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

Despite meaningful progress in the identification of risk factors and the development of highly effective clinical tools, deaths from cardiovascular disease continue to increase worldwide. Sparked by an obesity epidemic, the metabolic syndrome and the rising incidence of type 2 diabetes have led to an upsurge of cardiovascular risk. Although pharmacologic treatments with the statin class of drugs have reduced cholesterol levels and lowered mortality rates, several large controlled clinical trials, including the Scandinavian Simvastatin Survival Study, the Cholesterol and Recurrent Events trial, the Air Force/Texas Coronary Atherosclerosis Prevention studies, and Long-term Intervention with Pravastatin in Ischemic Disease study, have indicated that cardiovascular events continue to occur in two thirds of all patients. Follow-up studies, such as the Heart Protection Study and the Pravastatin or Atorvastatin Evaluation and Infection Therapy/Thrombolysis In Myocardial Infarction-22 trials, reinforced these earlier results. Although therapy with gemfibrozil, a fibric acid derivative, showed reduced occurrence of cardiovascular events in the Helsinki Heart Study and the Veterans Affairs HDL Intervention Trial, results of other studies, e.g., the Bezafibrate Intervention Program and the Diabetes Atherosclerosis Intervention study, showed less encouraging results. Although lifestyle modifications, such as improved diet and increased exercise levels, benefit general health and the metabolic syndrome and insulin resistance in particular, most people continue to resist changes in their daily routines. Thus, physicians must continue to educate their patients regarding an optimal balance of drug therapy and personal behavior.
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PMID:The forgotten majority: unfinished business in cardiovascular risk reduction. 1619 35

The metabolic syndrome and type 2 diabetes mellitus are both becoming more prevalent, and both increase the risk of cardiovascular disease. Many patients are not receiving appropriate treatment for the type of dyslipidemia that commonly occurs in these disorders--the so-called 'atherogenic lipid triad' of high serum triglyceride levels, low serum high-density lipoprotein cholesterol (HDL-C) levels, and a preponderance of small, dense, low-density lipoprotein cholesterol (LDL-C) particles. All of the processes involved in atherogenesis can be exacerbated by insulin resistance and/or the metabolic syndrome. Hypertriglyceridemia is a strong predictor of coronary heart disease. There is also an inverse relationship between serum levels of HDL-C and triglycerides in diabetic patients, with low serum HDL-C levels possibly representing an independent risk factor for cardiovascular disease. Small, dense, LDL-C particles are also highly atherogenic as they are more likely to form oxidized LDL and are less readily cleared. Insulin resistance, which is central to the metabolic syndrome and type 2 diabetes mellitus, leads to high levels of very low-density lipoprotein (VLDL), which contain a high concentration of triglycerides, resulting in high serum triglyceride levels and low serum HDL-C levels. Even though modification of the atherogenic lipid triad is probably one of the most effective methods of reducing cardiovascular risk, therapy for diabetic dyslipidemia is often directed to first lowering serum LDL-C levels with a HMG-CoA reductase inhibitor. This may leave substantial excess risk for cardiovascular disease in patients with these types of dyslipidemia. The results of recent trials evaluating HMG-CoA reductase inhibitors have been mixed, with two showing no significant effect on cardiovascular outcomes in subgroups of diabetic patients. The recent CARDS (Collaborative Atorvastatin Diabetes Study) showed that atorvastatin can reduce cardiovascular events in a trial specifically designed for a diabetic population, though the population had to have at least one other risk factor in addition to diabetes mellitus. Fibric acid derivatives, such as fenofibrate, bezafibrate and gemfibrozil, are potentially well suited to the treatment of dyslipidemia that is generally associated with type 2 diabetes mellitus and the metabolic syndrome, as they are usually more effective than HMG-CoA reductase inhibitors for normalizing serum levels of HDL-C and triglycerides. Promising results have been obtained from several trials of fibric acid derivatives including the BIP (Bezafibrate Infarction Prevention) study and the VA-HIT (Veterans Affairs Cooperative Studies Program HDL-C Intervention Trial; gemfibrozil). The FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial, a clinical outcomes trial specifically designed to evaluate fenofibrate in a large population of patients with type 2 diabetes mellitus, many of whom have the metabolic syndrome, is underway. The FIELD trial results should shed light on the efficacy and safety of fenofibrate in reducing cardiovascular morbidity in diabetic and metabolic syndrome patients and on the safety profile of combination therapy with fenofibrate and a HMG-CoA reductase inhibitor.
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PMID:Beyond low-density lipoprotein: addressing the atherogenic lipid triad in type 2 diabetes mellitus and the metabolic syndrome. 1625 26

The incidence of type 2 diabetes mellitus is expected to increase dramatically over the next decade. Patients with type 2 diabetes are at a much greater risk for cardiovascular disease (CVD) than are nondiabetic individuals. Consequently, the treatment of CVD risk factors is a healthcare priority in this patient population. Dyslipidemia is a major cardiovascular (CV) risk factor in patients with type 2 diabetes, and it is characterized by elevated triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, and a preponderance of small, dense low-density lipoprotein (LDL) particles. Subgroup analyses of clinical trial data suggest that treatment of the entire range of lipid abnormalities may reduce CV risk in this patient population. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are the best therapy for LDL cholesterol reduction. A number of statin trials have shown significant CV risk reduction through LDL cholesterol lowering in subgroups of patients with diabetes. The recently published Collaborative Atorvastatin Diabetes Study (CARDS), a placebo-controlled trial conducted solely in patients with type 2 diabetes, terminated 2 years earlier than its anticipated length owing to the significant reduction in number of CV events observed in patients randomized to receive low-dose atorvastatin versus placebo. These results suggest that low-dose statin therapy with atorvastatin results in significant reduction of CV events in patients with type 2 diabetes without prior CVD or high LDL cholesterol levels. Based on this evidence, patients with type 2 diabetes may be candidates for statin therapy regardless of LDL cholesterol level and in the absence of a previous CV event.
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PMID:Benefits of lipid-lowering therapy in patients with type 2 diabetes mellitus. 1635 2

The current Third Joint European Societies' Guidelines on Cardiovascular Disease Prevention in Clinical Practice reflect an active approach to cardiovascular disease (CVD) prevention. These guidelines have shifted the emphasis from coronary heart disease to total atherosclerotic CVD. A new risk prediction system, Systematic Coronary Risk Evaluation (SCORE), has been developed to define risk in terms of absolute 10-year risk of a fatal cardiovascular event. The definition of high risk has also been refined. The currently recommended goals for total and low-density lipoprotein (LDL) cholesterol are based on the evidence pool that was available at the time of publication. More recent evidence from the Heart Protection Study (HPS), the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), and the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial indicates that lowering LDL cholesterol levels beyond the currently recommended goals can produce incremental reductions in cardiovascular morbidity and mortality. Results from the recently completed Treating to New Targets (TNT) study lend further support to implementing lower lipid goals than those currently suggested by guidelines. Results from the ongoing Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL) trial may provide additional evidence in support of the implementation of lower lipid goals. Nevertheless, the scope of future guidelines extends well beyond lipid targets. Guidelines of the future are likely to provide increasingly comprehensive recommendations on combined risk reduction, to publicize the characteristics of healthy people by highlighting acceptable levels of all cardiovascular risk factors, and to refine the concept of evidence-based medicine by shifting the focus from drug therapy to preventive therapy.
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PMID:What impact will current trial data have on future guideline recommendations? 1635 7

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor. Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined. Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone. Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function. Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.
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PMID:Gout in solid organ transplantation: a challenging clinical problem. 1639 75

Guidelines from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) focus the need for the most intensive efforts to lower low-density lipoprotein cholesterol (LDL-C) in the patients at greatest risk of a major future clinical coronary heart disease event. Major clinical trials, such as Pravastatin or Atorvastatin Evaluation and Infection Therapy and the Heart Protection Study, demonstrated the value of lowering LDL-C levels in high-risk patients to well below the ATP III target of <100 mg/dL. In 2004, the NCEP writing group suggested that a more aggressive LDL-C goal of <70 mg/dL is an option when treating high-risk patients, particularly those with the presence of established cardiovascular disease plus major multiple risk factors (especially diabetes), severe and poorly controlled risk factors (ie, cigarette smoking), multiple criteria of the metabolic syndrome, or an acute coronary syndrome. With stricter targets, high-risk patients are less likely to achieve their cholesterol goals than lower risk patients. Recent large trials comparing rosuvastatin with other statin monotherapies have shown a greater LDL-C reduction and better attainment of goals with rosuvastatin. In addition, the MERCURY [Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy] trials demonstrate that switching to rosuvastatin significantly increased the percentage of patients who achieved their ATP III LDL-C targets.
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PMID:Rising to the challenge of treating high-risk patients. 1704 74

Recent reports have implicated osteoprotegerin (OPG) in cardiovascular disease processes. Endothelial and smooth muscle cells produce OPG and its expression in these cells is upregulated by inflammatory mediators. Statins, which besides their lipid lowering properties have various vasculoprotective effects, have been shown to regulate OPG expression in osteoblasts. We investigated whether statins affect the expression of OPG in human endothelial and smooth muscle cells. Using an ELISA we could demonstrate that statins reduce tumor necrosis factor-alpha (TNF-alpha)-induced OPG production in cultured human endothelial cells and smooth muscle cells. Atorvastatin also downregulated interleukin-1alpha (IL-1alpha)-induced OPG production in endothelial cells. A significant reduction of TNF-alpha-induced OPG was seen when statins were used in the nanomolar range. These results were confirmed at the level of specific mRNA expression by real-time-PCR. Using LDH leakage as a marker of cell damage we show that cell viability was not affected by statins at concentrations used in our study. The effect of statins on TNF-alpha-induced OPG production was reversed by mevalonate and geranyl-geranyl pyrophosphate at the level of protein production and at the level of mRNA expression, suggesting that it was brought about by inhibition of the mevalonic acid pathway and protein prenylation. Through our results we have added OPG to the list of molecules whose TNF-alpha-induced upregulation is counteracted by statins. If such an effect is also operative in the in vivo setting, one could postulate a role for statins in the modulation of cardiovascular disease processes possibly regulated by OPG.
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PMID:Statins decrease TNF-alpha-induced osteoprotegerin production by endothelial cells and smooth muscle cells in vitro. 1707 Jul 81

Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease, only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease (CKD). A 6-mo, prospective, randomized study was designed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD. Sixty-six patients with CKD (stages 2, 3, and 4) and LDL cholesterol levels > or =100 mg/dl were randomly assigned (2:1) to receive 20 mg/d atorvastatin (n = 44) or nonatorvastatin therapy (n = 22). Lipid profile, renal function, fibrinolytic balance (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1), and inflammatory markers (C-reactive protein [CRP], IL-1 beta, IL-6, and TNF-alpha) were measured before and 6 mo after atorvastatin was added to the treatment. Twenty-five age-matched individuals with normal renal function (estimated GFR >90 ml/min) were used as healthy control subjects. Patients with CKD had higher CRP, IL-1 beta, TNF-alpha, and IL-6 levels than age-matched population with normal renal function. t-PA concentration was higher in patients with CKD (P = 0.000). Plasminogen activator inhibitor-1 values were comparable in all patients. Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin. In addition to the hypolipidemic effect, atorvastatin treatment significantly reduced inflammatory parameters: CRP (median 4.1 to 2.9; P = 0.015), TNF-alpha (6.0 +/- 2.7 to 4.7 +/- 2.4; P = 0.046), and IL-1 beta levels (1.9 +/- 0.7 to 1.2 +/- 0.7; P = 0.001). These parameters remained unchanged in patients who were not treated with atorvastatin. Fibrinolytic parameters were not modified by atorvastatin treatment. Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects. Atorvastatin treatment, in addition to its beneficial effect on cholesterol levels, improved the inflammatory state of these patients without modifying fibrinolytic balance.
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PMID:Effects of atorvastatin on inflammatory and fibrinolytic parameters in patients with chronic kidney disease. 1713 Feb 67

Statins are effective drugs in the prevention of cardiovascular disease. Recent studies suggested that statins have additional beneficial effects on the vascular wall independent of their cholesterol-lowering effects. We investigated whether atorvastatin influences angiotensin-converting enzyme (ACE) production in differentiating human macrophages. Human peripheral blood monocytes (PBM) were isolated from fresh buffy coats. The cells were allowed to differentiate for 0-8 days in macrophage serum-free medium with 5 ng/ml granulocyte-macrophage colony-stimulating factor. Atorvastatin (0.005-0.5 microM), mevalonate (200-400 microM), geranylgeranyl pyrophosphate (1.25-2.5 microM), and/or farnesylpyrophosphate (FPP; 1.25-2.5 microM) was added on the second day of differentiation and then every other day. After incubation time, the ACE amount in intact macrophages was measured. ACE amount in PBM was low. A marked time-dependent ACE induction was noticed during differentiation of monocytes to macrophages. Atorvastatin treatment inhibited ACE induction during differentiation. In the presence of mevalonate, atorvastatin failed to downregulate ACE production. Cotreatment of the cells with atorvastatin and FPP reversed the suppressive effect of atorvastatin on ACE. In conclusion, atorvastatin inhibited ACE upregulation, normally occurring in differentiating human macrophages. This effect was mediated via the mevalonate pathway, and inhibition of FPP was probably involved. The finding that atorvastatin inhibited ACE upregulation may represent a novel pleiotropic action and an additional beneficial effect of statins in treatment of cardiovascular disease.
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PMID:Atorvastatin inhibits angiotensin-converting enzyme induction in differentiating human macrophages. 1715 48

In the general population, the relation between lipids and cardiovascular disease is clearcut, whereas it is highly controversial in chronic kidney disease (CKD) patients. This is primarily due to diverging results of retrospective observational trials. This study design often encounters confounding, especially in renal disease patients. Even if analyses are corrected for multiple influences, there might be unknown confounders changing the results. Prospective randomized trials assure that groups are comparable except for the intervention used. Confounding is eliminated by randomization. Nevertheless, the lipid discussion was restarted when two randomized, placebo-controlled, interventional trials on lipid-lowering therapy in renal patients have been published (Assessment of Lescol in Renal Transplantation and 4D Study [Atorvastatin in patients with type 2 diabetes on hemodialysis]). Surprisingly, both showed no significant reduction of the primary endpoint by statin therapy. In addition to other factors, this might be due to an altered pathogenesis of atherosclerosis in renal patients where multiple nontraditional cardiovascular risk factors are to be mentioned and different characteristics of cardiovascular disease with a high proportion of sudden cardiac death are present. This review will focus on dyslipidemia in renal failure and its treatment. The data published so far is summarized and grouped according to the different stages of CKD.
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PMID:Lipid metabolism in chronic kidney disease: the role of statins in cardiovascular risk. 1719 38


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