Changes In High-density Lipoprotein Cholesterol Research Articles

Metabolically healthy obesity is associated with longitudinal changes in high-density lipoprotein cholesterol in Chinese adults.

Whether metabolically healthy obesity (MHO) is associated with longitudinal changes in high-density lipoprotein cholesterol (HDL-C) remains unclear. MHO was defined as participants with overweight and obesity (BMI ≥ 24.0kg/m2, n = 2921), free of history of metabolic diseases, and without abnormalities of blood pressure, fasting blood glucose, hemoglobin A1c, lipid profile, carotid artery and liver ultrasonographic findings at baseline. Metabolically healthy normal weight (MHN) was defined as participants with normal weight (BMI < 24.0kg/m2, n = 9578) and without above-mentioned abnormalities. HDL-C, fasting blood glucose, hemoglobin A1c, and blood pressure were assessed annually. Glucose abnormality was considered if either FBG ≥ 5.6mmol/L or HbA1c ≥ 5.7%; while, high blood pressure (HBP) was considered if either systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 80mmHg during 5years of follow-up. Compared with the MHN group, the adjusted mean difference in HDL-C change rate was - 0.005mmol/L per year [95% confidence interval (CI) - 0.007, - 0.003] for MHO after adjustment for a series of potential confounders. Furthermore, transiting to abnormality of blood glucose, but not high blood pressure, was associated with lower cumulative average of HDL-C in MHN group, compared with those remained in metabolically healthy status. MHO and transiting from metabolically healthy to abnormality of blood glucose were associated with HDL-C in Chinese adults. III, cohort study.

Maternal preconception lipid profile and gestational lipid changes in relation to birthweight outcomes

In 575 women with 1–2 prior pregnancy losses; total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were evaluated preconception and throughout pregnancy to evaluate whether previously observed associations between third trimester maternal lipid profile and birthweight outcomes are driven by preconception lipids or lipid changes during pregnancy. Lipid trajectories were compared by pre-pregnancy body mass index (BMI) <25 or ≥25 kg/m2; logistic regression models evaluated preconception lipid concentration and change from preconception to 28 weeks with adjusted odds of large- or small-for-gestational age (LGA or SGA) neonate by BMI group. Preconception lipid concentrations and gestational lipid trajectories varied by BMI group (P < 0.001). Preconception lipids were not associated with LGA or SGA in either group. A 10 mg/dL increase in HDL-C change from preconception to 28 weeks was associated with decreased odds of LGA (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.46, 0.86) and 10 mg/dL increase in TG change associated with increased odds of LGA (OR = 1.05, 95% CI: 1.01, 1.1) overall. For ≥25 BMI only, 10 mg/dL increase in HDL-C change was associated with decreased SGA odds (OR = 0.35, 95% CI: 0.19, 0.64). Gestational lipid trajectories differed by BMI group and were differentially associated with birthweight outcomes, with HDL-C more strongly associated with healthy birthweight in women with BMI ≥25.

Modest improvement in CVD risk markers in older adults following quinoa (Chenopodium quinoa Willd.) consumption: a randomized-controlled crossover study with a novel food product.

To investigate the effect of consuming quinoa biscuits on markers of CVD risk over 4weeks in free-living older adults. A randomized-controlled, double-blind crossover trial was conducted in which consenting healthy adults aged 50-75years (n = 40) consumed 15g quinoa biscuits (60g quinoa flour/100g) or control iso-energetic biscuits (made using wheat flour) daily for 28 consecutive days (4weeks), in addition to their normal diet. Following a 6-week washout, participants consumed the alternate biscuit for a final 4weeks. Anthropometry and fasted blood samples were obtained before and after each intervention period. At the beginning of the trial, mean ± SD total cholesterol concentrations were 6.02 ± 1.22mmol/L (3.7-9.2mmol/L); 33 participants (82.5%) had high cholesterol (> 5mmol/L). No participants were lost to follow-up and there were no changes in habitual dietary intakes or levels of physical activity between each 4-week intervention period. Significantly greater decreases in total and LDL cholesterol concentrations (-0.30 ± 0.58 and -0.25 ± 0.38mmol/L, respectively), TC: HDL ratio (-0.11 ± 0.30), weight (-0.61 ± 0.89kg) and BMI (-0.22 ± 0.34kg/m2) were apparent following consumption of the quinoa versus control biscuits (all P < 0.05). Changes in triglycerides, HDL cholesterol, or PUFA or CRP concentrations were not significant between treatment groups. Consumption of novel quinoa biscuits produced small, but favorable changes in body weight, BMI, and circulating cholesterol concentrations, all of which may contribute to lowered CVD risk in older adults.

Plasma high-density lipoprotein cholesterol responses to endurance exercise training: A meta-analysis of randomized controlled trials

Background: Endurance exercise improves lipid and lipoproteins levels, while low high-density lipoprotein cholesterol (HDL-C) levels are risk factors for cardiovascular disease. There is a lack of evidence for the exercise characteristics in increasing lipids level, irrespective of the fact that endurance exercise increases lipids and lipoproteins level. The aim of this study was to clarify the effect and characteristics of endurance exercise in increasing HDL-C in randomized controlled trials. Methods: A search was performed for published studies between 1999 and 2014. Studies that assessed endurance exercise for ≥8 weeks and also reported the HDL-C levels pre- and post-training were included. The random effects model was used to measure the association between exercise and net change of HDL-C. Univariate regression analyses investigated the correlation of exercise characteristics. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity and the effect of potential confounders. The influence of pre-exercise lipid profile was assessed by meta-regression. Data were analyzed using Stata SE (12.0). Results: Fourteen studies with a total of 777 subjects were included. The mean HDL-C was reported to be increased and was statistically significant (weighted mean difference: 4.41 mg/dL; 95% confidence interval [CI]: 2.16–6.66 mg/dL, P < 0.001; I2 = 87.4%, P < 0.001). Univariate analysis indicated that exercise length was significantly associated with a net change of HDL-C (r = 0.56, P = 0.01). Nevertheless, there was no significant association between exercise frequency, duration, and total minutes. By subgroup analysis, exercise increased HDL-C level in Asia, Europe, and Africa and among all body mass index groups (P < 0.05). None of the studies omitted, in turn, seemed to substantially influence the effect of exercise on HDL-C by sensitivity analysis. Meta-regression showed that pre-exercise total cholesterol (TC) negatively correlated with net change of HDL-C (95% CI: 0.127, −0.018, r = −0073, P = 0.012). However, pre-exercise triglycerides, low-density lipoprotein cholesterol, and HDL-C did not correlate with a net change of HDL-C. Conclusions: Regular endurance exercise increases HDL-C level in any weight population. Exercise length of more than 8 weeks was the most important element of an exercise prescription. Among all lipid profiles, only the initial lower TC level responded better to exercise training and was more effective in increasing HDL-C level.

Ameliorative Effect of Pleurotus ostreatus on Lipid Levels and Atherogenic Indices in Hyperlipidemic Rats

Aim: To evaluate the effects of Pleurotus ostreatus on the lipid profile and atherogenic indices in Hyperlipidemic rats.&#x0D; Study Design, Place and Duration of Study: This case-control study was done for 60 days between March and April, 2017 at the department of Medical Laboratory Science and Department of Chemical Pathology, Babcock University, Ogun State, Nigeria.&#x0D; Methodology: Thirty male wistar rats weighing 117-130 g were divided randomly into 3 groups: Normolipidemic (NL) rats (fed with standard rodent chow), Hyperlipidemic (HL) rats (fed with standard rodent chow + duck yolk and reused oil), Hyperlipidemic Treated (HL+T) rats (fed with standard rodent chow + duck yolk and reused oil + 5% Pleurotus ostreatus powder). &#x0D; Changes in the animal body weights were measured in this study. Serum was obtained from fasting blood samples for the standard biochemical analyses of total cholesterol (TC), triglycerides (TG), High density lipoprotein cholesterol (HDL-C), creatinine, urea, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST). Low density lipoprotein (LDL), very low density lipoprotein (VLDL), TC/HDL, LDL/HDL and Log (TG/HDL) ratios were calculated.&#x0D; Results: The HL+T rats compared to HL rats had significantly reduced body weight, TC, TG, LDL, VLDL, TC/HDL, LDL/HDL and Log(TG/HDL) by 19.59%, 14.38%, 15.82%, 25.52%, 15.83%, 28.89%, 20.24% and 27.27% respectively (p ≤ 0.05) but recorded no significant change in HDL-C (p &gt; 0.05). Creatinine, urea, AST and ALT did not show any significant change in HL rats and HL+T rats (p &gt; 0.05).&#x0D; Conclusion: Treatment of hyperlipidemic male wistar rats with Pleurotus ostreatus reduced body weight, lipid levels (TC, TG, LDL, VLDL) and atherogenic indices (TC/HDL, LDL/HDL, Log (TG/HDL)) and appeared to have no detrimental effects on the liver and kidneys. These findings may provide insights and scientific basis for the promotion of the use of Pleurotus ostreatus in controlling hyperlipidemia and associated complications.

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.

Association of high-density lipoprotein particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial

High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS). The dal-Outcomes trial compared the CETP inhibitor dalcetrapib with placebo in patients with recent ACS. In a nested case-cohort analysis, total, large, medium, and small HDLPs were measured by nuclear magnetic resonance spectroscopy at baseline (4-12 weeks after ACS) in 476 cases with MACE and 902 controls. Hazard ratios (HRs; case-control) for 1-SD increment of HDLP or HDL-C at baseline were calculated with and without adjustment for demographic, clinical, laboratory, and treatment variables. Similarly, HRs for MACE were calculated for changes in HDLP or HDL-C from baseline to month 3 of assigned treatment. Over median follow-up of 28 months, the risk of MACE was not associated with baseline HDLP (adjusted HR = 0.98, 95% CI = 0.84-1.15, P = .81), any HDLP subclass, or HDL-C. Dalcetrapib increased HDL-C and total, medium, and large HDLP and decreased small HDLP but had no effect on MACE compared with placebo. There were no association of risk of MACE with change in HDLP or HDL-C and no interaction with assigned study treatment. Neither baseline HDLP nor the change in HDLP on treatment with dalcetrapib or placebo was associated with risk of MACE after ACS.

Low High-Density Lipoprotein Cholesterol to Monitor Long-Term Average Increased Triglycerides.

Increased triglyceride-rich remnants represent a causal risk factor for ischemic cardiovascular disease. We tested the hypothesis that low high-density lipoprotein (HDL) cholesterol can be used to monitor long-term high triglycerides/remnant cholesterol, just as high hemoglobin A1c (HbA1c) can be used to monitor long-term high glucose levels. We studied cross-sectionally 108 731 individuals, dynamically 1313 individuals with lipid measurement at 10 repeated visits, short-term 305 individuals during a fat load, and long-term 10 479 individuals with 2 lipid measurements 10 years apart. Levels of HDL cholesterol and triglycerides. Cross-sectionally, HDL cholesterol was inversely associated with triglycerides (R2 = 0.26) and remnant cholesterol (R2 = 0.26). Dynamically, major changes in triglyceride levels from measurement to measurement were mimicked by corresponding modest changes in HDL cholesterol. In the short-term after a fat load, median triglycerides increased 96% while HDL cholesterol decreased only 1%. Long-term, in individuals with measurements 10 years apart, those who initially had the highest triglycerides and corresponding lowest HDL cholesterol, still had highest triglycerides and lowest HDL cholesterol 10 years later. Prospectively, individuals with increased triglycerides/remnant cholesterol had increased risk of myocardial infarction; however, when the HDL cholesterol monitoring was removed, increased triglycerides/remnant cholesterol were largely no longer associated with increased risk of myocardial infarction. Low HDL cholesterol is a stable marker of average high triglycerides/remnant cholesterol. This suggests that low HDL cholesterol can be used to monitor long-term average high triglycerides and remnant cholesterol, analogous to high HbA1c as a long-term monitor of average high glucose levels.

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.

Elevated serum TC and LDL-C levels in Alzheimer’s disease and mild cognitive impairment: A meta-analysis study

Serum lipid levels such as triglyceride and cholesterol has been reported to play an important role in the pathophysiological process of Alzheimer disease (AD) and mild cognitive impairment (MCI). However, it still remains controversial in different studies. Here, we performed a meta-analysis to assess the importance of serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in AD and MCI patients. PubMed, China National Knowledge Infrastructure (CNKI) system database were used to identify 17 studies (10 AD-only + 4 MCI-only + 3 shared AD/MCI), including 2333 cases and 3615 healthy controls (HC). We found that compared with HC, both the serum TC levels [SMD = 0.58; 95%CI (0.25, 0.90); P = 0.001) and the serum LDL-C levels [SMD = 0.7780; 95%CI (0.3940, 1.1521); P = 0.000] were higher in cognitive impairment population (including AD and MCI) than those in HC, respectively. Furthermore, we analyzed the serum TC and LDL-C levels in AD and MCI patients. We found that the serum TC levels [SMD = 0.76; 95% CI (0.13, 1.40); P = 0.019]1 and the LDL-C levels [SMD = 1.40; 95% CI (0.70, 2.10; P = 0.000] were increased in AD patients. In the MCI patients, the serum TC levels [SMD = 0.30; 95%CI (0.01, 0.59); P = 0.041] had a significantly upward trend, while the LDL-C levels had no significant change, compared with HC subjects. However, there is no significant changes in HDL-C and TG levels in AD or MCI patients. Therefore, our results suggested that the elevated TC and LDL-C levels may be a potential risk factor for cognitive impairment.

Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate.

BackgroundIn human immunodeficiency virus (HIV) treatment, tenofovir alafenamide (TAF) is associated with greater increases in all fasting cholesterol subgroups compared with tenofovir disoproxil fumarate (TDF). Because lipid abnormalities may contribute to cardiovascular morbidity and mortality, cardiovascular risk assessment is integral to routine HIV care. This post hoc study evaluates the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naive adults living with HIV treated with TAF or TDF.MethodsParticipants (N = 1744) were randomized (1:1) to initiate TAF or TDF, each coformulated with elvitegravir/cobicistat/emtricitabine (studies GS-US-292-0104 and GS-US-292-0111). Eligibility for statin therapy and estimated 10-year ASCVD risk among adults aged 40–79 years treated with TAF or TDF for 96 weeks (W96) were analyzed based on American College of Cardiology/American Heart Association Pooled Cohort Equations. Categorical shifts in 10-year ASCVD risk from <7.5% to ≥7.5% by W96 on TAF versus TDF were calculated.ResultsParticipants initiating TAF versus TDF in the overall study population showed small but significant increases in median fasting lipid parameters at W96, including total cholesterol (191 vs 177 mg/dL; P < .001), low-density lipoprotein ([LDL] 119 vs 112 mg/dL; P < .001), and high-density lipoprotein ([HDL] 51 vs 48 mg/dL; P < .001), respectively. At baseline, 18% and 23% on TAF versus TDF had a 10-year ASCVD risk score ≥7.5%, with mean risk scores low overall for TAF versus TDF at baseline (4.9% vs 5.4%; P = .35) and W96 (6.1% vs 6.2%; P = .04). Increases in ASCVD risk from baseline to W96 were driven by both increasing age and changes in total cholesterol (TC) and HDL cholesterol. At W96, TC/HDL ratios (median) were 3.7 for both groups (P = .69). There was no difference between shifts in categorical risk for TAF versus TDF (9% vs 5%; P = .19). Eligibility for high-intensity statin therapy were similar for TAF versus TDF groups (19% vs 21%; P = .47).ConclusionsLipid changes with TAF as part of coformulated regimens do not substantively affect CVD risk profiles compared with TDF.

Effects of bariatric surgery in different obesity phenotypes: Tehran Obesity Treatment Study (TOTS).

Not all morbid obese patients suffer from metabolic co-morbidities; thus, a sub-group of metabolically healthy morbid obese (MHMO) individuals are identified. However, the role of bariatric surgery is not well understood in this subgroup. A total of 2244 morbid obese individuals aged 18-65 years undergoing bariatric surgery were selected. Patients were considered MHMO according to the joint interim statement (JIS) definition, as having two or less abnormalities in these five parameters: waist circumference (WC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), systolic or diastolic blood pressure (SBP or DBP), and fasting plasma glucose (FPG). Otherwise, they were considered metabolically unhealthy morbid obese (MUMO). Follow-up data were collected at 6, 12, and 24 months post-surgery. Prior to surgery, 36.2% of participants were MHMO and had significantly lower BMI, WC, TG, FPG, SBP, and DBP and higher HDL-C compared to MUMO. Both MHMO and MUMO participants showed a significant decrease in BMI, WC, TG, SBP, DBP, and FPG and increase in HDL-C and the percentage of excess weight loss (%EWL). Two-year post-operative changes (from baseline) of BMI, WC, and %EWL were greater in MHMO subjects and changes of TG, HDL-C, DBP, SBP, and FPG were greater in MUMO subjects. Further multivariate regression analysis for delta (∆) change in these characteristics revealed that only the delta (∆) changes of WC and %EWL were statistically different between the two phenotypes and were greater in MHMO subjects, 2 years after the surgery (- 3.077 cm decrease in WC and + 3.612% higher %EWL compared to MUMO subjects). Bariatric surgery is an effective method for reduction of metabolic abnormalities and weight loss in both MUMO and MHMO phenotypes. Benefits of this intervention are comparable between patients with these two obesity phenotypes.

Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

P6193Dalcetrapib reduces incident diabetes in patients with recent acute coronary syndrome

Abstract Background Among patients with acute coronary syndrome (ACS) who do not have diabetes, incident diabetes is common and associated with an adverse prognosis. Some data suggest that high density lipoprotein (HDL) has favourable effects on beta cell function and that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes in conjunction with increased HDL cholesterol (HDL-C) concentration. Dalcetrapib is a CETP inhibitor under ongoing evaluation as a potential cardiovascular therapy. Purpose We compared the effect of treatment with dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome (ACS). Methods In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg or placebo daily, beginning 4–12 weeks after ACS. Absence of diabetes at baseline was based upon medical history, no use of diabetes medication, haemoglobin A1c &lt;6.5%, and plasma glucose level &lt;7 mmol/L (if measured under fasting conditions) or &lt;11.1 mmol/L (if measured under non-fasting conditions). Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, use of a diabetes medication, HbA1c ≥6.5%, or two measurements of plasma glucose ≥7 mmol/L (fasting) or ≥11.1 mmol/L (non-fasting). The association of incident diabetes with baseline and on-treatment HDL-C was determined. Results At baseline, 10621 patients (67% of the trial cohort) did not have diabetes and formed the analysis cohort. Over median follow-up of 31 months, incident diabetes was identified in 392 of 5314 patients (7.4%) assigned to dalcetrapib and 505 of 5307 (9.5%) assigned to placebo (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.66–0.87; P&lt;0.001). This corresponds to an absolute reduction in incident diabetes of 2.1%, and a need to treat 47 patients (for 31 months) to prevent 1 case of diabetes. Kaplan-Meier estimates of the cumulative incidence of diabetes are shown in the Figure. Across both treatment groups, incident diabetes was inversely associated with baseline HDL-C (OR 0.98 for 1 mg/dL increase in baseline HDL-C; 95% CI 0.97–0.98, P&lt;0.001). In the dalcetrapib group, there was a further inverse association of incident diabetes with the change in HDL-C on assigned treatment (OR 0.98 for 1 mg/dL increase in HDL-C from baseline; 95% CI 0.97–0.99, P=0.002). Dalcetrapib was safe and generally well-tolerated in the trial. Conclusions In patients with recent ACS who do not have diabetes at baseline, incident diabetes is common. Dalcetrapib treatment reduced the relative risk of incident diabetes by 24% and the absolute risk by 2.1% over a median of 31 months. The reduction in incident diabetes with dalcetrapib was associated with increased HDL-C on treatment. Acknowledgement/Funding The dal-OUTCOMES trial was funded by F. Hoffmann LaRoche

A short-term religious “fast” from animal products has a minimal impact on cardiometabolic health biomarkers irrespective of concurrent shifts in distinct plant-based food groups

Plant-based diets may help improve measures of body fat, blood cholesterol, glucose metabolism, and inflammation. However, limited evidence suggests that the health effects of reducing animal products may depend on the quality of plant-based foods consumed as caloric replacements. This study examined how temporarily restricting consumption of meat, dairy, and egg (MDE) products for religious purposes influences cardiometabolic health biomarkers and whether any effects of MDE restriction on biomarkers are modified by concurrent shifts in calories, fish, and distinct plant-based foods. This study followed a sample of 99 individuals in the United States with varying degrees of adherence to Orthodox Christian (OC) guidance to abstain from MDE products during Lent, the 48-d period prior to Easter. Dietary composition was estimated from FFQs and 7-d food records; measures of body fat, blood lipids, glucose metabolism, and inflammation were collected prior to and at the end of Lent. Each serving decrease in MDE products was associated with an average -3.7% (95% CI: -5.5%, -2.0%; P<0.0001) and -3.6% (95% CI: -5.8%, -1.3%; P=0.003) change in fasting total and LDL blood cholesterol, respectively, which were partly explained by minor weight loss. However, the total/HDL cholesterol ratio did not significantly decrease due to an average -3.2% (95% CI: -5.8%, -0.6%; P=0.02) change in HDL cholesterol. No associations between MDE restrictions and shifts in measures of body fat, glucose, insulin, or C-reactive protein were observed. The data could not provide evidence that changes in cardiometabolic health biomarkers in relation to MDE restriction were modified by concurrent shifts in calories, fish, or plant-based foods. Temporary MDE restrictions practiced by this sample of OCs in the United States during Lent had minimal effects on cardiometabolic disease risk factors. Further research among larger samples of OCs is needed to understand how nutritionally distinct and complex combinations of plant-based foods may modify the health effects of religious fasting from MDE products.

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.

Macroprolactinaemia modulates cardiometabolic effects of fenofibrate in men with atherogenic dyslipidaemia: A pilot study.

Cardiometabolic effects of hypolipidaemic agents depend on plasma levels of monomeric prolactin. Although macroprolactinaemia seems to be associated with increased cardiometabolic risk, no previous study has investigated whether macroprolactinaemia modulates pleiotropic effects of hypolipidaemic agents. The study population included two age-, weight-, blood pressure- and lipid-matched groups of men: 12 men with elevated levels of big-big prolactin and 16 men with prolactin levels within the reference range. Because of atherogenic dyslipidaemia, all subjects were treated for 6months with fenofibrate (200mg daily). Glucose homeostasis markers and plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D, were determined in patients at the beginning and at the end of the study. Men with elevated levels of big-big prolactin were characterized by higher levels of hsCRP and fibrinogen and lower levels of 25-hydroxyvitamin D as well as decreased insulin sensitivity than subjects with prolactin levels within the reference range. In men without macroprolactinaemia, fenofibrate decreased circulating levels of total and LDL cholesterol, triglycerides, uric acid, hsCRP and fibrinogen, and increased concentrations of HDL cholesterol, homocysteine and 25-hydroxyvitamin D, as well as improved insulin sensitivity. In subjects with macroprolactinaemia, fenofibrate action was limited to the changes in HDL cholesterol, triglycerides, hsCRP and homocysteine. With the exception of homocysteine, cardiometabolic effects of fenofibrate were stronger in subjects without than in subjects with elevated levels of big-big prolactin. The results of the study indicate that macroprolactinaemia exerts a negative impact on cardiometabolic effects of fenofibrate.

Cholesterol and neurodegeneration: longitudinal changes in serum cholesterol biomarkers are associated with new lesions and gray matter atrophy in multiple sclerosis over 5 years of follow-up.

Cholesterol is an important structural component of myelin and essential for brain homeostasis. Our objective was to investigate whether longitudinal changes in cholesterol biomarkers are associated with neurodegeneration in multiple sclerosis (MS). This prospective, longitudinal study (n=154) included 41 healthy controls, 76 relapsing-remitting MS subjects and 37 progressive MS subjects. Neurological examination, brain magnetic resonance imaging and blood samples were obtained at baseline and at 5-year follow-up visits. Cholesterol biomarkers measured included plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol and the apolipoproteins ApoA-I, Apo-II, ApoB, ApoC-II and ApoE. Key cholesterol pathway single nucleotide polymorphisms were genotyped. Greater percentage increases in HDL-C and ApoA-I levels were associated with a lower rate of gray matter and cortical volume loss. Greater percentage increases in low-density lipoprotein cholesterol were associated with increases in new T2 lesions. The percentage increases in HDL-C (P=0.032) and ApoA-I (P=0.007) were smaller in patients with relapsing-remitting MS at baseline who converted to secondary progressive MS during the 5-year follow-up period. Changes in HDL-C and ApoA-I were associated with lipoprotein lipase rs328 genotype status. Increases in HDL-C and ApoA-I have protective associations with magnetic resonance imaging measures of neurodegeneration in MS.

Dietary Approaches to Stop Hypertension (DASH): potential mechanisms of action against risk factors of the metabolic syndrome.

The metabolic syndrome is a cluster of disorders dominated by abdominal obesity, hypertriacylglycerolaemia, low HDL-cholesterol, high blood pressure and high fasting glucose. Diet modification is a safe and effective way to treat the metabolic syndrome. Dietary Approaches to Stop Hypertension (DASH) is a dietary pattern rich in fruits, vegetables and low-fat dairy products, and low in meats and sweets. DASH provides good amounts of fibre, K, Ca and Mg, and limited quantities of total fat, saturated fat, cholesterol and Na. Although DASH was initially designed for the prevention or control of hypertension, using a DASH diet has other metabolic benefits. In the present review, the effect of each dietary component of DASH on the risk factors of the metabolic syndrome is discussed. Due to limited fat and high fibre and Ca content, individuals on the DASH diet are less prone to overweight and obesity and possess lower concentrations of total and LDL-cholesterol although changes in TAG and HDL-cholesterol have been less significant and available evidence in this regard is still inconclusive. Moreover, high amounts of fruit and vegetables in DASH provide great quantities of K, Mg and fibre, all of which have been shown to reduce blood pressure. K, Mg, fibre and antioxidants have also been effective in correcting glucose and insulin abnormalities. Evidence is provided from cross-sectional investigations, cohort studies and randomised controlled trials, and, where available, from published meta-analyses. Mechanisms are described according to human studies and, in the case of a lack of evidence, from animal and cell culture investigations.

National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio: a pooled analysis of 458 population-based studies in Asian and Western countries.

BackgroundAlthough high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries.MethodsWe pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group.ResultsSince ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China.ConclusionsHDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.