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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The issue of how far blood pressure (BP) should be lowered to achieve the greatest reduction in the risk of cardiovascular disease has been a matter of scientific debate. Although a few trials tried to answer this question, they failed to convincingly show the optimal target BP level, in part because of poor reproducibility and wide variability of conventional casual BP measurement used in these trials. On the other hand, in Japan, calcium antagonist (Ca-A) and angiotensin converting enzyme inhibitor (ACE-I) have been two major medications of initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also used now widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medication can give the greatest benefit in terms of reduced cardiovascular disease risk in the Japanese hypertensive patients.
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PMID:Study design of HOMED-BP: hypertension objective treatment based on measurement by electrical devices of blood pressure. 1271 76

Even well-conducted randomized controlled trials can only reduce uncertainty, not eliminate it. The trials presented in this article all have gaps, and like many studies, some raise more questions than answers. A summary of the current trials, however, can be presented as follows. For patients with essential hypertension who are at high risk for cardiovascular disease, the use of diuretic therapy (excluding simultaneous use of ACE or CCB) resulted in outcomes at least equivalent to the use of either ACE or CCB without diuretics. Naturally, the dilemma for clinicians is that these drugs are most often used in combination with thiazide diuretics, as indicated by the RENAAL trial where 80% of ARB were used with diuretics in patients with type II diabetes and known nephropathy. The increased risk of heart failure observed with ACE and CCB in that trial may be relevant only to patients in whom diuretics were not also used. The study does raise important awareness, however, that ACE or CCB use without diuretic therapy is no better than diuretic therapy, and may be associated with higher risk of certain outcomes. A substantial number of patients with essential hypertension might achieve adequate blood pressure control with diuretic monotherapy. If so, that certainly has important implications for the cost of medical care in this country. For African Americans with essential hypertension, ACE may have advantages as a component of therapy in comparison with CCBs or beta-blockers, although diuretics should probably be the cornerstone of therapy for them and supported by the Seventh Joint National Committee. For patients with proteinuric renal disease, whether associated with diabetes or hypertension, it should be considered inappropriate to use DHP CCB as monotherapy in any setting, whether as part of a clinical trial or in clinical practice. These drugs should not be considered as ethical placebo arms in trials, most especially in diabetic nephropathy, nor should they be used without an ACE or ARB in patients with proteinuric renal disease in the absence of documented contraindications or intolerance to ACE, ARB, or non-DHP CCB (which are now considered second-line agents for proteinuric renal disease, and are acceptable placebo or comparison arms in clinical trials). For patients with type I diabetes, ACE remain the cornerstone of therapy. Because of recent RENAAL and IDNT trial results, the greatest benefit for slowing progression of renal disease in type II diabetic nephropathy now belongs to ARBs. In contrast, however, the HOPE trial showed that ACE, specifically ramipril, had the greatest evidence for prevention of cardiovascular outcomes in patients with renal insufficiency, regardless of diabetic status. Cardiovascular outcomes were secondary end points in the RENAAL and IDNT trials, and with the exception of heart failure for losartan, no benefits on cardiovascular outcomes were statistically significant. Progression of renal disease has only been studied in a relatively small cohort of Israeli patients comparing enalapril with nifedipine. These gaps lead to a classic dilemma in medical decision-making. Because evidence has shown that patients with elevated serum creatinine (greater than or equal to 1.4 mg/dL) are just as likely to die from cardiovascular disease as they are to reach end-stage renal disease, which outcome should be the focus for clinicians, or for researchers? Using a strictly evidence-based approach, this question can only be answered by yet another large, long, randomized, controlled trial. Given the similarity of actions between the ARB and ACE, it is likely there is considerable overlap of both benefits and side-effects between the two, although ARB may have a lower incidence of cough and hyperkalemia. The decision of which antihypertensive agents to use will have to be tailored carefully to the needs of the patient and careful consideration of both medical and economic factors. Regardless of the choice between an ACE or ARB, however, post hoc analysis of clinical trials [21,47] and observational data clearly indicate that patients with chronic kidney disease, even if considered mild (ie, serum creatinine greater than or equal to 1.4 mg/dL) are at significantly greater risk of cardiovascular morbidity and mortality compared with those with better kidney function. As stated in a recent review by the authors of the HOPE trial [50], "the frequent practice of withholding ACE [or ARB] in patients with mild renal insufficiency is unwarranted," because not only are these patients precisely those who might benefit most from their use, but safety and tolerability are generally excellent. Based on the results of the AASK trial, the authors add the same for the use of ACE inhibitors in African Americans.
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PMID:What have we learned from the current trials? 1487 Oct 59

The metabolic syndrome leads to cardiovascular disease and type 2 diabetes mellitus, through multiple risks, such as insulin resistance, dyslipidemia, hyperinsulinemia, and hypertension. It also represents a disorder of partial genetic background as mutations of the peroxisome proliferator-activated receptor-gamma (PPAR-g). Thiazolidinedione agonists for the PPAR-g system are effective in control of insulin resistance and diabetes. Telmisartan has a molecular structure that imparts partial agonist properties with the PPAR-g molecule, which results in reductions in glucose and lipid metabolism. Administration of telmisartan to rats on a high-fat, high-carbohydrate diet leads to reductions in glucose, insulin, and triglyceride levels. The results imply that the ARB agent, telmisartan, could treat both the hemodynamic and metabolic aberrations seen in subjects with the metabolic syndrome, such as insulin resistance, glucose intolerance, and hypertension.
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PMID:Angiotensin-receptor blocking agents and the peroxisome proliferator-activated receptor-gamma system. 1606 Oct 40

The metabolic syndrome, defined as a cluster of visceral obesity, insulin resistance, dyslipidemia and elevated blood pressure, is associated with pro-thrombotic, pro-atherogenic and inflammatory risk factors that predispose to cardiovascular disease. Although activators of the peroxisome proliferator-activated receptors (PPARalpha,gamma,delta) in various combinations are under development for treating the metabolic syndrome, they are hampered by adverse effects related to increased adipogenesis, weight gain, fluid overload and carcinogenesis. The recent discovery that telmisartan and irbesartan, antihypertensive angiotensin II type 1 receptor (AT1-R) blockers (ARBs), were uniquely capable of activating PPARgamma, has provided a novel approach to addressing the multifactorial components of the metabolic syndrome. Both drugs have established favorable safety profiles and can activate PPARgamma at concentrations potentially achievable at therapeutic doses. Emerging studies have revealed that both these drugs have beneficial metabolic profiles. This information provides a strategic rationale and pharmacological platform for the development of novel dual ARB/PPARgamma agonists to target the metabolic syndrome and its cardiovascular sequelae, for which therapy is presently insufficient or non-existent. Beneficial effects of these agents include increased energy expenditure, improved lipid profile, increased insulin sensitivity, blood pressure reduction, and amelioration of the associated pro-inflammatory and pro-atherogenic risk profiles. The potential benefit for treatment of the metabolic syndrome, cardiovascular protection, and prevention of related end-organ complications could be of immense clinical value.
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PMID:Treating the metabolic syndrome using angiotensin receptor antagonists that selectively modulate peroxisome proliferator-activated receptor-gamma. 1629 56

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.
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PMID:Choice of antihypertensive drug in the diabetic patient. 1636 52

Type 2 diabetes has long been known to be associated with an increased risk of cardiovascular disease. Patients with type 2 diabetes have also been shown to benefit more from antihypertensive therapy than do non-diabetics with hypertension. The benefits of aggressive antihypertensive therapy are reflected in the recent reduction of blood pressure (BP) targets in international guidelines. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) have well-documented efficacy, and results from large-scale trials with highly selective angiotensin II (Ang II) receptor blockers (ARBs), such as valsartan, are awaited. The VALUE trial will provide the largest body of information yet on the comparative benefits of using an ARB or calcium channel blocker in hypertensive patients with diabetes.
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PMID:Cardiac, renal and vascular complications in the diabetic patient. 1719 15

More than 1 medication is required in many hypertensive patients to reach blood pressure (BP) goals, and initial treatment with 2 agents has been recommended for patients whose BP level is >20/10 mm Hg above target. Diuretics reduce BP levels and the incidence of target organ complications and together with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers, which are recommended in patients with comorbid cardiovascular disease, nephropathy, or diabetes, are effective antihypertensive combinations. Calcium channel blockers (CCBs) are also effective antihypertensive agents, and evidence suggests that a CCB/ACEI combination is well tolerated and also decreases the risk of cardiovascular and renal disease. Some evidence suggests that this combination may improve endothelial function more than either agent alone, and its use could potentially lead to better cardiovascular outcomes than a diuretic/ACEI or diuretic/ARB combination. The ongoing Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial compares these 2 effective combinations (ie, an ACEI/diuretic and ACEI/CCB) as initial treatment for reducing cardiovascular morbidity and mortality in older high-risk hypertensive patients. The results of this trial, when reported, should help to clarify the relative benefits of these different therapies.
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PMID:Combination therapy with an angiotensin-converting enzyme inhibitor and a calcium channel blocker. 1791 6

Hypertension is one of the leading risk factors for cardiovascular disease and represents a major health and economic burden. Most patients with high- or very high-risk hypertension have multiple cardiovascular risk factors with or without accompanying subclinical organ damage or established cardiovascular or renal disease. Patients with severe hypertension or with moderate hypertension and one to two additional risk factors have absolute 10-year risks of cardiovascular disease of 21-30% and 15-20%, respectively. Current European treatment guidelines recommend that antihypertensive therapy be initiated rapidly and aggressively in patients with high-risk hypertension. Most patients require two or more antihypertensive agents to achieve the strict blood pressure target of <130/80 mmHg. This article reviews the existing cost-effectiveness data on the use of angiotensin II receptor antagonists (blockers) [ARBs] in patients with high-risk hypertension. Aggressive ARB treatment of patients in the early (microalbuminuric) stages of diabetic nephropathy has a significant renoprotective effect, delaying the onset of overt (proteinuric) nephropathy. By slowing the progression of these patients to end-stage renal disease, substantial cost savings can be made. There is a paucity of cost-effectiveness data regarding the use of fixed-dose ARB plus thiazide diuretic combination therapies. Longitudinal cost-benefit studies of this attractive and efficacious first-line treatment option are needed.
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PMID:Economic benefits of treating high-risk hypertension with angiotensin II receptor antagonists (blockers). 1834 11

Angiotensin II type 1 (AT(1)) receptor antagonists (blockers) [ARBs] are highly selective for the AT(1) receptor and block the diverse effects of angiotensin II. When high BP is not controlled by low-dose ARB monotherapy, physicians need to employ another strategy, either high-dose ARB monotherapy or combination therapy with calcium channel antagonists (blockers) [CCBs], diuretics, or other agents. High-dose ARB monotherapy is more effective for decreasing proteinuria than low-dose ARB monotherapy or CCBs. Although the ARB valsartan has been shown to prevent coronary restenosis in a clinical study (Val-PREST [Valsartan for prevention of restenosis after stenting of type B2/C lesions]), it is still unclear whether ARBs help to prevent restenosis. The results reported by Peters in this issue highlight the relative efficacies of low- (80 mg/day) and high-dose valsartan (160-320 mg/day) for the prevention of in-stent restenosis after the implantation of bare-metal stents, and suggest that high-dose valsartan can reduce the in-stent restenosis rate, target lesion revascularization and target vessel revascularization rates, late lumen loss, and major adverse cardiac events rate more effectively than low-dose valsartan. A better understanding of the differences in the efficacies of high- and low-dose ARBs could be useful in the treatment of patients with cardiovascular disease and may resolve the issue of whether ARBs prevent coronary restenosis. Clinical benefits may be induced by complete blockade of the renin-angiotensin system using high-dose ARB monotherapy. Therefore, physicians need to select a strategy carefully; i.e. either high-dose ARB monotherapy or combination therapy.
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PMID:Which strategy is more effective for the treatment of cardiovascular disease: high-dose angiotensin II type 1 receptor antagonist monotherapy or combination therapy? 1842 91

New onset diabetes (NOD) is common among hypertensive patients, whether they are being treated for hypertension or not, and is associated with subsequently increased cardiovascular disease (CVD). Thiazide-like diuretics and beta-blockers are more likely to provoke hyperglycemia when compared with drugs that block the renin-angiotensin system, and calcium channel blockers. However, in contrast to the NOD arising during treatment with other antihypertensive drugs, the NOD that occurs during diuretic treatment, has not been shown to increase CVD, either in clinical trials, or during longer observational studies. In fact, blood pressure reduction achieved by diuretic treatment may avert the expected increase of CVD in NOD. Conventional blood pressure reduction (along with lipid lowering) is the proven approach to preventing CVD in diabetes, in whatever circumstances the diabetes occurs. Apprehensions relating to the potential onset of NOD should not influence the choice of the initial antihypertensive treatment choice, nor should it invariably lead to discontinuation of diuretics (although such a step may reverse hyperglycemia). NOD can also sometimes be eliminated by correcting hypokalemia with a potassium-sparing diuretic, and/or potassium supplementation, or by adding a potassium-conserving antihypertensive drug such as an ACEI, ARB, or an anti-aldosterone agent. If all these stratagems fail (or are unsuitable), and the diuretic is essential to blood pressure control, then hypoglycemic therapy is indicated. NOD does adversely affect quality of life, and is not to be accepted lightly. However, diuretic-induced hyperglycemia can be managed, and should be tolerated if a diuretic is essential for blood pressure control. In summary, the potential for occurrence of NOD certainly needs consideration, but it is not an insurmountable challenge, and must not compromise aggressive blood pressure control, which remains the primary tool for antihypertensive care.
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PMID:New onset diabetes during antihypertensive therapy. 1843 39


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