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Biomedical subjects

Franz H Messerli

Publications and source records attributed to Franz H Messerli.

69 records · Page 4Linked to original sources
PubMed2002

Is there an association between hypertension and cancer mortality?

BACKGROUND: Because of suggestions that hypertension may increase the long-term risk of cancer, we assessed the relation between hypertension and malignancy. METHODS: We conducted a MEDLINE search of English-language articles published between January 1966 and January 2000 using the terms hypertension or blood pressure, and neoplasm or cancer or malignancy. We reviewed prospective studies that reported cancer incidence or mortality in hypertensive and nonhypertensive patients, case-control studies that reported the prevalence of hypertension in cancer patients and controls, and references from identified articles. RESULTS: We identified 10 longitudinal studies that evaluated the association between blood pressure and cancer mortality in 47 119 subjects. Subjects with hypertension experienced an increased rate of cancer mortality during durations of follow-up ranging 9 to 20 years, with an age- and smoking-adjusted pooled odds ratio of 1.23 (95% confidence interval [CI]: 1.11 to 1.36). In 13 case-control studies, including 6964 cases of renal cell cancer and 9181 controls, the adjusted odds ratio for renal cell cancer among hypertensive patients, relative to normotensive counterparts, was 1.75 (95% CI: 1.61 to 1.90). No clear association was found between hypertension and cancer of other sites. CONCLUSION: Hypertension was associated with an increased risk of mortality from cancer, particularly renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2002

Why beta-blockers are not cardioprotective in elderly patients with hypertension.

Despite the fact that beta-blockers have been used for the treatment of hypertension for more than 30 years, no study has shown that their use reduces morbidity and mortality in the elderly. To the contrary, the British Medical Research Council trial in the elderly documented that although blood pressure was lowered effectively and significantly by atenolol, morbidity and mortality in the beta-blocker group did not differ from that of the placebo group. Not only was beta-blocker monotherapy not effective, but patients who received the combination of beta-blockers and diuretics fared consistently worse than those on diuretics alone. beta-blockers are less effective than diuretics in lowering blood pressure, and are poorly tolerated in the elderly. The reason for their inefficacy in the elderly may be related to their inherent unfavorable effect on systemic hemodynamics and pathophysiologic findings in the arterial tree, heart, kidneys, brain, and on the metabolism of lipids and carbohydrates. Decreased beta-adrenergic responsiveness with age and comorbid conditions makes beta-blockers unattractive. Thus, they should not be considered appropriate for first-line therapy of uncomplicated hypertension in the geriatric population.

Adrenergic beta-Antagonists↗
PubMed2002

Vasodilatory edema: a common side effect of antihypertensive therapy.

Vasodilatory edema, a common adverse effect of antihypertensive therapy with vasodilators, is related to several mechanisms, including arteriolar dilatation (causing an increase in intracapillary pressure), stimulation of the renin-angiotensin-aldosterone system, and fluid volume retention. Vasodilatory edema is dose-dependent and most common with direct arteriolar dilators such as minoxidil or hydralazine, and in decreasing order of frequency with the dihydropyridine calcium antagonists, a-blockers, antiadrenergic drugs, and nondihydropyridine calcium antagonists. Not all dihydropyridine calcium antagonists are created equal with regard to vasodilatory edema. At an equal antihypertensive efficacy, lercanidipine and lacidipine are associated with less vasodilatory edema than amlodipine and nifedipine. The addition of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) to a dihydropyridine calcium antagonist significantly reduces vasodilatory edema. In contrast, the addition of a diuretic has little effect on vasodilatory edema. Thus, low-dose combination therapy (of a dihydropyridine calcium antagonist with either an ACE inhibitor or an ARB) may be preferred over high-dose monotherapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Carcinogenicity of antihypertensive therapy.

Several studies have suggested that antihypertensive treatment may promote cancer through unknown mechanisms. Early retrospective studies implicated reserpine in breast cancer, but data from prospective studies and meta-analysis of several case-controlled studies showed only a weak association between reserpine and breast cancer which, although statistically significant, is of little clinical concern. Data from case-controlled studies and several cohort studies suggested an association between the use of a diuretic and the occurrence of renal cell cancer, particularly in women. A recent study showed an association between the use of a diuretic and the occurrence of colon cancer. Several prospective studies showed that treatment with atenolol may increase mortality from malignancy. However, other studies that analyzed data from several thousand patients could not confirm this association. In three prospective and a few case-controlled studies, angiotensin converting enzyme inhibitors were not associated with increased mortality from malignancy. In addition, a recent retrospective study showed that long-term use of angiotensin converting enzyme inhibitors had a protective effect against malignancy. Data from three large case-controlled studies and the combined data from eight randomized controlled studies and seven longitudinal studies showed a similar risk for malignancy among users and nonusers of calcium antagonists. Until further data from prospective clinical trials are available, we advise caution about long-term diuretic therapy in women. With regard to other antihypertensive drug classes, we suggest continuing the management of hypertension according to current treatment guidelines with little fear of any substantial cancer risk.

Animals↗
PubMed2002

Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting.

BACKGROUND: Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. METHODS: Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. RESULTS: In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels. CONCLUSIONS: Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.

Adult↗
PubMed2002

Calcium antagonists in hypertension: from hemodynamics to outcomes.

Hypertension, by definition, is a hemodynamic disorder. A high cardiac output and a normal systemic vascular resistance characterize the young hypertensive patient. As hypertension progresses, resistance becomes progressively elevated and cardiac output returns to normal. The elderly patient with hypertension has very high systemic vascular resistance and low cardiac output. Antihypertensive drugs should not only lower arterial pressure but also bring other hemodynamic parameters as well as functional and structural changes of the cardiovascular system back to normal. With the notable exception of the classic beta-blockers, all antihypertensive drug classes, including the vasodilating beta-blockers, increase or maintain cardiac output and lower systemic vascular resistance. Calcium antagonists, although a very heterogeneous group, have been shown to have a similar effect on systemic hemodynamics. Initially, the short-acting agents (even verapamil) produce a reflex increase in heart rate and cardiac output with a decrease in systemic vascular resistance. This reflexive cardiac acceleration is not seen with the extended-release or longer-acting formulations, which usually maintain cardiac output and decrease systemic resistance. Lercanidipine is a novel calcium antagonist that has been shown to differ from other dihydropyridines in that the incidence of vasodilatory edema for any given decrease in blood pressure is less pronounced. Whereas all dihydropyridine calcium antagonists dilate the afferent arteriole in the kidney, preclinical studies have shown that lercanidipine also produces dilation of the efferent vessel. Similar balanced pre- and postcapillary vasodilation may be an explanation for the lower incidence of vasodilatory edema seen clinically with lercanidipine. These micro- and macrovascular features make lercanidipine an attractive new member in the arsenal of the powerful dihydropyridine calcium antagonists.

Calcium Channel Blockers↗
PubMedDate not supplied

Calcium antagonists.

Calcium antagonists were introduced for the treatment of hypertension in the 1980s. Their use was subsequently expanded to additional disorders, such as angina pectoris, paroxysmal supraventricular tachycardias, hypertrophic cardiomyopathy, Raynaud phenomenon, pulmonary hypertension, diffuse esophageal spasms, and migraine. Calcium antagonists as a group are heterogeneous and include 3 main classes--phenylalkylamines, benzothiazepines, and dihydropyridines--that differ in their molecular structure, sites and modes of action, and effects on various other cardiovascular functions. Calcium antagonists lower blood pressure mainly through vasodilation and reduction of peripheral resistance. They maintain blood flow to vital organs, and are safe in patients with renal impairment. Unlike diuretics and beta-blockers, calcium antagonists do not impair glucose metabolism or lipid profile and may even attenuate the development of arteriosclerotic lesions. In long-term follow-up, patients treated with calcium antagonists had development of less overt diabetes mellitus than those who were treated with diuretics and beta-blockers. Moreover, calcium antagonists are able to reduce left ventricular mass and are effective in improving anginal pain. Recent prospective randomized studies attested to the beneficial effects of calcium antagonists in hypertensive patients. In comparison with placebo, calcium antagonist-based therapy reduced major cardiovascular events and cardiovascular death significantly in elderly hypertensive patients and in diabetic patients. In several comparative studies in hypertensive patients, treatment with calcium antagonists was equally effective as treatment with diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors. From these studies, it seems that a calcium antagonist-based regimen is superior to other regimens in preventing stroke, equivalent in preventing ischemic heart disease, and inferior in preventing congestive heart failure. Calcium antagonists are also safe and effective as first-line or add-on therapy in diabetic hypertensive patients. Heart rate-lowering calcium antagonists (verapamil, diltiazem) may have an edge over the dihydropyridines in post-myocardial infarction patients and in diabetic nephropathy. Thus, calcium antagonists may be safely used in the management of hypertension and angina pectoris.

Calcium Channel Blockers↗
PubMedDate not supplied

Long-term safety of antihypertensive therapy.

Lowering blood pressure (BP) in hypertensive patients reduces morbidity and mortality. However the long-term safety of some antihypertensive agents was a matter of concern. Diuretic, the gold standard treatment in hypertension may impair glucose tolerance and thereby accelerate the development of diabetes mellitus. It was also associated with increased cardiovascular mortality in diabetic patients. However, recent evidence showed that low-medium dose of thiazide diuretic especially when given in combination with potassium sparing agent is effective in reducing BP and cardiovascular morbidity and mortality. Beta blockers are less effective than other antihypertensive agents in the elderly. Therefore they may be appropriate as a first choice in young and middle-age hypertensives, and in those with fast heart rate, but they should not be considered appropriate as the first-line therapy in the elderly with uncomplicated hypertension. Several years ago a plethora of publications showed that short-acting calcium antagonists may increase the risk for myocardial infarction and cancer. A few years ago two studies showed that calcium antagonists are less effective than angiotensin converting enzyme inhibitors in preventing cardiovascular events in diabetic hypertensive patients. However, recent results from large prospective randomized studies showed that calcium antagonists reduce cardiovascular morbidity and mortality in diabetic and non-diabetic hypertensive patients. Some investigators have suggested that angiotensin receptor blockers (ARBs) may increase the risk of myocardial infarction in hypertensive patients. However, recent meta analyses refuted this conclusions and showed that ARBs are probably as effective as other antihypertensive agents in prevention of myocardial infarction. Despite the concern that has been raised regarding the long-term safety of some antihypertensive agents, it is clear that lowering BP is safe and beneficial.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Beta-blockers for primary prevention in hypertension: era bygone?

Beta-blockers are used commonly worldwide in clinical practice for lowering blood pressure. Most of the agents in this class are efficacious in reducing blood pressure, although they vary widely in their pharmacokinetic and pharmacodynamic properties. This variability may confer significant differences in clinical benefits associated with use of specific agents. Although commonly used in managing hypertension, the role of beta-blockers for primary prevention in uncomplicated hypertension has been controversial. Evidence from recent trials suggest relatively poor efficacy toward primary prevention and worse outcomes for certain end points, when compared with other blood pressure-lowering agents, Recently updated National Institute for Health and Clinical Excellence guidelines for England and Wales reflect this concern and have changed the indication for beta-blockers for blood pressure control from primary agents to use as an add-on agent in patients requiring multiple therapy. In this review, considering the extended debate on this topic, we discuss the general properties of beta-blockers and evidence from clinical trials supporting or refuting their use in various clinical scenarios. Newer beta-blockers have additional properties which may be beneficial. Although, whether these additional benefits will help in primary prevention is not clear.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Treatment of elderly hypertensive patients with a delayed-release verapamil formulation in a community-based trial.

This report of a practice-based clinical trial describes an open-label, multicenter dose-titration study of an elderly (age >or=65 years) subset of patients (N=628) with systolic blood pressures between 140 and 179 mm Hg or diastolic blood pressures between 90 and 109 mm Hg, to assess the effects of the Chronotherapeutic Oral Drug Absorption System (CODAS) formulation of verapamil hydrochloride. After starting 200 mg/d at bedtime, dosing was titrated to a maximum of 400 mg/d at 4-week intervals to achieve a target blood pressure of <140/<90 mm Hg using morning blood pressure measurements. Target blood pressure was reached in 57.1% of the elderly patients with CODAS verapamil monotherapy. A diastolic response (<90 mm Hg or a 10 mm Hg reduction from baseline) was achieved in 89.5% of these subjects, and a systolic blood pressure response (<140 mm Hg or 10% reduction from baseline) was attained in 75.5%. The percentages of patients achieving target blood pressure or the diastolic and systolic blood pressure responses were comparable to those previously reported for younger patients. It is notable that although 359 of the 628 patients reached control on treatment, 182 of the remaining 269 noncontrolled patients were not titrated to higher doses, indicating that even with a well tolerated drug there may be reluctance among clinicians to increase doses. CODAS verapamil was found to be efficacious and well tolerated among elderly hypertensive patients in this community trial.

Aged↗