"Cardioprotection"--not all calcium antagonists are created equal.
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Calcium Channel Blockers↗
Biomedical subjects
F H Messerli
Publications and source records attributed to F H Messerli.
Left ventricular hypertrophy. A crucial target for antihypertensive therapy.
The development of left ventricular hypertrophy (LVH) is one way that the heart compensates for the hemodynamic burden of sustained hypertension. However, this adaptation itself contributes to increased cardiovascular morbidity and mortality. In this article, Dr Messerli describes the causes and consequences of LVH and discusses the current therapeutic approach to patients with the condition.
Antihypertensive Agents↗
Antihypertensive therapy--going to the heart of the matter.
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Adrenergic beta-Antagonists↗
Antihypertensive therapy. Is it different in the elderly?
Pathophysiological mechanisms of pressure elevation are different in the elderly hypertensive patient than in middle-aged or young patients. The elderly patient is characterised by a decrease in cardiac output, renal blood flow, and intravascular volume and an increase in total peripheral resistance and vascular resistance. Elderly patients also, quite often, have target organ disease such as left ventricular hypertrophy and nephrosclerosis. Because of impaired baroreflexes and latent or overt cerebrovascular disease, the elderly patient is particularly susceptible to abrupt falls in arterial pressure. Clearly, these physiological findings have to be taken into account when prescribing antihypertensive therapy. Calcium channel blockers and converting enzyme inhibitors seem to be particularly useful in the geriatric population. A close match between the underlying pathophysiology of pressure elevation in a given patient and the pharmacological effects of a selected antihypertensive drug will provide more rational and convenient control of arterial pressure in our senior citizens.
Age Factors↗
Reversal of left ventricular hypertrophy: a desirable therapeutic goal?
It is controversial whether myocardial hypertrophy in essential hypertension represents an adaptive physiologic or pathological response to increased pressure load imposed on the heart. Cardiac structural adaptations in endurance athletes fulfill the criteria of physiologic hypertrophy: maintained cardiac performance and full reversibility of cardiac structural changes following cessation of endurance training. In contrast, there is some evidence that cardiac hypertrophy in arterial hypertension is a pathological process. Diastolic function of the left ventricle is impaired; systolic function, although maintained in the early stages of myocardial hypertrophy, becomes reduced beyond a critical mass; and cardiac structural changes are not fully reversible. An increasing number of prospective studies document that left ventricular hypertrophy in essential hypertension represents an independent risk factor for cardiovascular mortality and morbidity, in particular for sudden cardiac death. Ventricular arrhythmias were regarded as the pathophysiologic link between cardiac structural adaptation and the increased risk of sudden death due to left ventricular hypertrophy. Structural changes of the coronary circulation may represent one confounding factor in the relationship between left ventricular hypertrophy and its cardiovascular risk. As a consequence, optimal antihypertensive therapy should aim at reducing both arterial hypertension and left ventricular hypertrophy. Whether regression of myocardial hypertrophy indeed reduces cardiovascular risk cannot be definitively answered from the available data.
Cardiomegaly↗
Considerations in treating hypertension: focus on risk factors.
Left ventricular hypertrophy (LVH) in essential hypertension has been identified as a major and pressure independent risk factor for the occurrence of sudden death and other cardiovascular morbidity and mortality. Previous studies by our group have shown that patients with LVH exhibit more frequent and more severe ventricular ectopy than patients without LVH or normotensive subjects. These ventricular dysrhythmias are independent of the morphological form of LVH and occur in patients with normal coronary arteries. Most recent data from our laboratory documents that some calcium antagonists reduce LVH and, in parallel, suppress ventricular dysrhythmias. In contrast, antihypertensive therapy with a thiazide diuretic had no effect on ventricular dysrhythmias or LVH, despite the fact that blood pressure was lowered to the same extent as with the calcium channel blockers. What remains to be determined is whether or not the ominous prognosis of patients with LVH will be improved by specific antihypertensive therapy, that over and above lowering pressure, also improves hypertensive target organ disease, such as LVH and associated ventricular dysrhythmias.
Antihypertensive Agents↗
Left ventricular hypertrophy, arterial hypertension and sudden death.
Left ventricular hypertrophy has been identified as a powerful risk factor for sudden death and for general cardiovascular morbidity and mortality. Left ventricular hypertrophy has been documented as giving rise to ventricular ectopy, even in the absence of myocardial ischemia. Mechanisms of ectopic impulse generation in left ventricular hypertrophy are multifactorial and involve enlarged myocytes, focal areas of fibrosis, and subendocardial ischemia, as well as medial hypertrophy of the coronary arteries impeding homogeneous impulse propagation throughout the myocardium. Left ventricular hypertrophy can be reduced by specific antihypertensive therapy although not all antihypertensive agents are equally effective. A reduction of left ventricular hypertrophy with calcium antagonists, and possibly also with beta-blockers, has been shown to diminish ventricular arrhythmias. Whether or not such a reduction of left ventricular hypertrophy and suppression of ventricular ectopy will improve their unfavorable prognosis remains to be determined.
Antihypertensive Agents↗
Antihypertensive therapy in the elderly.
Recent studies have documented that arterial hypertension increases cardiovascular morbidity and mortality even in the geriatric population. Some elderly hypertensive patients, like younger patients, can benefit from antihypertensive therapy. Antihypertensive therapy should be carefully adjusted to suit the cardiovascular pathophysiology of elderly patients.
Age Factors↗
Disparate hemodynamic and sympathoadrenergic responses to isometric and mental stress in essential hypertension.
The hemodynamic and sympathoadrenergic responses during isometric handgrip and mental arithmetic tests were compared in 18 patients with mild essential hypertension. Mean blood pressure increased significantly after both maneuvers (27% during isometric stress and 10.7% during mental stress), but the increase was significantly higher during isometric stress (p less than 0.001). Both stressors increased the heart rate (p less than 0.001) and cardiac output (p less than 0.001). However, the total peripheral resistance behaved differently, for it increased during isometric stress (p less than 0.05) and remained unchanged during mental stress. Both stressors increased the epinephrine levels (p less than 0.005), but only isometric stress increased the norepinephrine levels (p less than 0.001). It is concluded that both stressors increase cardiac output by way of an increase in heart rate, but isometric stress also increases total peripheral resistance and thus causes a greater increase in arterial pressure. Isometric stress activates both the adrenergic and noradrenergic systems, thereby accounting for the exaggerated response in arterial pressure, whereas mental stress stimulates the adrenergic system only.
Adolescent↗
Hemodynamic and humoral effects of intravenous dilevalol in patients with moderate hypertension.
The acute hemodynamic and humoral responses to intravenous dilevalol (10 to 390 mg) were evaluated in 10 patients with moderate hypertension. Dilevalol, in doses of 30 mg or more, decreased arterial pressure (p less than 0.0001) through a decrease in total peripheral resistance (p less than 0.0001) associated with an increase in stroke volume and cardiac output (p less than 0.0001). Heart rate increased moderately at doses above 190 mg. Plasma norepinephrine levels increased (p less than 0.05), but epinephrine levels remained unchanged. Plasma renin activity and level of atrial natriuretic peptide decreased (p less than 0.01 and p less than 0.01, respectively). The hypotensive and humoral changes persisted 3 hours after the last dose. Dilevalol modified the pattern of hemodynamic response to isometric stress, slightly enhancing the increases in peripheral resistance and blunting increases in cardiac output and heart rate. The response in arterial pressure during administration of dilevalol remained similar to that seen in the pretreatment phase. The results show that dilevalol, when given intravenously in a dose of 30 to 90 mg, reduces arterial pressure by reducing total peripheral resistance without acceleration in heart rate. On the basis of these hemodynamic effects, dilevalol should be further evaluated for treatment of hypertensive emergencies.
Adult↗
Hypertension and sudden death. Disparate effects of calcium entry blocker and diuretic therapy on cardiac dysrhythmias.
This study was designed to evaluate the impact of antihypertensive therapy on cardiac dysrhythmias in 13 hypertensive patients who received calcium entry blockers and in 10 hypertensive patients who received hydrochlorothiazide. Mean arterial pressure fell to a similar extent in both treatment groups; however, left ventricular mass index decreased (from 102 +/- 4 to 95 +/- 2 g/m2) only in patients receiving calcium entry blockers, but not in those taking hydrochlorothiazide. The prevalence of premature ventricular contractions decreased 74% from 21 +/- 14/h to 5.7 +/- 6/h in the calcium entry blocker group, but did not change in the hydrochlorothiazide group (15 +/- 17/h to 16 +/- 13/h). Couplets, multiform contractions, ventricular tachycardia, and supraventricular tachycardia were completely abolished after calcium entry blocker therapy, whereas the prevalence of these arrhythmias remained unchanged during treatment with hydrochlorothiazide. We conclude that antihypertensive therapy with calcium entry blockers (but not with thiazide diuretics) reduces left ventricular mass and the prevalence and severity of ventricular dysrhythmias. Whether this reduction will improve the ominous prognosis of left ventricular hypertrophy and diminish the risk of sudden death remains unknown.
Adult↗
Cardiac performance after reduction of myocardial hypertrophy.
PURPOSE: The current study was performed to assess the functional sequelae of reducing left ventricular hypertrophy in patients with essential hypertension. PATIENTS AND METHODS: To analyze left ventricular function and contractility in patients with essential hypertension after reduction of left ventricular hypertrophy, 14 patients with essential hypertension and left ventricular hypertrophy were studied prospectively by echocardiogram (1) before, (2) during, and (3) after left ventricular mass had been reduced by antihypertensive therapy of 19 +/- 3 months' duration. All drugs were discontinued four weeks before the first and the third study. RESULTS: At the time of the third study, arterial pressure had returned to pretreatment values, and mean, peak, and isovolumetric (but not end-systolic) wall stress increased, whereas left ventricular mass remained diminished. Despite the increased pressure load to the heart, myocardial contractility was maintained or improved after reduction of left ventricular hypertrophy, as indicated by the ratio of end-systolic wall stress to end-systolic volume index (p less than 0.02) and by the relation of fractional shortening to end-systolic wall stress (p less than 0.06). End-diastolic volume, an indicator of preload, remained reduced after therapy (p less than 0.05). As a result, pump function of the left ventricle improved as shown by an increase in the ejection fraction (p less than 0.05), fractional fiber shortening (p less than 0.05), and velocity of circumferential fiber shortening (p less than 0.01). CONCLUSION: Thus, in patients with essential hypertension, reduction of myocardial hypertrophy by antihypertensive therapy appears to be beneficial rather than detrimental to cardiac pump performance.
Adult↗
Sex differences in cardiac adaptation to essential hypertension.
Left ventricular functional and structural adaptations to mild essential hypertension were assessed by 2D-guided M-mode echocardiography in a population of premenopausal and postmenopausal women (n = 29) who were matched with the same number of men with regard to mean arterial pressure, age and race. Premenopausal women had a thinner posterial wall (P less than 0.05), a smaller left ventricular systolic and diastolic diameter, and a smaller left ventricular mass than men with the same level of arterial pressure. Left ventricular performance indices, ejection fraction, velocity of circumferential fibre shortening, and the ratio of the end-systolic wall stress to the end-systolic volume index (a load-insensitive contractility index) were higher in women than in men. These sex differences were most pronounced before the menopause and tended to disappear thereafter. We conclude that in the presence of the same level of arterial pressure, women have smaller left ventricular dimensions and enhanced ventricular performance compared with men. These differences in cardiac adaptations between the genders may account for the lower risk of cardiovascular morbidity and mortality in premenopausal women with essential hypertension.
Adaptation, Physiological↗
Effects of antihypertensive therapy on hypertensive heart disease.
Left ventricular hypertrophy (LVH) is a common sequela of long-standing essential hypertension. LVH cannot be considered, however, an adaptive process only serving to normalize wall stress but can be considered one that significantly increases the risk of sudden death, myocardial ischemia, congestive heart failure, and other cardiovascular diseases. Patients with LVH exhibit impaired ventricular filling, ventricular arrhythmias, and myocardial ischemia even in the absence of coronary artery disease. LVH can be prevented or reversed by a variety of antihypertensive agents including calcium channel blockers and angiotensin converting enzyme inhibitors. Calcium channel blockers, more than angiotensin converting enzyme (ACE) inhibitors, suppress ectopic impulse generation, improve ventricular compliance, and alleviate myocardial ischemia while preserving or improving the contractile state. In contrast, ACE inhibitors can be particularly useful in patients with LVH and diminished ventricular contractility and in preventing chamber dilatation after myocardial infarct. These favorable cardiovascular effects of both calcium channel blockers and ACE inhibitors are a reason for optimism that carefully tailored therapy will ultimately diminish the well-documented risk of cardiovascular morbidity and mortality associated with LVH.
Angiotensin-Converting Enzyme Inhibitors↗
Lisinopril in the treatment of hypertension.
Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin-Converting Enzyme Inhibitors↗
Management of essential hypertension in the black patient: profiling as the initial approach to treatment.
The pathophysiology and course of hypertensive cardiovascular disease in the black population differ significantly from those of nonblacks. The hemodynamic and endocrine profiles are different, consequences of hypertension are more severe in blacks, and black patients are often less responsive to standard antihypertensive treatment. Safe and efficacious treatment can be achieved when drug therapy is directed at the specific underlying pathophysiologic abnormality in black patients. By closely matching cardiovascular pathophysiologic findings in a given patient with the pharmacologic effects of an antihypertensive agent, blood pressure can often be controlled with fewer adverse effects. In addition, blood flow to target organs and their function can be maintained or improved. Calcium channel blockers are especially well suited for the treatment of essential hypertension in black patients.
Adolescent↗
Hemodynamic, humoral and volume findings in systemic hypertension with isolated ventricular septal hypertrophy.
To analyze the hemodynamic, endocrine and volume characteristics of isolated septal hypertrophy (ISH) in established systemic hypertension, 22 patients with ISH were compared to 23 patients with symmetric hypertrophy and to 28 without left ventricular (LV) hypertrophy. Mean arterial pressure and 24-hour ambulatory pressure readings did not differ between the 2 groups. At the same level of arterial pressure, patients with ISH had a high cardiac index (p less than 0.02) and a faster heart rate (p less than 0.05); consequently, total peripheral resistance was decreased (p less than 0.05). Although there was no change in intravascular volume, central blood volume was expanded (p less than 0.02), and the ratio of central to peripheral blood volume was increased (p less than 0.02), thereby indicating peripheral venoconstriction. Patients with isolated ISH had greater responses of diastolic pressure and heart rate (p less than 0.05) to isometric stress than the other 2 groups. A hyperdynamic circulatory state is a hemodynamic hallmark of ISH in early essential hypertension that might be produced by increased sympathetic activity.
Adult↗
Immediate and short-term cardiovascular effects of a new converting enzyme inhibitor (lisinopril) in essential hypertension.
The immediate and short-term effects of lisinopril, a new converting enzyme inhibitor, on systemic and regional hemodynamics, cardiac structure and function and humoral indexes were evaluated in 10 patients with mild to moderate essential hypertension. A single oral dose of 5 mg lisinopril reduced mean arterial pressure from 118 to 104 mm Hg (p less than 0.01) and significantly increased (p less than 0.05) all load-dependent indexes of ventricular function (i.e., ejection fraction, velocity of circumferential fiber shortening and fractional fiber shortening rate). After 10 to 12 weeks of once-daily administration of lisinopril, mean arterial pressure remained reduced over a full 24-hour period (p less than 0.01), and was mediated through arteriolar dilation as expressed by the close correlation (r = 0.93, p less than 0.01) between changes in mean arterial pressure and changes in total peripheral resistance. Cardiac index decreased from 3.06 to 2.68 liters/min/m2 (p less than 0.01) without correlation to the decrease in arterial pressure (r = 0.06). Despite this reduction in cardiac index, renal blood flow increased from 861 to 1,053 ml/min (p less than 0.05) and renal vascular resistance decreased from 14 to 9 units (p less than 0.01). Left ventricular mass index decreased from 124 to 109 g/m2 (p less than 0.05), and left ventricular function remained unchanged. Thus, the decrease in arterial pressure produced by lisinopril was associated with improved renal hemodynamics and reduced left ventricular mass.
Adult↗