Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EFFICACY OF CALCIUM ANTAGONISTS: Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertensive therapy, with substantial blood pressure reduction in all age groups and races. CCBs improve endothelial function, may positively influence atherosclerosis in carotid arteries, reduce left ventricular hypertrophy, and hypertrophy of the resistance vessels, and improve arterial compliance. They do not adversely affect lipids and serum glucose. USE IN PRACTICE: CCBs are also a heterogenous class of drugs composed of the phenylalkylamine verapamil, the benzothiazepine diltiazem, and the large group of dihydropyridines (DHPs) with the prototype nifedipine, and an increasing number of newer agents (e. g. nitrendipine, nisoldipine, amlodipine, felodipine, lacidipine and lercanidipine). DHPs are primarily vasodilators, lowering blood pressure by decreasing peripheral vascular resistance at the level of the small arterioles which can be followed by an autonomic counterregulation especially in drugs with a rapid onset of action. This is markedly reduced or abolished in the treatment with the modern long acting DHPs and is also not the case in the treatment with non-DHPs. Prospective randomized controlled outcome studies demonstrated a significant reduction in stroke in elderly patients with isolated systolic hypertension compared with placebo (Syst-Eur [Syst-China]), and no significant differences in cardiovascular mortality and combined morbidity compared with diuretics, beta blockers or ACE-Inhibitors (STOP-2, INSIGHT, NORDIL, ALLHAT, INVEST). To normalize the blood pressure it is mostly necessary to combine antihypertensive drugs. Here are CCBs ideal partners for a therapy with ACE-inhibitors, AT1 antagonists or beta blockers (DHP) and diuretics (verapamil). With respect to the antihypertensive differential therapy the author recommends CCBs based on studies with the evidence grade 1-3; especially for elderly hypertensives (with isolated systolic neuhypertension and a high risk of stroke), for patients with COPD and asthma bronchiale, Raynaud's syndrome or Prinzmetal-angina, patients with diastolic function disturbances including diastolic heart failure or hypertensives with massive left ventricular hypertrophy (in combination with ACE or AT1 inhibitors).
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PMID:[Differential therapy with calcium antagonists]. 1468 11

Hypertension commonly leads to heart disease, in particular left ventricular hypertrophy, heart failure and coronary artery disease. Left ventricular hypertrophy and coronary artery disease are both often subclinical diseases in hypertensives. Symptomatic coronary artery disease in hypertension may be due to atherosclerosis in epicardial arteries, microvascular dysfunction, reduced fibrinolytic capacity, or left ventricular hypertrophy; the latter is present in 20-50% of patients with mild to moderate and in up to 90% of patients with severe hypertension. Left ventricular hypertrophy in hypertension is associated with a twofold increase in risk of myocardial infarction, sudden death and stroke, and a fourfold increase in risk of heart failure. While coronary artery disease is the most common cause of heart failure in men, hypertension and in particular untreated isolated systolic hypertension is the most common cause in women. Heart failure symptoms may be subtle in hypertension, like tiredness or reduced physical capacity. Echocardiography can reveal subclinical heart disease as well as serve as a guide to correct diagnosis and treatment.
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PMID:[Hypertension and heart disease]. 1503 15

Advanced glycation end products (AGEs) form by a nonenzymatic reaction between reducing sugars and biological proteins. These stable compounds accumulate slowly throughout the life span and contribute to structural and physiologic changes in the cardiovascular system such as increased vascular and myocardial stiffness, endothelial dysfunction, altered vascular injury responses, and atherosclerotic plaque formation. Mechanisms underlying these alterations include AGE cross-linking of collagen and AGE interactions with circulating proteins and AGE receptors. The clinical manifestations of AGE accrual-isolated systolic hypertension, endothelial and diastolic dysfunction, and atherosclerosis-underscore their role in increased cardiovascular risk associated with aging as well as diabetes and hypertension, conditions that enhance AGE formation. New pharmacologic agents that prevent AGE, break cross-links, or block AGE receptors reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque formation, and improve endothelial function. These agents promise to reduce the risk of isolated systolic hypertension, diastolic dysfunction, and diabetes, and thus, heart failure.
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PMID:Advanced glycation end product cross-linking: pathophysiologic role and therapeutic target in cardiovascular disease. 1518 29

The development of myocardial and large vessel stiffness with aging underlies the development of diastolic heart failure and isolated systolic hypertension. Nonenzymatic reaction between glucose and proteins (Maillard reaction) leading to collagen crosslinking in the myocardium and arterial wall has been implicated in age-related increase in cardiovascular stiffness. In the present issue, Chang et al. show that aminoguanidine, an inhibitor of protein crosslinking, retards age-related decline in the elastic properties of the left ventricle and arteries. The significance of these findings is discussed in this commentary.
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PMID:Pharmacological prevention of cardiovascular aging--targeting the Maillard reaction. 1524 27

Isolated systolic hypertension is the predominant type of hypertension in the elderly and is associated with cardiovascular complications such as stroke, coronary heart disease and heart failure. In this review, the role of arterial stiffness, endothelial function, atherosclerosis and oxidative stress in the pathogenesis of isolated systolic hypertension is extensively discussed. Placebo-controlled intervention trials such as the Systolic Hypertension in Europe Trial and the Systolic Hypertension in the Elderly Program have clearly shown that pharmacological treatment of isolated systolic hypertension improves outcome in the elderly. Nevertheless, isolated systolic hypertension remains the major subtype of untreated and uncontrolled hypertension.
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PMID:Prevalence, pathophysiology and treatment of isolated systolic hypertension in the elderly. 1535 Jan 77

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.
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PMID:Candesartan cilexetil in cardiovascular disease. 1550 Apr 28

High blood pressure, once believed to represent a normal and progressive component of the aging process, is now recognized as a manifestation of structural and physiologic abnormalities of aortic function. Elevated systolic blood pressure and increased pulse pressure unquestionably increase the risk of both fatal and nonfatal cardiovascular events, including stroke, myocardial infarction, and heart failure. Isolated systolic hypertension, defined as a systolic blood pressure >/= 140 mm Hg with a diastolic blood pressure < 90 mm Hg, affects most individuals aged 60 years and older. Several clinical trials have clearly demonstrated that treatment of hypertension significantly reduces the cardiovascular event rate. However, controversy continues as to the choice of antihypertensive agents and combinations of agents. It is both appropriate and necessary to treat elderly hypertensives aggressively to the same target blood pressures identified for younger patients. It is also appropriate to initiate treatment with lower doses of antihypertensive agents and to bring the pressure down more slowly, monitoring for orthostatic hypotension, impaired cognition, and electrolyte abnormalities.
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PMID:Hypertension in the elderly. 1552 93

Calcium channel blockers (CCBs), which include both dihydropyridines such as nifedipine and amlodipine and non-dihydropyridines (verapamil and diltiazem), are among the most widely prescribed agents for the management of essential hypertension. Several large outcome risk trials and comprehensive meta-analyses have found that CCBs reduce the cardiovascular morbidity and mortality associated with uncontrolled hypertension, including stroke. CCBs, however, appear less effective than angiotensin-converting enzyme inhibitors and diuretics for preventing heart failure and myocardial infarction. CCBs are among the agents listed as potential first-line therapy, either alone or in combination with other agents in hypertension management guidelines. Furthermore, CCBs are suitable for add-on therapy in combination with diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers. CCBs may be partially suitable for patients with comorbid Raynaud's syndrome, isolated systolic hypertension (dihydropyridine), or angina pectoris (non-dihydropyridine). The newer inherently long-acting dihydropyridine agents (e.g., lacidipine, lercanidipine), which are not currently available in the United States, appear to have comparable efficacy to older agents of the dihydropyridine class but may have an improved tolerability profile, especially with regard to peripheral edema.
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PMID:The role of existing and newer calcium channel blockers in the treatment of hypertension. 1553 95

Since the middle of the 20th century, most physicians and epidemiologists assessed the risks associated with hypertension based on the level of diastolic blood pressure (DBP). In a classic paper in 1971, the Framingham Heart Study clearly showed that systolic BP more accurately described the risk of all the complications we attribute to hypertension. It took 22 years until JNC V in 1993 also used systolic blood pressure (SBP) to define hypertension in US national guidelines. Since then, the paradigm has shifted dramatically. In JNC VI (1997) and JNC VII (2003), SBP has become the primary focus of risk stratification and treatment goals. This shift is a result of the Framingham results being confirmed by many others analyses, the most compelling of which is the recently published report of the Prospective Collaborative Study Group, which pooled 61 observational studies in more than 1 million volunteers with a collective experience of more than 12 million person-years. This group showed that the SBP level at baseline was a significantly more informative reading than DBP for predicting strokes and coronary heart disease (CHD). Furthermore, three trials of older individuals with isolated systolic hypertension, SHEP, SYST-Eur, and SYST-China, unambiguously demonstrated that effective antihypertensive therapy lowered the rate of strokes, heart failure, CHD, and even all-cause mortality. Finally, the World Health Organization (WHO)/International Society of Hypertension (ISH) Hypertension Trialists also showed that the level of SBP achieved in clinical trials comparing different antihypertensives with placebo and with each other was the strongest determinant of how effectively strokes and CHD events were reduced, although a similar relationship was not evident for heart failure. A recent metaregression analysis using new trials, many of which were used by the Trialists, and older studies not included in their analysis also showed that small differences in SBP can have a dramatic impact on cardiovascular outcomes. If there is one thing we have learned in the recent past, it is the need for us to focus on lowering SBP and getting it down to a reasonable goal. We have also learned that to do so, we will need to combine a variety of lifestyle and pharmacological approaches, always with combinations of drugs that will usually contain a low-dose thiazide-type diuretic with other antihypertensives.
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PMID:The paradigm has shifted to systolic blood pressure. 1559 67

Advanced glycation end product (AGE) formation that occurs with aging and diabetes leads to the cross-linking of proteins and subsequent changes in the physicochemical properties of tissues. Cellular responses to AGE that lead to either pathological conditions or removal of AGE are mediated by a number of receptors that have been identified on various cell types such as macrophages, endothelial cells, and smooth-muscle cells. Mechanisms by which AGE affect the cardiovascular system include AGE cross-linking of long-lived proteins such as collagen and elastin and altered cellular responses. Alagebrium (3-phenacyl-4,5-dimethylthiazolium chloride, ALT-711) is the first drug in a new class of thiazolium therapeutic agents that break established AGE cross-links between proteins. In animal studies, alagebrium was effective in reducing large artery stiffness, slowing pulse-wave velocity, enhancing cardiac output, and improving left ventricular diastolic distensibility. In human studies to determine safety and efficacy, alagebrium was safe and well tolerated. In the first phase 2 clinical study, alagebrium improved arterial compliance in elderly patients with vascular stiffening. In two subsequent phase 2 clinical studies, one addressing diastolic heart failure and the other addressing systolic hypertension, alagebrium was effective in improving cardiac function and uncontrolled systolic blood pressure, particularly in more severely affected patients. Additional clinical studies to determine the utility of alagebrium in treating cardiovascular disorders associated with aging are in progress.
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PMID:Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process. 1560 32


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