Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypertriglyceridemia attends the physiopathology of the atherosclerosis by various mechanisms: association of low levels of high density lipoprotein-cholesterol (HDL-c), modification of quality of low density lipoprotein-cholesterol (LDL-c), influence on hemostatic processes, association with other hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia distinguishes in primary and secondary. In primary forms the origin is essentially genetic, while the secondary ones are metabolic consequence of various pathologies (renal, thyroid, diabetes mellitus etc.). The hypertriglyceridemia's treatment is founded on a correct feeding and/or on eventual use of drugs. Apart from the secondary forms, in which is obligatory to treat at first the basal disease, the pharmacological therapy of the hypertriglyceridemia is suggested only in resistant cases to alone dietetic therapy and overall in presence of other factors of atherothrombotic hazard. The most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases inhibitors is the acarbose. It reduces the biosynthesis of very low density lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic metabolism. Atorvastatin and cerivastatin develop a greater action to reduce serum levels of triglycerides as to the foregoing ones because of the better selectivity of receptor binding, the greater halflife and inhibition of the apolipoprotein's B100 synthesis.
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PMID:[Treatment of hypertriglyceridemia. Current aspects]. 1093 25

Apolipoprotein (apo) E and C-I are plasma apolipoproteins that have been implicated in the etiology of atherosclerosis and obesity, respectively. Both proteins are synthesized and secreted by macrophages, though pharmacological regulation of their production is poorly understood. The authors compared the effect of 2 HMG-CoA reductase inhibitors, atorvastatin and cerivastatin, on the synthesis and secretion of apoE and apoC-I by THP-1 macrophages. Atorvastatin reduced medium apoE and cellular apoE mRNA of PMA-activated THP-1 cells in a dose-dependent manner (-24% and -22%, respectively, at 1-micromol/L, P < 0.01). ApoC-I in the medium was also reduced by atorvastatin in a dose-dependent manner, though to a lesser extent (-15% at 1-micromol/L, P < 0.05). Cerivastatin similarly reduced medium apoE (-20% at 1-micromol/L, P < 0.05) and cellular apoE mRNA (-31% at 1-micromol/L, P < 0.05), and significantly lowered cellular apoC-I mRNA (-15%, P < 0.05), but not apoC-I in the medium. In experiments with THP-1 macrophages loaded with cholesterol (ie, 24-hour incubation with acetyl-LDL), atorvastatin and cerivastatin (1-micromol/L) significantly (P < 0.05) reduced both medium apoE (-30% and -25%, respectively) and cellular apoE mRNA (-25% and -17%, respectively). A lower and less consistent effect was observed on medium apoC-I (-6% and -18%, respectively) and cellular apoC-I mRNA (-13% and -19%, respectively). These data demonstrate that statins have the capacity to reduce the synthesis and secretion of both apoE and apoC-I in THP-1 macrophages loaded or unloaded with cholesterol.
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PMID:Effect of atorvastatin on ApoE and ApoC-I synthesis and secretion by THP-1 macrophages. 1288 30

Both in Western countries and in third world countries there is an increasing incidence of obesity. Obesity per se or insulin resistance associated with obesity may increase cardiovascular risk factors including dyslipidemia, hypertension and Type 2 diabetes. Over the past decade the understanding has increased of specific mediators in the hypothalamus that are involved in regulating food intake and body weight. In obese humans fasting plasma lipids can be normal but postprandial lipid metabolism is abnormal with an accumulation of triglyceride-rich remnant lipoproteins. In viscerally obese men chylomicron remnant catabolism was markedly decreased when compared with lean individuals. The decreased clearance of chylomicron remnants in viscerally obese subjects may be explained by competition between chylomicron remnants and the increased hepatic production of VLDL for clearance by low density lipoprotein receptors. Increased food intake in rodent models of obesity was shown to be associated with a delay in the catabolism of remnant lipoprotein particles. Prevention of hyperphagia was found to correct the impairment in the metabolism of remnant lipoproteins. Under fasting and food restricted conditions the improvement of remnant metabolism was associated with an increased oxidation of remnant lipids as determined by a novel stable isotope breath test. Anti-obesity and lipid lowering drugs have been used for the treatment of obesity. Inhibitors of cholesterol synthesis inhibitors (statins) have been shown to be effective in treating dyslipidemia. Inhibition of cholesterol synthesis with Atorvastatin was shown to improve chylomicron metabolism by increasing chylomicron remnant catabolism in obese subjects as assessed by the newly developed stable isotope breath test.
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PMID:Obesity and post-prandial lipid metabolism. Feast or famine? 1502 94

There are no prospective data on the effect of a multitargeted treatment approach on cardiovascular disease (CVD) risk reduction in nondiabetic patients with metabolic syndrome (MetS). Furthermore, the optimal hypolipidemic drug treatment in these patients remains controversial. In this prospective, randomized, open-label, intention-to-treat, and parallel study, 300 nondiabetic patients with MetS, free of CVD at baseline, were studied for a period of 12 months. Age- and sex-matched subjects without MetS (n = 100) acted as controls. All patients received lifestyle advice and a stepwise-implemented drug treatment of hypertension, impaired fasting glucose, and obesity. For hypolipidemic treatment, the patients were randomly allocated to 3 treatment groups: atorvastatin (n = 100, 20 mg/d), micronized fenofibrate (n = 100, 200 mg/d), and both drugs (n = 100). Clinical and laboratory parameters, including the lipid profile and C-reactive protein (CRP), were assessed at the baseline and at the end of the study. The primary end point was the proportion of patients not having MetS or its component features at the end of the 12-month treatment period. The secondary end points were the difference in 10-year CVD risk (Prospective Cardiovascular Munster risk calculator) and the degree of CRP reduction. By the end of the study, 76% of the patients no longer had MetS, and 46% had only one diagnostic MetS factor. The estimated 10-year (Prospective Cardiovascular Munster) risk of all patients with MetS at baseline was 14.6%. This was reduced in the atorvastatin group to 6.4%, in the fenofibrate group to 9.2%, and in the combination group to 5.5% (P < .0001 for all vs baseline). The 10-year risks of the atorvastatin and combination groups were not different from that of the control group (5.0%). C-reactive protein was significantly reduced in all treatment groups, with the atorvastatin and combination groups having the greatest reduction (65% and 68%, respectively, P < .01 vs the fenofibrate group, 44%). Lipid values were significantly improved in all 3 treatment groups, with those on the combined treatment attaining lipid targets to a greater extent than those in the other 2 groups. A target-driven and intensified intervention aimed at multiple risk factors in nondiabetic patients with MetS substantially offsets its component factors and significantly reduces the estimated CVD risk. The atorvastatin-fenofibrate combination had the most beneficial effect on all lipid parameters and significantly improved their CVD risk status. Atorvastatin and combination treatment were more effective than fenofibrate alone in reducing CRP levels.
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PMID:Targeting vascular risk in patients with metabolic syndrome but without diabetes. 1609 57

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

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

The study comprised 35 patients with mixed hyperlipidaemia and coronary heart disease (CHD) risk factors (overweight or obesity, low physical activity, family history). Seventeen patients were administered atorvastatin in a dose of 10 mg and 18 -fluvastatin in a dose of 40 mg once daily at bed time for 6 weeks. The control group consisted of 12 clinically healthy subjects with no CHD risk factors. Blood samples for testing were collected from cubital vein of patients after hypolipaemic diet prior to and 6 weeks after drugs application and once in control group. Malondialdehyde (MDA) concentrations in erythrocytes and plasma were determined by the method of Placer et al. MDA concentrations in erythrocytes and plasma were significantly higher (p < 0.05) in patients than in healthy subjects. After 6-week atorvastatin therapy MDA concentrations in erythrocytes and plasma decreased to the values observed in healthy subjects. In fluvastatin group erythrocyte and plasma MDA concentrations were unchanged and still significantly higher in comparison to the healthy subjects. Atorvastatin, contrary to fluvastatin, decreases lipid peroxidation in CHD risk patients.
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PMID:[Estimation of antioxidative effect of atorvastatin and fluvastatin used in primary prevention of coronary heart disease--effect on lipid peroxidation]. 1642 89

Type 2 diabetes mellitus is the leading cause of macrovascular diseases and related death. Additionally, diabetes mellitus is frequently complicated by other cardiovascular risk factors, such as hypercholesterolemia, hypertension, obesity, hypercoagulability, and inflammation. We wanted to evaluate and compare the effects of treating with a one-year course of atorvastatin or simvastatin on inflammatory markers such as high sensitive C-reactive protein (hsCRP), fibrinogen, and ferritin in uncontrolled type 2 diabetic patients. Also, we planned to investigate the correlation between inflammatory markers and metabolic parameters. Fifty type 2 diabetic patients (30 women, 20 men; mean age: 49.9 +/- 8.5 years) were enrolled into the study. Twenty healthy subjects, matched on body mass index and age, were also included in the study as a control group. Diabetic patients were divided into two groups and received simvastatin or atorvastatin (Group S and A, respectively). After 1 year of statin treatment (Group A), there were significant decreases in total cholesterol (217.3 +/- 46.5-173.8 +/- 37.2 mg/dl; P < 0.0001), LDL-cholesterol (146.7 +/- 50.3-102.3 +/- 31.1 mg/dl, P < 0.0001), hsCRP (0.88 +/- 0.62-0.35 +/- 0.18 mg/dl, P < 0.0001), fibrinogen (258.2 +/- 16.9-215.5 +/- 10.6 mg/l; P < 0.0001), and ferritin (118.2 +/- 73.9-81.2 +/- 72.5 ng/ml, P < 0.0001) levels compared to basal values. In the S group, there were significant decreases in total cholesterol (224.4 +/- 61.2-175.0 +/- 47.8 mg/dl; P < 0.0001), LDL-cholesterol (140.9 +/- 56.7-110.9 +/- 42.2 mg/dl, P < 0.0001), hsCRP (0.98 +/- 1.3-0.46 +/- 0.25 mg/dl, P < 0.0001), fibrinogen (265.7 +/- 26.8-222.1 +/- 20.6 mg/l; P < 0.0001), and ferritin (136.7 +/- 101.1-85.6 +/- 32.1 ng/ml, P < 0.0001) levels compared to basal values. At the end of the study, hsCRP, fibrinogen, and ferritin levels were correlated with LDL (r = 0.42; P = 0.005, with hsCRP), (r = 0.40; P = 0.008, with fibrinogen), (r = 0.46; P = 0.002, with ferritin) and HDL (r = -0.50; P < 0.0001, with hsCRP), (r = -0.32; p = 0.042, with fibrinogen), (r = -0.48; P < 0.0001, with ferritin) cholesterol levels. Atorvastatin and simvastatin treatments were found to be effective for the control of hypercholesterolemia and resulted in a significant decrease in acute phase reactants in uncontrolled type 2 diabetic patients.
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PMID:Effects of one year simvastatin and atorvastatin treatments on acute phase reactants in uncontrolled type 2 diabetic patients. 1925 30

Considering that inflammation contributes to obesity-induced insulin resistance and that statins have been reported to have other effects beyond cholesterol lowering, the present study aimed to investigate whether atorvastatin treatment has anti-inflammatory action in white adipose tissue of obese mice, consequently improving insulin sensitivity. Insulin sensitivity in vivo (by insulin tolerance test); metabolic-hormonal profile; plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and adiponectin; adipose tissue immunohistochemistry; glucose transporter (GLUT) 4; adiponectin; TNF-alpha; IL-1 beta; and IL-6 gene expression; and I kappaB kinase (IKK)-alpha/beta activity were assessed in 23-week-old monosodium glutamate-induced obese mice untreated or treated with atorvastatin for 4 weeks. Insulin-resistant obese mice had increased plasma triglyceride, insulin, TNF-alpha, and IL-6 plasma levels. Adipose tissue of obese animals showed increased macrophage infiltration, IKK-alpha (42%, P < .05) and IKK-beta (73%, P < .05) phosphorylation, and TNF-alpha and IL-6 messenger RNA (mRNA) ( approximately 15%, P < .05) levels, and decreased GLUT4 mRNA and protein (30%, P < .05) levels. Atorvastatin treatment lowered cholesterol, triglyceride, insulin, TNF-alpha, and IL-6 plasma levels, and restored whole-body insulin sensitivity. In adipose tissue, atorvastatin decreased macrophage infiltration and normalized IKK-alpha/beta phosphorylation; TNF-alpha, IL-6, and GLUT4 mRNA; and GLUT4 protein to control levels. The present findings demonstrate that atorvastatin has anti-inflammatory effects on adipose tissue of obese mice, which may be important to its local and whole-body insulin-sensitization effects.
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PMID:Anti-inflammatory effect of atorvastatin ameliorates insulin resistance in monosodium glutamate-treated obese mice. 1980 Jun 37

To facilitate comprehensive cardiometabolic risk assessment, we developed a simple 12-point checklist of traditional and emerging risk factors. We recently analyzed data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial of 4162 high-risk patients hospitalized with recent acute coronary syndrome, and found that an increasing cardiometabolic risk factor count was associated with increasing risk of cardiovascular events over the next 2 years. In addition, we observed that the average number of risk factors a given patient had was 5, with some risk factors like obesity having clustering of additional risk factors, suggesting the need to assess the full list of risk factors to be able to provide comprehensive risk factor assessment and modification. We now have developed a 1-page patient encounter sheet to facilitate rapid assessment of these 12 cardiometabolic risk factors in a busy clinical office setting. It is hoped that with the simple risk assessment tool provided, clinicians would be able to comprehensively screen for and treat these traditional and nontraditional risk markers. As such, this could motivate both patients and physicians to work jointly toward reducing global cardiometabolic risk.
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PMID:Office-based global cardiometabolic risk assessment: a simple tool incorporating nontraditional markers. 2080 70


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