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)

Cardiovascular disease is the leading cause of death in Type 2 diabetes, which commonly occurs in patients with serious mental illnesses (SMIs). We determined the extent to which patients with diabetes and SMI, relative to diabetes patients without SMI, met American Diabetes Association goals for cholesterol and blood pressure, met criteria for the metabolic syndrome, and were prescribed medications known to reduce cardiovascular events. We found that less than half of diabetes patients, both with and without SMI, met recommended goals for cholesterol levels; even fewer had adequate blood pressure control. In addition, a substantial proportion of all diabetes patients met metabolic syndrome criteria. However, diabetes patients with SMI were less likely to be prescribed cholesterol-lowering statin medications, angiotensin-converting enzyme inhibitors, and angiotensin receptor blocking agents than diabetes patients without SMI. Patients with both diabetes and SMI are treated less aggressively for high cardiovascular risk than diabetes patients without mental disorders.
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PMID:Extent and management of cardiovascular risk factors in patients with type 2 diabetes and serious mental illness. 1677 56

G-protein-coupled receptor kinase (GRK) 2 regulates a plethora of cellular processes, including cardiac expression and function of key seven-transmembrane receptors (7TM receptors) such as the beta-adrenergic and angiotensin receptors (Penela P, Murga C, Ribas C, et al.: 2006. Mechanisms of regulation of G-protein-coupled receptor kinases [GRKs] and cardiovascular disease. Cardiovasc Res 69:46-56, Rockman HA, Koch WJ, Lefkowitz RJ: 2002. Seven-transmembrane-spanning receptors and heart function. Nature 415:206-212). Interestingly, these two G-protein-coupled receptor systems are targeted by modern heart failure treatment including beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Although GRK2 is ubiquitously expressed, its particular importance in the heart has been demonstrated by interesting phenotypes of genetically altered mice that suggest GRK2 inhibition can ameliorate heart failure. In essence, this work suggests GRK2 could be an endogenous receptor blocker targeting both the beta-adrenergic and angiotensin receptors in the heart. This notion immediately suggests it is important to understand the molecular mechanisms that regulate GRK2 activity in the heart. In this review, we provide a detailed presentation of the tight regulation of GRK2 expression levels and protein activity, and we discuss the cardiovascular GRK2 functions and possible therapeutic perspectives.
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PMID:Role of G-protein-coupled receptor kinase 2 in the heart--do regulatory mechanisms open novel therapeutic perspectives? 1678 51

The prevalence of type 2 diabetes mellitus continues to rise. Given the associated co-morbidities of obesity, hypertension and cardiovascular disease, the rising incidence of diabetes has important health consequences and efforts to reduce this incidence are critical. Although lifestyle modifications, including weight loss and exercise, are instrumental in the prevention of diabetes, pharmacological therapies that reduce the incidence of diabetes have the significant potential to lower risk. The results of several large clinical trials have demonstrated that treatment with ACE inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) may prevent or delay the onset of diabetes. These trials have demonstrated an approximately 15-30% reduction in the new onset of diabetes in those receiving ACE inhibitors and ARBs when compared with placebo or other active therapy. Although the exact mechanism underlying the effects are not entirely clear, multiple animal and human studies have demonstrated that the renin-angiotensin system plays an important role in glucose homeostasis. Although future prospective studies to clarify the role of ACE inhibitors and ARBs in preventing diabetes are ongoing, there is substantial existing evidence from completed trials that these agents may prevent the onset of diabetes.
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PMID:ACE inhibitors and angiotensin receptor antagonists and the incidence of new-onset diabetes mellitus: an emerging theme. 1682 95

Cardiovascular disease continues to be a tremendous worldwide problem, and drug therapy is a major modality to attenuate its burden. At present, conditions such as hypertension, dyslipidaemia and heart failure are pharmacologically managed with an empirical trial-and-error approach. However, it has been suggested that this approach fails to adequately address the therapeutic needs of many patients, and pharmacogenetics has been offered as a tool to enhance patient-specific drug therapy. This review outlines pharmacogenetic studies of common cardiovascular drugs, such as diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins and warfarin, ultimately highlighting considerations for future research and practice.
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PMID:Pharmacogenetics of chronic cardiovascular drugs: applications and implications. 1685 25

The endothelium is critically involved in modulating vascular tone through the release of vasodilator (mainly nitric oxide; NO) and vasoconstrictor agents. Under normal conditions the endothelium induces NO-mediated vasodilation, and opposes cell adhesion and thrombosis. Angiotensin II-induced generation of reactive oxygen species plays a key role in the pathophysiology of endothelial dysfunction by reducing NO bioavailability. Endothelial dysfunction is associated with several pathologic conditions, including hypertension and diabetes, and is characterized by altered vascular tone, inflammation, and thrombosis in the vascular wall. Inhibition of the renin-angiotensin-aldosterone system has induced beneficial effects on endothelial function in animals and humans. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists have improved endothelial function in hypertension and diabetes, slowed the progression of atherosclerosis, and reduced the risk associated with cardiovascular disease.
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PMID:Inhibition of the renin angiotensin system: implications for the endothelium. 1687 78

The renin-angiotensin system (RAS) plays a pivotal role in the progression of some forms of hypertension and cardiovascular disease. The development of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has provided physicians with effective and well-tolerated inhibitors of the RAS. However, it remains open to question whether ACE inhibitors and ARBs have fully delivered the reductions in cardiovascular risk that we might have expected. There is little doubt that in conditions such as chronic and acute heart failure or diabetic nephropathy these drugs have provided significant protection. But, in patients with high-risk hypertension, for instance, the anticipated benefits of RAS blockade have been less obvious. This article provides a critical assessment of the results of clinical trials of ACE inhibitors and ARBs across a variety of clinical conditions and assesses the potential need for new methods for blocking the renin system, including the use of renin inhibitors.
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PMID:Inhibiting the renin-angiotensin system to prevent cardiovascular diseases: do we need a more comprehensive strategy? 1691 23

The cardiovascular continuum describes the progression of pathophysiologic events from cardiovascular risk factors to symptomatic cardiovascular disease (CVD) and life-threatening events. Pharmacologic intervention early in the continuum may prevent or slow CVD development and improve quality of life. The renin-angiotensin-aldosterone system (RAAS) is central to the pathophysiology of CVD at many stages of the continuum. Numerous clinical trials of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have shown that RAAS blockade provides benefits to patients across the continuum. ARBs are as effective as ACE inhibitors in the treatment of hypertension; however tolerability and adherence to therapy appear to be improved with ARBs. Large clinical trials have shown that ARBs may provide therapeutic benefits beyond blood pressure control in patients with diabetes, heart failure or at risk of heart failure following a myocardial infarction. In addition, ARBs have been shown to provide protective effects in patients with impaired renal function or left ventricular hypertrophy. Additional clinical trials are ongoing to further characterize the role of ARBs in CVD management.
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PMID:Efficacy of Angiotensin receptor blockers in cardiovascular disease. 1691 47

Hypertension is the leading modifiable risk factor for stroke, including first-ever and recurrent stroke. The association between blood pressure (BP) and stroke risk is continuous and may be documented as low as 115/75 mm Hg. Because of this continuum of risk, and because most strokes occur in individuals with mild hypertension or even normal BP values, we are now beginning to recognize "prehypertension" as a stage in which early recognition and intervention may confer benefit. In addition to increased risk for ischemic and hemorrhagic stroke, hypertension may be associated with increased risk of cognitive impairment. Reductions in BP are reliably associated with reduced stroke risk. Some evidence suggests that certain agents, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, may have protective effects beyond BP lowering. Overall, the degree of BP lowering is key, and therefore most classes of BP-lowering agents may be recommended at this point. Many patients with hypertension will require more than one BP-lowering agent to control BP. Lifestyle modification is appropriate at all levels of intervention. Further studies are needed to ascertain the mechanisms of benefit of different classes of antihypertensive agents in the reduction of stroke and cardiovascular disease risk.
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PMID:Update on the management of hypertension to prevent stroke. 1703 69

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) treatment have a markedly shortened life expectancy in large part owing to cardiovascular disease (CVD), not explained by established risk factors. We tested the hypothesis that therapy with valsartan, an angiotensin receptor blocker and amlodipine, an antioxidant calcium channel blocker will reduce oxidative stress and the plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. We confirmed that compared with age- and gender-matched healthy controls, ESRD patients have excessive oxidative stress and arginine methylation as indexed by elevated plasma levels of oxidation products of lipids (13-hydroxyoctadecadienoic acid (13-HODE)), thiols (oxidized:reduced glutathione, oxidized glutathione (GSSG):GSH), proteins, and nucleic acids, and the methylation products ADMA and symmetric dimethylarginine (SDMA). We undertook a double blind, crossover study of equi-antihypertensive treatment with amlodipine and valsartan for 6 weeks each to test our hypothesis. Both treatments significantly reduced GSSG:GSH, 8-hydroxy 2-deoxyguanosine, ADMA, and SDMA levels and amlodipine reduced 13-HODE. We conclude that hypertensive patients with ESRD receiving HD have evidence of extensive oxidation of lipids, thiols, proteins, and nucleic acids and methylation of arginine that could contribute to CVD. Many of these changes can be reduced by short-term treatment with amlodipine and valsartan.
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PMID:Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis. 1713 31

The role of angiotensin II, the key mediator of the renin-angiotensin-aldosterone system, in the pathophysiology of cardiovascular disease is well known. Pharmacologic interruption of the activity of angiotensin II, either through blockade of the angiotensin receptor or inhibition of angiotensin-converting enzyme, is associated with a reduction in cardiovascular disease morbidity and mortality, as evidenced by accumulated data from large-scale, well-controlled clinical trials in high-risk populations. As the underlying mechanisms of vascular disease and the effects of blockade of the renin-angiotensin-aldosterone system on these processes have been further defined, the therapeutic focus has begun to shift toward prevention of disease progression at earlier stages. Continued research has identified early signs of vascular disease, such as endothelial dysfunction and vascular and cardiac remodeling, which occur long before clinical manifestations of cardiovascular disease become evident. Diagnostic tests are now available to assess otherwise healthy individuals for these signs. A preliminary trial is under way to evaluate the role of angiotensin receptor blockade as preventive treatment of individuals with early signs of vascular or cardiac disease.
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PMID:What is the role of angiotensin-receptor blockade in cardiovascular protection? 1707 Jan 45


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