Changes In Low-density Lipoprotein Cholesterol Research Articles

Short-term ozone exposure and metabolic status in metabolically healthy obese and normal-weight young adults: A viewpoint of inflammatory pathways

Unhealthy metabolic status increases risks of cardiovascular and other diseases. This study aims to explore whether there is a link between O3 and metabolic health indicators through a viewpoint of inflammatory pathways. 49 metabolically healthy normal-weight (MH-NW) and 39 metabolically healthy obese (MHO) young adults aged 18–26 years were recruited from a panel study with three visits. O3 exposure were estimated based on fixed-site environmental monitoring data and time-activity diary for each participant. Compared to MH-NW people, MHO people were more susceptible to the adverse effects on metabolic status, including blood pressure, glucose, and lipid indicators when exposed to O3. For instance, O3 exposure was associated with significant decreases in high-density lipoprotein cholesterol (HDL-C), and increases in C-peptide and low-density lipoprotein cholesterol (LDL-C) among MHO people, while only weaker changes in HDL-C and LDL-C among MH-NW people. Mediation analyses indicated that leptin mediated the metabolic health effects in both groups, while eosinophils and MCP-1 were also important mediating factors for the MHO people. Although both with a metabolically healthy status, compared to normal-weight people, obese people might be more susceptible to the negative effects of O3 on metabolic status, possibly through inflammatory indicators such as leptin, eosinophils, and MCP-1.

Hyperuricemia prevalence and its association with metabolic disorders: a multicenter retrospective real-world study in China.

BackgroundThe prevalence of hyperuricemia (HUA) and gout continues to increase in China. Research suggests that HUA may be related to many diseases other than gout. However, further population research is required to investigate the association between HUA and metabolic syndromes. This study sought to investigate the prevalence of HUA in an average population in China, and the association between serum uric acid (UA) levels and related metabolic disorders.MethodsThis multicenter retrospective real-world study examined the hospital information system data of 4 tertiary hospitals in 3 provinces in China. The data of patients aged between 18 and 80 years, who had attended at least 1 medical appointment at which their UA level was recorded, were analyzed to evaluate associations between UA levels and metabolic disorders.ResultsAmong the 374,506 enrolled subjects (49.7% male; mean age 51.5 years old), the overall prevalence of HUA and gout were 14.8% and 0.5%, respectively. The prevalence was higher among males than females (17.6% vs. 12.0%, 0.8% vs. 0.1%; both P<0.001). Groups exhibiting higher UA levels had increased adjusted odds ratios for dyslipidemia and chronic kidney disease (CKD) in both sexes. Changes in UA levels from the baseline were negatively correlated with changes in the estimated glomerular filtration rate and hemoglobin A1c among both sexes (all P<0.001), and were positively correlated with changes in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (all P<0.05) among males, and changes in TC, TG, LDL-C and glucose (all P<0.001) among females.ConclusionsHUA is associated with dyslipidemia and CKD both cross-sectionally and longitudinally. Similar phenomena were observed in both sexes.

Statin treatment and LDL-cholesterol treatment goal attainment among individuals with familial hypercholesterolaemia in primary care

ObjectivesGuidance recommends statin treatment in familial hypercholesterolaemia (FH) to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). We assessed statin prescribing rates and LDL-C treatment goal attainment...

Порівняльна характеристика впливу омега-3 поліненасичених жирних кислот, статинів та їх комбінування на показники ліпідного спектра крові, судинно-тромбоцитарного гомеостазу і варіативності ритму серця у хворих на цукровий діабет 2-го типу з кардіоваскуля

Актуальність. Особливу зацікавленість у лікуванні дисліпопротеїнемій (ДЛП) у хворих на цукровий діабет 2-го типу (ЦД-2) з кардіоваскулярною автономною нейропатією (КАН) викликає аналіз ефективності комбінування омега-3 поліненасичених жирних кислот (w-3 ПНЖК) і статинів, однак інформація про особливості їх використання неоднозначна, має фрагментарний характер, є предметом дискусії, а тому потребує подальшого уточнення. Мета. Проведення порівняльної характеристики впливу w-3 ПНЖК, статинів та їх комбінування на показники ліпідного спектра крові, судинно-тромбоцитарного гомеостазу і варіативності ритму серця (ВРС) у хворих на ЦД-2 з КАН. Матеріали та методи. Обстежено 75 хворих на ЦД-2 із функціональною стадією КАН. У крові визначали концентрацію глюкози, глікозильваного гемоглобіну, загального холестерину (ЗХС), тригліцеридів (ТГ), холестерину ліпопротеїнів високої (ХС ЛПВЩ) і низької щільності (ХС ЛПНЩ); вміст ендотеліну-1 (ЕТ-1), тромбоксану B2 (TXB2), 6-кетопростагландину F1a (6-ketoPGF1a), розраховували коефіцієнт атерогенності (КА), співвідношення TXB2/6-ketoPGF1a. З метою оцінки результатів короткотривалої ВРС використовували часові й спектральні параметри. Пацієнти з ЦД-2 та функціональною стадією КАН були стратифіковані на чотири групи і протягом трьох місяців, окрім цукрознижувальної терапії, отримували: 1-ша група (n = 21) — препарат w-3 ПНЖК 1 капс/добу; 2-га група (n = 22) — симвастатин 20 мг/добу; 3-тя група (n = 17) — препарат w-3-ПНЖК 1 г/добу і симвастатин 10 мг/добу; у контрольній (n = 15) — стандартну цукрознижувальну терапію протягом трьох місяців. Результати. Включення в лікувальні заходи препарату w-3 ПНЖК виявляло більш значуще порівняно з симвастатином зниження рівня ТГ, зменшення вмісту КА та збільшення концентрації ХС ЛПВЩ і не впливало на концентрацію ЗХС і ХС ЛПНЩ. Використання симвастатину супроводжувалось більш вірогідним зменшенням рівня ЗХС, ХС ЛПНЩ, КА, ТХВ2, TXB2/6-ketoPGF1a і зростанням вмісту ХС ЛПВЩ, ЕТ-1, 6-ketoPGF1a; часових і спектральних параметрів ВРС. Комбінація w-3 ПНЖК і симвастатину супроводжувалась найбільш вираженими, позитивними, вірогідними змінами ліпідного обміну, ендотеліальної функції, ТХВ2, TXB2/6-ketoPGF1a; часових і спектральних параметрів ВРС. Висновки. Отримані результати дозволяють вважати, що ефективність комбінованої терапії w-3 ПНЖК і симвастатином не пов’язана зі станом компенсації захворювання, а є результатом безпосереднього впливу цих фармакологічних агентів на досліджувані показники, що обґрунтовує доцільність її використання в лікуванні ДЛП у хворих на ЦД-2 і функціональну стадію КАН.

Development of a Portfolio Diet Score and Its Concurrent and Predictive Validity Assessed by a Food Frequency Questionnaire.

The Portfolio Diet, a plant-based portfolio of cholesterol-lowering foods, has been shown to reduce low-density lipoprotein cholesterol (LDL-C), and other cardiovascular risk factors, in randomized controlled trials (RCTs). It is not known if these beneficial effects translate to a lower incidence OF cardiovascular disease (CVD). To support examinations between Portfolio Diet adherence and disease, a Portfolio Diet score (PDS) was developed and its predictive and concurrent validity was assessed within the Toronto Healthy Diet Study, a six-month RCT in overweight adults. Predictive validity was assessed using change in the PDS measured by food frequency questionnaire (FFQ) and concomitant change in LDL-C from baseline to six months using multiple linear regression, adjusted for potential confounders (n = 652). Concurrent validity was assessed in a subset of participants (n = 50) who completed the FFQ and a 7-day diet record (7DDR) at baseline. The PDS determined from each diet assessment method was used to derive correlation coefficients and Bland–Altman plots to assess the between-method agreement. The change in PDS was inversely associated with change in LDL-C (β coefficients: −0.01 mmol/L (95% confidence intervals (CIs): −0.02, −0.002; p = 0.02). The correlation between the PDS from the FFQ and 7DDR was 0.69 (95% CIs: 0.48, 0.85). The Bland–Altman plot showed reasonable agreement between the score from the FFQ and 7DDR. These findings indicate predictive validity of the PDS with lower LDL-C, and reasonable concurrent validity of the PDS as assessed by an FFQ against a 7DDR.

Comparison of the Reductions in LDL-C and Non-HDL-C Induced by the Red Yeast Rice Extract Xuezhikang Between Fasting and Non-fasting States in Patients With Coronary Heart Disease.

Background: Xuezhikang, an extract of red yeast rice, effectively lowers fasting blood lipid levels. However, the influence of Xuezhikang on the non-fasting levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) has not been explored in Chinese patients with coronary heart disease (CHD).Methods: Fifty CHD patients were enrolled and randomly divided into two groups (n = 25 each) to receive 1,200 mg/d of Xuezhikang or a placebo for 6 weeks as routine therapy. Blood lipids were repeatedly measured before and after 6 weeks of treatment at 0, 2, 4, and 6 h after a standard breakfast containing 800 kcal and 50 g of fat.Results: The serum LDL-C levels significantly decreased, from a fasting level of 3.88 mmol/L to non-fasting levels of 2.99, 2.83, and 3.23 mmol/L at 2, 4, and 6 h, respectively, after breakfast (P < 0.05). The serum non-HDL-C level mildly increased from a fasting level of 4.29 mmol/L to non-fasting levels of 4.32, 4.38, and 4.34 mmol/L at 2, 4, and 6 h post-prandially, respectively, and the difference reached statistical significance only at 4 and 6 h after breakfast (P < 0.05). After 6 weeks of Xuezhikang treatment, the patients had significantly lower fasting and non-fasting serum levels of LDL-C and non-HDL-C (P < 0.05) than at pretreatment. The LDL-C levels were reduced by 27.8, 28.1, 26.2, and 25.3% at 0, 2, 4, and 6 h, respectively, and the non-HDL-C levels were reduced by 27.6, 28.7, 29.0, and 28.0% at 0, 2, 4, and 6 h, respectively, after breakfast. No significant difference was found in the percent reductions in the LDL-C and non-HDL-C levels among the four different time-points.Conclusions: Six weeks of Xuezhikang treatment significantly decreased LDL-C and non-HDL-C levels, with similar percent reductions in fasting and non-fasting states in CHD patients, indicating that the percent change in non-fasting LDL-C or non-HDL-C could replace that in the fasting state for evaluation the efficacy of cholesterol control in CHD patients who are unwilling or unable to fast.

A combination of single nucleotide polymorphisms is associated with the interindividual variability in the blood lipid response to dietary fatty acid consumption in a randomized clinical trial

Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes. We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions. In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression. Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18±0.04, butter: 3.31±0.04, MUFA: 3.00±0.04, PUFA: 2.81±0.04, CHO: 3.11±0.04 mmol/L; P<0.001) while endpoint TG concentrations were not (P=0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5±2.2% and 55.8±1.8%, respectively). Among the 22 candidate SNPs, only ABCA1-rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes. We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles.

The effect of honey on lipid profiles: a systematic review and meta-analysis of controlled clinical trials

Honey is known not only as a natural food but also as complementary medicine. According to the controversial evidence about the effects of honey on blood lipids, this meta-analysis was performed to investigate the potential effects of honey on lipid profiles. Relevant studies were identified by searching PubMed, Web of Science, Scopus, Embase and Cochrane databases. All human controlled clinical trials (either with a parallel or a crossover design) published in English that reported changes in serum lipid markers (total cholesterol (TC), TAG, LDL-cholesterol, HDL-cholesterol and LDL-cholesterol:HDL-cholesterol ratio) following honey consumption were considered. Standardised mean differences and their respective 95 % CI were calculated to assess the changes in lipid profiles following honey consumption by random effects model. Statistical heterogeneity, sensitivity analysis, publication bias and quality of the included studies were assessed, as well. The meta-analysis of twenty-three trials showed that honey had no significant effects on TC, TAG, LDL-cholesterol, HDL-cholesterol and LDL-cholesterol:HDL-cholesterol ratio. Significant heterogeneity was seen among the studies for all the studied factors (I2 index > 50 %). Subgroup analysis based on the lipid profile status, types of honey and intervention duration revealed no significant effect on TC, TAG, LDL-cholesterol and HDL-cholesterol. Quality of the evidences varied from very low to moderate according to various parameters. In conclusion, honey consumption did not affect serum lipid profiles (TC, TAG, LDL-cholesterol, HDL-cholesterol and LDL-cholesterol:HDL-cholesterol ratio).

Lipoprotein Particle Size Distributions in Response to a 6-Week Dietary Intervention Using Different Dairy Food Matrices Including Cheese and Butter

Abstract Objectives Most dietary guidelines recommend saturated fat (SFA) intakes to be &amp;lt; 10% of total energy intake, since SFA increase low-density lipoprotein cholesterol (LDL-c) levels, a known risk factor for cardiovascular disease (CVD). However, within LDL-c, small, dense LDL particles are more strongly related to CVD risk than large buoyant particles, and response to SFA vary for different foods. Dairy fat, when eaten as cheese, significantly lowers total cholesterol compared to butter. Here, we aimed to test the effect of the cheese matrix on lipoprotein particle size distribution response in overweight adults aged ≥ 50 years. Methods In this secondary analysis of a 6-week randomised parallel intervention(1); participants received ∼40g dairy fat in 1 of 4 treatments: (A) 120 g of full-fat cheddar cheese (FFCC); (B) reduced-fat cheese plus butter (RFC + B); (C) butter, calcium caseinate powder, and calcium supplement (CaCO3) (BCC); or (D) 120 g FFCC as per (A). Fasting EDTA blood samples at wk. 0 (baseline) and wk. 6 were analysed for lipoprotein particle size distribution via nuclear magnetic resonance (NMR) spectroscopy. To examine extremes in response, those with greatest reduction in LDL-c (n = 15, ‘positive’ responders) were compared to those with the greatest increase in LDL-c (n = 15, ‘negative’ responders). Results Correlation analyses between the change in cholesterol levels and change in particle size distribution suggest a relationship between change in LDL-c, HDL-c, and corresponding particle sizes, which differs dependent on the dairy fat matrix. The correlation of LDL-c and LDL particle (LDL-p) concentration weakened as less fat was present within a cheese matrix, as LDL-c decreased so did total LDL-p, due to larger LDL particles. The positive responders displayed a stronger relationship between change in cholesterol and lipoprotein levels, with the changes in cholesterol driven by the large LDL-p and large HDL-p. Conclusions Lipoprotein particle distribution is correlated with change in cholesterol levels after a 6-week intervention of dairy fat. The changes in LDL-c and HDL-c were driven by the less atherogenic, large LDL-p and large HDL-p which are inversely associated with CVD risk. The overall response in LDL-p to SFA appears to vary, dependent on the dairy food matrix in which the fat was eaten. Funding Sources Food for Health Ireland (FHI). Enterprise Ireland.

160-LB: PCSK-9 in Pregnancy: Longitudinal Changes and Correlations with Individual Lipid Levels

Background: Lipid levels increase during pregnancy, likely contributing a metabolic advantage to the fetus. While PCSK9 inhibits LDL receptor recycling to the cell surface and increases plasma LDL-C, changes in PCSK9 levels during gestation and correlations between PCSK9 and lipid levels across pregnancy have not been explored. Methods: We evaluated 42 women (first trimester BMI between 18.5 and 35 kg/m2) at two study visits: early (mean 15.5 weeks) and late (mean 34.1 weeks) gestation. Women with pregestational diabetes and multifetal pregnancies were excluded. PCSK9 and lipid levels were measured on fasting blood plasma. The Wilcoxon signed rank test was used to assess changes in each measure across pregnancy and Spearman’s correlation coefficient was used to assess the correlation between PCSK9 and individual lipids at early and late pregnancy and changes from early to late pregnancy. Results: 92% of participants were White. At first visit, the mean age was 30.4 yrs and BMI was 25.6 kg/m2. During gestation, levels of PCSK9 increased by 55% and significantly correlated with changes in total, VLDL, and LDL cholesterol, and triglyceride levels, but not Lp(a) or FFA levels (Table). Conclusion: PCSK9 levels rose over 50% during pregnancy and may account for between 16% and 36% of increases in total and LDL cholesterol, and triglyceride levels. Lp(a) levels also increase in pregnancy but are not related to PCSK9 levels. Disclosure C. H. Anadkat: None. J. Q. Purnell: Advisory Panel; Self; Novo Nordisk Pharma Ltd. N. E. Marshall: None. A. M. Valent: None. J. Boone-heinonen: None. K. Vesco: Research Support; Self; Pfizer Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098707)

Which Predicts Incident Cardiovascular Disease Better: A Plant-Centered Diet or a Low-Saturated Fat Diet? The Coronary Artery Risk Development in Young Adults (CARDIA) Study

ObjectivesA low-saturated fat diet has been suggested to reduce serum cholesterol and thereby presumably lower the risk of atherosclerotic cardiovascular disease (CVD). We compared associations of a low-saturated fat diet vs a plant-centered diet with lower serum low-density lipoprotein cholesterol (LDL-C) concentration and risk of incident CVD, coronary heart disease (CHD), and stroke. MethodsWe followed 4,887 Black and White men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, ages 18–30 years and free of CVD at baseline from 1985–86 (exam year 0) to 2018 (year 32). The A Priori Diet Quality Score (APDQS), a measure of plant-centered diet quality, was assessed in an interviewer-administered diet history at years 0, 7, and 20. Higher APDQS implies higher intake of nutritionally-rich plant foods with less high-fat meats and unhealthy plant foods. Low-saturated fat diet was judged by lower the Keys score, based on saturated fat, polyunsaturated fat, and dietary cholesterol intake. Linear and proportional hazards regression models were used, the latter with time-varying average APDQS and CVD outcomes, both adjusted for age, sex, race, education, energy intake, physical activity, smoking, and parental history of CVD (CVD outcome only). ResultsHigher APDQS had higher dietary fiber and lower total and saturated fat. Keys score and APDQS 7-year changes correlated similarly with lower concurrent LDL-C change. During the 32 year follow-up, we documented 280,135, and 92 incident cases of CVD, CHD, and stroke, respectively. LDL-C predicted CVD and CHD, but not stroke. APDQS, but not Keys score, was associated with a lower risk of each CVD outcome. Multivariable-adjusted HRs per 1-SD increment for the APDQS were 0.81 (95% CI: 0.68 – 0.96) for CVD, 0.78 (95% CI: 0.61 – 1.00) for CHD, and 0.71 (95% CI: 0.52 – 0.98) for stroke. The primary results for APDQS and for LDL-C were not substantially altered in mutually adjusted models. ConclusionsBoth a plant-centered and a low-saturated fat diet were associated with lower LDL-C. A plant-centered diet and LDL-C, but not a low-saturated fat diet, were associated with long-term CVD risk. Our findings imply that dietary strategies aimed solely to lower saturated fat may be less effective in reducing CVD burden than recommendations for a plant-centered diet. Funding SourcesHFHL, MnDRIVE, NHLBI.

Does four-week consecutive, dawn-to-sunset intermittent fasting during Ramadan affect cardiometabolic risk factors in healthy adults? A systematic review, meta-analysis, and meta-regression

AimsThis study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29–30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression. Data synthesisWe conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18–85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K = 77, number of subjects N = 3705, Hedge's g = −0.092, 95% confidence interval (CI): −0.168, 0.016); TG (K = 74, N = 3591, Hedge's g = −0.127, 95% CI: −0.203, 0.051); HDL-C (K = 68, N = 3528, Hedge's g = 0.138, 95% CI: 0.051, 0.224); LDL-C (K = 65, N = 3354, Hedge's g = −0.115, 95% CI: −0.197, −0.034); VLDL-C (K = 13, N = 648, Hedge's g = −0.252, 95% CI: −0.431, 0.073), DBP (K = 32, N = 1716, Hedge's g = −0.255, 95% CI: −0.363, 0.147), and HR (K = 12, N = 674, Hedge's g = −0.082, 95% CI: −0.300, 0.136). Meta-regression revealed that the age of fasting people was a significant moderator of changes in both HDL-C (P = 0.02) and VLDL-C (P = 0.01). Male sex was the only significant moderator of changes in LDL-C (P = 0.055). Fasting time duration was the only significant moderator of HDL-C (P = 0.001) at the end of Ramadan. ConclusionsRDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people.

Effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI): study protocol for a randomized, double-blind, placebo-controlled trial

BackgroundBilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI.MethodsThe effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months.DiscussionControlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI.Trial registrationClinicalTrials.gov NCT03620266. Registered on August 8, 2018.

Meta-analysis of randomized clinical trials comparing PCSK9 monoclonal antibody versus ezetimibe/placebo in patients at high cardiovascular risk

Background and aimsProprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) reduce circulating low-density lipoprotein cholesterol (LDL-C) by controlling the expression of LDL-receptor on the surface of hepatocytes. This meta-analysis aimed at evaluating the efficacy of PCSK9 mAbs on clinical and lipid-lowering outcomes. MethodsPubMed, Embase, and ClinicalTrials.gov were searched from inception until November 2020 for randomized controlled trials (RCTs) that compared PCSK9 mAbs with ezetimibe or placebo in patients at high cardiovascular risk. ResultsTwenty eight RCTs with a total of 89,115 participants were included. Compared with placebo, PCSK9 mAbs significantly reduced the risk of major adverse cardiac events (MACEs) (RR 0.83, 95% CI 0.79 to 0.88, p < 0.00001). However, no difference was observed in occurring MACEs between PCSK9 mAbs and ezetimibe (RR 0.70, 95% CI 0.40 to 1.20, p = 0.20). Secondary analyses show that PCSK9 mAbs were not superior to ezetimibe in preventing stroke (RR 0.38, 95% CI 0.09 to 1.69, p = 0.20), myocardial infarction (RR 0.95, 95% CI 0.47 to 1.90, p = 0.88), and cardiovascular death (RR 0.44, 95% CI 0.14 to 1.43, p = 0.17). Compared with placebo, PCSK9 mAbs significantly reduced the incidence of stroke (RR 0.75, 95% CI 0.66 to 0.86, p < 0.0001) and myocardial infarction (RR 0.81, 95% CI 0.76 to 0.87, p < 0.00001), but not the risk of cardiovascular death (RR 0.96, 95% CI 0.86 to 1.07, p = 0.45). As for lipid-lowering efficacy, PCSK9 mAbs markedly reduced percent change of LDL-C from baseline to week 12 and 24 compared to ezetimibe or placebo. ConclusionsIn patients at high cardiovascular risk, PCSK9 mAbs could effectively reduce MACEs, stroke, and myocardial infarction compared with placebo. However, PCSK9 mAbs were not superior to ezetimibe in preventing adverse cardiovascular events in our study; RCTs with long-term follow-up and cardiovascular events as the research endpoint are still needed.

Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing’s Syndrome (LOGICS): Results From a Double-Blind, Placebo-Controlled, Randomized Withdrawal Study

Endogenous Cushing’s syndrome (CS) is a rare, serious disorder caused by chronic cortisol excess. A phase 3, open-label study (SONICS) demonstrated efficacy and safety of levoketoconazole in adults with CS. LOGICS is a phase 3, double-blind (DB), placebo-controlled, randomized-withdrawal (R-W) study that investigated levoketoconazole in adults with CS via an open-label titration-maintenance (T-M) phase (14-19 weeks) followed by a DB R-W phase (~8 weeks) and a restoration phase (~8 weeks). The primary endpoint is the proportion of patients with loss of mean urinary free cortisol (mUFC) response during R-W (ie, mUFC ≥1.5x ULN or mUFC >40% above baseline if baseline was >1.0x ULN, or other rescue criterion met). Key secondary endpoints include mUFC normalization and changes in comorbidity biomarkers at the end of R-W. Of 84 patients dosed in LOGICS (12 SONICS-completers and 72 de novo), 79 were titrated (72 de novo) and 44 patients (39 from T-M and 5 direct roll-overs from SONICS) were randomized 1:1 to receive levoketoconazole (n=22) at an individualized therapeutic dose or a matching placebo regimen (n=22). The R-W population mean age was 44.3 years, 77% were female, 91% were white, mean weight was 83.2 kg, and 86% had Cushing’s disease. Selected results from an interim analysis at the end of R-W are presented. At the end of R-W, significantly more patients on placebo (95.5%) achieved primary endpoint of loss of mUFC response than those who continued on levoketoconazole (40.9%) (treatment difference [TD], -54.5%; 95% CI: -75.7, -27.4; P=0.0002). Similarly, the mUFC normalization rate at the end of R-W was significantly higher for levoketoconazole (50.0%) versus placebo (4.5%; TD, 45.5%; 95% CI: 19.2, 67.9; P=0.0015). Mean change from R-W baseline to end of R-W in total cholesterol was -1.4 mg/dL for levoketoconazole and +35.6 mg/dL for placebo (P=0.0004); mean change in LDL cholesterol was -0.2 mg/dL and +25.0 mg/dL, respectively (P=0.0056). Mean change in glycemia markers and high sensitivity C-reactive protein were not significantly different between treatment groups. 90% of levoketoconazole-treated patients across the T-M and R-W phases (n=80) had ≥1 treatment-emergent adverse event (AE); AEs led to treatment discontinuation in 19% (15/80) of patients, 11% (9/80) of which were considered treatment-related. The most common AEs were nausea (29%), hypokalemia (28%), and headache (21%); serious AEs drug related were reported in 4 patients (3 liver-related, 1 gastroenteritis, 1 hypokalemia); AEs of special interest included liver-related (11%), QT prolongation (10%), and adrenal insufficiency (10%). These LOGICS interim results confirm the safety and efficacy findings from SONICS, establishing treatment benefit as levoketoconazole specific. This evidence further supports the use of levoketoconazole as an important treatment option for endogenous CS. Support: Strongbridge Biopharma.

A Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528, and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study.

Background: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. Results: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. Conclusion: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.

Baseline low-density lipoprotein cholesterol predicts the benefit of adding ezetimibe on statin in statin-na\xefve acute coronary syndrome

We aimed to evaluate the effect of baseline low-density lipoprotein cholesterol (LDL-C) on the outcomes of patients with the acute coronary syndrome (ACS) receiving pitavastatin monotherapy or the combination of pitavastatin + ezetimibe. In the HIJ-PROPER study, 1734 ACS patients with dyslipidemia were randomly assigned to receive pitavastatin or pitavastatin + ezetimibe therapy. Statin-naïve participants (n = 1429) were divided into two groups based on the median LDL-C level (131 mg/dL) at enrollment. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia-driven coronary revascularization. The median follow-up was 3.2 years. In the < 131 mg/dL group (n = 686), LDL-C changes were − 34.0% and − 49.8% in the pitavastatin monotherapy and pitavastatin + ezetimibe-treated groups (P < 0.0001), respectively; in the ≥ 131 mg/dL group (n = 743), LDL-C changes were − 42.9% and − 56.4% (P < 0.0001, respectively. Kaplan–Meier analyses revealed that the primary endpoint was not significantly different between the treatment groups for the < 131 mg/dL group, however, it was significantly lower in patients treated with pitavastatin + ezetimibe in the ≥ 131 mg/dL group (Hazard ratio = 0.72, 95% confidence interval = 0.56–0.91, P = 0.007, P value for interaction = 0.012). Statin-naïve ACS patients with baseline LDL-C < 131 mg/dL did not clinically benefit from pitavastatin + ezetimibe, while patients with baseline LDL-C ≥ 131 mg/dL treated with pitavastatin + ezetimibe showed better clinical results than those treated with pitavastatin monotherapy.Clinical Trial Registration: Original HIJ PROPER study; URL: http://www.umin.ac.jp/ctr. Unique Identifier; UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Low-density lipoprotein cholesterol lowering in real-world patients treated with evolocumab.

BackgroundLow‐density lipoprotein cholesterol (LDL‐C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real‐world data on LDL‐C lowering with evolocumab in United States clinical practice.HypothesisWe assessed LDL‐C lowering during 1 year of evolocumab therapy.MethodsThis retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus®) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL‐C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL‐C was calculated based on the lowest LDL‐C value recorded during a 12‐month follow‐up period.ResultsThe mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid‐lowering therapy. Following evolocumab treatment, changes in LDL‐C from baseline were −60% in the overall cohort (median [interquartile range (IQR)] 146 [115–180] mg/dL to 58 [36–84] mg/dL) and −65% in the recent MI subgroup (median [IQR] 137 [109–165] mg/dL to 48 [30–78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL‐C < 70 mg/dL, respectively.ConclusionsIn this real‐world analysis, evolocumab was associated with significant reductions in LDL‐C comparable to that seen in the FOURIER clinical trial, which were durable over 1 year of treatment.

Short-term trajectories of exercise-induced plasma lipid changes in overweight females, with a focus on HDL-cholesterol.

Increased levels of plasma lipoproteins are among some of the modifiable risk factors for cardiovascular disease (CVD). Dietary changes and increased physical activity are the most powerful non-pharmacological interventions for achieving optimal plasma lipid levels. To investigate the effect of an intensive short-term lifestyle intervention on plasma lipid trajectories in overweight non-diabetic females. A total of 202 healthy overweight (body mass index (BMI) >27.5 kg/m2) females underwent an intensive short-term (ten-week) intervention (at least 4 units of one-hour exercise activity weekly at optimal energy intake) aimed at lowering body weight. Plasma lipid (total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG)) levels were examined at baseline and every 2 weeks over the course of the ten-week intervention. There was a significant decrease in BMI (Δ -4.7%, p < 0.001) and body weight (Δ -4.9%, p < 0.001) after the intervention. Positive changes (decreases) in TC (Δ -8%, p < 0.001), TG (Δ -9%, p < 0.001) and LDL-C (Δ -11%, p < 0.001) were observed immediately after 2 weeks, but levels did not decrease further thereafter. In contrast, HDL-C did not increase as expected: after 2 weeks of intervention, we observed a significant decrease of about 6% (p < 0.001) followed by a slow return to baseline values. But even after 10 weeks of intervention, HDL-C values had not reached the values detected at baseline. In overweight females, HDL-C decreased after short-term intensive lifestyle intervention. To confirm the protective effect of increased physical activity, plasma lipids need to be examined over a longer time period.

Influences of Ketogenic Diet on Body Fat Percentage, Respiratory Exchange Rate, and Total Cholesterol in Athletes: A Systematic Review and Meta-Analysis.

(1) Background: The purpose of the current meta-analysis was to investigate any positive or negative effects of ketogenic diets in athletes and provide an assessment of the size of these effects. (2) Methods: Databases were used to select relevant studies up to January 2021 regarding the effects of ketogenic diets in athletes. Inclusion criteria were as follows: data before and after ketogenic diet use, being randomized controlled trials and presenting ketogenic diets and assessments of ketone status. Study subjects were required to be professional athletes. Review studies, pilot studies, and studies in which non-athletes were included were excluded from this meta-analysis. The outcome effect sizes in these selected studies were calculated by using the standardized mean difference statistic. (3) Results: Eight studies were selected for this meta-analysis. Athletes who consumed the ketogenic diet had reduced body fat percentages, respiratory exchange rates, and increased total cholesterol compared to athletes who did not consume this diet. However, body mass index, cardiorespiratory fitness, heart rate, HDL cholesterol, glucose level, and insulin level were unaffected by the diet. (4) Conclusions: Ketogenic diets had a beneficial effect by decreasing body fat percentage, but athletes with high total cholesterol level need to be monitored when instituting a ketogenic diet. Our study sample size was limited; therefore, additional studies may be needed to confirm the current findings. Further studies need to be conducted on changes in LDL cholesterol, HDL cholesterol, total cholesterol and ratio of LDL to HDL cholesterol.