Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are potent cholesterol-lowering drugs. In addition to their cholesterol-lowering properties, statins exert a number of so-called 'pleiotropic', vasculoprotective actions that include improvement of endothelial function, increased nitric oxide (NO) bioavailability, antioxidant properties, stabilisation of atherosclerotic plaques, regulation of progenitor cells, inhibition of inflammatory responses and immunomodulatory actions. Pleiotropic actions of statins may have potential clinical impact in vascular disease beyond cholesterol lowering. The ongoing Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), for example, tests the effects of statins in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol (LDL-C) and elevated high-sensitivity C-reactive protein (hs-CRP). Additionally, previous studies have shown that although cholesterol is not an established stroke risk factor, statin therapy is associated with a reduction in the incidence of strokes. It is known that sudden withdrawal of statin treatment may acutely impair vascular function and increase morbidity and mortality in patients with vascular disease. Furthermore, the anti-inflammatory effects of statins may have clinical impact in a number of non-vascular conditions including multiple sclerosis and rheumatoid arthritis.
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PMID:Statins: potential new indications in inflammatory conditions. 1650 22

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this high-risk population, inflammation (interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C-reactive protein (hs-CRP), have been shown to independently predict mortality in ESRD patients. As CRP is so strongly associated with vascular disease it has been suggested that this hepatic-derived protein is not only a marker, but also a mediator, of vascular disease. Although in vitro data from studies on endothelial cells, monocytes-macrophages and smooth muscle cells support a direct role for CRP in atherogenesis, data from studies performed in vivo have been controversial. The causes of the highly prevalent state of inflammation in ESRD are multiple, including inflammatory signals associated with the dialysis procedure, decreased renal function, volume overload, comorbidity and intercurrent clinical events. As the prevalence of inflammation varies considerably between continents and races, dietary and/or genetic factors may have an impact on inflammation in ESRD. Elevated CRP in dialysis patients could be evaluated at three different levels: (i) national/regional level; (ii) dialysis unit level; and (iii) individual patient level.
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PMID:Inflammation in end-stage renal disease: the hidden enemy. 1650 30

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. Besides traditional risk factors, disturbances in mineral and bone metabolism and inflammation are thought to be responsible for the increased risk of death. In the last years C-reactive protein (CRP) has gained a lot of attention in the general population, especially with regard to its link with atherosclerosis. Although several studies suggest that CRP may be useful as a parameter in predicting future cardiovascular events in both the general population and in patients with end-stage renal disease, there is doubt about the clinical evidence of this assumption. A statistical association between CRP and cardiovascular disease was observed in various studies, but the predictive power of this association is markedly diminished when adjusted for other risk factors. The relative contributions of CRP as a marker, as a causative agent, or as a consequence of atherosclerotic vascular disease are unclear, both in the general population and in the dialysis population. The CRP levels are highly variable and influenced by intercurrent events in dialysis patients. In dialysis patients, it is possible to reduce the CRP levels by statins, although these agents do not reduce the cardiovascular mortality in diabetic dialysis patients.
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PMID:The predictive value of C-reactive protein in end-stage renal disease: is it clinically significant? 1655 22

In the present study, we used high sensitivity C-reactive protein (hs-CRP) analysis in combination with lipid screening [which has been reported to be a more valuable risk marker than other novel markers such as homocysteine (Hcy) and lipoprotein a] to perform cardiovascular risk assessment in peritoneal dialysis (PD) and hemodialysis (HD) patients. We selected 9 PD patients, 10 HD patients, and 9 control subjects for the study. In those patients, we determined levels of serum lipids, hs-CRP, Hcy, vitamin B12, folic acid, and leptin. Patients on PD had a significantly elevated hs-CRP concentration (3.14 +/- 0.79 mg/L) and ratio of total cholesterol (TC) to high density lipoprotein (HDL) cholesterol (4.71 +/- 0.40), and their cardiovascular risk was found to be three times that of control subjects. In HD patients, the elevation of hs-CRP was more profound (5.66 +/- 1.30), but their TC:HDL ratio fell within the normal range (3.18 +/- 0.13). However, a cardiovascular risk assessment of the HD group showed the same risk as in the PD group. Serum Hcy was also elevated in patients on PD (54.95 +/- 18.08 microl/L) and on HD (25.33 +/- 3.70 micromol/L) as compared with healthy subjects (13.76 +/- 0.94 micromol/L). Folic acid and vitamin B12 levels (needed to remethylate Hcy to methionine) were not compromised in the dialysis population. On the other hand, leptin secreted by adipose tissue was found to be mildly higher in PD patients (37.08 +/- 12.59 ng/mL). The mean leptin level in control subjects was 14.14 +/- 3.60 ng/mL. The proinflammatory and proangiogenic action of excess leptin may aggravate cardiovascular risk in PD patients. Increased values of known risk factors were found in dialysis patients on PD and on HD. However, lower levels of HDL cholesterol, higher cardiovascular risk assessment and Hcy levels, and mildly increased leptin levels seem to increase the potential threat of vascular disease in PD patients more than in HD patients.
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PMID:Cardiovascular risk assessment and homocysteine and leptin levels in peritoneal dialysis and hemodialysis patients. 1668 91

The risk factors for hypertension are only partly known, and accounts for the some of the deficiencies in current primary prevention strategies and in the design of new drugs for the management of this common condition. Recently, chronic low grade low-grade inflammation has been identified as an integral part in the pathogenesis of vascular disease. Of note, inflammation may also be implicated in the development of hypertension, either as a primary or secondary event. Indeed, several clinical studies have demonstrated increased numbers of well recognised pro-inflammatory markers, such as high sensitive C-reactive protein (hsCRP), in patients with hypertension, even after adjustment for potential confounding factors. Furthermore, elevated hsCRP levels have also been shown to be predictive for the development of hypertension in prehypertensive and normotensive patients. Pathophysiologically, inflammation has been implicated in both endothelial (dys)function and arterial stiffness in hypertension, with reduced availability of nitric oxide (NO) being integral to this process. Oxidative stress also appears to be a key feature in the reduced availability of NO and is aggravated by increased circulating angiotensin II (Ang II). Importantly, there is some evidence that drugs commonly used in the management of hypertension, such as statins, angiotensin converting enzyme inhibitors and Ang II receptor blockers have anti-inflammatory properties that can positively influence outcomes in patients with hypertension. The inflammatory state in hypertension may pose a new therapeutic target for future drug design.
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PMID:Is hypertension an inflammatory process? 1672 74

Premature coronary heart disease has emerged as a major cause of morbidity and mortality in systemic autoimmune diseases. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and that of atherosclerosis. Some of the most remarkable data in support of a link between autoimmunity and atherosclerosis comes from epidemiological studies of patients with autoimmune disorders (RA and SLE). Many epidemiologic observations have linked systemic inflammation with the cardiovascular events in autoimmune disease such as RA and SLE. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Systemic inflammation may be regarded as accelerating the atherosclerotic process. Systemic levels of soluble inflammatory mediators such as C-reactive protein (CRP) have been associated with cardiovascular risk in the general population. CRP, or more specifically high sensitivity-hsCRP, is a marker of systemic inflammation that has been identified as a valid biomarker of cardiovascular risk. Furthermore, the immunomodulatory and anti-inflammatory actions of statins may affect their utility in the context of chronic inflammatory autoimmune disease. Thus, effective control or dampening of inflammation, with such agents, should be included in the therapeutic armamentarium of autoimmune diseases with the aim of protecting against cardiovascular disease.
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PMID:Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. 1678 58

Inflammation is a key mechanism in the initiation, progression, and clinical sequelae of cardiovascular diseases (CVDs), including atherosclerosis, nephropathy, and cardiomyopathy. Angiotensin II, the major effector peptide of the renin-angiotensin-aldosterone system (RAAS), plays a significant role in the advent and perpetuation of these inflammatory diseases, most notably in atherogenesis. Consequently, suppression of the influence of angiotensin II by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce or potentially reverse atherosclerosis and other inflammation-associated CVDs. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors exert anti-inflammatory actions and prevent or reduce the development of atherosclerosis in animal models. Clinically, RAAS suppression reduces common carotid and femoral artery intima-media thickness, thus indicating moderation of the vascular disease process. These clinical benefits likely involve restraint of the deleterious effects of angiotensin II in addition to, or independent of, lowering blood pressure. Increasing evidence that the detection and monitoring of vascular inflammation are important tools in the management of atherosclerosis also implicates the RAAS in this pathogenic process. Inflammatory molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and C-reactive protein have potential diagnostic and prognostic values in CVD and are modified by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Monitoring these markers may be crucial for determining which agents, or combinations of agents, will result in the most clinically beneficial outcomes for patients. Large-scale trials are still required to determine the effects of the long-term suppression of inflammation on CVDs through the use of RAAS modulating agents, as well as to determine how closely markers of inflammatory activity may correlate with CVD outcomes.
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PMID:Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. 1712 70

There is considerable interest in the inflammatory hypothesis of vascular disease. Markers of inflammation predict vascular events, and inflammatory cells and molecules are critical elements within plaques and are especially prominent in unstable lesions. With respect to screening, concentrations of C-reactive protein (CRP), as determined by high-sensitivity assays, have been consistently shown to predict myocardial infarction and other vascular events independently of traditional risk factors. As a result, some authorities proposed potential inclusion of CRP in risk factor stratification. However, more recent evidence in the last two years from larger studies suggests that CRP concentrations are only around as half as predictive for vascular events as suggested in earlier reports. Furthermore, it now appears as if CRP measurements add little additional predictive value to current coronary heart disease risk prediction charts. The short-term variability of CRP is also problematic for risk factor screening. At the same time, other recent evidence questions the proposed causal role of CRP in atherogenesis. Therefore, the current focus in clinical practice should remain on established risk factors (e.g. smoking, lipids and blood pressure), both to determine coronary heart disease risk and to reduce it.
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PMID:High sensitivity C-reactive protein and cardiovascular disease: an association built on unstable foundations? 1682 74

Hyperglycemia increases cardiovascular disease risk, but the association between increasing glycemia and cardiovascular risk factors, angina, and coronary heart disease in normoglycemic subjects is less clear, particularly in Chinese. We report on possible associations in a large group of Mainland Chinese subjects. A total of 10,400 older subjects (> or = 50 years) were recruited, and vascular risk factors were measured, including anthropometry, blood pressure, and fasting plasma biochemical factors including glucose, lipid profile, and C-reactive protein (CRP). Subjects were categorized by glycemic status, and the relationship between glycemia and cardiovascular risk factors was investigated using analysis of variance and multiple linear regression analyses. Tertiles of fasting glucose levels showed a clear positive relationship with cardiovascular risk factors including age, obesity, blood pressure, lipid levels, and CRP (P < .001 for all). The overall prevalence of self-reported vascular disease was low, but significantly associated with increasing glycemia. Multiple regression showed that waist circumference (standardized regression coefficient beta = .10, P < .001), triglycerides (beta = 0.16, P < .001), CRP (beta = 0.06, P < .001), female sex (beta = .03, P = .007), high-density lipoprotein cholesterol (beta = -.02, P = .016), and mean arterial pressure (beta = .06, P < .001) were independently associated with fasting glucose levels. Among the normoglycemic subjects (n = 5190), increasing glycemia was still associated with increasing obesity indices, systolic blood pressure, triglyceride, and CRP levels (all P < .05). Increasing glycemia, even in the reference range, is associated with increasing prevalence of vascular risk factors. Control of these risk factors, particularly obesity, the most important avoidable independent determinant of glycemia in normoglycemic subjects, is critical to reduce the risk of the associated vascular disease.
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PMID:Association of vascular risk factors with increasing glycemia even in normoglycemic subjects in an older Chinese population: the Guangzhou Biobank Cohort Study. 1683 38

Serum cholesterol has long been recognized as an important risk factor for the development and progression of atherosclerotic vascular disease. For more than 30 years, improved outcomes with lipid lowering have been demonstrated. As a result of these data, the National Heart, Lung, and Blood Institute (NHLBI) convened the National Cholesterol Education Program-Adult Treatment Panel I (NCEP ATP I). This panel and similar ones around the world have served to set the standards for lipid lowering in clinical practice. Subsequent revisions of these standards (NCEP ATP II and III) have led to greater focus being placed on LDL, and targets for lowering LDL levels being based on patients' risk of subsequent coronary disease events. Since the publication of the NCEP ATP III guidelines, several large-scale clinical trials of cholesterol lowering have been conducted, the findings of which have the potential to impact on clinical practice standards. In this article we focus on current guidelines for lipid-lowering therapy, review the results and implications of important completed clinical trials, and consider the utility of additional targets for preventive therapy, such as C-reactive protein and HDL. We also consider the prospects for treatments in development and future goals.
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PMID:Update on lipid-lowering therapy and LDL-cholesterol targets. 1687 55


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