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Introduction: The prevalence of hyperlipidaemia is increasing, and patients with hyperlipidaemia are at increased risk of cardiovascular disease and atherosclerosis. In recent years, there has been a growing number of studies on tai chi for hyperlipidaemia. However, a systematic review on its efficacy and safety is not available. Therefore, this study aims to evaluate the efficacy and safety of tai chi for hyperlipidaemia., Methods and Analysis: Four English databases and four Chinese databases will be searched from their inception to May 2021: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database. Chinese and English randomised controlled trials related to tai chi for hyperlipidaemia will be included. Two reviewers should independently carry out study selection, data extraction and risk assessment of bias. The risk of bias in the study will be assessed by the Cochrane risk of bias tool. RevMan (V.5.4) statistical software will be applied for meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation system approach will be employed to assess the quality of evidence., Ethics and Dissemination: Ethical approval is not required because this protocol will not involve patients' individual information and jeopardise the rights of patients. The meta-analysis result will be reported in peer-reviewed journals or disseminated at related conferences., Osf Registration Number: DOI 10.17605/OSF.IO/79D2S., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the current two decades, dyslipidemia and increased blood glucose as metabolic abnormalities are the most common health threats with a high incidence among HIV/AIDS patients on antiretroviral (ARV) treatment. Scientific investigations and reports on lipid and glucose disorders among HIV infected communities are inadequate especially in those developing such as Malaysia. This cross-sectional survey was mainly aimed to evaluate the prevalence of metabolic abnormalities and associated risk factors among HIV infected population patients on ARV medication. Methods: In a single reference health center in Malaysia, 2739 adult HIV positive patients on antiretroviral therapy (ART) were studied cross-sectionally using medical records. Besides demographic variables and associated health disorders, those factors which can change the lipid and glucose levels were collected. Logistic Regression was used to find the potential risk factors (p < 0.05). Results: Majority of the studied population were male (81.1%) and aged between 30-49 (68.6%). Mean CD4 count was 474.25 (cells/mm3) while undetectable RNA viral load was common among 83.3 (%) of subjects. Among 1,583 patients with the recent blood lipid and glucose tests, increased levels of triglyceride (TG) and total cholesterol (TC) were frequently prevalent in half of the population as 59 (%) and 54.2 (%) while 28.7 (%), 35.1 (%) and 38.2 (%) had declined level of high-density lipoprotein (HDL), raised low-density lipoprotein (LDL) and fasting plasma glucose (FPG) which were less common. Dyslipidemia was common in 82.3 (%) of the subjects. Notably, medication with protease inhibitor (PI) was a potential risk for elevated triglyceride (odds ratio (OR) = 2.309, 95% confidence interval (CI) = 1.605-3.324, P = 0.001), high TC (OR = 1.561, 95% CI = 1.123-2.169, P = 0.008) and low HDL (OR = 1.449, 95% CI = 1.037-2.024, P = 0.029). As lifestyle factor, alcohol consumption results as significant risk factor for raised TG (OR = 2.653, 95% CI = 1.353-5.202, P = 0.004). Also having hepatitis raised risk of high FPG level (OR = 1.630, 95% CI = 1.197-2.220, P = 0.002) in this sample population. Conclusions: Dyslipidemia is highly common in Malaysian HIV subjects receiving ARV medication. Lifestyle modification, changing PI and switch to other ARV regimen can help in reduction of these abnormalities. Also suitable strategies and plans are necessary to prevent cardiovascular diseases in future. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the main cause of premature death in patients with chronic kidney disease (CKD). The underlying mechanisms of CVD in patients with mild to moderate CKD are different from those with end-stage renal disease (ESRD). While serum cholesterol is frequently elevated and contributes to atherosclerosis in many CKD patients, particularly those with nephrotic proteinuria, it is usually normal, even subnormal, in most ESRD patients receiving hemodialysis. CVD in the ESRD population is primarily driven by oxidative stress, inflammation, accumulation of the oxidation-prone intermediate-density lipoproteins, chylomicron remnants and small dense low-density lipoprotein particles as well as high-density lipoprotein deficiency and dysfunction, hypertension, vascular calcification, and arrhythmias. Only a minority of hemodialysis patients have hypercholesterolemia which is most likely due to genetic or unrelated factors. In addition, due to peritoneal losses of proteins which simulate nephrotic syndrome, peritoneal dialysis patients often exhibit hypercholesterolemia. Clearly when present, hypercholesterolemia contributes to CVD in the CKD and ESRD population and justifies cholesterol-lowering therapy. However, the majority of ESRD patients and a subpopulation of CKD patients with minimal proteinuria have normal or subnormal serum cholesterol levels and do not benefit from and can be potentially harmed by statin therapy. In fact the lack of efficacy of statins in hemodialysis patients has been demonstrated in several randomized clinical trials. This review is intended to provide an overview of the mechanisms responsible for the failure of statins to reduce cardiovascular morbidity and mortality in most ESRD patients and to advocate the adoption of individualized care principles in the management of dyslipidemia in this population. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A woman in her 30s with gestational diabetes presented at 36 weeks' gestation with reduced fetal movements and diminishing insulin requirements. In view of her gestation, she was induced and incidentally found to have profound hyponatraemia. Further biochemical investigations confirmed severe hypertriglyceridaemia and hypercholesterolaemia. This raises the possibility of secondary causes such as familial dysbetalipoproteinemia and polygenetic hypertriglyceridaemia. She was successfully managed by aggressive dietary modification. This involved a supervised fast followed by a fat-free diet. A fenofibrate was proposed but declined due to our patient's wish to breastfeed. Management required considerable input from the multidisciplinary team. Treatment options to consider are aggressive dietary restriction of fat or the addition of a cholesterol-lowering medication, such as a fibrate. In refractory cases, a supervised fast may be required or, in cases where complications have arisen, apheresis. The patient and her baby made a good recovery with no long-lasting health implications., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Diabetic neuropathy (DN) is common in patients diagnosed with diabetes mellitus. This often causes peripheral nerve damage. For many years vitamin B 12 and alpha-lipoic acid (ALA) have been regarded as components that can be used in reducing markers of inflammation and oxidative stress. In this study, we will explore the effectiveness of vitamin B 12 and ALA as a possible treatment for diabetic mellitus/neuropathy, emphasising markers of inflammation, lipid profile, and glucose metabolism., Methods and Analysis: We will conduct a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P). The search strategies and information sources for the literature will be PubMed, Google Scholar, Web of Science and Science direct. The literature search will include studies published from inception until 30 June 2022. All included studies will be evaluated for quality and risk of bias according to the Cochrane guidelines. To investigate the stability of the results, we will conduct a sensitivity analysis of the outcomes. All data analysis will be performed using Review Manager V.5. 4., Ethical and Dissemination: This systematic review and meta-analysis will not require ethical approval from an institution committee as it does not have direct participants. We will obtain all our data from previous studies. The findings will be disseminated through publications in peer-reviewed journals and presented at local and international seminars and conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls., Design: Matched case-control study with 8-year follow-up., Setting: Vastmanland County Hospital, Vasteras, Sweden., Participants: Consecutive patients with AMI admitted to the coronary care unit from March 2005 to May 2010 and age-matched and sex-matched controls from the general population., Outcome Measures: ACM., Results: Person-year at risk among patients with AMI and controls was 11 667 (cases: 5780 and controls: 5887). During follow-up, 199 patients and 84 controls died, implying 3.4 deaths among patients and 1.4 among controls per 100 person-years at risk. Unadjusted Cox analyses showed significantly increasing mortality by decreasing TC and LDL-C levels in both patients (HR=0.70, 95% CI 0.62 to 0.79, p<0.001, and HR=0.64, 95% CI 0.56 to 0.74, p<0.001) and controls (HR=0.73, 95% CI 0.60 to 0.89, p=0.002, and HR=0.74, 95% CI 0.59 to 0.93, p=0.010). After adjusting for clinical variables, the results for the patients remained significant. Cox analyses of the relations between mortality and TC and LDL-C below and above their respective medians revealed the following pattern., Patients: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians there were no relations with mortality., Controls: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians were LDL-C levels significantly positively related to mortality. Mean LDL-C level in patients with blood sampled >12 hours after symptom onset was 0.41 mmol/L lower than that in patients with blood sampled ≤12 hours (p=0.030). This LDL-C decrease was reasonably caused by ongoing AMI and reflects the difference in LDL-C levels between patients and controls., Conclusions: In patients with AMI, lower TC and LDL-C levels independently predict higher ACM. In their controls, LDL-C levels above the median independently predict higher ACM. This study adds to the body of evidence supporting the existence of a cholesterol paradox., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome phenotype in the liver and thus obviously associated with metabolic abnormalities, including insulin resistance-related to hyperglycaemic and hyperlipidaemia. The prevalence of NAFLD is increasing worldwide. However, currently, there is no consensus regarding the efficacy and safety of drugs used to treat patients with NAFLD/non-alcoholic steatohepatitis (NASH). Guanabenz acetate, a selective α2-adrenoceptor stimulator used in the treatment of hypertension, binds at a high-affinity constant to a nuclear transcriptional coregulator, helicase with zinc finger 2 (Helz2) and inhibits Helz2-medaited steatosis in the liver; chronic oral administration of guanabenz acetate produces a dose-dependent inhibition of lipid accumulation by inhibiting lipogenesis and activating fatty acid Β-oxidation in the liver of obese mice, resulting in improvement of insulin resistance and hyperlipidaemia. Taken all together, guanabenz acetate has a potentially effective in improving the development of NAFLD/NASH and metabolic abnormalities. In this randomised, open label, parallel-group, phase IIa study, we made attempts to conduct a proof-of-concept assessment by evaluating the efficacy and safety of guanabenz acetate treatment in patients with NAFLD/NASH., Methods and Analysis: A total of 28 adult patients with NAFLD or NASH and hypertension complications meeting the inclusion/exclusion criteria will be enrolled. Patients will be randomised to receive either 4 or 8 mg guanabenz acetate (n=14 per group). Blood tests and MRI will be performed 16 weeks after commencement of treatment. The primary endpoint will be the percentage reduction in hepatic fat content (%) measured using MRI-proton density fat fraction from baseline by at least 3.46% at week 16 after treatment initiation., Ethics and Dissemination: Ethics approval was obtained from the Ethics Committee of Yokohama City University Hospital before participant enrolment (YCU021001). The results of this study will be submitted for publication in international peer-reviewed journals, and the key findings will be presented at international scientific conferences. Participants wishing to know the results of this study will be contacted directly on data publication., Trial Registration Number: This trial is registered with ClinicalTrials.gov (number: NCT05084404)., Protocol Version: V.1.1, 19 August 2021., Competing Interests: Competing interests: ANakajima reports grants and research support from Gilead, Mylan EPD, EA Pharma, Kowa, Taisho, and Biofermin. ANakajima is a consulting adviser for Gilead, Boehringer Ingelheim, BMS, Kowa, Astellas, EA Pharma and Mylan EPD. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Physical activity (PA) plays a significant role in the treatment of type two diabetes (T2D). This study evaluated the effectiveness of PA counselling in primary healthcare (PHC) on clinical outcome measures in patients with T2D, comparing them with a registry-based controls., Setting: The study was carried out in North Karelia, Finland, among PHC clients who have been diagnosed with T2D in 2016-2018., Participants: The study population consisted of patients aged 19-87 years diagnosed with T2D (n=1803). Altogether 546 patients were referred to the PA educator of whom 521 participated the counselling. In totally 1382 sex, age, time of diagnosis and intervention time-matched controls were used to see the effect of intervention., Interventions: Patients with T2D followed up in PHC were offered to participate in PA counselling provided by trained PA educators. The number of counselling sessions and their content were tailored according to patients needs and willingness to participate. To assess the effects of PA to management of T2D clinical outcome measures such as weight and Haemoglobin A1c (HbA1c) and lipid levels were assessed using data from electronic patient records. Each patient was followed up from records at least for a year., Results: Weight and body mass index (BMI) decreased in both groups and mean yearly changes did not differ between the groups. HbA1c levels declined in the intervention and increased in the control group with statistically significant difference in the mean yearly change between the groups (p=0.001). The low-density lipoprotein declined in both groups. The decline was bigger in the intervention group, but the difference did not quite reach the statistical significance (p=0.096)., Conclusions: This study shows that PA counselling in PHC offers significant benefits in the treatment outcomes of T2D although no significant declines were not observed in the weight or BMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Atherosclerosis (AS) is an abnormal response within the vessel wall to endothelial dysfunction and inflammatory cellular processes. Taijiquan exercise as a moderate-intensity aerobic exercise can control or reverse AS by gradually reducing the deposition of cholesterol on the walls of blood vessels. Similarly, performing Baduanjin exercise, Liuzijue Qigong, Wuqinxi exercise and Yijinjing exercise has been found to have a positive effect on lipid metabolism in patients with AS. However, these studies focused only on middle-aged and older populations over 50 years of age and had short intervention periods, poor quality control and patient compliance, and no stratification by age and gender to observe the effects of traditional Chinese exercise (TCE) on patients with AS. Therefore, this meta-analysis will explore the specific effects of different TCE interventions on lipid metabolism in patients with AS through subgroup analysis of factors such as age, gender, intervention cycle and training method and lay the foundation of evidence-based medicine for the promotion of TCE in both clinical practice and the community., Methods and Analysis: A systematic approach will be completed to search the literature published up to 30 September 2021 in the following databases: Web of Science, PubMed, Embase, Cochrane Library, EBSCO and CNKI. Other databases will also be searched manually. Lipid metabolism is the primary outcome indicator. Data synthesis, sensitivity analysis, regression analysis, subgroup analysis and risk bias evaluation will be performed using RevMan V.5.3 software. In addition, funnel plots generated by Begg's and Egger's tests will be used to assess reporting bias., Ethics and Dissemination: Ethical approval and consent are not necessary as no primary data will be collected. The results of the study will be disseminated through carefully reviewed publications., Prospero Registration Number: CRD42022304283., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Obesity, defined as a body mass index ≥30 kg/m 2 , is one of the most prevalent health conditions worldwide. It is part of the metabolic syndrome, which encompasses arterial hypertension, dyslipoproteinaemia and diabetes. Obesity is viewed as a systemic disease with pathophysiological mechanisms on the molecular level. Dysfunction of the mitochondrion and systemic low-grade inflammation are among the proposed causes for the metabolic changes. In severe cases of obesity, laparoscopic sleeve gastrectomy, a bariatric operation, can achieve the desired weight loss and has been associated with clinical outcome improvement. Hitherto, the influence of patients' body composition on mitochondrial function and concomitant metabolic changes has not been fully understood. This study aims to quantify the patient's body composition before and after laparoscopic sleeve gastrectomy and to correlate these findings with changes in mitochondrial oxygen metabolism, metabolome and immune status., Methods and Analysis: In this prospective monocentric cohort study, patients undergoing laparoscopic sleeve gastrectomy (n=30) at Jena University Hospital (Germany) will be assessed before surgery and at four time points during a 1-year follow-up. Body composition will be measured by bioimpedance analysis. Non-invasive assessment of mitochondrial oxygen metabolism using protoporphyrin IX-triplet state lifetime technique (PPIX-TSLT) and blood sampling for, among other, metabolomic and immunological analysis, will be performed. The primary outcome is the difference in relative fat mass between the preoperative time point and 6 months postoperatively. Further outcomes comprise longitudinal changes of PPIX-TSLT and metabolic and immunological variables. Outcomes will be assessed using paired t-tests, Wilcoxon signed-rank tests and regression analyses., Ethics and Dissemination: The study was approved by the Ethics Committee of Friedrich Schiller University Jena (2018-1192-BO). Written informed consent will be obtained from all patients prior to enrolment in the study. The results will be published in peer-reviewed journals and presented at appropriate conferences., Trial Registration Number: DRKS00015891., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dyslipidaemia is different among patients with hypertension in different populations. The serum lipid profiles among Hakka patients with hypertension in southern China are still unclear., Methods: 35 448 patients with hypertension were enrolled in this study from January 2016 to October 2020, and their serum lipids were analysed., Results: Low high-density lipoprotein-cholesterol (HDL-C) (29.9%) accounted for the highest proportion in dyslipidaemia, followed by high triglyceride (TG) (20.7%), high total cholesterol (TC) (14.0%) and high low-density lipoprotein-cholesterol (LDL-C) (7.9%) in all subjects. The largest proportion of dyslipidaemia types was independent low HDL-C (12.7%). The proportion of low HDL-C was 15.5% in non-elderly men, 6.4% in non-elderly women, 16.7% in elderly men and 8.5% in elderly women, respectively. The largest proportion of dyslipidaemia types was independent high TG in non-elderly female patients (13.7%) and elderly patients (8.9%). The results showed that higher LDL-C, TC and TG levels in non-elderly patients than elderly patients. TG, TC and LDL-C levels decreasing with the increasing age, the differences were statistically significant. The levels of TG, TC, HDL-C and LDL-C in women were higher than in men among various age groups. Homocysteine level was increasing with increasing age., Conclusions: Serum lipid levels varied in different groups according to age and sex in patients with hypertension. Dyslipidaemia is more common in non-elderly patients than elderly. TG, TC and LDL-C levels were higher in female patients than male., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective To describe an entire litter of kittens with severe hyperlipidemia and subsequent successful, low-cost treatment that included high protein enteral support and parasite control. Previous case studies of similarly affected kittens have focused on a genetic etiology and on advanced interventions. The role of negative energy balance and additional factors influencing hyperlipidemia, as well as treatment and prognosis are discussed. Case Summary Three of 6 kittens died or were euthanized due to severe clinical signs attributable to multiorgan failure associated with subacute hyperlipidemia. The remaining 3 kittens, although subclinical, were found to have similar biochemical abnormalities, including severe anemia and hypertriglyceridemia. Flea treatment and weaning with assisted enteral support prevented the worsening of clinical signs and returned biochemical parameters to within reference intervals. Unique Information Provided Transient hyperlipidemia in kittens has been previously reported and successfully treated with administration of oxygen, blood transfusion, and diet change; these treatment recommendations may not always be financially feasible, resulting in euthanasia of affected kittens. In contrast, this report describes a successful, low-cost, outpatient approach of flea control, weaning, and introduction of a high protein enteral diet. It also highlights the importance of screening and treating seemingly unaffected littermates, provides new, previously unreported biochemical and histopathology findings, and proposes that negative energy balance is a significant factor in the development of transient hyperlipidemia in kittens. [ABSTRACT FROM AUTHOR]

Introduction: Retrospective and prospective studies show that stress at work is linked to an increased risk of hypertension, diabetes mellitus, and coronary heart disease. However, the nature of the contributory job stressors and biological mechanisms need further elucidation. Objectives: The study is aimed to determine the associations between aspects of the occupational stress index (OSI) and arterial hypertension, diabetes mellitus (DM) type 2, and lipid disorders in working middle-aged men and women. Methods: The cross-sectional study involved 989 middle-aged men and women in different occupations. The OSI was calculated by using standardized questionnaires. The total participation rate was 93%. Occupational stressors were divided into seven groups: High Demands, Strictness, Underload, Extrinsic Time Pressure, Noxious Exposure, Avoidance, and Conflict/Uncertainty. Serum lipid levels, glucoregulation, blood pressure, and cardiovascular risk factors were measured. Results: For both women and men, the total OSI score associated significantly with DM (women: odds ratio [OR] 2.4, 95% confidence intervals [CI] 1.67–3.45; men: 1.21, 1.15–1.45), any type of dyslipidemia (women: 1.54, 1.17–2.03; men: 1.31, 1.24–1.39), and arterial hypertension (women: 1.15, 1.10–1.21; men: 1.58, 1.49–1.68). The group as a whole showed associations between total OSI and low high-density lipoprotein (HDL) cholesterol, high total cholesterol, and high triglyceride levels. Of the OSI aspects, Underload associated significantly in both men and women with arterial hypertension (women: 3.48, 1.91–6.31; men: 2.71, 1.96–3.75) and dyslipidemia (women: 3.26, 2.13–4.99; men: 2.11, 1.76–2.52). Underload was also associated with several lipid abnormalities in the group as a whole. It associated with DM in women only (4.7, 2.84–7.81). All remaining OSI aspects also associated significantly and positively with DM in women only. Conversely, in male workers, but not female workers, High Demand, Conflict/Uncertainty, and Extrinsic Time Pressure associated significantly with arterial hypertension. Strictness and Conflict/Uncertainty associated positively with dyslipidemia in women only. Noxious Exposures associated positively with DM and arterial hypertension in women only. Conclusions: The study provides evidence for the association of work stress with metabolic disorders and hypertension. Total OSI associated significantly with DM type 2, arterial hypertension, and dyslipidemia in both genders. Different OSI aspects associated with these health issues in gender- and occupational-specific patterns. Underload, which represents lack of social communication, simple task preparation, and underestimation of working results, associated most strongly of all OSI aspects with disease in both the sexes. [ABSTRACT FROM PUBLISHER]

Background: Lipid disorders are common worldwide and contribute to a significant proportion of the burden of atherosclerotic cardiovascular diseases. Objectives: To determine the prevalence of lipid disorders among patients reporting at Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Design: Cross-sectional study. Setting: Directorate of Medicine and Polyclinic outpatient clinics of KATH. Participants: A total of 424 patients, 20 years and over reporting for the first time to KATH were recruited. 77 had neither diabetes mellitus (DM) nor systemic hypertension (HPT) (controls), 94 had only DM, 109 had only HPT and 144 had both. Methods: A questionnaire was administered after informed consent. Anthropometric measurements were then taken and blood investigations including total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and triglycerides (TG) were done. Low-density lipoprotein cholesterol (LDL) was calculated using the Friedwald formula. The atherogenic index or ratio was the ratio of TC to HDL. Results: The prevalence of lipid abnormalities was 60% for high TC, 32% for high TG, 17% for low HDL and 61% for high LDL. The mean (± standard deviation) TC was 5.33 (± 1.31) mmol/L, mean TG was1.52 (± 0.81) mmol/L, mean HDL was 1.65 (± 0.57) mmol/L and mean LDL was 3.42 (± 1.22) mmol/L. The mean atherogenic index was 3.40 and 9% of the participants had an atherogenic index more than or equal to 5. Conclusion: The prevalence of lipid disorders was high in adult patients in Kumasi and there is the need to increase awareness, screening, detection, treatment and control of these disorders. [ABSTRACT FROM AUTHOR]

Evidence has been provided that a sustained use (smoking) of cannabis (indian hemp, marijuana) leads to impaired psychomotor performance, interacting and interfering with the organism's endocannabinoid system. The effects are dependent on the used dose and the duration of such a habit and about one in ten consumers may develop dependence. More accentuated adverse effects were recorded in subjects with preexistent psychiatric illness and schizofrenics were found to be particularly vulnerable to cannabis, which triggered relapses and aggravation. The endocannabinoid system includes specific receptors (CB1 and CB2) and the lipidic endocannabinoids anandamide and 2-arachidonoilglycerol (2-AG), acting as activating ligands for the specific receptors. Enzymes ensuring the synthesis, as well as enyzmes involved in the degradation of endocannabinoids were also identified. A hyperactivation of this system leads to an exagerated appetite, hyperphagia, and subsequent obesity as well as to the development of an atherogenic dyslipidemia. The synthetic compound rimonabant, a blocker of the CB1 receptor reduced the exagerated appetite and the body weight, also normalising the plasma lipoprotein pattern. Unfortunately, adverse effects of such a therapy were reported emphasizing an increased incidence of depressive and/or anxious moods. Such observations were suggesting that the endocannabinoid system may also be involved in establishing a stable statisfied mood and connexions between this system and serotoninergic mediation were actually documented. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In previous studies of healthy volunteers, administration of atorvastatin with very large quantities of grapefruit juice increases exposure to atorvastatin by a mean factor of 3.3. However more typical quantities of grapefruit juice increased exposure only by a factor of 1.3. The effects of customary doses of grapefruit juice on the efficacy and safety of atorvastatin in patients requiring treatment with this drug have not been established. WHAT THIS STUDY ADDS • The present study is the first to evaluate changes in the lipid-lowering efficacy of atorvastatin, as well as subjective and laboratory assessments of safety, in a series of hyperlipidaemic patients on stable doses of atorvastatin who co-ingested typical quantities of grapefruit juice. The findings indicate a small elevation of serum atorvastatin concentrations due to grapefruit juice, but no meaningful enhancement of lipid-lowering effects, and no evidence of adverse liver or muscle effects. AIM To determine whether customary exposure to grapefruit juice (GFJ) alters serum concentrations, effectiveness, and potential adverse effects of atorvastatin in patients requiring the medication. METHODS Patients receiving extended treatment with atorvastatin (10, 20 or 40 mg day−1) at a stable dose received 300 ml day−1 of 100% GFJ for a period of 90 days. One cohort of patients (arm A, n= 60) continued on their current dose of atorvastatin; the second cohort (arm B, n= 70) reduced the daily dose by 50%. Serum atorvastatin, lipid profile, liver functions, and creatine phosphokinase (CPK) were measured at baseline and at 30, 60, and 90 days after starting GFJ. RESULTS In Arm A patients, co-ingestion of GFJ significantly elevated serum atorvastatin by 19% to 26% compared with baseline. Changes in lipid profile relative to baseline were negligible. There were no adverse effects on liver function tests or CPK. In arm B patients, serum atorvastatin declined by 12% to 25% compared to baseline, with a small but significant unfavourable effect in serum lipid profile. There were no adverse effects on liver function tests or CPK. CONCLUSION In patients on extended stable atorvastatin treatment, addition of daily GFJ in typical quantities slightly elevates serum atorvastatin concentrations, but has no meaningful effect on the serum lipid profile, and causes no detectable adverse liver or muscle effects. Reduction of atorvastatin dosage when moderate amounts of GFJ are co-ingested does not appear to be necessary. [ABSTRACT FROM AUTHOR]

Patients infected with the human immunodeficiency virus (HIV) are prone to a great number of lipid and lipoprotein disturbances, as a result of both the infection itself and direct effects on lipid metabolism from the drugs used to treat HIV infection. These lipid disorders account for at least part of the increased risk of cardiovascular disease seen in this population. In general, evaluation and interventions for dyslipidemia in HIV-infected individuals should follow guidelines established for the general population. Special consideration, however, must be given to the potential for adverse drug interactions between lipid lowering drugs and the agents used to treat HIV infection. In this review, we summarize what is known about the relative tendency of different antiretroviral drugs to alter lipid levels, and suggest an approach to intervention for dyslipidemia in this population. [Copyright &y& Elsevier]

Background Dyslipidaemia, a key risk factor for cardiovascular disease (CVD), is strongly influenced by genetic factors. Objective To identify genetic factors affecting blood lipid concentrations and CVD risk factors in the Korean population by a candidate gene association analysis. Methods 21 single nucleotide polymorphisms (SNPs) that have been reported as associated with lipid concentrations in people of European ancestry were selected and their associations with CVD risk factors in Korean populations assessed. Genotype data from 7616 subjects without diabetes or lipid-lowering drugs were obtained from the Korean Association Resource (KARE) project. Results After adjustment for age and gender, five SNPs were identified that were associated with high-density lipoprotein-cholesterol (HDL-C; rs4420638: p=2.09×10), 11 SNPs with low-density lipoprotein-cholesterol (LDL-C; rs12654264: p=1.29×10) and eight SNPs with triglycerides (TG; rs4420638: p=1.80×10). Through analysis of multiple associations with lipid traits, after adjustment for age, gender, body mass index, smoking, alcohol consumption and hypertension, five SNPs (rs693, rs17321515, rs174547, rs688, rs4420638) were identified that were strongly associated with at least two of the following: HDL-C, LDL-C and TG. Of these, rs693, which lies in the gene, was also significantly associated with the homoeostasis model assessment for insulin resistance (p=6.68×10) and γ-glutamyl transpeptidase (p=2.34×10), and rs174547, which lies in the gene and was significantly associated with fasting plasma glucose (p=1.48×10). Conclusion Several SNPs associated with lipid traits and CVD risk factors were identified. These findings may form the basis for further investigations to identify the causative polymorphisms in dyslipidaemia and CVD. [ABSTRACT FROM PUBLISHER]

Introduction The Li–Fraumeni Syndrome is caused by a germline mutation and is associated with a high risk of breast cancer at young ages. Basal (triple negative) breast cancers are now well recognised to be a typical sub-type of breast cancer developing in a large proportion of BRCA1 gene carriers. We considered whether a similar narrow sub-type of breast cancer was found in gene mutation carriers. Objective A hypothesis generating study to investigate whether there are specific breast tumour characteristics associated with germline mutations. Methods Pathological characteristics in 12 breast cancers arising in nine patients carrying pathogenic mutations were compared to a reference panel of 231 young onset breast tumours included in the POSH study. Results Patients carrying a mutation showed a significantly higher likelihood of developing a breast cancer with Human Epidermal growth factor Receptor (HER2) amplification (83%) when compared to the cohort of young onset breast cancer cases (16%); ER and PR status were equivalent between groups. Conclusion These findings suggest that breast cancer developing on a background of an inherited mutation is highly likely to present with amplification of HER2. [ABSTRACT FROM PUBLISHER]

Background: Cardiovascular disease caused by atherosclerosis remains a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). We evaluated the potential association of cardiovascular risk factors including asymmetric dimethyl L-arginine (ADMA) and the soluble receptor for advanced glycation end products (sRAGE) with preclinical atherosclerosis in patients undergoing kidney transplantation. Patients and Methods: In 92 males and 47 females undergoing the first cadaveric renal transplantation, ADMA, sRAGE and common risk factors including lipid parameters were evaluated as potential predictors of preclinical atherosclerosis defined as the Belcaro score (focused on advanced atherosclerotic changes) measured by ultrasound. Results: The prevalence of atherosclerotic changes was approximately 70% in men and women. In logistic regression, age, history of smoking, presence of diabetes mellitus, and plasma triglycerides were the strongest independent predictors for advanced atherosclerosis in the whole group. In unadjusted analyses advanced atherosclerosis was also associated with sRAGE in men and with the atherogenic index of plasma in women. Conclusion: Apart from traditional cardiovascular risk factors, plasma triglycerides were found to be strong and independent predictors of advanced atherosclerosis in patients with ESRD. In addition, sRAGE was associated with atherosclerosis in men and the atherogenic index of plasma in women. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Many reports provided strong evidence of the influence of genetic factors in the pathogenesis of psoriasis (Ps). A higher prevalence of lipid disorders in psoriatic patients has been reported. Because apolipoprotein E (apoE) is involved in lipid metabolism, APOE gene variants could be candidates to influence Ps-risk. However, data about the potential influence of the APOE genotypes in Ps are inconclusive. Our objective was to investigate the relationship between the common APOE-ε2/ε3/ε4 variation and Ps in a Caucasian population. Our study involved 331 unrelated Ps-patients and 400 healthy controls. Patients and controls were genotyped for the APOE-ε2/ε3/ε4 polymorphism, and allele and genotype frequencies were statistically compared between the two groups and between patients according to disease severity. Mean lipid values were also compared between the APOE genotypes. Allele and genotype frequencies did not differ between patients and controls. APOE-ε4 carriers were significantly more frequent in patients with severe Ps compared to controls ( P = 0.003) and to non-severe Ps ( P = 0.017). No significant difference in mean lipid values was found between the APOE genotypes. The APOE-ε4 allele could be a risk factor for developing a severe form of psoriasis. [ABSTRACT FROM AUTHOR]

Background:Although the human adenovirus-36 (Ad-36) has been associated with obesity and related lipid disorders in the United States, this association has yet to be identified in other countries. Therefore, we tried to determine whether Ad-36 is associated with obesity or lipid disorders in Korean schoolchildren.Method:A total of 318 Korean schoolchildren aged 6–15 years, who participated in the Ewha Womans University Obesity Research Study, were selected for a community-based cohort study. Non-obese and obese were defined as body mass index (BMI) <85th and 95th percentiles of the Korean reference BMI-for-age curves, respectively, according to International Obesity Task Force definitions. The cutoff points for lipid disorders were modified from the age-modified standards of the National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP) III metabolic syndrome criteria. The Ad-36 antibody was measured using a serum neutralization assay.Results:More obese participants than non-obese participants tested positive for the Ad-36 antibody (28.57 vs 13.56%, respectively; P=0.0174). Within the obese group, the participants who tested positive for the Ad-36 antibody had higher levels of triglycerides (TG) and total cholesterol than those who tested negative for the Ad-36 antibody (P<0.001). However, these associations were not present in the non-obese group. The unadjusted odds ratio (OR) for Ad-36 antibody positivity was greater in obese participants than non-obese participants (OR=2.550, 95% confidence interval (CI): 1.154–5.633). However, this OR seemed to be nonsignificant when age, sex and lipid variables were included in the analysis (OR=1.752, 95% CI: 0.763–4.020). The unadjusted OR for the elevated TG was significantly higher in participants who were Ad-36 antibody-positive than those who were Ad-36 antibody-negative (OR=2.511, 95% CI: 1.448–4.353). This trend remained constant even after adjustment for age, sex and obesity (OR=2.328, 95% CI: 1.296–4.181).Conclusion:Ad-36 seems to be strongly associated with lipid disorders in Korean schoolchildren regardless of obesity. [ABSTRACT FROM AUTHOR]

Patients with coronary artery disease (CAD) commonly have varying degrees of coexisting cerebrovascular disease (CVD) and chronic kidney disease (CKD), and proper management is complicated partly because of a lack of unifying guidelines. The aim of this article is to review the current literature and propose the optimal treatment regimen in patients with all three disease states. Angiotensin-converting enzyme inhibitors (ACE-I) should be universally administered. High-dose statin therapy to reach a target low-density lipoprotein (LDL) of 70–100 mg/dL is advocated, although patients with a history of cerebral bleeding must be carefully monitored for possible recurrence. Beta-blockers are appropriate after a recent coronary event, and amlodipine or thiazide diuretics should be used after a recent stroke (within 6 months). Patients with a history of stroke (with or without coexisting CAD and CKD) should receive aspirin (75–150 mg/day) indefinitely. Clopidogrel or aspirin plus extended-release dipyridamole (ER-DP) may be prescribed in patients allergic or resistant to aspirin. If stroke is attributable to cardiogenic embolism, anticoagulation is indicated. In patients with acute coronary syndromes (ACS) (excluding ST-elevated myocardial infarct) who undergo percutaneous coronary intervention (PCI), aspirin plus clopidogrel is indicated for secondary prevention for up to 12 months. There are no data supporting the use of aspirin plus clopidogrel in patients with CKD who develop ACS. Aspirin plus clopidogrel is contraindicated for stroke prevention. [ABSTRACT FROM AUTHOR]

Features of end-stage renal disease such as oxidative stress, inflammation, hypertension, and dyslipidemia are associated with accelerated atherosclerosis and increased risk of death from cardiovascular disease. By inhibiting the formation and increasing the disposal of oxidized lipids, HDL exerts potent antioxidant and anti-inflammatory actions. Given that apolipoproteinA-1 can limit atherosclerosis, we hypothesized that an apolipoproteinA-1 mimetic peptide, 4F, may reduce the proinflammatory properties of LDL and enhance the anti-inflammatory properties of HDL in uremic plasma. To test this, plasma from each of 12 stable hemodialysis patients and age-matched control subjects was incubated with 4F or vehicle. The isolated HDL and LDL fractions were added to cultured human aortic endothelial cells to quantify monocyte chemotactic activity, thus measuring their pro- or anti-inflammatory index. The LDL from the hemodialysis patients was more pro-inflammatory and their HDL was less anti-inflammatory than those of the control subjects. Pre-incubation of the plasma from the hemodialysis patients with 4F decreased LDL pro-inflammatory activity and enhanced HDL anti-inflammatory activity. Whether 4F or other apolipoproteinA-1 mimetic peptides will have any therapeutic benefit in end-stage renal disease will have to be examined directly in clinical studies.Kidney International (2009) 76, 437–444; doi:10.1038/ki.2009.177; published online 27 May 2009 [ABSTRACT FROM AUTHOR]

Background: Chronic renal failure (CRF) causes oxidative stress, inflammation, oxidation of lipoproteins, impaired maturation of HDL and accelerated atherosclerosis. Uptake of oxidized lipoproteins by macrophages via scavenger receptors (scavenger receptor class A type I--SR-AI, and lectin-like oxidized LDL receptor--LOX-1) leads to foam cell formation and atherosclerosis. HDL mitigates atherosclerosis by retrieving surplus cholesterol via ATP binding cassette transporter A1 (ABCA1) and ABCG1 transporters whose expression is regulated by liver X receptor (LXR). Free cholesterol reaching the surface of HDL is esterified by lecithin-cholesterol acyltransferase (LCAT) and sequestered in the core of HDL, thereby maximizing cholesterol uptake. In the liver, lipid-rich HDL unloads its lipid contents via reversible binding to SR-BI while lipid-poor HDL is degraded by the holo-receptor (ATP synthase beta-chain).Methods: Expression of the above molecules involved in reverse cholesterol/lipid transport was assessed in rats 8 weeks after 5/6 nephrectomy (CRF) or sham operation.Results: CRF caused heavy accumulation of neutral lipids, upregulation of SR-AI, LOX-1, LXRalpha/beta, ABCA1 and ABCG1 in the aorta, reduction in LCAT in the plasma and no significant change in either SR-BI or beta-chain ATP synthase in the liver.Conclusions: Lipid accumulation despite upregulation of the efflux (LXR, ABCA1, ABCG1) system in the aorta in CRF is largely due to upregulation of influx (SR-AI and LOX-1) pathway and LCAT deficiency. [ABSTRACT FROM AUTHOR]

The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol. [ABSTRACT FROM AUTHOR]

Abstract: Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder of which the molecular basis still remains to be elucidated. Since the HDL-associated enzyme serum paraoxonase (PON1) is associated with variation in serum lipids and lipoproteins, we determined whether variation in PON1 also contributes to the FCH phenotype. The study population consisted of 32 well-defined families with FCH, including 103 FCH patients and 240 normolipidemic relatives (NLR). In addition to plasma lipids and lipoproteins we determined PON1 activity (arylesterase- and paraoxonase activity) as well as the common genetic variants −107C>T, 55L>M and 192Q>R in the PON1 gene. The arylesterase activity was significantly higher in FCH patients when compared to NLR (P <0.001). In the total population, the PON1 genetic variants associated with the highest arylesterase activity (−107CC and 55LL) also associated with higher levels of total cholesterol, apolipoprotein B, triglycerides and VLDL-cholesterol and decreased levels of HDL-cholesterol. In support, the combination of the −107CC with the 55LL genotype associated with a significant increased risk for FCH when compared to the −107TT/55MM genotype (odds ratio 5.0 (95% CI, 1.3–19.1, P =0.02)). In conclusion, in this population of subjects from well-defined families with FCH, PON1 is biochemically and genetically associated with FCH. [Copyright &y& Elsevier]

Chronic renal insufficiency (CRI) is associated with a characteristic dyslipidemia. Findings in children with CRI largely parallel those in adults. Moderate hypertriglyceridemia, increased triglyceride-rich lipoproteins (TRL) and reduced high-density lipoproteins (HDL) are the most usual findings, whereas total and low-density lipoprotein cholesterol (LDL-C) remain normal or modestly increased. Qualitative abnormalities in lipoproteins are common, including small dense LDL, oxidized LDL, and cholesterol-enriched TRL. Measures of lipoprotein lipase and hepatic lipase activity are reduced, and concentrations of apolipoprotein C-III are markedly elevated. Still an active area of research, major pathophysiological mechanisms leading to the dyslipidemia of CRI include insulin resistance and nonnephrotic proteinuria. Sources of variability in the severity of this dyslipidemia include the degree of renal impairment and the modality of dialysis. The benefits of maintaining normal body weight and physical activity extend to those with CRI. In addition to multiple hypolipidemic pharmaceuticals, fish oils are also effective as a triglyceride-lowering agent, and the phosphorous binding agent sevelamer also lowers LDL-C. Emerging classes of hypolipidemic agents and drugs affecting sensitivity to insulin may impact future treatment. Unfortunately, cardiovascular benefit has not been convincingly demonstrated by any trial designed to study adults or children with renal disease. Therefore, it is not possible at this time to endorse general recommendations for the use of any agent to treat dyslipidemia in children with chronic kidney disease. [ABSTRACT FROM AUTHOR]

In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context in the search for genetic factors influencing the metabolic pathways. Particular physiological heterogeneity is addressed and procedures to handle this complex issue are suggested. [ABSTRACT FROM AUTHOR]

Abstract: Objectives and methods: DETECT is a cross-sectional study of 55,518 unselected consecutive patients in 3188 representative primary care offices in Germany. In a random subset of 7519 patients, an extensive standardized laboratory program was undertaken. The study investigated the prevalence of cardiovascular disease, known risk factors (such as diabetes, hypertension and dyslipidemia and their co-morbid manifestation), as well as treatment patterns. The present analysis of the DETECT laboratory dataset focused on the prevalence and treatment of dyslipidemia in primary medical care in Germany. Coronary artery disease (CAD), risk categories and LDL-C target achievement rates were determined in the subset of 6815 patients according to the National Cholesterol Education Program (NCEP) ATP III Guidelines. Results: Of all patients, 54.3% had dyslipidemia. Only 54.4% of the NCEP-classified dyslipidemic patients were diagnosed as ‘dyslipidemic’ by their physicians. Only 27% of all dyslipidemic patients (and 40.7% of the recognized dyslipidemic patients) were treated with lipid-lowering medications, and 11.1% of all dyslipidemic patients (41.4% of the patients treated with lipid-lowering drugs) achieved their LDL-C treatment goals. In conclusion, 80.3% of patients in the sample with dyslipidemia went undiagnosed, un-treated or under-treated. [Copyright &y& Elsevier]

Chronic renal failure (CRF) results in profound lipid disorders, which stem largely from dysregulation of high-density lipoprotein (HDL) and triglyceride-rich lipoprotein metabolism. Specifically, maturation of HDL is impaired and its composition is altered in CRF. In addition, clearance of triglyceride-rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentrations are elevated in CRF. Impaired maturation of HDL in CRF is primarily due to downregulation of lecithin-cholesterol acyltransferase (LCAT) and, to a lesser extent, increased plasma cholesteryl ester transfer protein (CETP). Triglyceride enrichment of HDL in CRF is primarily due to hepatic lipase deficiency and elevated CETP activity. The CRF-induced hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride-rich lipoproteins and their remnants are primarily due to downregulation of lipoprotein lipase, hepatic lipase, and the very-low-density lipoprotein receptor, as well as, upregulation of hepatic acyl-CoA cholesterol acyltransferase (ACAT). In addition, impaired HDL metabolism contributes to the disturbances of triglyceride-rich lipoprotein metabolism. These abnormalities are compounded by downregulation of apolipoproteins apoA-I, apoA-II, and apoC-II in CRF. Together, these abnormalities may contribute to the risk of arteriosclerotic cardiovascular disease and may adversely affect progression of renal disease and energy metabolism in CRF. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a prominent feature of chronic renal failure (CRF) and a major risk factor for atherosclerosis and the progression of renal disease. CRF-induced dyslipidemia is marked by hypertriglyceridemia and a shift in plasma cholesterol from HDL to the ApoB-containing lipoproteins. Several studies have demonstrated a favorable response to administration of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) in CRF. This study was intended to explore the effect of statin therapy on key enzymes and receptors involved in cholesterol metabolism. Accordingly, CRF (⅚ nephrectomized) and sham-operated rats were randomized to untreated and statin-treated (rosuvastatin 20 mg·kg-1·day-1) groups and observed for 6 wk. The untreated CRF rats exhibited increased total cholesterol-to-HDL cholesterol ratio, diminished plasma lecithin:cholesterol acyltransferase (LCAT) and the hepatic LDL receptor, elevated hepatic acyl-CoA:cholesterol acyl- transferase (ACAT), and no change in hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, or HDL receptor (SRB-1). Statin admin- istration lowered HMG-CoA reductase activity, normalized plasma LCAT, total cholesterol-to-HDL cholesterol ratio, and hepatic LDL receptor but did not significantly change either plasma total choles- terol, hepatic cholesterol 7α-hydroxylase, total ACAT activity, or SRB-1 in the CRF animals. Statin administration to the normal control rats led to significant increases in plasma LCAT and hepatic LDL receptor, significant reductions of total cholesterol-to-HDL cholesterol ratio, hepatic HMG-CoA reductase activity, and cholesterol 7α-hydroxylase abundance with virtually no change in plasma cholesterol concentration. Thus administration of rosuvastatin reversed LCAT and LDL receptor deficiencies and promoted a shift in plasma cholesterol from ApoB-containing lipoproteins to HDL in CRF rats. [ABSTRACT FROM AUTHOR]

Down-regulation of hepatic LDL receptor-related protein (LRP) in chronic renal failure.Background.Chronic renal failure (CRF) is associated with premature atherosclerosis, impaired high-density lipoprotein (HDL)-mediated reverse cholesterol transport, depressed clearance, and elevated plasma concentrations of very low-density lipoprotein (VLDL), chylomicrons, and their atherogenic remnants. LDL receptor-related protein (LRP) is a member of the LDL receptor gene family that is heavily expressed in the liver, and mediates removal of at least 30 different ligands, including VLDL remnants (IDL) and chylomicron remnants. This study was conducted to test the hypothesis that the well-known defect in clearance of IDL and chylomicron remnants in CRF may be indicative of diminished hepatic LRP abundance.Methods.Hepatic tissue LRP mRNA abundance[reverse transcription-polymerase chain reaction (RT-PCR)] and protein abundance (Western blot analysis) were determined in rats 8 weeks after 5/6 nephrectomy (CRF group) or sham operation (control group).Results.The CRF group exhibited hypertension, diminished creatinine clearance, increased plasma triglyceride concentration, and elevated total cholesterol-to-HDL cholesterol concentration ratio compared to the corresponding values found in the control group. This was associated with a significant down-regulation of hepatic LRP mRNA expression and immunodetectable LRP protein.Conclusion.CRF results in down-regulation of hepatic LRP. This abnormality can, at least in part, account for the previously documented elevation of plasma concentration and depressed clearance of chylomicron remnants and IDL in CRF. [ABSTRACT FROM AUTHOR]

HMG-CoA reductase, cholesterol 7α-hydroxylase, LDL receptor, SR-B1, and ACAT in diet-induced syndrome X.Background.Long-term consumption of Western diets can lead to acquired syndrome X, which presents with obesity, insulin resistance, hypertension, hyperlipidemia, and risk of atherosclerotic cardiovascular disease. While plasma lipid abnormalities in syndrome X have been well characterized, their molecular basis remains unclear. This study explored potential mechanisms of hypercholesterolemia in diet-induced syndrome X.Methods.Female Fischer rats were fed a high-fat, refined-carbohydrate (sucrose) diet (HFS) or standard rat chow (low-fat, complex carbohydrate, LFCC) for 20 months. Plasma lipids and hepatic tissue mRNA, protein, and/or activities of the key enzymes and receptors involved in cholesterol metabolism were determined.Results.The HFS group exhibited hypertension, hyperlipidemia, insulin resistance, obesity, significant down-regulation of hepatic cholesterol 7α-hydroxylase (the rate-limiting step in cholesterol catabolism) and low-density lipoprotein (LDL) receptor (LDL-R, the primary pathway of LDL clearance). In contrast, hepatic tissue acyl-coenzyme A:cholesterol acyltransferase (ACAT-2, the primary enzyme involved in intracellular esterification of cholesterol) and scavenger-receptor class B, type 1 (SR-B1 or HDL receptor) were up-regulated. While 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA expression was increased, its protein abundance and activity were unchanged, and HMG-CoA reductase-to-cholesterol 7α-hydroxylase ratio was increased in HFS-fed animals.Conclusion.Hypercholesterolemia in diet-induced syndrome X is associated with depressed cholesterol 7α-hydroxylase, diminished LDL-R, elevated ACAT, and increased HMG-CoA reductase-to-cholesterol 7α-hydroxylase ratio. These findings point to impaired hepatic catabolism and uptake of cholesterol and inappropriate cholesterol production capacity as the underlying causes of hypercholesterolemia in rats with diet-induced syndrome X. [ABSTRACT FROM AUTHOR]

We evaluated the myocardial function of rats with sugar-induced hypertriglyceridemia (HTG) and hypertension, and the effect of serum on myocardial performance in the isolated heart preparation. Also, the response to reperfusion after 30 minutes of global ischemia was investigated. Hearts from HTG rats developed lower ventricular pressure (VP) and the conduction rate was higher than in hearts from control rats (CR). The recovery of VP after ischemia was significantly lower in HTG than in CR hearts (p < 0.05). The HTG sera produced a higher increase in the VP and in the perfusion pressure. During reperfusion, the incidence of premature beats, ventricular fibrillation and tachycardia in HTG hearts was increased so hypertriglyceridemia caused alterations in the mechanical and electrical conduction of the myocardium and exacerbated the injury produced by ischemia-reperfusion. Also a circulating factor in the HTG serum induced a vasoactive response of the heart which was reflected in its mechanical performance. [ABSTRACT FROM AUTHOR]