Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homocysteine is considered to be an independent risk factor for atherosclerosis. Experimental animal models of hyperhomocysteinemia show aortic calcification, suggesting that this disorder is associated with aortic calcification in humans. A total of 28 patients with hyperlipidemia were enrolled into this study. The degree of aortic calcification at the level of the bifurcation and 1 cm proximal to the bifurcation was assessed by computed tomography of the aorta and the association between calcification of the aorta and the plasma level of homocysteine was then analyzed. The mean plasma homocysteine level in 28 patients was 8.7 microM. They were divided into 2 groups, high homocysteine level group (HHL; homocysteine level >8.7 microM) and low homocysteine level group (LHL; homocysteine level < = 8.7 microM). The degree of aortic calcification at the level of the bifurcation differed significantly between the two groups (19.1% vs. 10.5%; p < 0.01). We found that mild hyperhomocysteinemia was associated with aortic calcification, which suggests that interventions to reduce the plasma level of homocysteine may also reduce the severity of aortic calcification.
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PMID:Association of mild hyperhomocysteinemia with aortic calcification in hypercholesterolemic patients. 1186 36

Moderately elevated plasma homocysteine levels have been established as independent risk factors in vascular disease, including ischemic stroke. Recently, a common mutation (C677T) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene reducing the activity of MTHFR and increasing homocysteine levels in plasma was reported. The C677T MTHFR mutation may be a risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that the association with the MTHFR genotype may be different according to gender. To investigate the association for ischemic stroke, we conducted a case-control study of 77 hospital cases (49 men and 28 women) with ischemic stroke and 229 (120 men and 109 women) control subjects in Japanese. The prevalence of conventional vascular risk factors and MTHFR genotypes were determined in case and controls. After adjustment by multiple analysis in all there was no statistical significance in MTHFR genotypes. The conventional vascular risk factors such as diabetes mellitus (adjusted odds ratio [OR], 17.21), hypertension (adjusted OR, 4.67), smoking habit (adjusted OR, 4.70), and hyperlipidemia (adjusted OR, 2.73) were identified independently associated with ischemic stroke. With a separate sex analysis it was identified that the relationship of the MTHFR T/T gneotype was statisticaly significant in women (adjusted OR, 9.49; 95% CI, 1.75-51.47, P=0.0091). The relevance of the MTHFR T/T mutation appears to be restricted to women, suggesting a role of female hormones in the resistance to elevated homocysteine levels due to the MTHFR T/T mutation.
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PMID:Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke: sex difference in Japanese. 1187 Mar 35

Management of the conventional cardiovascular risk factors is insufficient to prevent the dramatic increase in atherosclerotic cardiovascular morbidity and mortality in patients with renal failure. Folate recently received attention as a potential alternative treatment option to decrease the excess cardiovascular risk in the uremic population. Folate administration is the principal treatment modality for hyperhomocysteinemia. Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is independently associated with increased odds for atherosclerotic cardiovascular disease. Several attempts have been made to normalize homocysteine levels in uremic patients with folate-based vitamin regimens. Although supraphysiologic doses of folic acid afford greater reductions in homocysteine levels than standard doses, the response to treatment is generally only partial and the large majority of ESRD patients have residual hyperhomocysteinemia. Several defects in folate metabolism have been described in uremia, which may explain the relative folate resistance in patients with renal failure, but their clinical relevance remains uncertain. It appears unlikely that the hyperhomocysteinemia in ESRD can be cured solely with folic acid supplements, since folate does not affect the prolonged plasma elimination of homocysteine, which is the primary defect in homocysteine metabolism in uremia. Folate restores endothelial dysfunction, associated with hyperlipidemia, diabetes and hyperhomocysteinemia. The beneficial effect appears to be independent of its homocysteine-lowering capacity and is possibly related to an improved bioavailability of nitric oxide. However, folate has failed to improve endothelial dysfunction in uremic patients. In the ESRD population, multiple metabolic and hemodynamic abnormalities adversely affect endothelial function. In addition, irreversible structural vascular disease already may be present. Folate should, therefore, probably be an integral part of an "endothelial protective regimen," consisting of lipid-lowering agents, antihypertensives and antioxidant vitamins and started very early in patients with renal failure. Before large-scale folate administration can be recommended, effects on hard endpoints of cardiovascular disease need to be demonstrated in randomized trials. Such trials are currently underway in patients with normal renal function at high risk for cardiovascular disease, and one trial has recently been initiated in stable renal transplant recipients.
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PMID:Is folate a promising agent in the prevention and treatment of cardiovascular disease in patients with renal failure? 1263 Nov 53

Oxidative modification of lipoproteins in vessel walls plays a key role in atherogenesis. Patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis despite severe hyperlipidemia. We analyzed antioxidative defense and oxidative stress in plasma and serum of patients with GSD Ia (n = 17) compared to patients with type I diabetes mellitus (DMI, n = 17), familial hypercholesterolemia (FH, n = 18), and healthy controls (n = 20). We measured the total radical-trapping antioxidant parameter (TRAP), single antioxidants (sulfhydryl groups, uric acid, vitamin C, alpha-tocopherol, coenzyme Q10), malondialdehyde, oxidized low density lipoprotein (LDL) antibodies, lipid profile [cholesterol, triglyceride, lipoprotein (a)], homocysteine, and hemoglobin (Hb)A(1C). TRAP levels were elevated in the GSD Ia group (p <.01) and correlated with elevated uric acid levels (r = 0.72, p =.001). None of the other plasma antioxidants correlated with TRAP levels. DMI patients showed decreased sulfhydryl groups (p <.01) and a reduced ubiquinol-10 fraction (p <.01). Malondialdehyde (p <.001) and oxidized LDL autoantibodies (p <.05) were increased in the diabetic group. In FH patients, parameters of oxidative stress and TRAP did not differ from controls. We conclude that in GSD Ia an increased antioxidative defense in plasma may protect against lipid peroxidation and thus against premature atherosclerosis. Furthermore, we demonstrated that in DMI increased oxidative mechanisms are already present in childhood.
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PMID:Plasma antioxidants in pediatric patients with glycogen storage disease, diabetes mellitus, and hypercholesterolemia. 1208 88

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. Various factors, both modifiable and non-modifiable, interact with the homocysteine metabolism and determine the plasma homocysteine concentrations. These include genetic abnormalities, age, sex and various nutritional and hormonal determinants, all of which play a role in atherosclerosis and accelerated peripheral and cardio-vascular disease (CVD). Several hormones modulate homocysteine metabolism and hence may play a role in the pathogenesis of CVD. The mechanisms involved are unclear. The association of hyperhomocysteinemia with diabetes mellitus is complex and may explain some of the risk of CVD in diabetics not explained by traditional risk factors. Much conflicting data exists in the literature on the role of insulin on homocysteine metabolism, although insulin affects the enzymes regulating the homocysteine metabolism. Treatment of hyperhomocysteinemia with vitamins lowers plasma homocysteine concentrations. Little data is available on the effect of this intervention on cardiovascular outcomes. This review briefly outlines the homocysteine metabolism, summarizes its hormonal determinants, and discusses the role of hyperhomocysteinemia in diabetes, hyperlipidemia and other endocrine disorders.
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PMID:Hormones and homocysteine. 1209 90

Proven effective alternative and adjunctive therapies for lipid lowering could be beneficial for patients with hyperlipidemia. We evaluated a 90% soluble fiber for its ability to alter lipid, lipoprotein, and homocysteine levels in the setting of coadministered folate and B vitamins. Patients (n = 119) were randomized to either the fiber and vitamin combination, or placebo. Fasting lipid, glucose, and homocysteine concentrations, and body mass index (BMI) were obtained at baseline and weeks 4 and 8. Both between-group (Wilcoxon rank-sum test) and within-group (paired t test) comparisons were used to evaluate treatment effects. After 6 weeks of a diet therapy (National Cholesterol Education Program [NECP] Step I) run-in period, subjects in both groups had similar low-density lipoprotein cholesterol (LDL-C) levels (159 mg/dL v 158 mg/dL). The treated group showed a 7.1% +/- 11.6% reduction by 4 weeks, which was maintained at 8 weeks (7.9% +/- 11.0%). Placebo patients had a slight increase in LDL-C values over the same period (+2.4% +/- 11.7%), for a 10.3% difference between groups. The treatment effect was statistically significant both between groups (P <.001) and within the active-treatment group (P <.001) after the 8-week intervention. Apolipoprotein B (ApoB) levels in a representative subset of the treated group (n = 53) decreased by 20% (P =.004). The fiber blend neither raised triacylglycerol (TG) (P =.95) nor lowered high-density lipoprotein cholesterol (HDL-C) levels (P =.54), and lowered homocysteine (active, 9.8 to 8.7/micromol/L, P =.02; placebo, 9.4 to 9.2 /micromol/L, P =.98). Thus, a significant LDL-C lowering effect, with parallel Apo B reduction, was demonstrated for this fiber/vitamin combination. No adverse changes on TG or HDL-C levels were noted, and folate/B vitamin benefits attributed to homocysteine reduction were preserved. Concurrent administration of fiber and vitamins represents a preventive approach that may reduce the need for concomitant lipid-lowering therapies or serve as an adjunct therapy.
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PMID:Fiber-multivitamin combination therapy: a beneficial influence on low-density lipoprotein and homocysteine. 1220 Jul 62

Fibric acid derivatives are a class of hypolipidaemic drugs used in the treatment of patients with hypertriglyceridaemia, mixed hyperlipidaemia and diabetic dyslipidaemia. Fibrate therapy results in a significant decrease in serum triglycerides and an increase in high-density lipoprotein (HDL) cholesterol levels. The latest drugs of this class are also effective in lowering low-density (LDL) cholesterol levels and can change the distribution of LDL towards higher and larger particles. The effects of fibrates on lipid metabolism are mostly mediated through the activation of peroxisome proliferator-activated receptors (PPARalpha). A number of angiographic and clinical trials have confirmed that fibrates can slow the progression of atherosclerotic disease and decrease cardiovascular morbidity and mortality. Recently published data suggest that the ability of fibrates to prevent atherosclerosis is not related only to their hypolipidaemic effects but also to other 'pleiotropic effects', such as their anti-inflammatory, antioxidant and antithrombotic effects, as well as their ability to improve endothelial function. Interestingly, fibrates may favourably influence the thrombotic/fibrinolytic system. In fact, most of these drugs can significantly decrease plasma fibrinogen levels and inhibit tissue factor expression and activity in human monocytes and macrophages. Some studies have shown that fibrates can improve carbohydrate metabolism in patients with dyslipidaemia, including diabetic patients. Among fibrates only fenofibrate can significantly decrease serum uric acid levels by increasing renal urate excretion. Fibrates, with the possible exception of gemfibrozil, can significantly increase serum creatinine and homocysteine levels. Finally, a reduction in serum alkaline phosphatase and gamma glutamyltranspeptidase (gammaGT) activity is a well-documented effect of therapy with fibrates. The fibrates are generally well-tolerated drugs with few side-effects. The most important side-effect is myositis, which is observed in patients with impaired renal function or when statins are given concomitantly.
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PMID:Effects of fibrates on serum metabolic parameters. 1274 Jan 59

Hyperhomocysteinemia (HHCY) is a consequence of disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological and clinical studies have proven HHCY to be an independent risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Trials in progress may clarify the "causality" of high homocysteine (HCY) concentrations and will assess the value of HCY lowering therapy. HHCY is also seen as a risk factor for neurodegenerative diseases such as cognitive impairment, dementia, Alzheimer's disease, and also for depression. There is a high prevalence of HHCY as a syndrome of vitamin shortage in elderly subjects, which strongly increases with advancing age. Elderly people have a high frequency of vitamin B12 deficiency which is more reliably diagnosed by measurement of serum methylmalonic acid and holotranscobalamin II, the metabolically active B12 fraction, than by total serum vitamin B12. Subjects who follow a strict vegetarian diet also have a high prevalence of HHCY caused by vitamin B12 deficiency. For prevention of neurological damages an early diagnosis of vitamin B12 deficiency is important. Furthermore, HHCY is a factor in the pathogenesis of neural tube defects and preeclampsia. HCY should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in adipose subjects, in elderly people, in vegetarians, in postmenopausal women, and in early pregnancy.
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PMID:Hyperhomocysteinemia: a new risk factor for degenerative diseases. 1238 6

The mortality rate among dialysis patients is high. Although guidelines have been in place to improve outcomes in dialysis patients, new emphasis is being placed on better management of patients who are pre-end-stage renal disease (pre-ESRD)-patients with chronic kidney disease (CKD). Spearheaded by the National Kidney Foundation, the National Institute of Health, and the nephrology community at large, an effort is underway to improve the care of patients with kidney disease. We hope that improvement in health and outcomes of patients with kidney disease will be optimized through attention to care before the development of advanced renal disease. Cardiovascular disease (CVD) is an important comorbidity of chronic kidney disease, and reducing cardiovascular events in this population is an important goal for the people who care for chronic kidney disease patients. In this article, we review the available literature regarding certain risk factors for cardiovascular disease: proteinuria, hyperglycemia, hypertension, homocysteine, hyperlipidemia, and inflammation. When possible, recommendations for treatment are provided based on the information reviewed.
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PMID:Comorbidity and cardiovascular risk factors in patients with chronic kidney disease. 1243 94

Asian Indians who have settled overseas and those in urban India have increased risk of coronary events. Reasons for this increased risk are thought to be genetic but are yet unclear. Advances in molecular cardiology have revealed a number of single nucleotide polymorphisms associated with atherosclerosis. In this review, gene polymorphisms that have been associated with coronary diseases among Indians are discussed. Topics include the genes involved in hyperlipidemia, hypertension, and homocysteine. Mutations in the low-density lipoprotein receptor (LDLR) gene resulting in familial hypercholesterolemia have strong association with premature atherosclerosis. Common polymorphism of the apolipoproteins (apo) B-100 and E genes have been associated with variation in lipid and lipoprotein levels. Recently identified polymorphisms in the apoC3 (T-455C, C-482T), and cholesteryl ester transfer protein (CETP) (B1/B2 allele) genes are associated with increased triglycerides and reduced high-density lipoprotein (HDL)-levels, a feature now also common among Asian Indians. Angiotensin-converting enzyme-deletion (DD) polymorphism has been shown to influence beta-blocker therapy in heart failure. Mutations in methylenetetrahydrofolate reductase (C667T), cystathionine beta-synthase (T833C), and methionine synthase (A2756G) genes cause hyperhomocysteinemia, an independent risk factor for atherothrombosis. As the genetics of atherosclerosis continues to evolve, these factors along with the newer emerging factors may become a part of the routine assessment, aiding prediction of future coronary events.
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PMID:Gene polymorphism and coronary risk factors in Indian population. 1247 35


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