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Biomedical subjects

F H Messerli

Publications and source records attributed to F H Messerli.

At least 91 records · Page 5Linked to original sources
PubMed1997

Cardiac effects of combination therapy.

Control of hypertension and treatment of concomitant pathophysiologic conditions require use of multiple drugs. Unfortunately, most studies regarding hypertensive disease have focused on monotherapy. Thus, our knowledge of combination therapy in the treatment of hypertension is, to a great extent, extrapolation from monotherapy. Angiotensin converting enzyme (ACE) inhibitors in combination with calcium antagonists should be particularly efficacious in reducing left ventricular hypertrophy (LVH). Drug classes that either stimulate the renin-angiotensin system or the sympathetic nervous system are less likely to reduce LVH and should be avoided. In hypertensive patients with congestive heart failure, amlodipine should be added to triple therapy with an ACE inhibitor, whereas in the postmyocardial ischemia patient, verapamil may exert some additional beneficial effects with regard to reinfarction rates. Given that two drugs when used separately are beneficial in a disorder does not necessarily mean that their combination is equally or even more beneficial. Thus, combination therapy should primarily be used for lowering arterial pressure and only secondarily to possibly improve concomitant pathophysiologic conditions associated with hypertensive heart disease.

Antihypertensive Agents↗
PubMed1997

Combination therapy and target organ protection in hypertension and diabetes mellitus.

Both essential hypertension and diabetes mellitus affect the same major target organs-the brain, the fundi, the heart, and the kidneys. The common denominator of hypertensive/diabetic target organ disease is the vascular tree. Both hypertension and diabetes are well identified risk factors for atherogenesis. Coronary artery disease is much more common in diabetic hypertensive patients than in patients suffering from hypertension or diabetes alone. Typical for the diabetic hypertensive heart are extensive degenerative changes and a greater degree of hypertrophy compared with the nondiabetic hypertensive heart. The combined presence of hypertension and diabetes concomitantly affects glomerular filtration rate and renal blood flow, thereby greatly accelerating a decrease in renal function. Hypertension accelerates the development of diabetic retinopathy; hypertensive/diabetic cerebral disease leads to vascular dementia, transient ischemic attacks, and strokes. A decrease in the hemodynamic and glycemic burden is the primary goal in the management of the hypertensive diabetic patients. Both diuretics and beta-blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. In contrast, the postsynaptic alpha-blockers, the calcium antagonists, and the angiotensin-converting enzyme inhibitors have been reported to be either neutral or beneficial with regard to the overall metabolic risk factor profile. The combination of a heart rate lowering calcium antagonist, particularly verapamil, with an ACE inhibitor offers some potential to either prevent or reverse target organ disease associated with hypertension and diabetes.

Diabetes Complications↗
PubMed1997

Renal and systemic hemodynamics in black and white hypertensive patients.

Greater mortality and morbidity for cardiovascular events and renal complications have been reported in black than in white hypertensive patients. In this study we examined whether race per se affected markers of early target organ damage in a population of black and white hypertensive patients in whom casual as well as ambulatory blood pressure measurements were obtained. We assessed renal and systemic hemodynamics by measuring mean arterial pressure invasively, renal blood flow by 131I-para-aminohippuric acid clearance, and cardiac output by the indocyanine dye dilution technique. Left ventricular structure was determined by two-dimensional guided M-mode echocardiography. No significant differences in cardiac output, total peripheral resistance, renal blood flow, and renal vascular resistance were found between the two racial populations. Indices of myocardial structure were also comparable between black and white hypertensive patients. This was true regardless whether all patients were analyzed, or male patients only, or only those with elevated ambulatory blood pressure measurements. When defining arterial pressure by 24-h ambulatory monitoring, no differences in early target organ damage can be found between black and white patients with mild essential hypertension.

Adult↗
PubMed1997

Systemic and regional hemodynamic effects of gallopamil in patients with essential hypertension.

Systemic and regional hemodynamics were assessed in 10 patients with uncomplicated mild to moderate essential hypertension before and during gallopamil therapy. Cardiac output was measured in triplicate with indocyanine dye. Plasma volume and renal blood flow were measured radioisotopically. Immediately following the initial dose of a slow-release (SR) formulation of gallopamil, a significant fall in arterial pressure associated with a decreased total peripheral resistance and a reflex increase in heart rate and cardiac output were seen. Then, after 8-12 weeks of treatment, arterial pressure and total peripheral resistance remained reduced, but heart rate and cardiac output returned to pretreatment levels. Gallopamil also produced significant reductions in renal and splanchnic vascular resistance. Plasma volume and total blood volume did not change. Thus, gallopamil reduced arterial pressure and vascular resistances without fluid retention or prolonged reflexive changes.

Calcium Channel Blockers↗
PubMed1997

Effects of combination therapy on the heart.

The presence of left ventricular hypertrophy (LVH) usually indicates that hypertension is moderately severe and that combination therapy will be required to control blood pressure (BP). Unfortunately, most studies on the reduction of LVH have been done with monotherapy. Our knowledge of combination therapy in the treatment of hypertensive heart disease is to a great extent extrapolation from monotherapy. Angiotensin-converting enzyme (ACE) inhibitors in combination with calcium antagonists ought to be particularly efficacious in reducing LVH. Drug classes that either stimulate the renin angiotensin system or the sympathetic nervous system are less likely to reduce LVH and should be avoided. In hypertensive patients with congestive heart failure, amlodipine should be added to triple therapy with an ACE inhibitor, whereas in the post myocardial ischemia patient, verapamil may exert some additional beneficial effects with regard to reinfarction rates. Of note, given that two drugs when used separately are beneficial in a disorder does not necessarily mean that their combination is equally or even more beneficial. Thus, combination therapy should primarily be used for lowering arterial pressure and only secondarily to possibly improve concomitant pathophysiologic conditions associated with hypertensive heart disease.

Antihypertensive Agents↗
PubMed1997

Disparate effects of ACE-inhibitors and calcium antagonists on left ventricular structure and function in essential hypertension.

The present study was designed to compare the effects of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists-the two drug classes thought to be most effective in reducing left ventricular hypertrophy-on arterial pressure, left ventricular structure and function in patients with essential hypertension. After a placebo period of 4 weeks, a population of 96 patients were treated either with one of five different ACE inhibitors or one of six different calcium antagonists. Cardiac structure and function was assessed by 2D-guided M-mode echocardiography. Whereas both drug classes lowered arterial pressure to the same extent, ACE inhibitors had a more pronounced effect on posterior and septal wall thickness and left ventricular mass index than calcium antagonists. Diastolic function, as measured by peak filling rate and duration of rapid filling, improved in both treatment groups to the same extent. However, systolic performance, as assessed by midwall fractional fibre shortening, was significantly improved by ACE inhibitors only. Myocardial contractility (end-systolic wall stress/end-systolic volume index) showed no significant change in the ACE inhibitor group but decreased after treatment with calcium antagonists. We conclude that both calcium antagonists and ACE inhibitors lower arterial pressure and increase left ventricular filling to the same extent. However, compared with calcium antagonists, ACE inhibitors had a more pronounced effect on left ventricular mass and improved systolic ventricular performance in patients with essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Complementary actions and risk reduction: the rationale for combination of an angiotensin converting enzyme inhibitor with a non-dihydropyridine calcium antagonist.

REQUIREMENTS FOR DRUG REGISTRATION: Current drug registration procedures by the United States Food and Drug Administration (FDA) require at least two placebo-controlled factorial- and/or parallel-study designs. The statistical and graphical analysis of a factorial-design study allows the investigator to identify the optimal dose of the combination but these comparisons require considerable overall patient numbers for statistical power. In contrast, parallel-design studies require about 150 matched patients in each of the four arms. DRUG COMBINATIONS: In an effect to compare combination studies across antihypertensive drug classes, we examined data from studies that formed the basic of past registration applications to the FDA. Our review findings indicated that combined antihypertensive effects were, at best, approximately additive for a number of different combinations. However, this takes no account of the advantages of drug combinations in allowing reduced dosages of each drug with fewer adverse effects than monotherapy. CALCIUM ANTAGONISTS: In the case of calcium antagonists, physicians must differentiate between rapid-onset or short-acting dihydropyridines, which raise the heart rate and plasma noradrenaline, and longer-acting newer calcium antagonists. Recent evidence indicates that the combination of a long-acting calcium antagonist and an angiotensin converting enzyme inhibitor is particularly effective in reducing cardiovascular risk. CONCLUSIONS: Combining drugs with different mechanisms of action seems to be a reasonable and effective way of treating hypertension. It is essential, however, to establish the efficacy and safety of all new drug combinations by performing carefully designed clinical studies that fulfill the stringent FDA requirements.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Cyclosporine-induced hypertension: evidence for maintained baroreflex circulatory control.

BACKGROUND: The clinical use of cyclosporine as an immunosuppressive agent enhanced long-term survival in transplant recipients at the expense of a high incidence of induced hypertension. Altered neurovegetative (autonomic) cardiovascular control is suspected as a mechanism of this form of hypertension. METHODS: Spectral analysis of systolic arterial pressure and R-R interval variability (electrocardiographic recordings) were performed, and the index alpha of baroreflex gain was computed in four groups of subjects matched for age: 13 orthotopic heart transplant recipients; 13 solid organ transplant recipients; 13 patients with essential hypertension; and 18 control subjects with normal blood pressure. All but the control subjects were treated with similar dihydropyridine calcium entry blockers. Heart and solid organ transplant recipients also received cyclosporine. RESULTS: R-R variance was lowest in the heart transplant recipients. The spectral profile of R-R interval was suggestive of sympathetic predominance in the patients with hypertension, but not in the solid organ transplant recipients or the control subjects. Systolic blood pressure variability and low frequency component (a marker of sympathetic vasomotor modulation) were similar in the four groups. The index alpha was 1.8 +/- 2.2 in heart transplant recipients, 11.7 +/- 6.6 in solid organ transplant recipients, 7.3 +/- 3.6 in patients with hypertension, and 13.5 +/- 6.4 msec/mm Hg in control subjects (p = 0.0001). CONCLUSIONS: These data indicate that (1) cyclosporine-induced hypertension in heart transplant recipients is associated with a loss of baroreflex function as a result of cardiac denervation-related uncoupling; (2) compared with patients with hypertension, organ transplant recipients with hypertension demonstrated a maintained baroreflex function as indicated by a lack of reduction of the index alpha; (3) baroreflex heart rate control in dihydropyridine-treated cyclosporine-induced hypertension is well maintained.

Adult↗
PubMed1996

Safety of calcium antagonists: dissecting the evidence.

Based on reports about short-acting calcium antagonists, several recent publications have questioned the safety of agents in this class, particularly of nifedipine. However, these articles contain major limitations and pitfalls; one includes several errors. This does not imply that acute-release nifedipine is safe; in fact, it is well known that short-acting nifedipine can cause a precipitous and potentially dangerous fall in arterial pressure. Calcium antagonists differ from each other in clinically significant ways; therefore, conclusions about one type of calcium antagonist are not automatically applicable to others. Preliminary evidence supports the safety and efficacy of long-acting calcium antagonists.

Calcium Channel Blockers↗
PubMed1996

Angiotensin II receptor inhibition. A new therapeutic principle.

Angiotensin II receptor antagonists represent a new class of drugs that provide a site-specific blockade of the effects of angiotensin II. Losartan potassium, the first compound of this drug class, has recently become available in the United States. The clinical experience with angiotensin II receptor antagonists has demonstrated that these drugs are safe and efficacious for the treatment of hypertension and, possibly, congestive heart failure. Unlike with angiotensin-converting enzyme inhibitors, the incidence of cough observed with angiotensin receptor antagonists is similar to that with placebo. Although several angiotensin receptors have been characterized, the effects of losartan and other angiotensin receptor antagonists under development are selective for the angiotensin II type 1 receptor. Unlike angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists do not inhibit bradykinin metabolism or enhance prostaglandin synthesis. The antihypertensive efficacy of the angiotensin receptor antagonists has been documented to be similar to that of angiotensin-converting enzyme inhibitors. If the findings of clinical studies corroborate the initial reports on efficacy and safety, it seems likely that the angiotensin receptor antagonists will be added to the list of drugs that have been deemed suitable for first-line therapy in the treatment of hypertension and congestive heart failure.

Angiotensin II↗
PubMed1996

Diabetic and hypertensive heart disease.

OBJECTIVE: To review the literature on the cardiac effects of diabetes mellitus and hypertension. DATA SOURCES: A MEDLINE search of English-language articles published between 1980 and January 1996 was done using the terms diabetes mellitus, hypertension or blood pressure, and heart. References cited in identified articles were also reviewed. STUDY SELECTION: Selected studies were divided into those addressing coronary artery disease or myocardial ischemia and those addressing nonischemic cardiomyopathy and its sequelae. Preference was given to articles about the cardiac complications of both diabetes mellitus and hypertension. RESULTS: Patients with diabetes and hypertension have a higher incidence of coronary artery disease than do patients with diabetes or hypertension alone. The former patients also show impaired systolic and diastolic function and have more severe left ventricular hypertrophy as documented by echocardiography and at autopsy. The structural myocardial damage seen in these patients has been attributed primarily to hypertension; the myocellular dysfunction has been attributed primarily to diabetes. In diabetic hypertensive patients with cardiomyopathy, coronary artery disease as well as structural and functional cardiac abnormalities are more pronounced than would be expected from either diabetes or hypertension alone. CONCLUSIONS: Considerable evidence from both experimental animal models and humans points to hypertension as a critically important factor in the pathogenesis of severe heart disease in persons with diabetes. The pathogenetic sequelae of diabetes and hypertension are devastating to the heart and often lead to premature congestive heart failure, sudden cardiac death, and acute myocardial infarction. Strict control of arterial pressure and glycemia may prevent or even ameliorate heart disease in patients with hypertension and diabetes.

Animals↗