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1.
Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial.
Ishibashi, S, Arai, H, Yokote, K, Araki, E, Suganami, H, Yamashita, S, ,
Journal of clinical lipidology. 2018;(1):173-184
Abstract
BACKGROUND To overcome the concerns associated with the use of fibrates, pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor modulator, was developed. In a previous phase 2 trial, we showed excellent efficacy and safety of pemafibrate in patients with dyslipidemia. OBJECTIVE The objective of the study was to evaluate the efficacy and safety of pemafibrate over 24 weeks in adults with dyslipidemia in comparison with fenofibrate. METHODS In this multicenter, 24-week, double-blind, clinical study, 225 patients with high triglyceride (TG; ≥150 mg/dL [1.7 mmol/L] and <500 mg/dL [5.7 mmol/L]) and relatively low high-density lipoprotein cholesterol (<50 mg/dL [1.3 mmol/L] in men or 55 mg/dL [1.4 mmol/L] in women) levels were randomized to receive either pemafibrate at 0.2 or 0.4 mg/d or fenofibrate 106.6 mg/d. RESULTS Pemafibrate 0.2, 0.4 mg/d and fenofibrate significantly reduced TG levels from baseline by -46.2%, -45.9%, and -39.7%, respectively. As compared with fenofibrate, the least squares mean differences (95% confidence intervals) in TG were -6.5% (-12.0, -1.1) and -6.2% (-11.6, -0.8) in pemafibrate 0.2 and 0.4 mg/d respectively, which showed the superiority of these doses of pemafibrate to 106.6 mg/d of fenofibrate. The incidence rates of adverse drug reactions in pemafibrate groups (2.7% and 6.8%) were significantly lower than that in the fenofibrate group (23.7%). Pemafibrate significantly decreased alanine aminotransferase and gamma-glutamyltransferase levels, whereas fenofibrate increased both of them. The increments of serum creatinine and cystatin C were smaller in pemafibrate than those in fenofibrate. CONCLUSIONS Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety.
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2.
Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a Selective Inhibitor of p70 S6 Kinase-1.
Leohr, JK, Luffer-Atlas, D, Luo, MJ, DeBrota, DJ, Green, C, Mabry, TE, Suico, JG
Journal of clinical pharmacology. 2018;(4):412-424
Abstract
The safety, pharmacokinetic, and pharmacodynamic effects of LY2584702, a selective inhibitor for p70 S6 serine/threonine protein kinase-1, were evaluated in healthy dyslipidemic volunteers. LY2584702 was tolerated well as a monotherapy and dose-dependently reduced low-density lipoprotein cholesterol and triglycerides by up to 60% and 50%, respectively, without significantly changing high-density lipoprotein cholesterol levels in plasma. LY2584702 also dose-dependently decreased factor V activity. Alanine aminotransferase elevations were noted in 2 subjects when LY2584702 was given with atorvastatin. We suspect that the formation of 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) during metabolism may have contributed to some of the adverse effects of LY2584702, and the contribution of 4-APP to the pharmacology merits further investigation. Although clinical investigation of LY2584702 has been terminated because of hepatotoxicity risk, we suggest that a selective inhibitor of p70 S6 serine/threonine protein kinase-1 with a larger margin of safety and without the possibility of being metabolized to 4-APP may be useful in the treatment of dyslipidemia.
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3.
[Data on prevalence of dyslipidemia and lipid values in Turkey: Systematic review and meta-analysis of epidemiological studies on cardiovascular risk factors].
Kayıkçıoğlu, M, Tokgözoğlu, L, Kılıçkap, M, Göksülük, H, Karaaslan, D, Özer, N, Abacı, A, Yılmaz, MB, Barçın, C, Ateş, K, et al
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2018;(7):556-574
Abstract
OBJECTIVE Dyslipidemias, primarily hypercholesterolemia, are independent and strong predictors of cardiovascular (CV) events. The frequency of dyslipidemia is very important in terms of determining CV prevention policies. In order to determine the up-to-date frequency of CV risk factors in Turkey, a meta-analysis of the epidemiologic studies carried out in the last 15 years was performed. This article presents the results on the dyslipidemia data including hypercholesterolemia principally. METHODS Epidemiological studies conducted during the last 15 years and having the potential to represent the general population in Turkey were searched in databases (Ovid Medline, Web of Science Core Collection, and Turkish Academic Network and Information Center [ULAKBIM]) and web pages (Ministry of Health, Turkey Statistical Institute, Turkish Society of Cardiology, Nephrology and Endocrinology Associations). A total of 7 studies including lipid data were found. Systematic review and meta-analysis of the studies with low bias score were performed. Crude values of the prevalence of hypercholeterolemia, hypertriglyceridemia and low HDL and mean lipid levels were calculated. Random effects model was used in meta-analysis. RESULTS The prevalence of hypercholesterolemia defined as a LDLcholesterol >130 and/or ≥130 mg/dL, was 29.1% (95% CI 23.6-35.0) in the general population, 30.2% in females (%95 CI 24.7-36.1), and 27.8% in males (95% CI 22.3-33.6). The prevalence of low HDLcholesterol (≤50 mg/dL for females and ≤40 mg/dL for males) was calculated as 46.1% (95% CI 42.4-49.9) in the whole group, 50.7% (95% CI 47.7-53.6) in females and 41.1% (95% CI 36.1-46.3) in males. The prevalence of hypertriglyceridemia (>150 mg/dL) was 36.5% (95% CI 30.6-42.5) in general, 32.0% (95% GA 26.6-37.8) in females and 41.3% (95% CI 34.9-47.8) in males. CONCLUSION Dyslipidemia constitutes a major public health problem in Turkey. In the adult population, almost 3 of 10 have hypercholesterolemia, one of 2 has a low HDL-cholesterol, and 1 of 3 has high triglycerides levels.
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4.
Association between lipid profile and the prevalence of asthma: a meta-analysis and systemic review.
Su, X, Ren, Y, Li, M, Zhao, X, Kong, L, Kang, J
Current medical research and opinion. 2018;(3):423-433
Abstract
OBJECTIVE To explore the association of asthma with serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglyceride. METHODS PubMed, Cochrane, and Embase databases were systematically searched through November 2015 using the following search terms: dyslipidemia, HDL, LDL, triglyceride, cholesterol, and asthma. Eligible studies included randomized controlled trials (RCTs), retrospective, cohort, and cross-sectional studies. Sensitivity analysis and publication bias were performed. RESULTS Twenty studies were included in the analysis, with a total 32,604 patients (3,458 in the asthma group and 29,146 in the control group). The pooled analysis found that the mean difference between groups was significantly higher in the asthma group for levels of LDL (6.026 mg/dL, 95% CI = 2.696-9.356, p < .001) and total cholesterol (8.161 mg/dL, 95% CI = 3.006-13.316, p = .002) compared with the control group. No association was observed between asthma and control groups for levels of HDL (mean difference = -0.728, 95% CI = -3.146-1.691, p = .555) or triglycerides (mean difference = 1.436, 95% CI = -2.768-5.640, p = .503). CONCLUSIONS Levels of LDL and total cholesterol were higher in patients with asthma than non-asthmatic patients.
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Dietary management of dyslipidaemias. Is there any evidence for cardiovascular benefit?
Anagnostis, P, Paschou, SA, Goulis, DG, Athyros, VG, Karagiannis, A
Maturitas. 2018;:45-52
Abstract
Specific dietary strategies are the mainstay of management in most cases of dyslipidaemia, prior to or simultaneously with the initiation of a lipid-lowering agent. The exact approach differs according to the type of dyslipidaemia. In particular, a reduction in carbohydrates (mainly foods with a high glycaemic index) and their substitution with mono- and polyunsaturated fatty acids is the main strategy in patients with high levels of triglycerides (Tg) and/or low levels of high-density lipoprotein cholesterol (HDL-c). A reduction in saturated and trans fatty acids, combined with an increased intake of specific dietary components, such as plant sterols, soy protein and red yeast rice, constitutes the more efficacious dietary approach in cases where levels of total cholesterol and low-density lipoprotein cholesterol (LDL-c) are elevated. A reduction in excessive body weight is beneficial in every type of dyslipidaemia, whereas increased physical activity is mostly effective in cases with low HDL-c and high Tg levels. With respect to the potential cardiovascular benefit of these dietary interventions, there is currently evidence for the Mediterranean diet. Potential benefit may derive also from single dietary components of that diet, such as legumes, fruits, vegetables, nuts and omega-3 fatty acids, although to a lesser extent than with that general dietary pattern. The purpose of this review is to outline current knowledge regarding the recommended specific dietary pattern according to the type of dyslipidaemia and the evidence for the potential cardiovascular benefits of such approaches.
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Study of Saroglitazar in Treatment Of Pre-diabetes with Dyslipidemia: STOP-D.
Bhosle, D, Bhosle, V, Bobde, J, Bhagat, A, Shaikh, H, Kadam, R
The Journal of the Association of Physicians of India. 2018;(3):14-7
Abstract
OBJECTIVES Patients with prediabetes are not only at increased risk of progression to type 2 diabetes, but they are also at high risk of developing cardiovascular risk compared to normoglycemic people. Further, prediabetes is also often associated with abnormal lipid levels (dyslipidemia). We therefore aimed to evaluate the effect of Saroglitazar in patients with prediabetes and dyslipidemia. METHODS This was a prospective, single centre, single arm study involving patients with pre-diabetes and dyslipidemia. Subjects with baseline HbA1c 5.7-6.4% and dyslipidemia (Total cholesterol > 200mg/dl, LDL-C > 130 mg/dl, triglycerides > 150 mg/dl and HDL< 40 mg/dl) were enrolled in this study. Subjects with on-going medications affecting blood glucose or lipids were excluded from the study. Saroglitazar 4mg once daily was administered for a period of 24 weeks. The primary outcome was change in serum triglycerides and secondary outcome parameters included changes in other lipid parameters and HbA1c levels at 24 weeks follow-up. RESULTS Forty patients with prediabetes and dyslipidemia were enrolled in the study. At 24 weeks follow-up, serum triglycerides was significantly reduced from 348 ± 86.98 mg/dl to 216.4 ± 72.34 mg/dl (P <0.0001). HbA1c was significantly reduced from 6.3 ± 0.16 % to 5.5 ± 0.30 % after 24 weeks of Saroglitazar therapy (P<0.0001). There were significant improvements observed in other lipid parameters at 24 weeks follow-up period. Saroglitazar was found to be safe and well tolerated, no serious adverse event reported during entire study period. CONCLUSION Saroglitazar is safe and effective in prediabetes with dyslipidemia by exerting its dual lipid lowering and glycemic actions.
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Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial.
Zelicha, H, Schwarzfuchs, D, Shelef, I, Gepner, Y, Tsaban, G, Tene, L, Yaskolka Meir, A, Bilitzky, A, Komy, O, Cohen, N, et al
Clinical nutrition (Edinburgh, Scotland). 2018;(4):1145-1153
Abstract
BACKGROUND & AIMS Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. METHODS We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. RESULTS Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m2) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). CONCLUSIONS Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. GOVIDENTIFIER NCT01530724.
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8.
Prevalence of dyslipidaemia among adults in Africa: a systematic review and meta-analysis.
Noubiap, JJ, Bigna, JJ, Nansseu, JR, Nyaga, UF, Balti, EV, Echouffo-Tcheugui, JB, Kengne, AP
The Lancet. Global health. 2018;(9):e998-e1007
Abstract
BACKGROUND The burden of dyslipidaemia in Africa remains inadequately characterised. We aimed to estimate the prevalence of dyslipidaemia in African adults from hospital-based and community-based studies. METHODS In this systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase, African Journals Online, and African Index Medicus for studies published between Jan 1, 1980, and July 31, 2017, without language restriction. We assessed methodological quality of all cross-sectional studies reporting on the prevalence of elevated concentrations of total cholesterol, LDL cholesterol, or triglycerides, or low concentrations of HDL cholesterol in adults residing in African countries. We excluded reports on Africans living outside Africa, studies of individuals selected on the basis of existing dyslipidaemia or those including children and adolescents, and case series with a small sample size. The most frequently used cutoffs in the included studies were chosen for the subgroup analysis. We used random-effect model meta-analysis to derive the pooled prevalence of elevated total cholesterol, low HDL cholesterol, elevated LDL cholesterol, and elevated triglyceride concentrations. This study is registered with PROSPERO, number CRD42014015376. FINDINGS 181 studies (309 207 participants) were included in the meta-analysis. The pooled prevalence of dyslipidaemia in the general population from population-based studies was 23·6% (95% CI 18·4-29·2) for elevated concentrations of total cholesterol with a cutoff of at least 5·2 mmol/L, 41·1% (33·0-49·4) for low concentrations of HDL cholesterol with a cutoff of less than 1·0 mmol/L, 25·7% (16·2-36·6) for elevated concentrations of LDL cholesterol with a cutoff of at least 3·3 mmol/L, and 16·5% (11·8-21·6) for elevated concentrations of triglycerides with a cutoff of at least 1·7 mmol/L. INTERPRETATION The prevalence of dyslipidaemia is high in the general adult population in Africa. Ongoing efforts to reduce cardiovascular diseases in Africa should integrate effective detection and treatment of dyslipidaemia. FUNDING None.
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9.
Lipids: a personal view of the past decade.
Katsiki, N, Mikhailidis, DP
Hormones (Athens, Greece). 2018;(4):461-478
Abstract
The past decade has witnessed considerable progress in the field of lipids. New drugs have been "rapidly" developed and some of these drugs have already been evaluated in event-based large trials. This evidence has led to the guidelines recommending new, more aggressive treatment goals for low-density lipoprotein cholesterol (LDL-C) levels. Although LDL-C remains the principal goal for cardiovascular disease (CVD) risk reduction, there has also been considerable interest in other lipid variables, such as high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a). Statin intolerance is now considered a very important topic in daily clinical practice. This has resulted in more attention focusing on non-statin drugs [e.g., ezetimibe and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors] and statin-related side effects. The latter mainly involve muscles, but there is also a need to consider other adverse effects associated with statin use (e.g., new onset diabetes). New specific areas of statin use have attracted interest. For example, statin-loading before procedures (e.g., coronary stenting), the prevention of stroke, and the treatment of non-alcoholic fatty liver disease (NAFLD). Statins will remain the most widely used drugs to treat dyslipidaemia and decrease CVD risk. However, we also need to briefly consider some other lipid-lowering drugs, including those that may become available in the future.
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10.
Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial.
Ray, KK, Leiter, LA, Müller-Wieland, D, Cariou, B, Colhoun, HM, Henry, RR, Tinahones, FJ, Bujas-Bobanovic, M, Domenger, C, Letierce, A, et al
Diabetes, obesity & metabolism. 2018;(6):1479-1489
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Abstract
AIM: To compare alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM-DYSLIPIDEMIA trial (NCT02642159). MATERIALS AND METHODS The UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non-HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non-HDL cholesterol from baseline to week 24. RESULTS The randomized population comprised 413 individuals (intention-to-treat population, n = 409; safety population, n = 412). At week 24, the mean non-HDL cholesterol reductions were superior with alirocumab (-32.5% difference vs UC, 97.5% confidence interval -38.1 to -27.0; P < .0001). Overall, 63.6% of alirocumab-treated individuals were maintained on 75 mg every 2 weeks. Alirocumab also reduced LDL cholesterol (-43.0%), apolipoprotein B (-32.3%), total cholesterol (-24.6%) and LDL particle number (-37.8%) at week 24 vs UC (all P < .0001). Consistent with the overall trial comparison, alirocumab reduced non-HDL cholesterol to a greater degree within each UC stratum at week 24. The incidence of treatment-emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated haemoglobin, or change in number of glucose-lowering agents, was seen. CONCLUSIONS In individuals with T2DM and mixed dyslipidaemia on maximally tolerated statin, alirocumab showed superiority to UC in non-HDL cholesterol reduction and was generally well tolerated.