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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is more prevalent and severe in African descendent populations living outside Africa than in any other population. Given this greater burden of hypertension in blacks, it is increasingly necessary to refine strategies to prevent the disorder as well as improve its treatment and control. This review assesses results from clinical trials on lifestyle and pharmacologic interventions to identify which approaches most effectively prevent adverse hypertension-related outcomes in African descendent populations. The Dietary Approaches to Stop Hypertension (DASH) study provided evidence that a carefully controlled diet rich in fruits, vegetables, low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (i.e., the DASH diet) reduces blood pressure in blacks and is well accepted. The combination of the DASH diet with reduction in dietary sodium below 100 mmol/d may provide a reduction in blood pressure beyond that reached by the DASH diet alone. Physical exercise and interventions to reduce psychological stress may also reduce blood pressure in blacks. Strong evidence from numerous studies is a compelling argument for continuing to recommend diuretics and beta blockers as first-line antihypertensive therapy for persons of all races. Some new studies also favor angiotensin-converting enzyme inhibitors as first-line antihypertensive drugs. The African American Study of Kidney Disease and Hypertension provided evidence that an angiotensin-converting enzyme inhibitor-based treatment program is more beneficial than calcium channel blockers and beta blockers in reducing the progression of renal failure in blacks with hypertensive nephropathy. Studies in patients with diabetes have also shown evidence that both angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists are more effective than other classes of antihypertensives in reducing adverse renal events. Studies to evaluate the effects of the new antihypertensives in improving outcomes in blacks living outside the United States are needed.
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PMID:Meeting the challenge to improve the treatment of hypertension in blacks. 1468 94

A significant subgroup of patients with diabetes mellitus are predisposed to developing diabetic nephropathy and it is in this subgroup that other diabetes- related complications, and in particular greatly increased cardiovascular disease risk, are concentrated. The high personal, social and financial costs of managing end-stage renal failure and the other complications associated with diabetic nephropathy make a powerful case for screening and effective intervention programmes to prevent the condition or retard its progression. As major breakthroughs in finding genetic susceptibility factors remain elusive, screening efforts continue to be based on microalbuminuria testing, despite increasing recognition of its limitations as a positive predictor of nephropathy. Interventions have been extensively studied, but results remain conflicting. Economic evaluations of such screening and intervention programmes are essential for health planners, yet models of the cost/benefit ratio of such interventions often rely on a rather slim evidence base. Where economic models are developed, they are frequently based on those papers that propound the greatest clinical benefits of a given intervention, leading to a possible over-estimation of the advantages of the chosen approach. Furthermore, the benefits of even such generally accepted interventions as ACE inhibitor treatment are less firmly established than generally appreciated. Lifestyle interventions are instinctively attractive, but are by no means a low-cost option (as is often assumed by both medical professionals and politicians). This review critically assesses the evidence for clinical efficacy and economic benefit of microalbuminuria screening and interventions such as intensive glycaemic control, antihypertensive treatment, ACE inhibition and angiotensin receptor blockade, dietary protein restriction and lipid-modifying therapy. The various costs associated with diabetic nephropathy are so great that even expensive interventions may have a favourable cost/benefit ratio, provided they are truly effective.
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PMID:Cost-effective strategies in the prevention of diabetic nephropathy. 1472 79

Patients with multiple cardiovascular risk factors benefit from having them all controlled, but this rarely occurs. Fifty-seven primary care providers were enrolled in a program to monitor cardiovascular risk factor control. Data were obtained on 7315 hypertensives. This analysis focuses on 3460 high-risk hypertensives including 2199 with diabetes and 1261 with clinical cardiovascular disease. Blood pressures were <140/90 mm Hg and <130/80 mm Hg in only 44.3% and 20.4% of diabetics and 49.6% and 26.6% nondiabetics, respectively, despite the use of an average of 2.7+/-1.8 antihypertensive medications. Among high-risk dyslipidemic hypertensives, the low-density lipoprotein cholesterol level was <100 mg/dL in only 34% of diabetic and 33% of nondiabetic patients. Among 1696 diabetic hypertensives, the most recent glycosylated hemoglobin value averaged 7.5%, with 46.6% less than 7%. Among 805 diabetic, dyslipidemic hypertensives, all three risk factors were controlled to goal in only 6.6% with higher rates in whites than in African Americans (14.8% vs. 1.6%, p<0.001). An angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or both were prescribed in 89.9% of diabetic and 70.8% of nondiabetic patients, p<0.05. Primary care providers use evidence-based combination therapy in high-risk hypertensive patients with and without diabetes. These findings confirm the low rates of multiple risk factor control and highlight challenges of reaching evidence-based goals in primary care.
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PMID:A statewide primary care approach to cardiovascular risk factor control in high-risk diabetic and nondiabetic patients with hypertension. 1472 20

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.
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PMID:Calcium channel antagonists in the treatment of hypertension. 1472 56

Restenosis rates after coronary stent implantation in complex lesions are between 30 and 50%. Neointimal hyperplasia promoted by complex interaction between cellular and acellular elements, such as cytokines and growth factors, is thought to be the primary process responsible for restenosis. The risk of in-stent restenosis is increased in patients with a history of restenosis after percutaneous transluminal coronary angioplasty, in long lesions, in total occlusions, in patients with diabetes mellitus, in small vessels, in the proximal parts of the left anterior descending coronary artery and in cases of stent oversizing. In-stent restenosis represents a serious economic burden on society because treatment strategies include expensive approaches such as cutting-balloon angioplasty, rotational atherectomy and brachytherapy. A number of pharmacological agents, including ACE inhibitors, have been unsuccessful in preventing restenosis. Alternative procedures such as brachytherapy, radioactive stents and drug-eluting stents are under evaluation. Although sirolimus- or paclitaxel-eluting stents have been associated with very low restenosis rates over durations of 6 to 12 months, the long-term efficacy and tolerability of this approach is currently being investigated. Although ACE inhibitors have failed in reducing restenosis rates, the selective angiotensin II type 1 (AT(1)) receptor antagonist valsartan has shown encouraging results in the single-center Valsartan for Prevention of Restenosis after Stenting of Type B2/C lesions trial (ValPREST). The ValPREST trial is the first randomized, placebo-controlled study to have evaluated the effect of an angiotensin receptor antagonist on in-stent restenosis in a moderate number of patients. Compared with ACE inhibitors, angiotensin receptor blockers exert additional effects on the pathophysiological processes which lead to restenosis. Angiotensin receptor antagonists may affect several mechanisms involved in neointimal hyperplasia such as decreasing circulating cytokine and growth factor levels and reducing neutrophil activation, especially after stenting in acute coronary syndromes, but the results need to be confirmed in a large multicenter trial. The question whether long-term therapy, with an oral angiotensin receptor antagonist, is cost-effective and whether angiotensin receptor antagonists should be used as an add-on therapy to drug-eluting stents, requires clarification.
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PMID:Can angiotensin receptor antagonists prevent restenosis after stent placement? 1472 76

Management of hypertension in diabetic nephropathy is challenging and generally requires a minimum of three different and complementary antihypertensive agents to achieve the recently recommended blood pressure (BP) goal of <130/80 mm Hg in order to reduce cardiovascular (CV) risk and preserve kidney function. Commonly used antihypertensive combinations include an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, agents that have compelling indications for use in diabetic renal disease, added to a diuretic, generally a thiazide-type agent. If additional therapy is required, either a beta-blocker or calcium antagonist may be added. Beta-blockers are particularly effective in people with a high sympathetic drive, i.e. high pulse rates, to lower BP and reduce CV risk while reducing proteinuria and slowing decline of kidney function. In light of this information, it is disturbing that a recent analysis of the NHANES III database indicates that only about 11% of people with diabetic kidney disease have achieved the target BP of <130/80 mm Hg. Recent data from Denmark demonstrate that focusing on total CV risk reduction among people with diabetes, including achievement of recommended BP and lipid goals along with the use of aspirin, exercise and a proper diet, can reduce the absolute risk of a CV event by 20% over less intensive treatment.
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PMID:Diabetes and chronic kidney disease: tragedy and challenge. 1473 21

The brain renin-angiotensin system (RAS), which is comprised of a variety of peptides including angiotensin II, angiotensin III and angiotensin IV acting on AT<inf>1</inf>, AT<inf>2</inf> and AT<inf>4</inf> receptors, is important in cognition and anxiety. Perturbation of the RAS improves basal cognition and reverses age-, scopolamine-, ethanol- and diabetes-induced deficits. In studies of dementias and Alzheimer's disease (AD), some studies have shown that antihypertensive drugs, including angiotensin-converting enzyme inhibitors, have some moderate effects on cognitive decline, but that the angiotensin receptor antagonist losartan has a significantly beneficial effect. These findings suggest that angiotensin receptor ligands may have potential in the prevention or even reversal of vascular dementias and AD. With respect to depression and anxiety, there is similar experimental evidence from animal models that drugs acting on the RAS may be antidepressant or anxiolytic, but insufficient clinical data exist. Such effects, if proven, could promote the use of such agents in the treatment of hypertension coexisting with depression or anxiety.
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PMID:Angiotensin as a target for the treatment of Alzheimer's disease, anxiety and depression. 1499 14

Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) slows nephropathy progression in patients with or without diabetes. These drug classes have proven therapeutic benefits, particularly in patients with renal insufficiency (ie, serum creatinine level 133-265 micromol/L [1.5-3.0 mg/dL]). This class of drugs could also provide renoprotective effects that are nonblood pressure-dependent when used as part of combination antihypertensive therapy in patients with more advanced renal disease. Although many studies demonstrate the use of ACE inhibitors and ARBs to delay the decline in renal function and reduce proteinuria, many physicians fail to use these drug classes in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise. Thus, because of these issues, patients are deprived of known strategies that delay progression of renal disease. A strong association exists between acute increases in serum creatinine of up to 30% to 35% after initiating ACE inhibitor therapy and long-term preservation of renal function. This association is predominantly present in people with a baseline serum creatinine of up to 3 mg/dL and usually stablizes within 2 to 3 months of therapy given blood pressure is reduced to goal. Moreover, the appropriate use of diuretics mitigates against profound increases in serum potassium. Thus, withdrawal of an ACE inhibitor in such patients should occur only when the rise in creatinine exceeds this threshold over a shorter period of time or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues. 1501 29

Besides cyclooxygenase and NO-synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization (EDHF), is involved in the relaxation of the vascular smooth muscle cells. EDHF has been demonstrated unequivocally in various blood vessels from different species, including human, and is likely to play an important role in cardiovascular physiology. This alternative pathway involves the activation of two populations of endothelial potassium channels, the small conductance and intermediate conductance calcium-activated potassium channels (SK(Ca) and IK(Ca), respectively). EDHF-mediated responses are clearly altered in various pathological conditions (ageing, hypertension, atherosclerosis, hypercholesterolemia, heart failure, ischemia-reperfusion, angioplasty, eclampsia, diabetes, sepsis). Therapeutic or adjutant interventions (angiotensin converting enzyme inhibitors, antagonist of the angiotensin receptor, estrogen, omega-3 polyunsaturated fatty acids, polyphenol derivatives, potassium and/or calcium intake) can restore these responses, suggesting that the improvement of the EDHF pathway contributes to the observed beneficial effect of these various substances. However, the improvement or restoration of EDHF responses has not been, yet, the direct purpose of any pharmaceutical effort. Activating endothelial IK(Ca) and/or SK(Ca) or increasing their expression as well as improving myo-endothelial communication, for instance by increasing the expression of connexin(s), could become interesting therapeutic targets.
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PMID:EDHF: new therapeutic targets? 1502 34

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Monotherapy of hypertension is often ineffective, since it controls approximately 50% of the blood pressure of hypertensive patients. For lowering blood pressure to less than 140/90 mmHg (or <130/80 mmHg among people with diabetes or chronic renal disease) according to JNC-7 guidelines, combination therapy of two or more drugs is often necessary. The combination of a diuretic with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is effective and provides the additional benefit of blocking the effects of angiotensin II, which is responsible for cardiovascular remodeling and its complications. ARBs may have an advantage over the ACEIs because they block the action of all angiotensin II directly, whereas ACEIs are ineffective in blocking angiotensin II generated by nonclassical ACE pathways. Valsartan (Diovan, Novartis) is one of the seven currently approved ARBs in the USA for the treatment of hypertension, and it has been shown to be very effective in controlling blood pressure given once-daily in doses of 80-160 or 320 mg. Its fixed combination with hydrochlorothiazide (HCT) is even more effective in controlling blood pressure in 70% of the cases. The most commonly used combinations are valsartan/HCT (Diovan/HCT), 80/12.5 and 160/12.5 mg given once-daily.
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PMID:Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan/HCT). 1503 Feb 62


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