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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30

Calcium deposits account for most of the dry weight of atherosclerotic lesions. Previously considered uncommon, vascular calcification is now known to be present in 80% of significant lesions and in at least 90% of patients with coronary artery disease. Previously considered a passive process, it is increasingly recognized as an active, regulated process. Previously considered benign, it is now becoming recognized as a major risk factor for cardiovascular events, and a major contributor to systolic hypertension, heart failure, plaque rupture and stenosis. To confirm the similarity of vascular calcification with embryonic osteogenesis, we demonstrated the expression of bone morphogenetic protein in calcified human lesions, and we developed an in vitro model of vascular calcification that provides a useful experimental system for elucidating the molecular regulation of this process, which we have shown to include alkaline phosphatase induction and expression of bone matrix proteins and differentiation factors. Understanding the regulatory mechanisms of vascular calcification will allow future therapeutic approaches to prevent and possibly reverse this disease and its clinical consequences.
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PMID:Role of molecular regulation in vascular calcification. 922 60

Improvements in the identification and control of hypertension have helped define populations at risk for hypertension and delineated the role of hypertension as a risk factor in ischemic heart disease and heart failure. Epidemiologic data document the high prevalence of hypertension among the elderly and black populations. Beginning in the 1970s, a new perspective on the identification and treatment of hypertension began to emerge with greater emphasis on blood pressure control, particularly among these high-risk groups. By the early 1990s, most hypertensive individuals were being treated and blood pressure was under control in 55% of hypertensive persons overall. Although the importance of elevated diastolic pressure has traditionally been emphasized, in recent years the clinical implications of isolated systolic hypertension and the benefit of treating elevated systolic pressure have been recognized. Coronary heart disease is associated with definite hypertension (> or =160/95); however, the presence of other risk factors such as elevated plasma levels of cholesterol and high-density lipoprotein cholesterol, cigarette smoking, and diabetes mellitus create a synergy with even mild hypertension (140-159/90-94 mm Hg) to increase coronary risk. A different situation is present for cardiac failure. Data from the Framingham Heart Study demonstrate that hypertension, myocardial infarction, angina pectoris, diabetes mellitus, left ventricular hypertrophy, and valvular heart disease were associated with an increased relative risk for cardiac failure. The relative risk for cardiac failure was greatest for persons with a previous myocardial infarction, and hypertension and previously diagnosed coronary heart disease were important precursors of cardiac failure.
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PMID:An epidemiologic perspective of systemic hypertension, ischemic heart disease, and heart failure. 937 42

Two problems in the treatment of hypertension continue to be largely unsolved. The first, and more simple, is our inability to adequately control blood pressure in the majority of hypertensive patients. This not only reflects the difficulty of retaining patients in effective treatment programs, but also of convincing physicians to strive for optimal blood pressure levels. There is a continuing need for new antihypertensive drugs and combinations to help accomplish these goals. The second major problem is that the major clinical endpoints, including coronary events and renal failure, have not been adequately reduced by traditional therapies. Standard regimens, particularly those including diuretics, have protected against strokes and heart failure. Our improved understanding of vascular biology in hypertension has directed interest to the mechanisms in hypertensive patients that might accelerate atherosclerosis and vascular events in these individuals. This involves addressing the concomitant metabolic risk factors that comprise the "Hypertension Syndrome," and, perhaps of equal importance, finding therapies that directly inhibit unwanted types of growth and proliferative activities within the walls of critical arteries. Many substances within the endothelium and the vascular wall may participate as initiators or mediators of pathology, but most information thus far has focused on the renin-angiotensin system. Angiotensin converting enzyme inhibitors (and potentially angiotensin receptor blockers) have provided coronary and renal protection in various cardiovascular conditions, though not yet in formal hypertension trials. Calcium channel blockers have also shown promise, including recent stroke and cardiovascular benefits in patients with isolated systolic hypertension, but, again, definitive coronary data in hypertension are awaited. Unless concomitant conditions mandate the selection of a particular antihypertensive drug class, physicians currently have a dilemma: should they choose drugs from older classes that have not provided full protection? Or, should they prescribe newer agents with exciting potential but with, as yet, unproved endpoint benefits in hypertension? Until currently ongoing prospective trials of antihypertensive therapy are completed, physicians must be guided by their own interpretations of the available data.
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PMID:Translating data on antihypertensive drugs into clinical practice. 965 68

Hypertension is an important risk factor for cardiovascular disease (CVD) in patients with normal renal function. After reviewing over two decades of clinical trial data and an even longer history of epidemiologic data, multiple consensus panels worldwide have made recommendations for the aggressive treatment of hypertension using both lifestyle modification and drug therapy. These data and recommendations provide the basis of the recommendations for preventing CVD in patients with renal disease. Most patients should have elevated blood pressure (BP) lowered to less than 140 mm Hg systolic and less than 90 mm Hg diastolic. Earlier and more aggressive intervention is recommended in high-risk hypertensive patients with risk factors (especially diabetes mellitus) or evidence of target organ damage or clinical CVD. Lifestyle changes are indicated as either initial therapy or concomitant therapy in all hypertensive patients to lower BP and to normalize other CVD risk factors. There is general agreement that clinical outcome data from controlled clinical trials should guide the selection of antihypertensive agents. Currently, these data are only available for thiazide diuretics and beta-blockers for most hypertensive patients with normal renal function and for the dihydropyridine calcium channel blockers in older hypertensive patients with isolated systolic hypertension. However, data may support the use of other agents in hypertensives with selected comorbidity (eg, ACE inhibitors in heart failure, beta-blockers after myocardial infarction, and so forth). However, with only 25% of hypertensive patients controlled to less than 140/90 mm Hg, achieving blood pressure control remains the most important goal in managing hypertension in this population.
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PMID:Prevention of cardiovascular disease in hypertensive patients with normal renal function. 982 Apr 66

Hypertension is a major modifiable risk factor for cardiovascular diseases. After decades of improvement, population surveys demonstrate disturbing downward trends in the rates of awareness, treatment, and control of this disorder in recent years. Over this same time period, there has been a slight increase in the incidence of strokes, and a steady rise in the incidence of end-stage renal disease and the prevalence of congestive heart failure, conditions in which hypertension plays a prominent role. Results of recent studies support the possibility that lifestyle modifications may be effective for prevention of hypertension. Treatment of established hypertension involves lifestyle modifications and drug therapies designed to control blood pressure and reduce overall cardiovascular risk. Both threshold blood pressure levels for initiating drug therapy and goal blood pressure levels with treatment are individually determined based on the presence or absence of additional cardiovascular risk factors and hypertension target organ injury or clinical cardiovascular disease. Recent clinical trials support the value of lower goal blood pressures for patients with diabetes, heart failure, and renal disease. The presence or absence of comorbid conditions often determines specific drug choices. Diuretics and beta-blockers remain the drugs of choice in uncomplicated hypertension. Additional studies confirm the benefits of treating isolated systolic hypertension in the elderly. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provides a practical, evidence-based resource to help health care providers meet the public health challenges of preventing and controlling hypertension.
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PMID:A review of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 1019 76

Calcium antagonists continue to have a place in the treatment of hypertension, despite recent concerns regarding their safety and long-term capacity to alter the natural history of cardiovascular disease. Results of a well-designed cohort study concerning a very elderly population suggested that administration of shorft-acting nifedipine is linked to an increase in mortality, particularly when a high dose is administered and when the initiaol blood pressure is below 160/90 mmHg. The risk of using short-acting verapamil, however, was no greater than that of beta-blockade. These differences can be attributed at least in part to the low catecholamine profile of verapamil and to the marked rapid adrenergic activation with short-acting nifedipine. Current evidence sujggests that less catecholamine activation occurs during the chronic use of long-acting dihydropyridine agents. Two recent studies have shown that the combination of verapamil and an angiotensin converting enzyme inhibitor reduces numbers of cardiovascular disease events among postinfarct patients with heart failure, and that the dihydropyridine nitrendipine reduces poor outcome measures, such as stroke incidence, in treating systolic hypertension in the elderly. In my view, apparent hazards such as the precipitation of myocardial infarction and cancer are discounted by the available evidence. While we await further major trials concerning outcomes, general safety can be related to a preference for administering those long-acting agents that do not stimulate and may even inhibit adrenergic responses, and the avoidance of possible adverse effects through the use of combination therapies, such as verapamil plus an angiotensin converting enzyme inhibitor or nifedipine plus a beta-blocker.
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PMID:Ongoing clinical outcome studies of calcium antagonists. 1021 33

The pumping function of the left ventricle depends both on its ability to empty and its capacity to fill at a low pressure. Diastolic dysfunction occurs when filling of the left ventricle necessary to produce an adequate cardiac output requires an elevated pulmonary venous pressure. Diastolic dysfunction can be secondary to systolic dysfunction or occur with normal systolic function (primary diastolic dysfunction). Primary diastolic dysfunction most commonly results from systolic hypertension, left ventricular hypertrophy, and aging. Primary diastolic dysfunction is an important cause of heart failure, especially in elderly patients. Diastolic dysfunction can be recognized from the pattern of mitral valve flow velocity measured by Doppler echocardiography. Strategies to improve diastolic function include: control of systolic blood pressure, preservation of sinus rhythm, and avoidance of tachycardia.
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PMID:Diastolic Dysfunction. 1034 45

Systolic hypertension is a major risk factor for cardiovascular disease. The determinants of systolic blood pressure are peripheral resistance and arterial compliance. Arterial vasoconstriction, vascular growth and fluid retention, induced by the renin-angiotensin system directly or indirectly by enhancing sympathetic nervous system activity, are important factors in increasing peripheral resistance, decreasing arterial compliance and, consequently, elevating systolic blood pressure. Selective blockade of the angiotensin II type 1 (AT1) receptor represents a novel mechanism for interrupting the renin-angiotensin system. This provides the additional benefit of blocking angiotensin II generated by non-angiotensin-converting-enzyme pathways without altering either bradykinin metabolism or the potential beneficial effects of AT2 receptor stimulation. Eprosartan is a potent (1.4 nmol/l) AT1 receptor antagonist that inhibits angiotensin-II-induced vascular contraction in a competitive manner. Eprosartan is effective in reducing disease progression in animal models of hypertension, heart failure, renal disease and stroke. Furthermore, eprosartan causes a large increase in arterial compliance in hypertensive rats fed high-salt and high-fat diets. Eprosartan also possesses sympathoinhibitory activity as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, other angiotensin II receptor antagonists, such as losartan, used at equivalent angiotensin II blocking activity, do not appear to alter sympathetic nervous system activity. Angiotensin II receptor antagonists, such as eprosartan, that have the ability to block both the direct effects of angiotensin II and the indirect effects mediated by enhanced sympathetic neurotransmission, may represent an important advance in the treatment of elevated systolic blood pressure.
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PMID:Pharmacological mechanism of angiotensin II receptor antagonists: implications for the treatment of elevated systolic blood pressure. 1046 64

Arterial (and predominantly aortic) stiffening with age is now acknowledged as the cause of isolated systolic hypertension, and the predominant cause of cardiac failure in the elderly. Aortic stiffening is gauged clinically from increase in brachial pulse pressure, but this underestimates change with age, since aortic pulse pressure increases far more than brachial (on account of substantial amplification of the peripheral arterial pressure pulse in young adults). Aortic stiffness can be measured as pulse wave velocity, but this too underestimates ill effects on the heart and central vessels, since the direct effect is amplified by early return of wave reflection. Ill effects of arterial stiffening can best be assessed through analysis of pressure wave contour from the carotid or radial site. Exploitation of relatively constant brachial transfer function enables the central aortic pressure wave to be synthesised from the radial pulse. This new clinical approach links traditional sphygmography (originally introduced in France) with conventional cuff sphygmomanometry, and is being evaluated in clinical and epidemiological studies.
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PMID:Mechanical principles. Arterial stiffness and wave reflection. 1047 73


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