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Biomedical subjects

F H Messerli

Publications and source records attributed to F H Messerli.

At least 73 records · Page 4Linked to original sources
PubMed1998

The heart in the hypertensive elderly.

Left ventricular (LV) mass progressively increases throughout life, reaching its greatest magnitude in senescence. In the normotensive elderly, left ventricular hypertrophy (LVH) is mostly a consequence of a degenerative process in connective tissue. In hypertensive patients, LVH results from an increase in muscle mass and fibrotic tissue. LVH by echocardiographic criteria can be found in up to 50% of elderly patients with hypertension. Although associated with aging, LVH is associated with a higher rate of non-fatal and fatal cardiovascular events. Even in the absence of coronary stenosis, LVH is associated with reduced coronary reserve, increased number of arrhythmias and progressive deterioration in LV function. Conceivably, an increase in interstitial fibrosis and cross-linking collagen in the senescent heart is responsible for an increase in myocardial stiffness and diastolic abnormalities. Regression of LVH has been demonstrated not only to improve left ventricular filling and coronary reserve but also to diminish cardiac arrhythmias. Although few studies have demonstrated that the reduction of LV mass is associated with better cardiovascular prognosis, it seems reasonable to consider it a goal of antihypertensive therapy. Of all anti-hypertensive agents, angiotensin-converting-enzyme inhibitors seem to be the most powerful in reducing LV mass.

Age Distribution↗
PubMed1998

Comparative tolerability profile of hypertensive crisis treatments.

Hypertensive crisis is defined as a severe elevation in BP and is classified as either urgency or emergency. In hypertensive urgency there is no end-organ injury and no evidence that acute BP lowering is beneficial. Indeed, rapid uncontrolled pressure reduction may be harmful. Therefore, in hypertensive urgencies BP should be lowered gradually over 24 to 48 hours using oral antihypertensives. When the cause of transient BP elevations is easily identified, appropriate treatment should be given. When the cause is unknown, an oral antihypertensive should be given. The efficacy of available treatments appear similar; however, the underlying pathophysiological and clinical findings, mechanism of action and potential for adverse effects should guide choice. Captopril should be avoided in patients with bilateral renal artery stenosis or unilateral renal artery stenosis in patients with a solitary kidney. Nifedipine and other dihydropyridines increase heart rate whereas clonidine, beta-blockers and labetalol tend to decrease it. This is particularly important in patients with ischaemic heart disease. Labetalol and beta-blockers are contraindicated in patients with bronchospasm and bradycardia or heart blocks. Clonidine should be avoided if mental acuity is desired. In hypertensive emergency there is an immediate threat to the integrity of the cardiovascular system. BP should be immediately reduced to avoid further end organ damage. Sodium nitroprusside is the most popular agent. Nitroglycerin (glyceryl trinitrate) is preferred when there is acute coronary insufficiency. A beta-blocker may be added in some patients. Loop diuretics, nitroglycerin and sodium nitroprusside are effective in patients with concomitant pulmonary oedema. Enalaprilat is also theoretically helpful, especially when the renin system might be activated. Initial treatment of aortic dissection involves rapid, controlled titration of arterial pressure to normal levels using intravenous sodium nitroprusside and a beta-blocker. If beta-blockers are contraindicated, urapidil or trimetaphan camsilate are alternatives. Hydralazine is the drug of choice for patients with eclampsia. Labetalol, urapidil or calcium antagonists are possible alternatives if hydralazine fails or is contraindicated. For patients with catecholamine-induced crises, an alpha-blocker such as phentolamine should be given; labetalol or sodium nitroprusside with beta-blockers are alternatives. There are few, if any, comparative or randomised trials providing definitive conclusions about the efficacy and safety of comparative agents. Some investigators recommend decreasing the diastolic BP to no less than 100 to 110 mm Hg. A reasonable approach for most patients with hypertensive emergencies is to lower the mean arterial pressure by 25% over the initial 2 to 4 hours with the most specific antihypertensive regimen.

Acute Disease↗
PubMed1998

Fixed drug combinations in the treatment of hypertension: how to identify the optimal dose.

RATIONALE FOR DRUG COMBINATIONS: The most common reason for combining different drugs is to achieve an additional fall in arterial pressure. It therefore seems reasonable to combine drugs with different mechanisms of actions. NEED FOR CLINICAL TRIALS: However, the effects of combination therapy on the heart and other target organs remains poorly documented. Most of what we know with regard to combination therapy on hypertensive heart disease is based on extrapolation from monotherapy. The fact that two drugs when used separately are beneficial in a disorder does not necessarily imply that their combination is equally or more beneficial in the same disorder. Thus, it will become important to establish efficacy and safety of new drug combinations on hypertensive target organs and on morbidity and mortality by performing carefully designed clinical trials.

Antihypertensive Agents↗
PubMed1998

Effect of calcium antagonists on sympathetic activity.

OBJECTIVE: We evaluated the effects of calcium antagonists on sympathetic activity in hypertensive patients by searching Medline for English language articles published between 1975 and May 1996 using the terms calcium antagonists, sympathetic nervous system and catecholamines. METHODS: Data from clinical studies reporting only the effects of calcium antagonists on blood pressure, heart rate and plasma norepinephrine (NE) levels in patients with hypertension were analysed according to class of calcium antagonist (dihydropyridine vs non-dihydropyridine), their duration of action (short-acting (SA) vs long-acting (LA)) and treatment duration. RESULTS: We identified 63 studies involving 1252 patients. Acutely after single dosing, SA calcium antagonists decreased mean arterial pressure by 13.7 +/- 1.1% and increased heart rate by 13.7 +/- 1.4% and NE levels by 28.6% +/- 2.5%. Change in NE levels correlated with change in heart rate (r = 0.59, P < 0.01) and inversely with change in arterial pressure (r = 0.46, P < 0.05) in patients taking dihydropyridine calcium antagonists acutely. With sustained therapy, both classes of SA calcium antagonists increased NE levels. Whereas NE levels remained slightly elevated and heart rate unchanged with LA dihydropyridine calcium antagonists, both heart rate and NE levels decreased with LA non-dihydropyridine calcium antagonists. SA calcium antagonists stimulate sympathetic activity when given acutely and over the long term, irrespective of their molecular structure. In contrast, sympathetic activation is less pronounced with LA dihydropyridine calcium antagonists and falls with LA non-dihydropyridine calcium antagonists. CONCLUSIONS: The present findings offer a possible pathophysiological explanation for the increase in morbidity and mortablity observed in some studies using SA calcium antagonists.

Blood Pressure↗
PubMed1997

Effect of calcium antagonists on plasma norepinephrine levels, heart rate, and blood pressure.

To evaluate the effects of calcium antagonists on sympathetic activity in hypertensive patients, a MEDLINE search for English language articles published between 1975 and May 1996 using the terms calcium antagonists, sympathetic nervous system, and catecholamines was conducted. Clinical studies only reporting the effects of calcium antagonists on blood pressure, heart rate, and plasma norepinephrine (NE) levels in patients with hypertension were included. Data were combined and analyzed according to class of calcium antagonist (dihydropyridine vs nondihydropyridine), their duration of action (short-acting [SA] vs long-acting [LA]), and treatment duration. We identified 63 studies involving 1,252 patients. Acutely after single dosing, SA calcium antagonists decreased mean arterial pressure by 13.7 +/- 1.1% and increased heart rate by 13.7 +/- 1.4% and NE levels by 28.6 +/- 2.5%. Change in NE levels correlated with change in heart rate (r = 0.59, p <0.01) and inversely with change in arterial pressure (r = 0.46, p <0.05) in patients taking dihydropyridine calcium antagonists acutely. With sustained therapy, both classes of SA calcium antagonists increased NE levels. Whereas NE levels remained slightly elevated and heart rate unchanged with LA dihydropyridine calcium antagonists, both heart rate and NE levels decreased with LA nondihydropyridine calcium antagonists. SA calcium antagonists stimulate sympathetic activity when given acutely and over the long term, irrespective of their molecular structure. Sympathetic activation is less pronounced with LA dihydropyridine calcium antagonists and decreases with LA nondihydropyridine calcium antagonists. These data offer a possible pathophysiologic explanation for the increase in morbidity and mortality observed in some studies using SA calcium antagonists.

Adult↗
PubMed1997

Salt. A perpetrator of hypertensive target organ disease?

Experimental and clinical data suggest salt intake to be an important factor in the pathogenesis of essential hypertension. However, the relationship between dietary sodium and blood pressure has been found to be relatively weak, perhaps because causal blood pressure levels fluctuate considerably. We hypothesized that a closer correlation could be expected between salt intake and the degree of hypertensive target organ disease. We reviewed the literature for studies dealing with 24-hour urinary sodium excretion (as a measure of salt intake) and hypertensive target organ disease as assessed by left ventricular structure and function, microproteinuria, cerebrovascular disease, and arterial compliance. Salt intake as assessed by 24-hour urinary sodium excretion was found to be a close independent determinant of left ventricular mass in 9 different studies worldwide. A reduction in dietary sodium has been shown to reduce left ventricular hypertrophy. There is clinical and experimental evidence, particularly in salt-sensitive patients, that salt intake directly affects hypertensive renal disease, cerebrovascular disease, and compliance of large arteries. The close and partially independent correlation between salt intake and hypertensive target organ disease suggests dietary sodium to be a direct perpetrator of cardiovascular disease.

Cerebrovascular Disorders↗
PubMed1997

Comparison of early target organ damage between blacks and whites with mild systemic arterial hypertension.

As greater mortality and morbidity from target organ damage in arterial hypertension have been reported for black than for white hypertensives, we examined in a matched-pair analysis whether race per se affected markers of early target organ damage at similar levels of blood pressure. After controlling for the confounding factors such as age, sex, weight, and arterial pressure that interact with hypertension-related target organ damage, no racial disparities could be detected between matched black and white hypertensive patients.

Adult↗
PubMed1997

Cardiac effects of calcium antagonists in systemic hypertension.

The calcium antagonists are a class of heterogeneous drugs, with a wide spectrum of direct and indirect cardiac effects that vary a great deal from one drug to another and depend upon formulation and duration of action. Calcium antagonists act by decreasing total peripheral resistance to lower arterial pressure. As a consequence, reflex tachycardia, increased cardiac output, and increased plasma catecholamine and plasma renin activity are commonly seen, particularly with the initial dose and with short-acting dihydropyridines. The abrupt vasodilation can paradoxically elicit angina and even acute myocardial infarction. These hemodynamic and neuroendocrine changes are less pronounced with the long-acting formulations. Most calcium antagonists diminish automaticity of the sinus node, slow conduction in the atrioventricular node, and have little, if any, effect on the automaticity of the myocytes. The dihydropyridines generally have less effect on automaticity and cardiac conduction than nondihydropyridines. The negative inotropic effect is most profound with nondihydropyridines and is greatly reduced or absent with newer dihydropyridines, such as isradipine, felodipine, amlodipine, and nisoldipine. Long-acting calcium antagonists generally improve myocardial oxygenation by unloading the heart, increasing coronary blood flow, and reducing myocardial oxygen consumption. Thus, calcium antagonists have a variety of beneficial effects in patients with hypertensive heart disease: they reduce left ventricular hypertrophy and its sequelae, such as ventricular dysrhythmias, impaired filling and contractility, and myocardial ischemia. Ongoing studies should provide a more conclusive answer regarding the efficacy and safety of calcium antagonists.

Calcium Channel Blockers↗
PubMed1997

Nifedipine trials.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed1997

"Cardioprotection"--not all calcium antagonists are created equal: second round.

In contrast to short-acting dihydropyridine calcium antagonists, heart-rate lowering calcium antagonists have been shown to be beneficial in some patients for prevention of reinfarction. The study of Hansen et al in this present issue shows that the addition of verapamil to trandolapril reduces event rates by >60% in patients after myocardial infarction who are in congestive heart failure. These findings are provocative and should be corroborated in a perspective, randomized trial.

Calcium Channel Blockers↗
PubMed1997

Cardiovascular effects of a trandolapril/verapamil combination in patients with mild to moderate essential hypertension.

The cardiovascular effects of a combination of trandolapril and verapamil were evaluated in 14 patients with mild to moderate essential hypertension. This combination therapy decreased arterial pressure mainly through a decrease in total peripheral resistance without causing an increase in heart rate or cardiac output: left ventricular mass was significantly reduced, cardiac systolic function improved, and plasma volume and renal blood flow remained unchanged.

Aged↗
PubMed1997

Hypertension in special populations.

Essential hypertension is a common disorder, and a variety of antihypertensive drugs are available to lower blood pressure in the normal range. Identifying special subpopulations by differences in age, gender, race, and body weight has taught clinicians to be more selective in antihypertensive therapy. The rationale for this selectivity is often speculative and has not been corroborated by any hard data. It is hoped that some of the prospective, randomized trials currently in progress will throw some light on this question.

Aged↗