardiac outputs. Data support the use of beta-blockers for patients intolerant or unresponsive to calcium channel blockers. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have little value when used early after liver transplant but may have a more pronounced role during the later periods. Diuretics may be of value in combination with other drugs, especially to counteract the potassium-retaining effects of calcineurin inhibitors. Treatment of post liver transplantation hypertension in patients with co-morbid conditions such as coronary artery disease, diabetes mellitus, congestive heart failure, and renal disease will likely require combination therapy.     

Behandlung der Hypertonie bei Adipositas

BACKGROUND: Hypertension and obesity are common medical conditions independently associated with increased cardiovascular risk. Many large epidemiological studies have demonstrated associations between body mass index and blood pressure, and there is evidence to suggest, that obesity is a causal factor in the development of hypertension in obese subjects. Weight Reduction and maintenance is an essential first step in the treatment of obesity-associated hypertension. Weight reduction may be achieved by behavior modification, diet, and exercise or by the use of anti-obesity medication. However, the long-term outcomes of weight management programs for obesity are generally poor, and most hypertensive patients will require antihypertensive drug therapy. PATHOPHYSIOLOGY: Obese hypertensive patients often have metabolic abnormalities known to be exacerbated by commonly used antihypertensive agents but also obesity per se is often associated with endorgan damage including left ventricular hypertrophy, glomerular hyperfiltration and microalbuminuria, congestive heart failure or sudden cardiac death. Furthermore they have revealed volume expansion, increased cardiac output, and lower total peripheral resistance than lean patients. Hypertension in obese patients appears to be related to both increased sympathetic nervous system activity and activation of the renin-angiotensin system. Where antihypertensive therapy is necessary, the aim should be to use agents based on the hemodynamic and metabolic background and that have benefits beyond blood pressure lowering and improve the conditions most commonly linked with obesity-associated hypertension, such as hyperlipidaemia, Type II diabetes, left ventricular hypertrophy, coronary artery disease, or congestive heart failure. PHARMACOTHERAPY: Based on their favorable metabolic profiles, it would appear that ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, moxonidine and alpha-blockers can lower blood pressure without worsening the metabolic abnormalities, that is just one aspect of the problem. Yet, most guidelines fail to provide specific advice on the pharmacological management of hypertension in obese patients. This may be due to the fact that there are currently no studies that have addressed the efficacy of specific antihypertensive agents in reducing mortality in obese-hypertensive patients. This paper reviews the theoretical reasons for the differential use of the major classes of antihypertensive agents in the pharmacological management of obesity-related hypertension and also considers the potential role of anti-obesity agents.     

Hypertension and the heart

It has been clearly demonstrated that left ventricular (LV) hypertrophy is a strong blood pressure independent risk factor for cardiovascular morbidity and mortality in the general population, in primary and secondary hypertension and in cardiac patients. LV hypertrophy in arterial hypertension develops in response to an increased afterload, but underlying pathophysiological mechanisms include a variety of non-haemodynamic factors. Due to the prognostic importance of LV hypertrophy, normalisation of LV mass emerged as a desirable goal of antihypertensive treatment. Indeed, several prospective studies now indicate that regression of LV hypertrophy reduced cardiovascular complications. As a consequence, the question was raised whether certain antihypertensive drugs differ in their ability to reduce LV mass. Several comparative studies and meta-analyses have been carried out to resolve this issue. The available data seem to indicate that angiotensin-converting enzyme (ACE)-inhibitors and calcium channel blockers were more potent than beta-blockers in their ability to reduce LV hypertrophy, with diuretics in the intermediate range. The role of new antihypertensive agents such as angiotensin II AT1-receptor blockers appears similar to the one of ACE-inhibitors, since in some studies angiotensin II AT1-receptor blockers were superior to beta-blockers and diuretics. Various aspects of LV hypertrophy including its prevalence, determinants, prognosis and regression are discussed in this article.     

Pharmacotherapy in congestive heart failure: reflections on diabetes,clinical trials,and cardiovascular morbidity and mortality

Hypertension and diabetes are commonly found conditions, which predispose to premature cardiovascular morbidity and mortality. A strong consensus has emerged in support of aggressive blood pressure reduction in order to forestall the almost inevitable complications that follow from being a hypertensive diabetic. As of yet though it is not clearly determined as to what represents the best class(es) of antihypertensive medications to effect such blood pressure reduction. In this regard, considerable debate has arisen as to the cost/benefit ratio of dihydropyridine calcium channel blockers in the hypertensive diabetic. Although studies such as the Fosinopril vs. Amlodipine Cardiovascular Events Trial and the Appropriate Blood Pressure Control in Diabetes study would seem to argue against the use of dihydropyridine calcium channel blockers in the diabetic hypertensive, other studies such as the subset analyses of the Syst-Eur and the Syst-China and the Hypertension Optimal Treatment study provide almost compelling evidence for the safety of low to moderate doses of a dihydropyridine calcium channel blockers in this population. Safety issues of dihydropyridine calcium channel blockers will remain unresolved until the release of the Antihypertensive and Lipid Lowering Study to Prevent Heart Attack results at which time a resolution to this question should be forthcoming. (c)2000 by CHF, Inc.     

Does treatment of hypertension decrease the incidence of atrial fibrillation and cardioembolic stroke?

Hypertension is the most common disease affecting humans. Statistical surveys indicate that approximately one billion individuals worldwide suffer from this serious condition. The spotlight of the present review is on the cardiac involvement in patients with hypertension and especially on the possibility that treatment of increased blood pressure may abolish the incidence of cardiac arrhythmia and particularly atrial fibrillation. Modern therapeutic approach based on the electrical and structural remodeling process in the hypertensive heart with a consequent administration of ACE inhibitors and AT1 receptor blockers represent new and more efficient option compared to other antihypertensive drugs, such as calcium channel blockers, beta-blockers and thiazide-type diuretics and might be useful in the prevention of atrial fibrillation and incidence of stroke.     

Managing the hypertensive patient with ischemic heart disease

Thiazide diuretics, b-blockers, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors are all superior to placebo for the primary prevention of coronary events in patients with hypertension. Recent studies have shown that ACE inhibitors are better than other antihypertensive agents in lowering overall cardiovascular morbidity and mortality, especially stroke. Blood pressure should be aggressively lowered (to < 140/90 mm Hg), especially in diabetic patients (to < 130/80 mm Hg), but care should be exercised in lowering the diastolic blood pressure below 65 mm Hg in patients with significant occlusive coronary artery disease. Hypertension in patients with stable angina should be treated with a b-blocker (alternatively a calcium channel blocker) together with an ACE inhibitor. Patients with hypertension and acute coronary syndrome (unstable angina or myocardial infarction) should be treated with a b-blocker, and with an ACE inhibitor if there is left ventricular dysfunction. A thiazide diuretic and/or a dihydropyridine calcium channel blocker could be added for blood pressure control. Calcium channel blockers should be avoided if there is significant left ventricular dysfunction.     

Use of calcium channel blockers and angiotensin-converting enzyme inhibitors after cardiac transplantation

PURPOSE OF REVIEW: Hypertension, dyslipidemia, and diabetes are very common problems following heart transplantation and may contribute to the development and progression of graft coronary artery disease. This article reviews current data on clinical use of angiotensin-converting enzyme inhibitors and calcium channel blockers in patients who have had heart transplants. RECENT FINDINGS: Angiotensin-converting enzyme inhibitors and calcium channel blockers are established therapy for patients with cardiovascular disease. Use of these medications correlates with decreasing cardiovascular morbidity and mortality. SUMMARY: After heart transplantation, hypertension associated with calcineurin inhibitors can be managed effectively with antihypertensive therapy, but it may require use of more than one antihypertensive agent. Calcium channel blockers and angiotensin-converting enzyme inhibitors have been associated with improved outcome measures in graft coronary artery disease.     

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.     

Effects of calcium channel blockers on atherosclerosis: new insights

Atherosclerotic disease is the most frequent cause of death in the western world.The key role of calcium ions in atherogenesis has created interest in the antiatherogenic potential of calcium channel blockers. Nifedipine, administered in a long-acting gastrointestinal transport system (GITS) formulation, was shown to have similar efficacy to the diuretic co-amilozide in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).Two side-arm studies of INSIGHT suggest that nifedipine GITS has a greater antiatherosclerotic effect than diuretic therapy, which may signal additional cardiovascular protection in the long term. This paper reviews the evidence for the antiatherogenic properties of calcium channel blockers and discusses their clinical implication.     

Treatment of elderly hypertension with Ca channel blockers

Many studies have shown that treatment with calcium channel blockers (CCB) decreases cardiovascular mortality and morbidity in elderly hypertensive patients. Many CCBs are now commercially available in Japan. CCBs recently developed have long lasting hypotensive effect and improve patient's compliance. CCB is one of the first line drugs for elderly hypertensive according to the recent international guidelines. Guidelines of Japanese Society of Hypertension (JSH2004) also recommend CCB as a first line drug in elderly hypertensive patients. We summarize the results of the studies using CCB in elderly hypertensive patients and the therapeutic strategy using CCB in elderly hypertensive patients.     

From Hypertension to Heart Failure

The prevalence of heart failure is increasing in modern societies. Hypertension is a major contributor to the development of heart failure, whether through the development of left ventricular hypertrophy and diastolic dysfunction or by promoting atherosclerosis and myocardial infarction, which eventually leads to systolic dysfunction and left ventricular dysfunction. Effective therapy for hypertension can prevent more than 50% of heart failure events. Most studies done in the last three decades have used β blockers with diuretics as the modality of therapy. These agents have been shown to effectively prevent the development of heart failure. More recent comparative studies have shown that use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are also effective in preventing heart failure. Calcium channel blockers, however, seem to be less effective in preventing development of heart failure in patients with hypertension. It needs to be emphasized that the most important variable in preventing heart failure is the appropriate treatment of hypertension.     

L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts

Since the recognition of the importance of calcium ions to cardiac contractility, the effects of alterations in calcium homeostasis on cardiac myocyte function have attracted immense attention. However, the possibility that changes in extracellular calcium concentration or the administration of calcium channel blockers may exert significant effects on cardiac fibroblasts has not hitherto been explored. This communication presents evidence, for the first time, that EGTA, calcium-free incubation and L-type calcium channel blockers increase endogenous superoxide production in adult rat cardiac fibroblasts. A combination of ryanodine and EGTA was found to have an even greater effect. The observations indicate that extracellular calcium levels influence endogenous superoxide production in cardiac fibroblasts and support the postulation that myocardial fibroblasts may contribute to the cardiac effects of calcium channel blockers and alterations in extracellular calcium concentration.     

老年高血压的治疗策略

高血压是老年人群中的常见疾病,目前老年高血压已成为重要的公共卫生问题。老年高血压的治疗策略主要为：在改善生活方式等非药物治疗措施的基础上,选择合适的降压药物治疗使血压达标。常用的五类降压药物,噻嗪类利尿剂、钙通道拮抗剂、血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、β受体阻滞剂均可作为一线降压药物用于老年高血压的起始和维持治疗、单药或优化联合治疗。老年人降压治疗应遵循个体化原则,宜平稳、缓慢,降压药物起始剂量要小,逐渐增加剂量。治疗过程中须注意监测药物不良反应和其他心血管危险因素及合并疾病的治疗,并长期坚持治疗。     

Ventricular Hypertrophy and Hypertension

Left ventricular hypertrophy (LVH) is a strong, independent predictor of cardiovascular events and all-cause mortality. Patients with LVH are at increased risk for stroke, coronary heart disease, congestive heart failure, and sudden cardiac death. Hypertension is a major influence on the development of LVH. The prognostic power of LVH is likely multifactorial. LVH represents both a manifestation of the effects of hypertension and other cardiac risk factors over time as well as an intrinsic condition causing pathologic changes in cardiac structure and function. Angiotensin II plays a central role in the development of LVH. Several antihypertensive treatments, especially angiotensin II receptor blockers, can reverse LVH and improve cardiovascular outcomes independent of blood pressure reduction. Further studies are required to determine if these agents should become first-line therapy for all patients with hypertension and LVH.     

Management of the elderly person after myocardial infarction

Elderly persons after myocardial infarction should have their modifiable coronary artery risk factors intensively treated. Hypertension should be treated with beta blockers and angiotensin-converting enzyme inhibitors. The blood pressure should be reduced to <140/85 mmHg and to > or = 130/80 mmHg in persons with diabetes or renal insufficiency. The serum low-density lipoprotein cholesterol should be reduced to <100 mg/dl with statins if necessary. Aspirin or clopidogrel, beta blockers, and angiotensin-converting enzyme inhibitors should be given indefinitely unless contraindications exist to the use of these drugs. Long-acting nitrates are effective antianginal and antiischemic drugs. There are no Class I indications for the use of calcium channel blockers after myocardial infarction. Postinfarction patients should not receive Class I antiarrhythmic drugs, sotalol, or amiodarone. An automatic implantable cardioverter-defibrillator should be implanted in postinfarction patients at very high risk for sudden cardiac death. Hormonal therapy should not be used in postmenopausal women after myocardial infarction. The two indications for coronary revascularization are prolongation of life and relief of unacceptable symptoms despite optimal medical management.     

Effect of different antihypertensive drug classes on central aortic pressure

Central aortic systolic blood pressure (BP) is an important determinant of cardiac workload and cardiac hypertrophy. The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels. It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner.In a double-blind crossover study, we measured the effects of the four major drug classes compared with placebo on central aortic pressure. Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus. The study was undertaken in patients aged 65 to 85 years with systolic BP >150 mm Hg at study entry. Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods.Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme (ACE) inhibitors or beta-blocking drugs. On placebo, central aorta augmentation pressure and index were 23 mm Hg and 33.3%; on ACE inhibitors the values were 18 mm Hg and 30%; on beta-blockers, 26 mm Hg and 38.5%; on calcium channel blockers, 16 mm Hg and 28%; and on diuretics, 17 mm Hg and 28.8%. The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes (P <.05), and augmentation pressures on ACE inhibitors, calcium channel blockers, and diuretics were less than on placebo (P <.05). The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics.Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs. The clinical importance of this discrepancy needs to be evaluated.