Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systolic blood pressure is a major cardiovascular risk factor which is often associated with arterial stiffness. Markers of arterial stiffness, such as pulse pressure and carotid-femoral pulse wave velocity, have been proved independent predictors of cardiovascular risk. Recent evidence suggests that the renin-angiotensin system is involved in the pathogenesis of systolic hypertension and arterial stiffness. Outcome trials have shown impressive cardiovascular protection by reducing systolic blood pressure (BP) with drug treatment. However, in clinical practice systolic hypertension remains largely uncontrolled, first, because systolic BP goal is more difficult to be reached than diastolic and, second, because physicians are often reluctant to intensify treatment in patients with systolic BP close to 150 mmHg. Recent trials have focused on the effects of antihypertensive drugs not only on blood pressure, but also on pulse pressure and pulse-wave velocity. Blockade of the renin-angiotensin-aldosterone system, using angiotensin-converting enzyme inhibitors and more recently angiotensin receptor blockers, has been shown to provide beneficial effects on arterial stiffness that appear to be independent of their antihypertensive effects. Recent outcome trials have shown significant cardiovascular protection with angiotensin receptor blockers. These drugs have an excellent placebolike profile of adverse effects which is maintained when these drugs are combined with low-dose diuretics. Therefore, an angiotensin receptor blocker-based treatment strategy appears to be an attractive and evidence-based approach for the management of systolic hypertension, the reduction of arterial stiffness and the prevention of cardiovascular disease.
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PMID:Angiotensin receptor blockade in the challenging era of systolic hypertension. 1531 61

At least 17 million people in the United States have diabetes mellitus, and another 50 million have hypertension. These chronic diseases increasingly coexist in our aging population. Both diseases are important predisposing factors for the development of cardiovascular disease (CVD) and renal disease, and the coexistence of these risk factors is a very powerful promoter of CVD and renal disease. There is accumulating evidence that the rigorous treatment of hypertension and other risk factors such as dyslipidemia and hyperglycemia considerably lessens the burden of CVD and renal disease in patients with diabetes mellitus. There is considerable evidence that strategies addressing diet and exercise reduce the development of diabetes and are an important component of treatment in persons who have established diabetes. There are also considerable data suggesting that the treatment strategies that interrupt the renin-angiotensin system have special benefits in patients with diabetes and may prevent the development of clinical diabetes in hypertensive patients with impaired glucose tolerance. Data from a recent study indicate that the control of systolic blood pressure, using a diuretic agent as part of antihypertensive therapy, reduces the risk of stroke and other CVD end points. Recent reports indicate that angiotensin receptor-blocking agents decrease the rate of development of proteinuria and diabetic renal disease. These observations will likely have a significant impact on treatment of hypertension in patients with type 2 diabetes mellitus.
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PMID:Treatment of hypertension in patients with diabetes. 1545 59

Angiotensin II is important in the development of cardiovascular disease. In the present study, angiotensin II receptor mRNA levels were quantified by real-time polymerase chain reaction (real-time PCR) in human coronary arteries from patients with ischemic heart disease and controls. Furthermore, the suitability of artery culture for studying angiotensin receptor changes was evaluated by in vitro pharmacology and real-time PCR. The angiotensin type 1 (AT1) receptor mRNA levels were down-regulated in human coronary arteries from patients with ischemic heart disease as compared to controls (P<0.05). Culture of coronary arteries for 48 h induced down-regulation of the angiotensin AT1 and AT2 receptor mRNA levels and also a less efficacious angiotensin II-induced vasoconstriction (Emax=103+/-2% before and 23+/-7% after artery culture, P<0.001). Artery culture may thus be a suitable method for studying angiotensin receptor regulation.
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PMID:Ischemic heart disease down-regulates angiotensin type 1 receptor mRNA in human coronary arteries. 1549 9

Hypertension rarely occurs in isolation, and many hypertensives have additional risk factors for cardiovascular disease in addition to elevated blood pressure. Each patient's cardiovascular disease risk profile should be determined individually, and the treatment approach tailored to each case. Cardiovascular disease risk factors and high blood pressure are closely linked, suggesting that the ideal treatment should not only lower blood pressure, but also effectively lower overall risk. This is likely to require more than one drug, and one of the most effective and safe combinations is that of an angiotensin receptor blocker with a diuretic. The completion of one of the most important trials undertaken to explore risk factors and anti-hypertensive treatment, the Valsartan long-term evaluation trial (VALUE), will certainly enhance understanding for the role of combination treatment in high-risk patients, as well as contribute to the design of rational treatments for blood pressure control.
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PMID:The case for blood pressure control in risk groups. 1552 18

The renin-angiotensin system is a key target for drugs combating cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT1 receptor) blockers are well known. However, angiotensin peptides can be generated through a number of pathways besides the classic system. This review outlines some of these pathways, their relation to the classic system and the likely effect of inhibiting them. Renin is still the key enzyme in angiotensin peptide generation and seems to be the only route to angiotensin I formation in vivo. Renin inhibitors may have some advantages in terms of specificity. Also, by blocking angiotensin I generation, the production of downstream bioactive angiotensin I metabolites should also be blocked. Chymase, a mast cell serine protease, cleaves angiotensin I to produce angiotensin II and may be important at sites of inflammation such as atherosclerotic plaque. Angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase structurally related to ACE but resistant to ACE inhibitors, has a protective effect on cardiac function. Neutral endopeptidase 24.11 breaks down both atrial natriuretic peptide and angiotensin II. Inhibiting it potentiates the action of endogenous atrial peptide but only affects circulating angiotensin II when basal levels are above normal. Dual inhibitors of ACE and endopeptidase 24.11 may be of value where there is both sodium retention and increased angiotensin II. Targeting the renin-angiotensin system by gene therapy or antibody treatment may provide a longer-term treatment for hypertension.
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PMID:Targeting the renin-angiotensin system: what's new? 1563 41

Diabetic nephropathy is the number one cause of endstage renal disease in the United States. Blood pressure is most important in delaying the progression of renal disease in persons with diabetes and, agents that block the renin angiotensin system (RAS) should be the primary agents used to achieve blood pressure reduction. There is debate regarding which method of RAS blockade should be used as primary therapy in persons with diabetes. There are not significant differences between angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) with regard to renal outcomes. Consideration of the enormously high rates of cardiovascular disease (CVD) in persons with diabetes and renal disease is the primary factor in choosing agents for blood pressure reduction. The ACE inhibitors and ARBs have been shown to reduce cardiovascular events in persons with diabetes and, there are recent comparable trials between the 2 classes. Some studies and meta-analyses show ACE inhibitors as being superior with regard to cardioprotection. In our nephrology clinic, we find that patients who presented on an ACE inhibitor had significantly lower CVD than those on ARBs (49.2% vs 70.1% prevalence of CVD, ACE inhibitor vs ARB respectively, P=.042). We conclude that ACE inhibitors should be strongly considered as the primary method of RAS inhibition in persons with diabetes.
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PMID:Therapeutic controversies in hypertension management: angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers in diabetic nephropathy? ACE inhibitors. 1572 89

High blood pressure plays a key role in the progression of renal failure. Hypertension is a common presentation of kidney disease and an almost invariable accompaniment of renal failure. Hypertension is also a major contributor to cardiovascular disease, the major cause of morbidity and mortality in renal failure. Hypertension is both cause and consequence of renal failure, but the precise nature and prevalence of hypertensive nephrosclerosis as a cause of renal failure remains controversial. There is strong evidence that hypertension accelerates the progression of experimental renal disease and that control of blood pressure is effective in preventing this progression. Hypertension, both accelerated and "benign" (a misnomer), has long been recognised as a poor prognostic feature in human renal disease and more recently in renal allograft survival. Blood pressure control is very effective in retarding renal disease progression. There are compelling indications for angiotensin-converting enzyme inhibitors in both non-diabetic and type 1 diabetic nephropathies, and for angiotensin receptor blockers in type 2 diabetic nephropathy. Most patients will require combination drug therapy to control blood pressure and reduce both progression of renal failure and the associated cardiovascular morbidity and mortality.
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PMID:Progression of renal failure -- the role of hypertension. 1572 14

Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.
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PMID:Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes. 1574 96

The National Heart, Lung, and Blood Institute assembled an ad hoc working group to evaluate opportunities for new major clinical trials in the field of hypertension. The mandate of this working group was to consider the possible designs of major randomized clinical trials focused on clinical outcomes that might merit significant investment by the National Institutes of Health. The group concluded that the ideal pragmatic clinical trial would have a factorial design and include a population at elevated risk of cardiovascular disease events. Subjects would be randomized to a target of systolic blood pressure <130 versus 130 to 150 mm Hg for adequate separation of means. Initial treatment with thiazide diuretic would be followed by randomization to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, calcium channel blocker, or aldosterone antagonist. A third drug could be added according to a protocol. DNA, proteins, and metabolites would be collected in a sample adequate to assess differential impact of treatment on outcome as a function of genotype, proteomic, and metabolomic expression. Subclinical markers and images would also be measured in a sample of patients to develop evidence of ability to predict ultimate effect on clinical outcomes. This ideal trial would take place within a network, funded for at least a decade, aimed at connecting primary care providers with hypertension specialists. Within the network, substudies or independent studies would be coordinated to develop a continuously improving base of knowledge about the effective delivery of hypertension care.
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PMID:Major clinical trials of hypertension: what should be done next? 1591 39

Congestive heart failure (CHF) is a life-threatening cardiovascular disease that is increasing in prevalence. It is a common cause of death and is accompanied by high direct and indirect costs for treatment. The current situation faced by patients and the medical community with regard to this ailment is one of high mortality, repeated hospitalizations, and combination therapies. The various classes of pharmacological agents that are currently used for patients suffering from CHF include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), aldosterone antagonists, beta-blockers, calcium channel blockers (CCBs), digitalis drugs, diuretics, inotropic agents, nitrates, and vasodilators. While these agents are all important therapeutic tools in the treatment of CHF, the prognosis for patients with CHF remains poor. Thus improvement of the current pharmacological armamentarium is greatly needed. An endogenous peptide, B-type natriuretic peptide (BNP), has been increasingly utilized in the setting of acute CHF since its approval in 2001. This peptide, or a derivative thereof, has great potential for the treatment of patients at various stages in the progression of heart failure. This review provides an overview of current pharmacological strategies in CHF and addresses potential future developments in the use of BNP for the treatment of CHF.
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PMID:Congestive heart failure: pharmacological agents and the potential of B-type natriuretic Peptide. 1597 94


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