Search PubMed⌕ Search

Biomedical subjects

F H Messerli

Publications and source records attributed to F H Messerli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Does diuretic therapy increase the risk of renal cell carcinoma?

Several studies have suggested that systemic hypertension as a disease or its therapy could increase the risk for malignancies. Diuretics reduce cardiovascular morbidity and mortality and constitute a cornerstone in the antihypertensive arsenal. To analyze the relation between diuretic therapy and the risk of malignancies, we conducted a comprehensive review of pertinent previous publications by searching the MEDLINE database for related articles in all languages published between January 1966 and April 1998. Within the past decade, we found 9 case control studies and 3 cohort studies in which the relation between diuretic use and renal cell carcinoma was examined. In the case control studies, the odds ratio of renal cell carcinoma occurring in patients treated with diuretics averaged 1.55 with a 95% confidence interval of 1.42 to 1.71 (p <0.00001) compared with nonusers of diuretics. In the 3 cohort studies of 1,226,229 patients, diuretic therapy was associated with a more than twofold risk of renal cell carcinoma when compared with patients not on diuretics. In 1 cohort study, and in the 7 case control studies in which the effects of gender were reported, women had a higher odds ratio (2.01, confidence interval 1.56 to 2.67) than men (1.69 confidence interval 1.34 to 2.13). Thus, cumulative evidence, possibly stronger in women than in men, suggests that the long-term use of diuretics may be associated with renal cell carcinoma. Although diuretics remain the best documented drug class to reduce morbidity and mortality in systemic hypertension, our data suggest a need for continued vigilance to assess the risk-benefit ratio of all drugs used for long-term therapy of cardiovascular disorders.

Carcinoma, Renal Cell↗
PubMed1999

Current trials.

Explore the source record for details and available documents.

Adrenergic beta-Antagonists↗
PubMed1999

Carcinogenicity of cardiovascular drugs.

Antihypertensive treatment may promote cancer through unknown mechanisms. Early retrospective studies implicated reserpine in breast cancer, but the drug was later absolved by prospective analyses. 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. 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 two prospective studies, angiotensin-converting enzyme (ACE) inhibitors were associated with increased mortality from malignancy, but a few case-controlled studies showed no association between use of ACE inhibitors and malignancy. In addition, a recent retrospective study showed that long-term use of ACE inhibitors had a protective effect against malignancy. In some studies, calcium antagonists were implicated in increasing the risk for cancer; however, two large case-controlled studies and the combined data from nine observational studies showed a similar risk for malignancy among users and nonusers of a calcium antagonist. Ongoing long-term prospective studies will tell us more about the carcinogenicity of cardiovascular drugs.

Adrenergic beta-Antagonists↗
PubMed1999

Hypertension and sudden cardiac death.

Left ventricular hypertrophy (LVH) has been identified as one of the strongest blood pressure-independent risk factors for sudden death, acute myocardial infarction, congestive heart failure, and other cardiovascular morbidity and mortality. Hypertensive patients with LVH have a significantly greater prevalence of premature ventricular contractions and complex ventricular arrhythmias than do patients without LVH or normotensive patients. Antihypertensive therapy reduces LVH, although not all antihypertensive drugs are equipotent in this regard. Angiotensin-converting enzyme inhibitors are probably the most effective in reducing LVH, followed by calcium antagonists, diuretics, and beta-blockers. The effect of angiotensin receptor blockers on left ventricular mass is unclear at the present, some studies showing a reduction, some studies showing no effect. A reduction in LVH has been shown to diminish LVH-associated arrhythmias. However, it remains to be shown that patients with LVH and ventricular ectopy are at a higher risk for sudden death than those without ventricular ectopy and that the reduction of LVH-associated ventricular ectopy indeed confers a clinical benefit that exceeds the one from the reduction of arterial pressure alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Combinations in the treatment of hypertension: ACE inhibitors and calcium antagonists.

Hypertension control and management of concomitant pathophysiologic conditions may require use of multiple drugs. However, most studies in hypertensive disease have focused on monotherapy. Therefore, our knowledge of combination therapy in the treatment of hypertension is largely extrapolated from these monotherapy studies. Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonist combinations should be particularly efficacious in reducing hypertensive target organ disease. Both of these drug classes have been shown to reduce complications of hypertensive heart disease and renal disease progression. With regard to hypertensive vascular disease, both ACE inhibitors and calcium antagonists have documented benefits. However, their use together in left ventricular hypertrophy and in patients with coronary heart disease, although promising, must be proved through carefully designed, prospective, randomized trials.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Beta-blockers and diuretics: to use or not to use.

The present review scrutinizes the recommendations of many guidelines to use beta-blockers and diuretics as first-line therapy in hypertension. These recommendations were ostensibly based on multiple prospective randomized trials attesting to a reduction of morbidity and mortality with both beta-blockers and diuretics in monotherapy as well as in combination. Although diuretic-based therapy has been shown to prevent strokes (and, to a lesser extent, heart attacks, and cardiovascular and all-cause mortality), no such data are available for beta-blockers. To the contrary, a recent metaanalysis documented that although blood pressure was lowered significantly by beta-blockers, this drug class was ineffective in preventing coronary heart disease, and cardiovascular and all-cause mortality (odds ratio 1.01, 0.98, and 1.05, respectively). Patients who received a combination of beta-blockers and diuretics fared consistently worse than those taking diuretics alone. Although diuretics have an unparalleled track record of safety and efficacy, the recent findings suggesting that long-term use increased the risk for renal cell carcinoma (RCC) is of concern. Over the past decade, an association between RCC and diuretic therapy has been documented in nine case control studies (odds ratio 1.55, confidence interval [CI] 1.42-1.71). In three cohort studies, diuretic therapy was associated with a greater than twofold increased risk of RCC. The risk of RCC increased with cumulative diuretic doses. In the elderly, a low-dose diuretic probably remains a good choice for antihypertensive therapy; however, in middle-aged patients, particularly in women, diuretics should be avoided for the long-term treatment of hypertension. Sweeping recommendations for the use of beta-blockers and diuretics as preferred therapeutic strategies are inappropriate and a more sophisticated drug therapy regimen is often needed.

Adrenergic beta-Antagonists↗
PubMed1999

[Calcium antagonists in cardiovascular diseases--a valuable controversy, but unnecessary panic].

Taking into consideration the available data in 1998, we believe that short-acting calcium antagonists should no longer be used in hypertensive patients. The practice of using oral or sublingual nifedipine in hypertensive emergency or pseudoemergency should be abandoned because it can lead to serious side effects such as syncope, myocardial infarction, stroke and even death. However, the use of a low dose of the long-acting formulations seems to be safe and promising in patients with essential hypertension. In the Hypertension Optimal Treatment (HOT) trial a calcium-antagonist based combination therapy reduced blood pressure by over 20 mmHg in most of the nearly 19,000 patients. Cardiovascular mortality in this study was with 3.8 per 1000 patient years clearlylower as compared to 6.5 per 1000 patient years reported in previous intervention trials. A long-acting dihydropyridine calcium antagonist was used in 78% of these patients. Clearly the calcium antagonists controversy was helpful in alerting physicians to the fact that hypertension remains a surrogate endpoint and that not all drugs that reduce blood pressure will reduce morbidity and mortality to the same extent. What was completely unnecessary, however, was the inappropriate news media coverage to the calcium blocker controversy that led to panic and confusion among patients and frustration among physicians. In this context we should perhaps remember the first rule in the treatment of Sir George Pickering: "Never frighten your patients."

Calcium Channel Blockers↗
PubMed1998

The calcium antagonist controversy: a posthumous commentary.

In 1995, some retrospective reports showed that certain patients treated with short-acting calcium antagonists were at increased risk for myocardial infarction and had a higher mortality rate compared with patients treated with other cardiovascular drugs. Subsequent reports attempted to establish a connection between calcium antagonists and disorders as diverse as malignancy, Parkinsonism, cognitive dysfunction, and suicide. However, other retrospective studies and, more compelling, several prospective studies have reported that calcium antagonists exert a beneficial effect on morbidity and mortality in a variety of cardiovascular disorders such as hypertension, ischemic heart disease after myocardial infarction, and congestive heart failure due to dilated cardiomyopathy. Calcium antagonists are a heterogeneous drug class, and distinct differences have been documented between short- and long-acting, as well as between dihydropyridine and nondihydropyridine, agents. Sympathetic activation, which is a risk factor for coronary events, occurs with short-acting agents only and is absent with long-acting calcium antagonists. Recent data make it extremely unlikely that calcium antagonists increase the risk of malignancy by affecting apoptosis or immunosuppression or both. Long-acting calcium antagonists have distinct benefits in patients with hypertension and diabetes and may be more beneficial than other drugs in patients with diabetes and left ventricular hypertrophy.

Calcium Channel Blockers↗
PubMed1998

Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review.

OBJECTIVE: To assess antihypertensive efficacy of beta-blockers and their effects on cardiovascular morbidity and mortality and all-cause morbidity compared with diuretics in elderly patients with hypertension. DATA SOURCE: A MEDLINE search of English-language articles published between January 1966 and January 1998 using the terms hypertension (drug therapy) and elderly or aged or geriatric, and cerebrovascular or cardiovascular diseases, and morbidity or mortality. References from identified articles were also reviewed. DATA SELECTION: Randomized trials lasting at least 1 year, which used as first-line agents diuretics and/or beta-blockers, and reported morbidity and mortality outcomes in elderly patients with hypertension. DATA SYNTHESIS AND RESULTS: Ten trials involving a total of 16164 elderly patients (> or =60 years) were included. Two thirds of the patients assigned to diuretics were well controlled on monotherapy, whereas less than a third of the patients assigned to beta-blockers were well controlled on monotherapy. Diuretic therapy was superior to beta-blockade with regard to all end points and was effective in preventing cerebrovascular events (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.51-0.72), fatal stroke (OR, 0.67; 95% CI, 0.49-0.90), coronary heart disease (OR, 0.74; 95% CI, 0.64-0.85), cardiovascular mortality (OR, 0.75; 95% CI, 0.64-0.87), and all-cause mortality (OR, 0.86; 95% CI, 0.77-0.96). In contrast, beta-blocker therapy only reduced the odds for cerebrovascular events (OR, 0.75; 95% CI, 0.57-0.98) but was ineffective in preventing coronary heart disease, cardiovascular mortality, and all-cause mortality (ORs, 1.01, 0.98, and 1.05, respectively). CONCLUSIONS: In contrast to diuretics, which remain the standard first-line therapy, beta-blockers, until proven otherwise, should no longer be considered appropriate first-line therapy of uncomplicated hypertension in the elderly hypertensive patient.

Adrenergic beta-Antagonists↗
PubMed1998

Aging and essential hypertension: effect of left ventricular hypertrophy on cardiac function.

This study was designed to analyze the cardiac effects of aging and of hypertension in patients with essential hypertension and with or without left ventricular hypertrophy (LVH). Thirty-one patients <55 years old and 66 patients >64 years old with essential hypertension were divided according to the presence or absence of LVH. Cardiac functional structure was assessed by 2D-guided M-mode echocardiography. The peak filling rate and the duration of rapid filling were obtained by digitizing septal and posterior wall echoes. In the older group only was systolic function significantly impaired in subjects with LVH when compared with subjects without LVH [velocity of circumferential fiber shortening (L/msec): 1.40+/-0.24 v 1.18+/-0.25; fractional fiber shortening (%): 43.06+/-5.02 v 36.26+/-7.1; ejection fraction (%): 81.1+/-5.1 v 73.13+/-9.2; P < .05]. Older patients, even without LVH, showed a longer duration of rapid filling (321.0+/-108.3 msec) and lower peak filling rate (7.01+/-1.86 cm/sec) in comparison with younger persons with or without LVH. In the older subjects the increase in left ventricular mass was associated with a decrease of velocity of circumferential fiber shortening (r = -0.48, P < .01), fractional fiber shortening (r = -0.40, P < .01), and ejection fraction = -0.50, P < .01), whereas there was no correlation in the younger group. The present findings of impaired diastolic filling even in the absence of LVH in the elderly, and the deterioration of systolic function parallel to the increase in LV mass suggest that aging is associated with a decrease in the number of functioning contractile elements per unit of cardiac mass.

Adult↗