Changes In Low-density Lipoprotein Cholesterol Research Articles

Computerized clinical decision support system for diabetes in primary care does not improve quality of care: a cluster-randomized controlled trial

BackgroundThe EBMeDS system is the computerized clinical decision support (CCDS) system of EBPNet, a national computerized point-of-care information service in Belgium. There is no clear evidence of more complex CCDS systems to manage chronic diseases in primary care practices (PCPs). The objective of this study was to assess the effectiveness of EBMeDS use in improving diabetes care.MethodsA cluster-randomized trial with before-and-after measurements was performed in Belgian PCPs over 1 year, from May 2017 to May 2018. We randomly assigned 51 practices to either the intervention group (IG), to receive the EBMeDS system, or to the control group (CG), to receive usual care. Primary and secondary outcomes were the 1-year pre- to post-implementation change in HbA1c, LDL cholesterol, and systolic and diastolic blood pressure. Composite patient and process scores were calculated. A process evaluation was added to the analysis. Results were analyzed at 6 and 12 months. Linear mixed models and logistic regression models based on generalized estimating equations were used where appropriate.ResultsOf the 51 PCPs that were enrolled and randomly assigned (26 PCPs in the CG and 25 in the IG), 29 practices (3815 patients) were analyzed in the study: 2464 patients in the CG and 1351 patients in the IG. No change differences existed between groups in primary or secondary outcomes. Change difference between CG and IG after 1-year follow-up was − 0.09 (95% CI − 0.18; 0.01, p-value = 0.06) for HbA1c; 1.76 (95% CI − 0.46; 3.98, p-value = 0.12) for LDL cholesterol; and 0.13 (95% CI − 0.91; 1.16, p-value = 0.81) and 0.12 (95% CI − 1.25;1.49, p-value = 0.86) for systolic and diastolic blood pressure respectively. The odds ratio of the IG versus the CG for the probability of no worsening and improvement was 1.09 (95% CI 0.73; 1.63, p-value = 0.67) for the process composite score and 0.74 (95% CI 0.49; 1.12, p-value = 0.16) for the composite patient score. All but one physician was satisfied with the EBMeDS system.ConclusionsThe CCDS system EBMeDS did not improve diabetes care in Belgian primary care. The lack of improvement was mainly caused by imperfections in the organizational context of Belgian primary care for chronic disease management and shortcomings in the system requirements for the correct use of the EBMeDS system (e.g., complete structured records). These shortcomings probably caused low-use rates of the system.Trial registrationClinicalTrials.gov, NCT01830569, Registered 12 April 2013.

Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin.

ObjectiveThe aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events.MethodsOne-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed.ResultsAfter 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (−45.5%±19.9% and −45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p=0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p=0.79). The percentage change in the other lipid profiles was not significantly different. Although generic- and proprietary rosuvastatins modestly affected creatine kinase and blood pressure, respectively, the changes were all within normal ranges. Incidence of adverse events did not differ between the receivers of the 2 formulations.ConclusionThe new generic rosuvastatin was non-inferior to the proprietary rosuvastatin in terms of lipid-lowering efficacy. The rosuvastatin formulations did not exhibit clinically significant non-lipid effects with good safety profiles. Our study provides comprehensive data regarding 2 rosuvastatin formulations in East Asian subjects.Trial RegistrationClinicalTrials.gov Identifier: NCT03949374

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

BackgroundLipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). ObjectivesA pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). MethodsOne to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. ResultsBaseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). ConclusionsBaseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis

SummaryBackgroundAntipsychotic treatment is associated with metabolic disturbance. However, the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear. Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain. We aimed to compare and rank antipsychotics on the basis of their metabolic side-effects, identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation, and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment.MethodsWe searched MEDLINE, EMBASE, and PsycINFO from inception until June 30, 2019. We included blinded, randomised controlled trials comparing 18 antipsychotics and placebo in acute treatment of schizophrenia. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, and glucose concentrations. We did meta-regressions to examine relationships between metabolic change and age, sex, ethnicity, baseline weight, and baseline metabolic parameter level. We examined the association between metabolic change and psychopathology change by estimating the correlation between symptom severity change and metabolic parameter change.FindingsOf 6532 citations, we included 100 randomised controlled trials, including 25 952 patients. Median treatment duration was 6 weeks (IQR 6–8). Mean differences for weight gain compared with placebo ranged from −0·23 kg (95% CI −0·83 to 0·36) for haloperidol to 3·01 kg (1·78 to 4·24) for clozapine; for BMI from −0·25 kg/m2 (−0·68 to 0·17) for haloperidol to 1·07 kg/m2 (0·90 to 1·25) for olanzapine; for total-cholesterol from −0·09 mmol/L (−0·24 to 0·07) for cariprazine to 0·56 mmol/L (0·26–0·86) for clozapine; for LDL cholesterol from −0·13 mmol/L (−0.21 to −0·05) for cariprazine to 0·20 mmol/L (0·14 to 0·26) for olanzapine; for HDL cholesterol from 0·05 mmol/L (0·00 to 0·10) for brexpiprazole to −0·10 mmol/L (−0·33 to 0·14) for amisulpride; for triglycerides from −0·01 mmol/L (−0·10 to 0·08) for brexpiprazole to 0·98 mmol/L (0·48 to 1·49) for clozapine; for glucose from −0·29 mmol/L (−0·55 to −0·03) for lurasidone to 1·05 mmol/L (0·41 to 1·70) for clozapine. Greater increases in glucose were predicted by higher baseline weight (p=0·0015) and male sex (p=0·0082). Non-white ethnicity was associated with greater increases in total cholesterol (p=0·040) compared with white ethnicity. Improvements in symptom severity were associated with increases in weight (r=0·36, p=0·0021), BMI (r=0·84, p<0·0001), total-cholesterol (r=0·31, p=0·047), and LDL cholesterol (r=0·42, p=0·013), and decreases in HDL cholesterol (r=–0·35, p=0·035).InterpretationMarked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles. Increased baseline weight, male sex, and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change, and improvements in psychopathology are associated with metabolic disturbance. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of patients, carers, and clinicians.FundingUK Medical Research Council, Wellcome Trust, National Institute for Health Research Oxford Health Biomedical Research Centre.

Prevalence of Dyslipidemia in Students from Han, Uygur, and Kazakh Ethnic Groups in a Medical University in Xinjiang, China

In the present study, we aimed to evaluate the prevalence of dyslipidemia in students from different ethnic groups in Xinjiang. It is an observational, cross-sectional study. The sample of 7096 students aged 21–25 years was randomly selected from the clinic of Xinjiang Medical University. Baseline data, serum concentration of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) were reported. The prevalence of changes in lipid profile according to Body mass index (BMI) in three ethnic groups was calculated. Compared with Han and Uygur students, TC, LDL-C, TG and FPG levels were lower in kazakh sutdents, while HDL-C level was lower in Uygur students. The prevalence of high TC change was higher in Uygur students, and high LDL-C change was higher in Han students. The prevalence of low HDL-C change was higher in Uygur students, and high TG change was lower in Kazakh students. The prevalence of high TC, LDL-C, TG and low HDL-C changes was observed in normal weight, overweight and obesity groups according to the nutritional status by BMI among students of each ethnic group. The present study demonstrated the prevalence of dyslipidemia in students from different ethnic groups, and enriched the limited data on the early prevention and treatment of dyslipidemia and cardiovascular diseases in Xinjiang medical students crowd.

Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial.

We aimed to assess the effect of 10 mg/day of rosuvastatin plus eicosapentaenoic acid (EPA) versus 2.5 mg/day of rosuvastatin on the extent of neoatherosclerosis using optical coherence tomography (OCT). We randomly assigned 50 patients with non-obstructive neoatherosclerotic plaques detected on OCT to receive either rosuvastatin 10 mg/day and EPA 1,800 mg/day (intensive therapy group) or rosuvastatin 2.5 mg (standard therapy group). Follow-up OCT was performed one year later to evaluate serial changes in neoatherosclerosis. The serum low-density lipoprotein cholesterol (LDL-C) level decreased significantly from baseline to 12-month follow-up in the intensive therapy group (89 mg/dL to 70 mg/dL; p<0.001), while no change occurred in the standard therapy group. Lipid index change and percent changes in macrophage grade were significantly lower in the intensive therapy group than in the standard therapy group (-53.6 vs 310.1, p=0.001; -37.0% vs 35.3%, p<0.001; respectively). Percent changes in lipid index and macrophage grade were positively correlated with the changes in serum LDL-C and C-reactive protein levels, and negatively correlated with the change in serum EPA/arachidonic acid and 18-hydroxyeicosapentaenoic acid (EPA bioactive metabolite) level. Compared with rosuvastatin 2.5 mg/day, rosuvastatin 10 mg/day and EPA 1,800 mg/day significantly stabilised non-obstructive neoatherosclerotic plaques. UMIN ID: UMIN000012576. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014711.

Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis.

Very low calorie ketogenic diet (VLCKD) has been proposed as a promising option to achieve a significant weight loss in a short time period. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in patients with overweight and obesity. Four databases were searched on May 2019. Studies reporting data on body weight, body mass index (BMI), waist circumference, body composition, blood pressure, HbA1c, lipids, and markers of liver and kidney function were selected. Discontinuation was also assessed. Twelve studies were included. VLCKD was associated with weight losses of -10.0kg (I2= 6%) and - 15.6kg (I2= 37%) in studies with a ketogenic phase up to and of at least four weeks, respectively. The weight lost during the ketogenic phase was stable in the subsequent follow-up up to two years (p = 0.12). Also, VLCKD was associated with reductions of BMI (-5.3kg/m2), waist circumference (-12.6cm), HbA1c (-0.7%), total cholesterol (-28mg/dl), triglycerides (-30mg/dl), AST (-7U/l), ALT (-8U/l), GGT (-8U/l), systolic and diastolic blood pressure (-8 and - 7mmHg, respectively). No changes in LDL cholesterol, HDL cholesterol, serum creatinine, serum uric acid and serum potassium were found. Serum sodium increased during VLCKD (+1.6mEq/l). The overall prevalence of patients discontinuing VLCKD was 7.5% and this was similar to patients undergoing a low calorie diet (p = 0.83). The present review supports the use of VLCKD as an effective strategy for the management of overweight and obesity. Future guidelines should include a specific recommendation for this intervention.

Efficacy and Safety of High-Dose Atorvastatin in Moderate-to-High Cardiovascular Risk Postmenopausal Korean Women with Dyslipidemia.

ObjectivePostmenopausal women show a more atherogenic lipid profile and elevated cardiovascular risk compared to premenopausal women. The aim of this study was to investigate the efficacy and safety of high-dose atorvastatin on the improvement of the blood lipid profile of postmenopausal women in Korea.MethodsThis study is a prospective, open-label, single-arm clinical trial that was conducted in 3 teaching hospitals. Postmenopausal women with a moderate-to-high cardiovascular risk, according to guidelines from the Korean Society of Lipid & Atherosclerosis, were enrolled. Participants were administered 20 mg of atorvastatin daily for the first 8 weeks, and if the targeted low-density lipoprotein cholesterol (LDL-C) level was not achieved, the dose was increased to 40 mg for the second 8 weeks. The primary endpoint was percentage change of LDL-C from baseline after 16 weeks of drug administration.ResultsForty-four women were enrolled, 28 of whom (75.6%) had diabetes mellitus. By the end of treatment period (16 weeks) all patients had achieved LDL-C target levels, with 33 (94.2%) of the participants achieving it after only 8 weeks of administration. After 16 weeks, LDL-C decreased by 45.8±16.7% (p<0.001) from the baseline, and total cholesterol (33.2±10.9%; p<0.001), triglyceride (24.2±37.5%; p=0.001), and apolipoprotein B (34.9±15.6%; p<0.001) also significantly decreased. Blood glucose and liver enzyme levels slightly increased, but none of the participants developed serious adverse events that would cause them to prematurely withdraw from the clinical trial.Conclusion20 and 40 mg atorvastatin was effective and safe for treating dyslipidemia in postmenopausal Korean women with moderate-to-high cardiovascular risk.

ApoF knockdown increases cholesteryl ester transfer to LDL and impairs cholesterol clearance in fat-fed hamsters

Cholesteryl ester transfer protein (CETP) regulates intravascular lipoprotein metabolism. In vitro studies indicate that ApoF alters CETP function by inhibiting its activity with LDL. To explore in vivo the complexities driving ApoF's effects on CETP, we developed a siRNA-based hamster model of ApoF knockdown. In both male and female hamsters on chow- or fat-fed diets, we measured lipoprotein levels and composition, determined CETP-mediated transfer of cholesteryl esters (CEs) between lipoproteins, and quantified reverse cholesterol transport (RCT). We found that apoF knockdown in chow-fed hamsters had no effect on lipoprotein levels or composition, but these ApoF-deficient lipoproteins supported 50-100% higher LDL CETP activity in vitro. ApoF knockdown in fat-fed male hamsters created a phenotype in which endogenous CETP-mediated CE transfer from HDL to LDL increased up to 2-fold, LDL cholesterol increased 40%, HDL declined 25%, LDL and HDL lipid compositions were altered, and hepatic LDLR gene expression was decreased. Diet-induced hypercholesterolemia obscured this phenotype on occasion. In fat-fed female hamsters, ApoF knockdown caused similar but smaller changes in plasma CETP activity and LDL cholesterol. Notably, ApoF knockdown impaired HDL RCT in fat-fed hamsters but increased sterol excretion in chow-fed animals. These in vivo data validate in vitro findings that ApoF regulates lipid transfer to LDL. The consequences of ApoF knockdown on lipoproteins and sterol excretion depend on the underlying lipid status. By minimizing the transfer of HDL-derived CE to LDL, ApoF helps control LDL cholesterol levels when LDL clearance mechanisms are limiting.

P6192Effects of evolocumab on LDL-C by race and ethnicity: an analysis of double-blind and open-label extension studies

Abstract Background/Introduction Cardiovascular risk factors and clinical outcomes of atherosclerotic cardiovascular disease (ASCVD) vary amongst racial and ethnic groups. Purpose To examine the effects of evolocumab on low-density lipoprotein cholesterol (LDL-C) levels and achievement of LDL-C target goals by race or ethnicity. Methods Data from global phase 2 and 3 studies with at least 12 weeks of treatment with approved evolocumab doses vs. placebo or ezetimibe were included in this analysis (n=4375). Results were analysed by patient characteristics (statin intolerance, type 2 diabetes, heterozygous familial hypercholesterolaemia, and hypercholesterolaemia/mixed dyslipidaemia), self-identified race (White, Black/African American, and Asian), and self-identified ethnicity (Hispanic/Latino). Key outcomes included percent change in LDL-C, achievement of LDL-C &lt;1.8 mmol/L (&lt;70 mg/dL), and LDL-C achievement of at least 50% reduction. Results After 12-week evolocumab treatment, mean percent change in LDL-C from baseline ranged from approximately −52% to −59% for white patients to −49% to −67% for non-white patients, across all groups with adequate sample size (n&gt;20) (Table). LDL-C &lt;1.8 mmol/L was achieved in 43–84% of white patients and 62–94% of non-white patients receiving evolocumab (n&gt;20). Similarly, 63–78% of white patients and 58–86% of non-white patients achieved at least a 50% reduction in LDL-C. The magnitude of treatment effect on mean percent change in LDL-C differed significantly only between white and non-white patients with diabetes (interaction p-values of treatment by race for evolocumab every 2 weeks p&lt;0.001; once monthly p=0.007). This was driven by a greater reduction in Asian patients. Mean (standard deviation) percent change in LDL-C levels from baseline, % Achievement of LDL-C &lt;1.8 mmol/L (70 mg/dL)/LDL-C achievement of at least 50% reduction, % Population White Non-White Non-Hispanic Black or African American Asian Hispanic/Latino* White Non-White Non-Hispanic Black or African American Asian Hispanic/Latino* Statin-Intolerant† −55.4 (14.8) −46.3 (20.9) −46.0 (13.4) −49.0 (29.3) −54.6 (12.3) 42.9 / 68.6 26.7 / 60.0 14.3 / 42.9 50.0 / 83.3 0 / 66.7 n=210 n=15 n=7 n=6 n=3 Diabetes‡ −51.5 (25.6) −66.5 (21.2) −50.4 (22.2) −69.6 (20.2) −59.7 (20.5) 82.3 / 63.0 93.9 / 82.0 90.0 / 62.5 95.1 / 86.6 89.2 / 75.3 n=440 n=395 n=40 n=305 n=158 HeFH§ −57.3 (19.7) −64.1 (12.0) −73.8 (4.1) −60.5 (12.8) −35.8§§ 66.1 / 73.7 61.5 / 84.6 100 / 100 53.3 / 80.0 0 / 0 n=236 n=26 n=3 n=15 n=1 Hyper-cholesterolaemia/ −58.8 (19.2) −65.5 (17.0) −51.2 (19.4) −69.4 (13.9) −54.6 (20.3) 83.3 / 77.6 89.7 / 86.0 74.4 / 60.5 94.7 / 93.5 79.1 / 69.2 Mixed Dyslipidaemia¶ n=1399 n=437 n=86 n=339 n=91 Hyper-cholesterolaemia/ −59.4 (17.1) −58.4 (16.9) −52.8 (19.4) −65.8 (10.3) −56.7 (22.1) 80.2 / 78.5 85.7 / 75.7 82.4 / 67.6 96.7 / 93.3 77.3 / 68.2 Mixed Dyslipidaemia†† n=605 n=70 n=34 n=30 n=44 1-Year Study‡‡ −52.1 (27.7) −48.6 (29.2) −50.8 (22.0) −49.5 (29.4) −43.0 (43.1) 84.4 / 67.4 73.6 / 57.5 74.5 / 59.6 76.5 / 58.8 82.1 / 60.7 n=436 n=106 n=47 n=34 n=28 †GAUSS-1, -2 studies; ‡BANTING and BERSON studies; §RUTHERFORD-1, -2 studies; ¶Placebo comparator: MENDEL-1, -2, LAPLACE-TIMI-57, LAPLACE-2 and YUKAWA-1, -2 studies; ††Ezetimibe comparator: MENDEL-2 and LAPLACE-2 atorvastatin cohorts; ‡‡DESCARTES; §§Standard deviation could not be calculated due to insufficient sample size. *A total of 22 patients receiving evolocumab self-identified as Hispanic Black. Conclusion Reduction in LDL-C levels with evolocumab treatment was similar across race and ethnicity, apart from the diabetes population where Asian patients had a greater reduction in LDL-C. Acknowledgement/Funding Amgen Inc.

Effects of glucose-lowering on outcome incidence in diabetes mellitus and the modulating role of blood pressure and other clinical variables: overview, meta-analysis of randomized trials.

Randomized controlled trials (RCTs) of antidiabetic agents started in the 1960s. Updated meta-analyses of RCTs investigating glucose-lowering in patients with type 2 diabetes mellitus are lacking. Also, no previous attempt was made to evaluate the role of blood pressure (BP) reduction and LDL cholesterol (LDL-C) change on outcome incidence following glucose-lowering. Three main clinical questions were investigated: the extent of different outcome reductions by glucose-lowering in patients with diabetes, the proportionality of outcome reductions to glycated hemoglobin (HBA1c) reductions and whether ongoing BP and LDL-C difference in RCTs can change glucose-lowering outcome effects. PubMed between 1960 and January 2019 (any language), Cochrane Collaboration Library and previous overviews were used as data sources to identify and select all RCTs comparing the glucose-lowering drugs with placebo or less intense treatment (intentional glucose-lowering RCTs); comparing glucose-lowering drugs with placebo without glucose-lowering intention, but HBA1c difference (nonintentional glucose-lowering RCTs); enrolling type 2 diabetes mellitus patients; and reporting ongoing SBP and DBP difference. We excluded RCTs of acute care, glucose intolerance, type 1 diabetes, multiple interventions applied and glucose-lowering by lifestyle or other interventions. Risk ratios and 95% confidence intervals, of seven fatal and nonfatal outcomes and of treatment-related discontinuations were calculated (random-effects model) before and after adjustment for the ongoing BP difference, while LDL-C difference was also considered. The relationships of different outcome reductions to HBA1c reductions were investigated by meta-regressions. A total of 25 RCTs (174 235 individuals, follow-up 3.5 years) were eligible, and the resulted ongoing SBP/DBP difference was -1.4/-0.4 mmHg. Both before and after adjustment for BP difference, glucose-lowering reduced CHD (coronary heart disease) and both composites of major cardiovascular events were reduced by a mean of 8 and 5%, respectively, while before BP-adjustment the risk of treatment-related discontinuations was increased by 26% and the risk of stroke and all-cause death was reduced by 7 and 6%, respectively. Logarithmic risk ratios were related to HBA1c reductions for the composite of CHD and stroke and for treatment-related discontinuations. Glucose-lowering had no differential outcome effects, before and after estimate adjustment for the ongoing BP difference, at different HBA1c thresholds and targets, as well as when both baseline BP and achieved BP, overall cardiovascular risk and diabetes mellitus duration were considered as dichotomous effect modifiers. Although heart failure incidence was found increased by 15% in the early glucose-lowering RCTs, this effect faded away in contemporary RCTs. LDL-C change was overall trivial and did not change glucose-lowering outcome effects. Meta-analyses of all glucose-lowering RCTs involving patients with diabetes provide precise estimates of benefits for CHD and major cardiovascular events after consideration of the resulting ongoing BP difference. No benefit or harm on mortality, heart failure and stroke were noticed, while discontinuations related to adverse events because of treatment were increased following glucose-lowering. The extent of glucose-lowering is proportionally related to changes of CHD and stroke composite, and treatment-related discontinuations.

P5320Reduction in high-sensitivity C-reactive protein by pitavastatin was associated with improved outcomes in Japanese patients with stable coronary artery disease: results from REAL-CAD study

Abstract Background The effect of statins on lowering high sensitivity C-reactive protein (hs-CRP) as well as low density lipoprotein cholesterol (LDL-C) has been associated with reduced risk for cardiovascular events in patients with elevated hs-CRP. However, it remains unclear whether this statin effect applies to low-risk patients with stable coronary artery disease (CAD). In this pre-specified sub-study within the REAL-CAD trial, we explored the association between achieved LDL-C/hs-CRP levels and cardiovascular events in Japanese patients with stable CAD who were treated with pitavastatin 1 mg or 4 mg/day. Methods The REAL-CAD trial randomly allocated 13,054 patients with stable CAD to pitavastatin 1 mg or 4 mg/day. LDL-C and hs-CRP were measured at baseline and at 6 months after randomization. We excluded those patients without 6-month data and those with endpoint events before 6 months (N=1915). The primary endpoint of the study was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. Outcomes were assessed by landmark analysis beyond 6 months among 4 groups that were configured based on LDL-C (median) and hs-CRP (median) targets: achieving neither target, achieving LDL-C target only, achieving hs-CRP target only, and achieving both targets. Data were adjusted for baseline characteristics including age, gender, diabetes and baseline values of LDL-C and hs-CRP. Results Median LDL-C and hs-CRP levels were 88 mg/dL and 0.52 mg/L at baseline and 80 mg/dL and 0.48 mg/L after 6 months, respectively. There was no correlation between the change in LDL-C and hs-CRP levels from baseline to 6 months (correlation coefficient: 0.009, P=0.331). Of the 11,677 patients included in the study, 25.1% (N=2799) achieved both LDL-C and hs-CRP targets, 25.3% (N=2282) met neither target, 24.8% (N=2765) met only the hs-CRP target, and 24.7% (N=2753) met only the LDL-C target. Risk of primary endpoint occurrence was significantly lower in those achieving either or both targets than in those meeting neither target (Figure A). In the subgroup analysis stratified by the randomized dose of pitavastatin, the risk for the primary endpoint was significantly lower in patients achieving both targets in both the 1mg and 4 mg arms, and in patients achieving only hs-CRP target in the 1 mg arm (Figure B, C). Figure 1 Conclusions In this subanalysis of the REAL-CAD trial, the hs-CRP lowering effect of pitavastatin was independent from LDL-C lowering. Lower achieved hs-CRP was associated with lower risk for cardiovascular events in Japanese patients with stable CAD. Acknowledgement/Funding Public Health Research Foundation, The company manufacturing the study drug (Kowa Pharmaceutical Co Ltd) was one of the entities providing financial s

Association between individual cholesterol and proteinuria response and exposure to atorvastatin or rosuvastatin.

AimThe PLANET trials showed that atorvastatin 80 mg but not rosuvastatin at either 10 or 40 mg reduced urinary protein to creatinine ratio (UPCR) at similar effects on LDL‐cholesterol. However, individual changes in both UPCR and LDL‐cholesterol during treatment with these statins varied widely between patients. This inter‐individual variability could not be explained by patients’ physical or biochemical characteristics. We assessed whether the plasma concentrations of both statins were associated with LDL‐cholesterol and UPCR response.Materials and methodsThe PLANET trials randomized patients with a UPCR of 500‐5000 mg/g and fasting LDL‐cholesterol >2.33 mmol/L to a 52‐week treatment with atorvastatin 80 mg, rosuvastatin 10 mg or 40 mg. For the current analysis, patients with available samples at week 52 and treatment compliance >80% by pill count were included (N = 295). The main outcome measurements were percentage change in UPCR and absolute change in LDL‐cholesterol (delta LDL) from baseline to week 52.ResultsMedian (interquartile range) plasma concentration at week 52 for atorvastatin 80 mg was 3.9 ng/mL (IQR: 2.1 to 8.7), for rosuvastatin 10 mg 1.0 ng/mL (IQR: 0.7 to 2.0) and for rosuvastatin 40 mg 3.5 ng/mL (IQR: 2.0 to 6.8). Higher plasma concentration of statin was associated with larger LDL‐cholesterol reductions at week 52 [rosuvastatin r = −0.40 (P < .001); atorvastatin r = −0.28 (P = .006)]. The plasma concentration of both statins did not correlate with UPCR change [rosuvastatin r = 0.07 (P = .30); atorvastatin r = 0.16 (P = .13)].ConclusionsIndividual variation in plasma concentrations of rosuvastatin and atorvastatin was associated with LDL‐cholesterol changes in patients. The individual variation in UPCR change was not associated with the plasma concentration of both statins.

Improvement of endothelial dysfunction is mediated through reduction of remnant lipoprotein after statin therapy in patients with coronary artery disease

BackgroundRemnant lipoproteinemia with high levels of low-density lipoprotein cholesterol (LDL-C) is a high risk for endothelial dysfunction. Statins are the first-line lipid-lowering drugs for this combined hyperlipidemia. However, it remains undetermined whether reduction of remnant lipoprotein mediates the relationship between improvement in endothelial dysfunction and reduction of LDL-C level after statin treatment. MethodsA total of 122 coronary artery disease (CAD) patients with impaired flow-mediated dilation (FMD; <5.5%), high levels of LDL-C (≥100 mg/dL), and remnant-like lipoprotein particle cholesterol (RLP-C) (≥5 mg/dL) were examined in this study. The lipid profiles and FMD were measured before and after 6–9 months of statin treatment. The association between changes in LDL-C levels and its relationship with changes in FMD was investigated. Furthermore, mediation analysis was performed to assess the changes in RLP-C level as a mediator of the relationship between the reduction in LDL-C level and improvement of FMD. ResultsTreatment with statins improved FMD in 69 (56.5%) patients. Patients with improved FMD showed lower percent changes of LDL-C, triglyceride (TG), RLP-C, RLP-C/TG, and C-reactive protein (CRP) levels, and higher percent change of HDL-C level, compared to patients who did not show improved FMD. The percent changes in FMD levels had a significant inverse correlation with the percent changes in LDL-C, (r = −0.18, p = 0.03), RLP-C (r = −0.39, p < 0.001), RLP-C/TG (r = −0.34, p < 0.001), and CRP (r = −0.27, p < 0.01). Mediation analysis showed that the relationship between reduction in LDL-C and improvement of FMD was mediated by reduction of RLP-C (34.5%), RLP-C/TG (24.4%), and CRP (24.9%) levels. ConclusionImprovement of remnant lipoproteinemia may be an important mediator for the relationship between improvement of endothelial dysfunction and LDL-lowering after statin treatment in patients with CAD.

Whole egg consumption compared with yolk-free egg increases the cholesterol efflux capacity of high-density lipoproteins in overweight, postmenopausal women

Postmenopausal women are at higher risk for cardiovascular disease (CVD) than their younger counterparts. HDL cholesterol is a biomarker for CVD risk, but the function of HDL may be more important than HDL cholesterol in deciphering disease risk. Although diet continues to be a cornerstone of treatment and prevention of CVD, little is known about how diet affects the functionality of HDL. The aim of this study was to characterize the effects of whole eggs compared with yolk-free eggs on HDL function and composition in overweight, postmenopausal women and determine how changes in HDL composition are related to HDL functional parameters. The study was a 14-wk, single-blind, randomized crossover dietary trial with two 4-wk intervention periods in 20 overweight, postmenopausal women. The crossover treatments were frozen breakfast meals containing 100 g of liquid (∼2) whole eggs compared with 100 g of (∼2) yolk-free eggs per day, separated by a 4-wk washout. Fasting blood samples were taken at the beginning and end of each treatment period to determine the effects on HDL composition and function. Cholesterol efflux capacity increased in the whole-egg treatment (mean ± SD percentage change: +5.69% ± 9.9%) compared with the yolk-free egg treatment (-3.69% ± 5.3%) (P<0.01), but there were no other significant changes in HDL functions or antioxidant or inflammatory markers. ApoA-I, total cholesterol (TC), LDL cholesterol, and HDL cholesterol also did not change in response to the egg treatment. The consumption of 2 whole eggs/d by overweight, postmenopausal women showed a significant increase in cholesterol efflux capacity. This increase in cholesterol efflux capacity was seen without significant changes in apoA-I, TC, LDL cholesterol, or HDL cholesterol, supporting the idea that HDL function rather than HDL cholesterol should be addressed in this population. This trial was registered at clinicaltrials.gov as NCT02445638.

Lipid findings from the Diabetes Education to Lower Insulin, Sugars, and Hunger (DELISH) Study

BackgroundA carbohydrate-restricted (CR) diet can improve glycemic control in people with type 2 diabetes mellitus (T2DM). There are concerns, however, that the high dietary fat content of CR diets can increase low-density lipoprotein cholesterol (LDL-C), thus increasing cardiovascular disease (CVD) risk. Quantifying CVD risk associated with changes in LDL-C in the context of CR diets is complicated by the fact that LDL-C reflects heterogeneous lipids. For example, small LDL particle number (sLDL-P) is more closely associated with CVD risk than is total LDL-C, and CR diets tend to decrease the proportion of sLDL-C in LDL-C, which standard lipid measures do not indicate. Advanced lipoprotein assays, such as nuclear magnetic resonance (NMR) testing, can subfractionate lipoproteins by size and density and may better depict the effects of CR diets on CVD risk.MethodsAdults (N = 58) with T2DM (n = 37 women; baseline HbA1c ≥ 6.5%) completed a 6-month group-based CR diet intervention. We obtained a standard lipid panel, advanced lipoprotein assays (NMR testing), and two 24-h diet recalls at baseline and post-intervention (6 months). Participants also completed home-based blood ketone testing (a biological index of dietary adherence) during the final five weeks of the intervention.ResultsFrom baseline to post-intervention, participants had increased mean HDL-C, decreased triglycerides and triglyceride/HDL ratio, decreased mean sLDL-P, and increased LDL size, which reflect reductions in CVD risk (ps < 0.05). Participants did not have statistically significant changes in total cholesterol, non-HDL-C cholesterol, LDL-P, or HDL-P. Twelve participants (23.1%) had a ≥ 5% increase in sLDL-P. Exploratory analyses revealed that participants with sLDL-P increases of ≥ 5% reported larger increases in servings of red meat than participants without sLDL-P increases of ≥ 5% (+ 0.69 vs − 0.29 servings; p = 0.033). Changes in saturated fat intake were not associated with changes in sLDL-P.ConclusionsAmong most participants, we observed changes in several lipid measures consistent with decreased CVD risk. Approximately one in four participants evidenced increases in sLDL-P. Further research should clarify whether individuals with increased sLDL-P after implementing a CR diet can reverse observed increases by limiting red meat consumption.Trial registrationClinicalTrials.gov, NCT03207711, Registered 6/11/2017. Retrospectively registered.

Statin Dosing Instructions, Medication Adherence, and Low-Density Lipoprotein Cholesterol: a Cohort Study of Incident Statin Users.

Robust evidence is lacking on optimal timing of statin administration and its impact on patient outcomes. This study aims to evaluate among incident statin users the relationship between those prescribed evening vs. daily dosing instructions, medication adherence, and changes in low-density lipoprotein cholesterol (LDL-c). This is an observational cohort study at Sutter Health, a community-based healthcare system, 2010-2016. Patients were ≥ 35years of age as of the first statin prescription (baseline), with 12 to 36months of electronic health record activity before and after baseline. Incident use was defined as no statin prescription in 12months prior to baseline. Differences in medication adherence (proportion of days covered ≥ 0.80) over 12months from baseline and mean change in LDL-c between 12 and 24months from baseline were measured using regression modeling, adjusting for baseline demographics and clinical, prescriber, and statin characteristics. Among 31,252 patients with valid statin prescriptions between 2010 and 2016, 5099 eligible incident statin users (mean age, 63years) were identified, of whom 53% were prescribed evening and 47% daily dosing instructions. No difference in likelihood of statin adherence over 12months was observed for evening vs. daily dosing (adjusted odds ratio [OR] 0.90; 95% CI 0.75, 1.08). No differences were observed in mean change in LDL-c (adjusted mean difference 1.42mg/dL; 95% CI - 1.02, 3.89) or likelihood of attaining LDL-c < 70mg/dL (adjusted OR 0.83; 95% CI 0.67, 1.04) for evening vs. daily dosing over a mean of 19months follow-up. Among incident statin users from a real-world clinical setting, those with daily and evening dosing instructions had similar adherence rates and mean changes in LDL-c. Given potential clinical equipoise for evening and daily dosing, clinicians should consider patient-tailored statin dosing instructions to reduce potentially unnecessary regimen complexity.

Efficacy of l-carnitine supplementation for management of blood lipids: A systematic review and dose-response meta-analysis of randomized controlled trials

Background and aiml-carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l-carnitine supplementation on lipid profiles. Methods and resultsWe performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model.In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l-carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: −8.53 mg/dl, 95% CI: −13.46, −3.6, I2: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: −5.48 mg/dl, 95% CI: −8.49, −2.47, I2: 94.5) and triglyceride (TG) (56 arms-MD: −9.44 mg/dl, 95% CI: −16.02, −2.87, I2: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I2: 92.2). l-carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l-carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l-carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l-carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides. Conclusionl-carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration.

COMPARATIVE CHARACTERIZATION OF ANTIOXIDANT PROFILE OF VITAMIN-E AND RED DATES IN PLACEBO AND TESTED GROUPS OF HYPERLIPIDEMIC PATIENTS

Antioxidants are nutrients that help minimize free-radical damage to the body. Free radicals are highly reactive compounds that are created in the body during normal metabolic functions or introduced from the environment, such as by exposure to pollution and other toxins. Inherently unstable, free radicals contain "extra" energy which they try to reduce by reacting with certain chemicals in the body, which interferes with the cells' ability to function normally. Current study compared antioxidant characteristics of vitamin-E and red Dates. It was placebo-controlled conducted study conducted at general hospital Lahore Pakistan from January 2018 to march 2018. LDL-cholesterol was calculated as total cholesterol- HDL-cholesterol-VLDL-cholesterol;VLDL-cholesterol was measured directly after ultracentrifugation. After one month therapy their post treatment lipid profile was determined and analyzed statistically by using SPSS version 2.2.01 2013. Paired‘t’ test was applied for mean values with SD of the parameters before and after treatment. Results showed highly significant change in LDL-cholesterol of group-II patients but HDL-cholesterol was increased 6.6 mg/dl, still it was significant change with p-value of &lt;0.01. In group-III LDL-cholesterol was decreased 10.9 mg/dl which is significant change with p-value &lt;0.01. HDL-cholesterol in this group was increased 4.2 mg/dl which is non significant with p-value of &gt;0.05. Study concluded that red dates have antioxidant potential by lowering LDL-cholesterol in human plasma. But this effect is not comparable with hypolipidemic effects of Vitamin E as it also increases good cholesterol i.e. HDL-cholesterol.

Statin treatment increases lipoprotein(a) levels in subjects with low molecular weight apolipoprotein(a) phenotype

Background and aimsWe aimed to evaluate the effect of statin treatment initiation on lipoprotein(a) [Lp(a)] levels in patients with dyslipidemia, and the interactions with the apolipoprotein(a) [apo(a)] phenotype, LPA single nucleotide polymorphisms (SNPs) and change in LDL cholesterol. MethodsThe study population consisted of patients with dyslipidemia, predominantly familial hypercholesterolemia, who first initiated statin treatment (initiation group; n = 39) or were already on stable statin treatment for at least 4 months (control group; n = 42). Plasma Lp(a) levels were determined with a particle-enhanced immunoturbidimetric assay before and at least 2 months after start of statin treatment in individuals of the initiation group, and at two time points with an interval of at least 2 months in the control group. High and low molecular weight (HMW and LMW, respectively) apo(a) phenotype was determined by immunoblotting, and the common LPA SNPs rs10455872, rs3798220 and rs41272110 by Taqman assay. ResultsPlasma Lp(a) levels did not increase significantly in the initiation group (median 20.5 (IQR 10.9–80.7) to 23.3 (10.8–71.8) mg/dL; p = 0.09) nor in the control group (30.9 (IQR 9.2–147.0) to 31.7 (IQR 10.9–164.0) mg/dL; p = 0.61). In patients with the LMW apo(a) phenotype, Lp(a) levels increased significantly from 66.4 (IQR 23.5–148.3) to 97.4 (IQR 24.9–160.4) mg/dL (p = 0.026) in the initiation group, but not in the control group and not in patients characterized by the HMW apo(a) phenotype. Interactions with common LPA SNPs and change in LDL cholesterol were not significant. ConclusionsStatins affect Lp(a) levels differently in patients with dyslipidemia depending on the apo(a) phenotype. Statins increase Lp(a) levels exclusively in patients with the LMW apo(a) phenotype.