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An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients.

BACKGROUND: The newer antipsychotic agents exhibit a superior safety profile compared with conventional antipsychotic agents in terms of extrapyramidal symptoms. Previous studies have suggested an association between olanzapine treatment and hyperlipidemia. We evaluated this association using a large health care database. METHODS: The study was derived from the England and Wales-based General Practice Research Database, composed of 3.5 million subjects followed up between June 1, 1987, and September 24, 2000. A total of 18 309 individuals diagnosed as having schizophrenia were identified. A 6:1 matched nested case-control design was used. Conditional logistic regression was used to derive adjusted odds ratios (ORs), controlling for sex, age, and other medications and disease conditions influencing lipid levels. Antipsychotic drug exposure was defined as the receipt of at least 1 prescription for an antipsychotic medication within the 3 months before the date of diagnosis of hyperlipidemia. RESULTS: There were 1268 incident cases of hyperlipidemia in the cohort, matched to 7598 control subjects. Olanzapine use was associated with nearly a 5-fold increase in the odds of developing hyperlipidemia compared with no antipsychotic exposure (OR, 4.65; 95% confidence interval [CI], 2.44-8.85) (P<.001) and more than a 3-fold increase compared with those receiving conventional agents (OR, 3.36; 95% CI, 1.77-6.39) (P<.001). Risperidone was not associated with increased odds of hyperlipidemia compared with no antipsychotic exposure (OR, 1.12; 95% CI, 0.60-2.11) (P =.72) or conventional antipsychotic exposure (OR, 0.81; 95% CI, 0.44-1.52) (P =.52). CONCLUSIONS: We observed a strong association between olanzapine exposure and hyperlipidemia in schizophrenic patients. The possible metabolic consequences of olanzapine use should be given serious consideration by treating physicians.

Adult↗

Apolipoprotein E phenotypes and hyperlipidemia.

Apolipoprotein E phenotypes were determined in 361 patients with hyperlipidemia and in controls. The E2 isoform was significantly more frequent in the group of hyperlipidemics (P less than 0.0005). This was not due to a higher frequency of E-2/2 homozygotes with type III hyperlipoproteinemia, but rather to a significantly higher frequency of E2 heterozygotes (P less than 0.0005). Subgrouping of hyperlipidemics into patients with a) hypertriglyceridemia, b) hypercholesterolemia and c) mixed hyperlipidemia revealed i) that isoform E2 was significantly more frequent in patients with hypertriglyceridemia (0.001 greater than P greater than 0.005), ii) that isoform E4 was significantly more frequent in patients with hypercholesterolemia (0.01 greater than P greater than 0.005) and iii) that isoforms E2 (P less than 0.005) and E4 (0.05 greater than P greater than 0.025) were both more frequent in patients with mixed hyperlipidemia. Roughly 20% of patients with mixed hyperlipidemia had one of the rare phenotypes E-4/4, -4/2 or -2/2. We conclude that alleles epsilon 2 and epsilon 4 both contribute to the susceptibility for, and/or phenotypic expression of hyperlipidemia. Whereas the gene epsilon 2 seems to exert its influence on plasma lipoproteins by an abnormal gene product (E2) that has reduced binding activity to lipoprotein receptors, the mechanism underlying the association of the epsilon 4 gene with hyperlipidemia is presently unclear.

Apolipoproteins↗

Comparison of lipid levels, hyperlipidemia prevalence and its risk factors between Guangxi Hei Yi Zhuang and Han populations.

BACKGROUND: Hyperlipidemia is a risk factor for atherosclerotic events. Differences in lipid levels may exist in different races. Han is the largest group and Zhuang is the largest minority among the 56 nationalities in China. Geographically and linguistically, Zhuang can be classified into 43 ethnic subgroups, among which Hei Yi (means black worship and black dress) Zhuang, living in Napo County bordering northeast Vietnam and with a population of about 50,000, is a special ethnic group, and the most conservative with a unique culture. Little is known about the lipid levels in this population. The aim of this study was to compare the lipid levels, prevalence of hyperlipidemia, and risk factors in Hei Yi Zhuang and Han populations. METHODS: A total of 1068 people of Hei Yi Zhuang nationality were surveyed by a cluster sampling. Blood pressure, height, weight, serum lipid and apolipoprotein (Apo) levels were measured, and body mass index (BMI) was calculated. The results were compared with those in 933 people of Han nationality who also live in that district. RESULTS: The levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and Apo B in Hei Yi Zhuang nationality were significantly lower than those in Han nationality (p <0.05-0.001), but the levels of high-density lipoprotein cholesterol and the ratio of Apo A1 to Apo B in Hei Yi Zhuang nationality were significantly higher than those in Han nationality (p <0.001 and 0.05, respectively). The prevalence rates of hypercholesterolemia, hypertriglyceridemia, and hyperlipidemia in Hei Yi Zhuang and Han nationalities were 25.00 vs. 28.72% (p >0.05), 12.45 vs. 14.36% (p >0.05), and 31.37 vs. 35.91% (p <0.05); respectively. The prevalence of hyperlipidemia in Hei Yi Zhuang or Han population was positively correlated with age, BMI, blood pressure, and alcohol consumption (p <0.05-0.001), respectively, but was not associated with gender or cigarette smoking in both nationalities (p >0.05). CONCLUSIONS: The current study reveals that there were significant differences in lipid levels and prevalence of hyperlipidemia between Hei Yi Zhuang and Han ethnic groups, but no significant differences in the detected risk factors for hyperlipidemia between the two ethnic groups, which might result from the comprehensive role of different dietary habits, life style, and level of physical activity, as well as genetic background.

Adult↗

Resolution of hyperlipidemia after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Hyperlipidemia is an established risk factor for development of coronary artery disease. The aim of our study was to examine the changes in serum lipid profiles of morbidly obese patients complicated by hyperlipidemia, who underwent laparoscopic gastric bypass. STUDY DESIGN: We retrospectively reviewed the charts of 95 morbidly obese patients with documented hyperlipidemia who underwent laparoscopic gastric bypass. Mean duration of hyperlipidemia was 44+/- 56 months. Hyperlipidemia was defined as an elevated level of triglycerides (> 150 mg/dL) or total cholesterol (> 200 mg/dL). Changes in lipid profile of a subset of patients with subnormal levels of high-density lipoprotein cholesterol ( 130 mg/dL), and very-low-density lipoprotein cholesterol (> 40 mg/dL) were also examined. Fasting lipid profiles were measured preoperatively and at 3-month intervals. RESULTS: There were 68 women (72%) with a mean age of 43 +/- 10 years. Mean body mass index was 47+/- 5 kg/m2. Mean percentage of excess body weight loss at 12 months postoperatively was 66%. One year after gastric bypass, mean total cholesterol levels decreased by 16%; triglyceride levels decreased by 63%; low-density lipoprotein cholesterol levels decreased by 31%; very-low-density lipoprotein cholesterol decreased by 74%; total cholesterol/high-density lipoprotein cholesterol risk ratio decreased by 60%, and high-density lipoprotein cholesterol levels increased by 39%. Also, within 1 year, 23 of 28 (82%) patients requiring lipid-lowering medications preoperatively were able to discontinue their medications. CONCLUSIONS: Weight loss after laparoscopic gastric bypass substantially improves lipid profiles in morbidly obese patients who have hyperlipidemia. Improvement in lipid profiles was observed as early as 3 months postoperatively and was sustained at 1 year. Improvement of lipid profiles after laparoscopic gastric bypass can reduce health risks associated with high levels of atherogenic lipoproteins.

Adult↗

Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia.

AIMS: Beneficial effects of statin treatment on cardiovascular morbidity and mortality has been not entirely explained by the reduction in LDL-cholesterol level. We hypothesised that antioxidant activity of statins may contribute to their salutary cardiovascular effects. The aim of the present study was to examine effect of simvastatin treatment on some parameters of LDL oxidation and antioxidant protection in patients with hypercholesterolemia and combined hyperlipidemia. Furthermore, we were interested, whether the effect of treatment is related to the type of hyperlipidemia. PATIENTS AND METHODS: Fourty-two patients (12 males, 30 females, mean age 60+/-10 years) were included in the present study. Fourteen patients had hypercholesterolemia defined as total cholesterol>5.0 mmol/l. Twenty-eight patients had combined hyperlipidemia defined by total cholesterol>5.0 mmol/l and triglycerides>1.7 mmol/l. Simvastatin was administered to patients during 8-week period in a daily dose of 20mg. Oxidation of LDL was measured by assessment of circulating conjugated diene (CD) and malondialdehyde (MDA) level. Antioxidant properties of blood were assessed based on measurement of total antioxidant status (TAS) and glutathione peroxidase (GPx) activity. RESULTS: Besides expected significant decrease in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels, simvastatin treatment also reduced significantly circulating CD by 41% (p<0.0001) and MDA level non-significantly by 6% (p=0.078). Simvastatin treatment resulted in an increase of GPx activity by 38% (p<0.0001), but did not have a significant effect on TAS. Patients with combined hyperlipidemia had significantly higher baseline CD (p<0.01) and consequently significantly greater absolute and relative decrease (46% versus 23%) in circulating CD (DeltaCD), when compared with patients with hypercholesterolemia. The increase in GPx activity was significant only in patients with combined hyperlipidemia (p<0.0001). In the multiple stepwise linear regression analysis, both baseline triglyceride (r(2)=0.32; p=0.004) and LDL cholesterol (r(2)=0.08; p=0.05) levels were significant independent predictors of DeltaCD after simvastatin treatment. CONCLUSION: Simvastatin treatment significantly reduced circulating conjugated diene level and led to an increase in glutathione peroxidase activity. These effects were more pronounced in patients with combined hyperlipidemia than in hypercholesterolemia. The results suggest that simvastatin possesses certain antioxidant properties, which may contribute to its beneficial cardiovascular effect.

Aged↗

Serum leptin levels in patients with hyperlipidemias.

Leptin is a protein hormone produced by adipocytes that reflects the body fat content. The aim of our study was to compare serum leptin levels in randomly selected untreated males and females with hypercholesterolemia and combined hyperlipidemia and in healthy control subjects matched for age and body mass index and to study the relations between leptin and serum lipids and lipoproteins. No statistically significant differences in serum leptin levels were found between the male control group (5.26 +/- 2.81 ng/mL(-1)) and the male group with hypercholesterolemia (8.16 +/- 3.85 ng/mL(-1)) or combined hyperlipidemia (7.51 +/- 4.83 ng/mL(-1)) and between the female control group (13.0 +/- 8.12 ng/mL(-1)) and the female group with hypercholesterolemia (15.36 +/- 8.89 ng/mL(-1)) or combined hyperlipidemia (18.63 +/- 10.15 ng/mL(-1)). Leptin concentration in male group with hypercholesterolemia did not differ significantly from the female control group; in the other male groups, leptin levels were significantly lower than those of the other female groups. Serum leptin levels in all studied groups except for the male group with hypercholesterolemia positively correlated with body mass index. Serum leptin levels correlated negatively with high-density lipoprotein cholesterol in the female group with hypercholesterolemia (r = -0.67, P < 0.01) and the male group with combined hyperlipidemia (r = -0.56, P < 0.01). A positive correlation between serum leptin and high-density lipoprotein cholesterol (r = 0.67, P < 0.01) and between leptin and lipoprotein (a) (r = 0.71, P < 005) was found in female group with combined hyperlipidemia. No other significant relationships between leptin and serum lipids or lipoproteins were found. We conclude that serum leptin levels in patients with hyperlipidemias do not significantly differ from those healthy control subjects matched by age and body mass index.

Adult↗

Abdominal obesity and expression of familial combined hyperlipidemia.

OBJECTIVE: To investigate the role of abdominal and body obesity on the prevalence of hyperlipidemia, in particular, hypertriglyceridemia, hypercholesterolemia, and high apolipoprotein B levels, in familial combined hyperlipidemia (FCHL) relatives and their spouses. RESEARCH METHODS AND PROCEDURES: In FCHL relatives (n = 618) and spouses (n = 297), prevalence data of hyperlipidemia and high apolipoprotein B levels and their age and gender-corrected odds ratios (ORs) were calculated for sex-adjusted categories of waist-to-hip ratio (WHR), waist circumference, and BMI. RESULTS: Increments of BMI, waist circumference, and WHR increased the frequency of hyperlipidemia. In the whole study population (relatives and spouses combined), frequency of hypertriglyceridemia showed a significant interaction only between WHR categories and FCHL. This was studied further after stratification of relatives by multivariable logistic regression analyses corrected for age and gender. Predominant expression of hypertriglyceridemia was observed with higher categories of WHR in FCHL relatives (prevalence up to 57.6%, OR 8.48 in highest vs. lowest WHR category, p < 0.001) but not in spouses (up to 32.9%, OR 1.05 in highest vs. lowest WHR category, not significant). DISCUSSION: Both in spouses and FCHL relatives, increments in BMI and waist circumference increased the prevalence of hyperlipidemia. Specifically, in FCHL relatives, WHR was the most informative determinant of the expression of hyperlipidemia, in particular, hypertriglyceridemia. The data indicate that FCHL develops against a background of abdominal obesity.

Abdomen↗

[Excessive hyperlipidemia during pregnancy (author's transl)].

1) In two patient with excessive hyperlipidemia diet in the post-partum days resulted in a rapid reduction of the high neutral fats in the serum which were 6,150 mg/dl and 6,290 mg/dl respectively. In one patient the hyperlipidemia was reduced by diet during the pregnancy. The course of the pregnancies and the puerperium were uneventful. Complications during delivery were not related to the hyperlipidemia. Coagulation defects were not tested.--2) Excessively high serum lipid values of the mother only had a minor influence on the serum lipid values of the mother only had a minor influence on the serum lipid values of the infants. The infants had slightly elevated values compared to controls. One infant was tested at age 7 months and showed definitely elevated lipids with higher values than neonatally. A familial hyperlipidemia was confirmed in this case.--3) The milk fat values (Total Cholesterol and Neutral fats) were not influenced by the hyperlipidemia. Breast feeding was therefore safe.--4) Both infants of the mothers with hyperlipidemia had neonatal hyperbilirubinaemia with values of maximal 16.2 mg% and 16.7 mg% which required phototherapy.

Adult↗

Effects of Saiko-ka-ryukotsu-borei-to in patients with hyperlipidemia.

We measured and compared levels of platelet-derived microparticles (PMPs), monocyte-derived microparticles (MMPs), CD62P on activated platelets, soluble E-selectin (sE-selectin), and anti-oxidized low density lipoprotein (LDL) antibody in hyperlipidemia patients and control subjects. Binding of anti-GPIIb/IIIa and anti-GPIb monoclonal antibodies to platelets was not significantly different between hyperlipidemia patients and controls. However, expression of CD62P on platelets and levels of PMPs were higher for hyperlipidemia patients than in controls, although the difference between groups in CD62P expression was not significant (PMPs: 534 +/- 63 vs. 388 +/- 47, p < 0.05; CD62P: 9.1% +/- 1.45 vs. 7.3% +/- 1.15, N.S.). Although there were no differences in expression of CD36 and CD40 by monocytes between the two groups, levels of MMPs were higher in hyperlipidemia patients than in controls (MMPs: 147 +/- 21 vs. 59 +/- 8, respectively, p < 0.01). Levels of anti-oxidized LDL antibody and sE-selectin were also higher in hyperlipidemia patients. We studied the effects of Saiko-ka-ryukotsu-borei-to on levels of these factors in patients with elevated triglyceride levels. After Saiko-ka-ryukotsu-borei-to treatment, levels of CD62P, PMPs, sE-selectin, and anti-oxidized LDL antibody were reduced significantly. Levels of triglycerides, total cholesterol and MMPs also decreased, but the changes were not significant. These findings suggest that Saiko-ka-ryukotsu-borei-to prevents the development of vascular complications in hyperlipidemia patients.

Aged↗

Effects of demographic, dietary and other lifestyle factors on the prevalence of hyperlipidemia in Guangxi Hei Yi Zhuang and Han populations.

BACKGROUND: Han is the largest nationality and Zhuang is the largest minority among 56 nationalities in China. Hei Yi (means black-worship and black dressing) Zhuang is a special subgroup of 43 ethnic subgroups of Zhuang. There are limited data about the effect of environmental factors on the prevalence of hyperlipidemia in this population. The aim of this study was to determine the effects of demographic, dietary, and other lifestyle factors on the prevalence of hyperlipidemia in Hei Yi Zhuang and Han populations. DESIGN: We performed a cross-sectional study of 1166 randomly selected people of Hei Yi Zhuang aged 7-84 years from seven villages in Napo County, Guangxi, China; and 1018 people of Han aged 6-89 years from nine villages in the same region. METHODS: Information on demographic characteristics, dietary patterns, and other lifestyle factors was collected by standard questionnaires. Blood pressure, height, weight, waist circumference, serum lipids and apolipoproteins were measured, and body mass index (BMI) was calculated as a measure of weight relative to height. RESULTS: The prevalence rates of hypercholesterolemia, hypertriglyceridemia and hyperlipidemia in Hei Yi Zhuang and Han were 23.6 versus 27.0% (P>0.05), 12.3 versus 14.4% (P>0.05) and 29.9 versus 34.2% (P<0.05), respectively. The prevalence of hyperlipidemia was positively correlated with age, BMI and blood pressure (P<0.05- 0.001) in Hei Yi Zhuang, whereas it was positively associated with age, BMI, blood pressure and alcohol consumption in Han (P<0.01-0.001). There was no significant correlation between the prevalence of hyperlipidemia and sex or cigarette smoking in Hei Yi Zhuang, Han or a combined population of Hei Yi Zhuang and Han (P>0.05), and alcohol consumption in Hei Yi Zhuang (P>0.05). CONCLUSION: The current study reveals that there is a significant difference in the prevalence of hyperlipidemia and its risk factors between Hei Yi Zhuang and Han, which might result from different demographic characteristics, dietary habits and other lifestyle factors.

Adult↗

Impaired free fatty acid suppression during hyperinsulinemia is a characteristic finding in familial combined hyperlipidemia, but insulin resistance is observed only in hypertriglyceridemic patients.

Insulin resistance has been associated with hypertriglyceridemia, combined hyperlipidemia, and familial combined hyperlipidemia (FCHL). Whether all FCHL patients with different types of dyslipidemia have low insulin sensitivity has not been evaluated. We measured insulin sensitivity by the hyperinsulinemic euglycemic clamp with indirect calorimetry in 110 healthy controls and in 105 nondiabetic, FCHL family members: in 50 without dyslipidemia, in 19 with hypercholesterolemia (total cholesterol >/=7.7 mmol/L), in 22 with hypertriglyceridemia (total triglycerides >/=2.4 mmol/L in men 2.4 mmol/L in women), and in 14 with combined hyperlipidemia. During the hyperinsulinemic clamp, FCHL family members had higher free fatty acid levels than did controls (0.06+/-0.06 [mean+/-SD] in controls versus 0.16+/-0.11 in relatives without dyslipidemia versus 0.15+/-0. 07 in hypercholesterolemic patients versus 0.29+/-0.14 in hypertriglyceridemic patients versus 0.27+/-0.17 mmol/L in patients with combined hyperlipidemia; P<0.001 after adjustment for age, sex, and body mass index). Relatives without dyslipidemia (16.4+/-4.4 micromol. kg(-1). min(-1), P=0.001) and patients with hypertriglyceridemia (12.8+/-3.8 micromol. kg(-1). min(-1), P<0.001) and with combined hyperlipidemia (13.7+/-3.1 micromol. kg(-1). min(-1), P<0.001) had lower rates of insulin-stimulated glucose oxidation than did controls (19.4+/-4.7 micromol. kg(-1). min(-1)). Also, the rates of nonoxidative glucose disposal were lower in patients with hypertriglyceridemia (P=0.001) and combined hyperlipidemia (P=0.011) than in controls. In contrast, subjects with hypercholesterolemia and control subjects had similar rates of insulin-stimulated glucose uptake. We conclude that a defect in free fatty acid suppression during hyperinsulinemia, probably located in adipose tissue, is characteristic for all FCHL patients with varying types of dyslipidemia, whereas insulin resistance in skeletal muscle is observed only in FCHL patients with elevated triglyceride levels.

Adult↗

Approaches to the treatment of hyperlipidemia in the solid organ transplant recipient.

OBJECTIVE: To review the literature investigating increased lipid concentrations in transplant recipients and the use of lipid-lowering agents in this population. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the terms transplantation, hyperlipidemia, immunosuppression, and therapy including diet, gemfibrozil, bile acid sequestrants, nicotinic acid, probucol, and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Selected literature, including controlled studies, was used in this review. STUDY SELECTION: Articles published since 1970 pertaining to hyperlipidemia in solid organ transplant recipients. Emphasis was placed on clinical trials that investigated approaches to the treatment of hyperlipidemia in transplant recipients. DATA EXTRACTION: Original articles and reviews were obtained to select material pertinent to the objectives. DATA SYNTHESIS: Descriptions of lipid concentrations in the transplant patient and treatment approaches used, including potential complications, were reviewed. CONCLUSIONS: Hyperlipidemia is an important risk factor for coronary heart disease in the solid organ transplant patient. Treatment alternatives include diet modification and, in most cases, pharmacologic intervention that should be based on the type of hyperlipidemia. The HMG-CoA reductase inhibitors are effective agents in the treatment of hyperlipidemia in the transplant recipient and generally are used as single therapy in low dosages to minimize the risk of myositis or rhabdomyolysis.

Humans↗

Suppression of hyperlipidemia-associated cataracts in diabetic rats with the lipoprotein lipase activator NO-1886.

Diabetic cataracts are thought to be caused by hyperglycemia associated with disturbed glucose metabolism. Diabetes mellitus often involves abnormal lipid metabolism in addition to abnormal glucose metabolism. To date, however, very few studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The present study was undertaken to determine whether this actually is a risk factor for diabetic cataracts and to confirm that the onset of cataracts associated with diabetes mellitus can be suppressed by correction of hyperlipidemia. When rats with streptozotocin (STZ)-induced diabetes mellitus were fed an ordinary diet, cataracts became evident at 9 weeks in 26.7% of animals, and increased to an incidence of 73.3% after 10 weeks of STZ treatment. However, in rats with STZ-induced diabetes mellitus that were fed a cholesterol rich diet to induce severe hyperlipidemia, cataracts were observed one week earlier, after 8 weeks of treatment, in 36.0% of animals, with an increase to a 52.0% incidence and a 76.0% incidence after 9 and 10 weeks of STZ treatment, respectively. Hyperlipidemia was therefore associated with an earlier onset and an elevated incidence of diabetic cataracts. When the lipoprotein lipase (LPL) activator NO-1886 was administered to diabetic rats which had developed severe hyperlipidemia, they showed a decrease in plasma total cholesterol, triglyceride and non-high density lipoprotein (non-HDL)-cholesterol levels and an increase in high density lipoprotein (HDL)-cholesterol level, and the onset of diabetic cataracts was markedly suppressed. The results of this study suggest that hyperlipidemia and low HDL-cholesterol levels may be risk factors for the onset of diabetic cataracts, and that this onset can be suppressed if measures are taken to alleviate these risk factors. The LPL activator NO-1886 may be useful in preventing the onset of diabetic cataracts.

Animals↗

[Hyperlipidemia: complex pathophysiology caused by multiple genetic and environmental factors--in considering the approaches to preventive medicine].

In Japan, over the last 40 years, the change in lifestyle, particularly the westernization of the diet, has led to increased frequency of "lifestyle-related disorders" such as, hyperlipidemia, diabetes mellitus, and atherosclerosis. Consequently, the morbidity and mortality due to coronary heart disease have increased, and the prevention of this disorder is now one of the major concerns when considering the quality of life of individuals and the public health policy. Hyperlipidemia, particularly hypercholesterolemia, is one of the major risk factors of atherosclerosis. Therefore, the clarification of the mechanisms of the development of hyperlipidemia is important in the consideration of the prevention and management of atherosclerotic disorders. Genetic and epidemiological studies have provided compelling evidence that genetic factors, environmental influences and the interaction between them all contribute to the development of this complex disorder. Various unexpected mechanisms of the development of hyperlipidemia have been elucidated by analyzing some hereditary disorders. Furthermore, the cloning of the genes involved in the maintenance of cholesterol and/or lipid homeostasis has made it possible to investigate the molecular mechanisms of the development of hyperlipidemia in detail. Elucidation of the genetic and environmental factors and detailed understanding of the molecular pathophysiology of hyperlipidemia are essential in the pursuit of evidence-based preventive medicine and health policy.

Animals↗

Hyperlipidemia and transplantation: etiologic factors and therapy.

Hyperlipidemia is a well-recognized complication of renal transplantation. In long-term survivors of renal transplantation, cardiovascular disease accounts for the majority of patient deaths. In the cyclosporine era, cardiovascular disease has surpassed infection as the number one cause of death. Risk factors in the transplant population for hyperlipidemia include age, male sex, diabetes, prednisone dose, graft impairment, obesity, and antihypertensive therapy. Recently, cyclosporine has been implicated as an aggravating factor in the development of hyperlipidemia after transplantation, although its role has been controversial. Because renal transplant recipients have other significant risk factors for the development of coronary artery disease, the amelioration of hyperlipidemia may improve long-term patient survival. Because most late deaths occur in patients with a functioning graft, long-term graft survival could also be improved. The role of corticosteroids in the development of hyperlipidemia is well established. Recent studies employing corticosteroid withdrawal after transplantation have shown a marked reduction in cholesterol despite the use of cyclosporine. Data on corticosteroid withdrawal in living related transplants at our center show a significant reduction in total cholesterol after steroid withdrawal. Data from heart transplant recipients under corticosteroid-free protocols show a similar reduction in total cholesterol. Other treatments for hyperlipidemia include diet and cholesterol-lowering agents, such as Mevacor (lovastatin; Merck Sharp & Dohme, West Point, PA). The efficacy of lowering cholesterol in this high-risk population is unknown.

Adrenal Cortex Hormones↗

Strategies for minimizing hyperlipidemia after cardiac transplantation.

Allograft coronary artery disease represents a major limitation to long-term survival after cardiac transplantation. Hyperlipidemias have been linked to the development of native coronary atherosclerosis, and hyperlipidemic states have correlated with the severity of allograft coronary artery disease. Heart transplant recipients typically manifest increases in plasma levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months following transplantation. Factors known to promote post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine (interference with clearance and increased oxidizability of LDL), sirolimus (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol levels and is associated with a decreased incidence and progression of allograft coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine, increasing the risk of myostitis when they are used in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in heart transplant recipients. Gemfibrozil has proved effective in transplant recipients when there is isolated marked elevation of plasma triglyceride levels. When hyperlipidemia persists despite therapy, some benefit may result with conversion from cyclosporine to tacrolimus. Although a definitive link between hyperlipidemia and allograft coronary disease has yet to be proven, available evidence points to abnormal lipid metabolism as part of the complex etiologic machinery driving the process of 'chronic rejection'. Consensus exists within the transplant community that a HMG-CoA reductase inhibitor such as pravastatin, should be part of the routine post-transplant drug regimen, and persistent hyperlipidemia should be aggressively treated.

Cholesterol, Dietary↗

Hyperlipidemia in persons using antipsychotic medication: a general population-based birth cohort study.

BACKGROUND: Shortly after phenothiazines were introduced, they were found to elevate serum triglyceride and total cholesterol levels. During the past decade, an increasing body of literature has also documented this effect in atypical antipsychotics. Previous studies of antipsychotic-associated hyperlipidemias are based on clinical samples, mostly from case series. We studied the prevalence of hyperlipidemia in subjects who did and did not take antipsychotic medication in a prospective, general population-based birth cohort. METHOD: The study sample consisted of 5654 members of the unselected Northern Finland 1966 Birth Cohort who participated in the 1997-1998 clinical examination at 31 years of age. Blood samples were taken after an overnight fast, and serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels were determined. Health habits and other possible correlates for hyperlipidemia were assessed using a questionnaire. The sample was analyzed in 4 categories according to use of antipsychotic medication: (1) atypical, (2) typical, (3) atypical and typical (for the 3 antipsychotic categories, total N = 45), and (4) no antipsychotic medication (N = 5609). Nonparametric tests and multiple logistic regression analysis were used to measure the effect of antipsychotics on serum lipids. RESULTS: High lipid levels were found in persons treated with both atypical and typical medication (mean total cholesterol = 233 mg/dL, mean triglycerides = 163 mg/dL). Mean total cholesterol and triglycerides were also high in subjects who used only typical medication (215 mg/dL and 148 mg/dL, respectively). The prevalence of hypercholesterolemia, high LDL cholesterol, and hypertriglyceridemia was high in persons using antipsychotic medication (31.1%, 20.0%, and 22.2%, respectively) compared with persons not using such medication (12.2%, 10.2%, and 7.0%, respectively). After we adjusted for risk factors for hyperlipidemia (sex, diet, waist circumference, physical exercise, smoking, and alcohol consumption), the results of logistic regression analysis showed that in persons treated with antipsychotic medication the risk of hypercholesterolemia was 2.8 (95% CI = 1.4 to 5.6); of hypertriglyceridemia, 2.3 (95% CI = 1.0 to 5.4); and of high LDL cholesterol, 1.6 (95% CI = 0.7 to 3.5). CONCLUSION: Lipid levels in subjects who used both atypical and typical medication and those who used only typical medication were high even in young age. As these persons are at special risk of hyperlipidemia, their lipid levels should be regularly monitored, and a cholesterol-lowering diet, as well as medication, should be considered. The results indicate an elevated risk of hyperlipidemia in persons using antipsychotic medication independent of the other risk factors assessed.

Adult↗

[The effect of atorvastatin on the expression of CD55, CD59 in patients with hyperlipidemia].

OBJECTIVE: To study the expressions of CD55 and CD59 in patients with hyperlipidemia and the effects of atorvastatin on it, and to identify the possible influential factors. METHODS: We selected 67 patients with hyperlipidemia, and 24 healthy people matched in terms of age, sex and body weight as control. The expressions of CD55 and CD59 on white blood cells were detected by flow cytometry, and their relationships to blood lipids, complement activation indexes (C(5a), sC(5b-9)), inflammatory factors (high sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6 were analyzed. 24 patients with hyperlipidemia were treated with atorvastatin for 8-12 weeks and the expressions of CD55 and CD59 were measured before and after atorvastatin therapy. RESULTS: The mean fluorescence intensity (MFI) of CD55 lymphocytes and monocytes were decreased in patients with hyperlipidemia compared with control (2.07 +/- 0.28 vs 2.29 +/- 0.44 and 3.45 +/- 1.02 vs 4.33 +/- 2.32, P < 0.01 and P < 0.05, respectively). CD55 positive lymphocyte MFI was negatively correlated with waist circumference, waist-hip ratio, hsCRP and C(5a). C(5a) was negatively correlated with the MFIs of CD55 positive lymphocytes, monocytes, granulocytes, and positively with TG and diastolic blood pressure. After atorvastatin therapy, the MFIs of CD59 positive lymphocytes, monocytes and granulocytes increased (4.34 +/- 1.16 vs 3.69 +/- 0.76, 4.52 +/- 1.36 vs 3.91 +/- 0.89, 5.67 +/- 1.72 vs 4.56 +/- 1.03, P < 0.05, < 0.05 and < 0.01 respectively), which were not correlated with changes of blood lipids. CONCLUSIONS: The expression of CD55 is down-regulated in hyperlipidemia, which might be influenced by obesity, abdominal distribution of adipose tissue and inflammatory status of hyperlipidemia, but not by blood lipids. The expression of CD55 is related with complement activation; The expression of CD59 is up-regulated after atorvastatin treatment independently of blood lipids.

Aged↗