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)

Several agents (e.g. chemical or physical) present in the work environment may be harmful for the cardiovascular system. Recent studies on the cardiovascular diseases linked to hyperlipidemia have demonstrated a strong correlation between high lipoprotein(a) [Lp(a)] levels and Coronary Heart Disease (CHD). In particular, the severity of this pathological condition correlates well with the molecular weight (MW) of the apolipoprotein(a) [apo(a)] isoforms supporting Lp(a) (low MW = high risk; high MW = low risk), which are characterized by a high degree of individual variability. Since apo(a) isoforms are genetically determined, a genetic predisposition for CHD has been identified, i.e. the apo(a) phenotype is considered a marker of genetic susceptibility for cardiovascular risk. After a brief presentation of the main occupational cardiovascular risk factors (e.g. carbon disulfide, carbon monoxide, noise, psycho-physical stress) and of the most updated theories on atherogenesis, the present review proposes to utilize the measurement of the plasmatic Lp(a) level to screen for occupational cardiovascular risk susceptibility. Apo(a) phenotype characterization of workers with medium-high Lp(a) levels is then suggested. Our proposal may be realized by means of simple and relatively unexpensive laboratory methods.
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PMID:[Apolipoprotein(a) phenotypes as markers of genetic susceptibility for cardiovascular risk in occupational medicine]. 1077 32

It has been reported recently that a number of cytokines, mainly tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFalpha, IL-1beta, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFalpha and IL-1beta levels were significantly increased from 38.24 +/- 17.85 pg/ml and 2. 60 +/- 3.64 pg/ml pre-HD to 48.86 +/- 25.21 and 3.49 +/- 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0. 05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFalpha and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNFalpha and IL-1beta during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFalpha overproduction.
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PMID:Cytokine release and serum lipoprotein (a) alterations during hemodialysis. 1084 73

The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD) refractory to diet and lipid lowering drugs is poor. A new therapeutic option for such patients is regular treatment with low density lipoprotein (LDL) apheresis. In total 33 patients (16 males, 17 female, aged 43.8+/-14.3 years), suffering from severe HLP resistant to diet and lipid lowering drugs, were treated for 62.3+/-21.3 (range, 1-113) months with LDL-apheresis. Four different LDL-apheresis systems were used: the dextran sulfate adsorption for 28 of 33 (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter, Germany), LDL-hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the immunoadsorption system with special antilipoprotein (a) columns for 1 of 33 patients (Lipopak, Pocard, Russia). Before applying LDL-apheresis, 27 of 33 patients suffered from CHD with severe angina pectoris symptoms, a history of myocardial infarction or coronary artery venous bypass (CAVB). With LDL-apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28% for Lp(a), and 38% for triglycerides were reached. Severe side-effects, such as shock or allergic reactions, were very rare (0.5%). In the course of treatment an improvement in general well-being and increased performance were experienced in 29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to 100% of nitrate medication was observed. Regarding the different apheresis systems used, there were no significant differences with respect to the clinical outcome and concerning total cholesterol, LDL, HDL, and triglyceride concentrations. But, in respect to elevated lipoprotein (a) levels, the immunoadsorption method using special anti-lipoprotein (a) columns seems to be the most effective (-57% versus -25% [Kaneka, p < 0.05] or -23% [Baxter, p < 0.05]). The present data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe HLP, refractory to maximum conservative therapy, is effective and safe in long-term application.
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PMID:Low density lipoprotein apheresis in treatment of hyperlipidemia: experience with four different technologies. 1091 23

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

Elevated plasma lipoprotein (a) (Lp[a]) and cardiac events show a modest but significant association in various clinical studies. However, the influence of high Lp(a) on the gene expression in blood monocytes as a major cell involved in atherogenesis is poorly described. To identify genes influenced by elevated serum Lp(a), the gene expression was analyzed on a complementary DNA microarray comparing monocytes from a patient with isolated Lp(a) hyperlipidemia and coronary heart disease with monocytes from a healthy blood donor with low Lp(a). By using this approach, numerous genes were found differentially expressed in patient-versus-control monocytes. Verification of these candidates by Northern blot analysis or semiquantitative polymerase chain reaction in monocytes from additional patients with Lp(a) hyperlipidemia and healthy blood donors with elevated Lp(a) confirmed a significant induction of plasminogen activator inhibitor type 2 (PAI-2) messenger RNA (mRNA) in monocytes from male, but not from female, individuals with high Lp(a), indicating that this observation is gender specific. This led also to increased intracellular and secreted PAI-2 protein in monocytes from male probands with Lp(a) hyperlipidemia. Plasminogen activator inhibitor type 1 (PAI-1) mRNA was found suppressed only in the patients' monocytes and not in healthy probands with high Lp(a) levels. Purified Lp(a) induced PAI-2 mRNA and protein and reduced PAI-1 expression in monocytes isolated from various controls. The finding that PAI-2 is elevated in monocytes from male patients with isolated Lp(a) hyperlipidemia and male healthy probands with high Lp(a) and that purified Lp(a) up-regulates PAI-2 in control monocytes in vitro indicate a direct, but gender-specific, effect of Lp(a) for the induction of PAI-2 expression.
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PMID:Lipoprotein (a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes. 1115 26

Cardiovascular disease is the major cause of death in patients with end-stage renal disease (ESRD). ESRD patients are almost invariably hypertensive. They all have acquired combined hyperlipidemia and increased Lp(a), hyperhomocysteinemia, decreased physical activity, psychosocial stress, insulin resistance, procoagulant factors, left ventricular hypertrophy, and increased oxidative stress. Diabetes mellitus, a major risk factor for both cardiovascular disease and ESRD, has become the commonest cause of ESRD. If ESRD patients choose to smoke, the additive risk is profound. Moreover, ESRD patients are becoming older and are often menopausal if female. Finally, ESRD patients have a dramatic tendency for vascular and cardiac calcification, probably related to hyperphosphatemia and hyperparathyroidism. Cardiovascular disease is also a major risk in patients with decreased renal function of nearly any degree. Data from the HDFP study showed that patients with a serum creatinine concentration > 1.5 mg/dl had a profoundly higher risk of cardiovascular disease than patients with creatinine values below this value. These data were recently corroborated in the HOPE study. Microalbuminuria (MAU), with or without diabetes mellitus, indicates increased cardiovascular disease risk even without decreases in glomerular filtration rate. We found earlier that nondiabetic hypertensive patients with MAU had much higher rates of myocardial infarction, stroke, and peripheral vascular disease, than similar hypertensive patients without MAU. In conclusion, the presence of decreased renal function or MAU is a major cardiovascular risk factor. ESRD can be regarded as a catastrophic risk factor. Prophylactic measures known to be effective in reducing the risk from cardiovascular disease are grossly underused. Unfortunately, they are less effective in patients with renal disease, and new strategies are needed.
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PMID:Renal disease as a risk factor for cardiovascular disease. 1119 57

We conducted an open-label study to test the effects of atorvastatin on serum lipids, lipoprotein(a) [Lp(a)] and plasma fibrinogen levels. A total of 90 dyslipidaemic, non-smoking patients (45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia) aged 48 +/- 11 years were studied. The patients were treated with 20 mg of atorvastatin for 24 weeks, in a single nocturnal dose. At baseline and every eight weeks, the fasting lipid profile, together with serum Lp(a) and plasma fibrinogen levels (Clauss method), were measured. Atorvastatin was highly effective in normalising the serum lipid profile. No significant change in median serum Lp(a) levels was observed in the whole group of patients (0.14 g/l before, vs. 0.16 g/l after, treatment) as well as in patients with raised (> 0.30 g/l) baseline levels (n = 32). A small non-significant increase of plasma fibrinogen was found (3.04 g/l vs. 3.14 g/l) after 24 weeks of atorvastatin administration. The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia. In conclusion, our findings suggest that the effect of atorvastatin on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinically relevant. Furthermore, any rise in fibrinogen levels that may occur is likely to be transient in nature. Further studies are necessary to clarify this issue. There was no evidence that atorvastatin influences serum Lp(a) levels.
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PMID:The effect of atorvastatin on serum lipids, lipoprotein(a) and plasma fibrinogen levels in primary dyslipidaemia--a pilot study involving serial sampling. 1126 11

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.
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PMID:Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis. 1151 Sep 16

To clarify the influence of elevated serum lipoprotein (a) (Lp(a)) concentration on ischemic heart disease (IHD) and the perforating artery occlusion type of cerebral infarction (CI) in elderly patients with type 2 diabetes, we measured the serum levels of Lp(a) of type 2 diabetic patients (n = 158, 81 men and 77 women). The group was followed up prospectively for 4 years and the incidence of IHD or CI was monitored. The diagnosis of CI was confirmed by computed tomography and that of IHD, which includes myocardial infarction and angina pectoris, was diagnosed by electrocardiogram and blood chemistry examination, Lp(a) concentrations of 20 mg/dl or more were identified as elevated Lp(a) levels and Lp(a) concentrations of less than 20 mg/dl were identified as normal Lp(a) levels. A Kaplan-Meier survival analysis (log-rank test) assessed the time to event rate stratified by an Lp(a) cutoff point of 20 mg/dl. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis. The probability of IHD events was significantly higher in the elevated Lp(a) group than in the normal Lp(a) group without a history of IHD but was similar in the two groups for those patients with a history of IHD. There was no significant difference between the elevated Lp(a) group and the normal Lp(a) group with regard to CI events in patients without a history of CI and with a history of CI. On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of IHD were significant predictors of IHD and hypertension, hyperlipidemia and a history of CI were significant predictors of CI. These results show that elevated serum Lp(a) concentrations is an independent risk factor for IHD, but not for the perforating artery occlusion type of CI in type 2 elderly diabetic patients.
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PMID:[A four-year prospective study on the influence of serum elevated lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type 2 diabetes]. 1152 63

Most but not all epidemiologic studies have shown that lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD). Lp(a) levels are also strongly genetically influenced. The purpose of this study was to evaluate the association between Lp(a) levels in adult offspring and parental CVD mortality in 61 kindreds with familial forms of hyperlipidemia. The study sample consisted of offspring-parent pairs in which offspring had fasting Lp(a) measurements and parents had 20-year vital status data and standardized cause-of-death classification if deceased. Linear regression analyses, using a robust variance estimator, were performed separately for 241 offspring with known maternal history (114 mothers) and 194 offspring with known paternal history (93 fathers). Maternal history of CVD mortality was significantly (p=0.004) associated with 2.4-fold higher median Lp(a) levels in offspring compared with those with no maternal history, independent of diabetes, lipid-lowering medications and hormone use. No association was observed between paternal CVD mortality and offspring Lp(a) levels (p=0.505). Adjusting for apolipoprotein(a) kringle 4 number did not alter these parent-specific associations. In conclusion, Lp(a) levels in offspring may be associated with maternal but not paternal history of CVD mortality. This parent-specific finding needs to be confirmed in other samples of high-risk families.
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PMID:Lipoprotein(a) as a risk factor for maternal cardiovascular disease mortality in kindreds with familial combined hyperlipidemia or familial hypertriglyceridemia. 1159 20


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