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)

Lp(a) is an independent risk factor for recurrent atherosclerotic heart disease in men and women after menopause. Excess levels of Lp(a) are seen in both males and females, more common in Africans, African Americans, and Asian populations than in whites. Since the standard lipid profile does not report Lp(a), it has to be ordered separately. Screening for Lp(a) should be considered under the following circumstances: (a) patient or family history of premature atherosclerotic heart disease, (b) familial history of hyperlipidemia, (c) established atherosclerotic heart disease with a normal routine lipid profile, (d) hyperlipidemia refractory to therapy, and (e) history of recurrent arterial stenosis. Treatment options are (a) a new extended-release form of niacin 3 to 4 g daily (although most effective in lowering Lp(a) and in reducing atherosclerotic heart disease mortality rates, its use may be limited because of side effects); (b) estrogen replacement after menopause, (however, concomitant progesterone therapy dilutes the effectiveness of estrogens); (c) lowering LDL with statins (generally effective in atherosclerotic heart disease but has no effect on Lp(a) levels), (d) aspirin and antibiotics (may be effective when C-reactive protein levels are high); and (e) folic acid (reduces homocysteine levels). The general measures that halt the progression of CAD should always be adhered to, namely, maintaining normal weight, a daily exercise program, blood pressure control, a low-cholesterol-forming diet, and daily aspirin.
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PMID:Lp(a) lipoprotein--an independent risk factor for coronary heart disease after menopause. 1115 87

In a consecutive case series, cross-sectional study of 275 women referred for therapy of hyperlipidemia, (75 [27%] on estrogen replacement therapy [ERT]), our specific aim was to determine whether ERT-mediated thrombophilia and heterozygosity for the thrombophilic 20210 G/A prothrombin gene mutation interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD). Of the 275 women, 100 (36%) had ATCVD; 10 (3.6%) were heterozygous for the 20210 G/A prothrombin gene mutation. In women without the 20210 G/A prothrombin gene mutation, 15 of 71 (21%) on ERT had ATCVD versus 78 of 194 (40%) not on ERT (X(2) = 8.31, P =.004). By stepwise logistic regression, in 261 women with ATCVD risk factor data, positive explanatory variables for ATCVD included the 20210 G/A prothrombin mutation (risk odds ratio, 5.8; 95% confidence intervals [CI], 1.4 to 30.2; P =.021) and a 20210 G/A prothrombin gene mutation*ERT interaction term (risk odds ratio, 2.70; 95% CI, 1.4 to 5.4; P =.004). ATCVD events were more likely in 2 subgroups of women (ERT minus [-] and 20210 G/A prothrombin gene mutation -) or (ERT plus [+] and 20210 G/A prothrombin gene mutation +), P =.004. Other positive explanatory variables for ATCVD events included age (P =.004), triglycerides (P =.012), lipoprotein (a) (P =.03), and homocysteine (P =.032). ERT may be protective against ATCVD when the thrombophilic 20210 G/A prothrombin gene mutation is absent, whereas the 20210 G/A prothrombin gene mutation may increase risk for ATCVD, particularly in the presence of ERT. We suggest that the 20210 G/A prothrombin gene mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the thrombophilic prothrombin gene mutation (4%) in whom ERT is contraindicated because of increased risk for ATCVD and thromboembolism, and a second, much larger group of women without the 20210 G/A prothrombin gene mutation (96%) in whom ERT may possibly reduce risk for ATCVD.
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PMID:Interaction of estrogen replacement therapy with the thrombophilic 20210 G/A prothrombin gene mutation for atherothrombotic vascular disease: a cross-sectional study of 275 hyperlipidemic women. 1123 Jul 92

The effect of fenofibrate (FEN), compared with placebo (PL), on total plasma homocysteine (tHcy) levels in the fasted and fed states has been examined. Twenty men with established coronary artery disease (CAD) or with at least two cardiovascular risk factors, who had elevated plasma triglyceride levels (> 2.3 mmol/l) and reduced HDL-C levels (< 0.91 mmol/l), and in whom a fibric acid derivative was clinically indicated were studied. The study was a randomized, PL controlled, double-blind study designed to test the effect of micronized FEN on postprandial lipemia. Plasma tHcy levels were investigated as a post-hoc analysis. After a 4-week dietary stabilization period, patients were randomized to PL or FEN (200 mg/day) for 8 weeks, followed by an 8-h postprandial study, consisting of 1 g fat/kg body weight (35% cream). The methionine content of cream was approximately 0.53 mg/ml. A 5-week washout period was then followed by a second 8-week treatment period (FEN or PL), at the end of which a second postprandial study was undertaken. Blood was sampled in the fasted state (0 h) and postprandially at 2, 4, 6 and 8 h. Plasma was stored at -80 degrees C for homocysteine, vitamins B(6), B(12) and folate measurements. FEN caused a marked decrease in all triglyceride-rich lipoprotein parameters, no change in LDL-C, and an increase in HDL-C levels. Fen treatment was associated with an increase in fasting tHcy (PL: 10.3+/-3.3 micromol/l to FEN: 14.1+/-3.8 micromol/l, 40.4+/-20.5%, P < 0.001) and fed tHcy levels 6 h post-fat load (PL: 11.6+/-3.3 micromol/l vs. FEN: 17.1+/-5.4 micromol/l, P < 0.001). Homocysteine levels were increased by the fat load; PL: 14% (P < 0.001) and FEN: 21%, P < 0.001 at the 2, 4, 6 and 8 h time points. Change in tHcy level on FEN was not associated with changes in plasma levels of folate, vitamins B(6) or B(12) or creatinine. Amino acid analysis revealed that methionine and cysteine were significantly increased on FEN (P < 0.005). The incidence of hyperhomocysteinemia (defined as tHcy level >14 micromol/l) was PL: 2/20 (10%) and FEN: 9/20 (45%) (chi(2) = 4.51, P = 0.034). There was no correlation between changes in plasma triglyceride levels and tHcy levels. Since tHcy is considered an emerging cardiovascular risk factor, the ability of FEN to increase plasma tHcy levels could potentially mitigate the potential of this drug to protect against cardiovascular disease.
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PMID:Fenofibrate raises plasma homocysteine levels in the fasted and fed states. 1125 17

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.
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PMID:[Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease]. 1130 24

Stroke places a tremendous burden on health resources throughout the world. Improved detection and modification of risk factors could reduce the impact of this disease. Important non-modifiable risk factors for ischemic stroke include age, gender, ethnicity, and heredity. Modifiable risk factors include hypertension, cardiovascular disease, diabetes, hyperlipidemia, asymptomatic carotid stenosis, cigarette smoking, and alcohol abuse. Data from the Northern Manhattan Stroke Study provide new insights into these stroke risk factors. In this study, African-Americans and Hispanics had a greater incidence of stroke, with almost a twofold increase compared with Caucasians. The protective effect of physical activity and moderate alcohol consumption was confirmed and further established as modifiable risk factors. The independent effects of lipids, apolipoproteins, and lipoprotein were also clarified. High-density lipoprotein was shown to be protective against ischemic stroke (particularly atherosclerotic stroke subtypes). Conversely, lipoprotein-a increased the risk for stroke. The ratio of apolipoprotein b to apolipoprotein a-1 was shown to be associated with carotid atheroma. In addition, newer risk factors, including homocysteine and chronic infection (Chlamydia pneumoniae and periodontal disease), are being studied as predictors of ischemic stroke. With these recent advances in the understanding of risk factors, the ability to detect or modify the risk for ischemic stroke should lead to a substantial reduction in the number of people killed or disabled by stroke each year.
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PMID:Newer risk factors for stroke. 1155 52

Patients with chronic uremia have a substantially elevated risk of death from cardiovascular disease than do the general population. Although uremic and nonuremic groups share some of the risk factors for cardiovascular mortality, such as older age, diabetes, and inflammation, other factors appear to affect cardiovascular mortality in the opposite direction. For example, being overweight and having hyperlipidemia are established risk factors in the general population, whereas lower body mass index and lower plasma cholesterol have been shown to be risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This paradoxical phenomenon is explained by two facts: (1) that malnutrition is a strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid levels are lowered in malnutrition. However, it is not known whether atherosclerosis is promoted by malnutrition or by low cholesterol level. Because the cardiovascular mortality rate is theoretically the product of event rate and fatality rate after an event, risk factors for cardiovascular mortality could fall into two categories: those raising the event rate and those affecting the fatality rate. Some factors could work both ways. Patients with ESRD show a significant increase in both event rate and fatality rate. Dyslipidemia is an independent factor affecting atherosclerotic arterial wall changes and cardiovascular events in ESRD. Other factors affecting the cardiovascular event rate in ESRD include diabetes and an elevated homocysteine level. In contrast, factors associated with poor survival after an event include diabetes and anemia. Malnutrition could be a factor causing the fatality rate to rise, although there is no direct evidence supporting this possibility. Further studies are needed to show the differential effects of a risk factor on event rate and fatality rate. Patients with ESRD would have a better chance of living longer by better management of the two categories of risk factors.
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PMID:Paradox of risk factors for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia? 1157 13

Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies have proven, that hyperhomocysteinemia is a risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to be associated with an alteration of endothelial and smooth muscle cell function leading to an accelerated formation of reactive oxygen species. An increased endothelial expression of adhesion molecules will then lead to an enhanced deposition of oxidized LDL in the vessel wall with the formation of foam cells. Additionally, hyperhomocysteinemia interferes with the coagulation system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin deficiency in elderly subjects which strongly increases with age. Elderly people have a high frequency of vitamin B12 deficiency which can be diagnosed more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B12. Subjects following a strict vegetarian diet also have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12 deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a factor in the pathogenesis of neural tube defects and pre-eclampsia. An early diagnosis of vitamin B12 deficiency is important for the prevention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, and in early pregnancy. A specific diagnosis of an underlying vitamin deficiency is important for adequate treatment. Individuals with homocysteine level >12 micromol/l should increase and/or supplement their dietary intake of vitamins.
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PMID:The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. 1159 31

According to contemporary views, the endothelium is not only a barrier separating blood from surrounding tissues, but a dynamic, heterogeneous organ, which possesses many secretory, metabolic and immunologic functions. Endothelial cells produce mediators, which regulate blood flow, influence platelet adhesion and aggregation, coagulation and fibrinolysis and also immunological response. Endothelial dysfunction is defined as an imbalance between vascular relaxing and contracting factors, between procoagulant and anticoagulant mediators or growth-inhibiting and growth-promoting substances. The definition is often confined to dysfunction of the vessel wall tonus control. The endothelial dysfunction frequently proceeds structural changes in vessels, as e.g. atherosclerotic plaque formation, neointima formation and vessel wall remodelling. This dysfunction has been confirmed in systemic hypertension, atherosclerosis, cardiac syndrome X, heart failure, using various invasive and non-invasive techniques. There are pharmacologic and non-pharmacologic methods to modify endothelial functions. It is obligatory to reduce risk factors of atherosclerosis, which lead to endothelial cell damage, i.e. hypertension, hyperlipidemia, cigarette smoking, estrogen deficiency and elevated levels of homocysteine. The role of physical exercise, low-cholesterol diet, discontinuation of smoking is emphasised. Among drugs statins, angiotensin-converting enzyme inhibitors and hormone replacement therapy are considered particularly beneficial. The importance of angiotensin receptor antagonists, endothelin receptor antagonists, L-arginine, growth factors and calcium-channel blockers for the improvement of endothelial function is studied.
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PMID:[Vascular endothelium--function, disorders and clinical modification probes]. 1171 25

Individuals with diabetes are at high risk of cardiovascular (CV) disease, a risk that is significantly greater in the presence of traditional CV risk factors (hyperlipidaemia, hypertension, prothrombotic state). Glucose control and management of these risk factors decreases but does not eliminate CV events, reflecting the complexity of atherosclerosis. Novel risk factors (C-reactive protein, lipoprotein a, homocysteine, and endothelial dysfunction) have been proposed and are potentially modifiable. However, clinical trials data are not yet available to guide therapy. At this time, no single agent can achieve adequate risk reduction in patients with diabetes. Even with the use of multiple agents and classes of agents to manage CV risk, 75% of patients with diabetes are expected to die from CV causes. Despite the recent advances in primary and secondary prevention of CV events, new approaches are needed. Data from the Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated that CV risk can be further reduced by the addition of the ACE inhibitor ramipril to the existing treatment regimen of high-risk patients with diabetes.
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PMID:Attenuating CV risk factors in patients with diabetes: clinical evidence to clinical practice. 1184 49

Interventions to modify cardiovascular risk factors have the greatest benefit in individuals at greatest risk of a cardiovascular event, not necessarily those with the most extreme levels of any particular risk factor. Patients with vascular disease are readily identified, but risk calculation in those without disease provides a way of integrating several risk factors to identify individuals at greatest risk. Equations have been derived from different epidemiological studies (Framingham, PROCAM, etc.) to estimate the risk of different clinical end-points [coronary heart disease (CHD) or cardiovascular disease (CVD)]. Some algorithms have been adapted to produce risk charts' or 'tables'; others have been modified to incorporate additional risk factors. Current UK guidelines all endorse calculation of CHD risk using the Framingham algorithm. This predicts risk well for some North European populations but less reliably in low-risk populations. It does not incorporate some risk factors, including serum triglycerides, family history, C-reactive protein, or homocysteine. Risk calculation should not be used in those with evidence of vascular disease, genetic hyperlipidaemia or a strong family history of CHD, and should be interpreted with caution in non-Caucasians. Measurement of high-density lipoprotein (HDL)-cholesterol is essential for accurate risk calculation. This has significant cost and workload implications for the laboratory. The way a laboratory reports results should be designed in such a way as to facilitate simple and accurate risk calculation.
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PMID:HDL-cholesterol and cardiac disease: which table to use? 1185 84


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