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BackgroundLipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPLs) are each independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs predict coronary artery disease (CAD) severity and outcomes in a contemporary, statin-treated cohort is not well established.ObjectivesThis study sought to evaluate the relationships between Lp(a) particle concentration and OxPLs associated with apolipoprotein B (OxPL-apoB) or apolipoprotein(a) (OxPL-apo[a]) with angiographic CAD and cardiovascular outcomes.MethodsAmong 1,098 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study, Lp(a), OxPL-apoB, and OxPL-apo(a) were measured. Logistic regression estimated the risk of multivessel coronary stenoses by Lp(a)-related biomarker level. Cox proportional hazards regression estimated the risk of major adverse cardiovascular events (MACEs) (coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) in follow-up.ResultsMedian Lp(a) was 26.45 nmol/L (IQR: 11.39-89.49 nmol/L). Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R ≥0.91 for all pairwise combinations). Lp(a) and OxPL-apoB were associated with multivessel CAD. Odds of multivessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI: 1.03-1.18; P = 0.006), 1.18 (95% CI: 1.03-1.34; P = 0.01), and 1.07 (95% CI: 0.99-1.16; P = 0.07), respectively. All biomarkers were associated with cardiovascular events. HRs for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI: 1.03-1.14; P = 0.001), 1.15 (95% CI: 1.05-1.26; P = 0.004), and 1.07 (95% CI: 1.01-1.14; P = 0.02), respectively.ConclusionsIn patients undergoing coronary angiography, Lp(a) and OxPL-apoB are associated with multivessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident cardiovascular events. (Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868).

[Display omitted] [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPLs) are each independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs predict coronary artery disease (CAD) severity and outcomes in a contemporary, statin-treated cohort is not well established. This study sought to evaluate the relationships between Lp(a) particle concentration and OxPLs associated with apolipoprotein B (OxPL-apoB) or apolipoprotein(a) (OxPL-apo[a]) with angiographic CAD and cardiovascular outcomes. Among 1,098 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study, Lp(a), OxPL-apoB, and OxPL-apo(a) were measured. Logistic regression estimated the risk of multivessel coronary stenoses by Lp(a)-related biomarker level. Cox proportional hazards regression estimated the risk of major adverse cardiovascular events (MACEs) (coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) in follow-up. Median Lp(a) was 26.45 nmol/L (IQR: 11.39-89.49 nmol/L). Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R ≥0.91 for all pairwise combinations). Lp(a) and OxPL-apoB were associated with multivessel CAD. Odds of multivessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI: 1.03-1.18; P = 0.006), 1.18 (95% CI: 1.03-1.34; P = 0.01), and 1.07 (95% CI: 0.99-1.16; P = 0.07), respectively. All biomarkers were associated with cardiovascular events. HRs for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI: 1.03-1.14; P = 0.001), 1.15 (95% CI: 1.05-1.26; P = 0.004), and 1.07 (95% CI: 1.01-1.14; P = 0.02), respectively. In patients undergoing coronary angiography, Lp(a) and OxPL-apoB are associated with multivessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident cardiovascular events. (Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868) [Display omitted] [ABSTRACT FROM AUTHOR]

Background We asked whether, after excluding familial hypercholesterolemia, individuals with high low-density lipoprotein cholesterol ( LDL -C) or triacylglyceride levels and a family history of the same hyperlipidemia have greater coronary artery disease risk or different lipidomic profiles compared with population-based hyperlipidemias. Methods and Results We determined incident coronary artery disease risk for 755 members of 66 hyperlipidemic families (≥2 first-degree relatives with similar hyperlipidemia) and 19 644 Finnish FINRISK population study participants. We quantified 151 circulating lipid species from 550 members of 73 hyperlipidemic families and 897 FINRISK participants using mass spectrometric shotgun lipidomics. Familial hypercholesterolemia was excluded using functional LDL receptor testing and genotyping. Hyperlipidemias ( LDL -C or triacylglycerides >90th population percentile) associated with increased coronary artery disease risk in meta-analysis of the hyperlipidemic families and the population cohort (high LDL -C: hazard ratio, 1.74 [95% CI, 1.48-2.04]; high triacylglycerides: hazard ratio, 1.38 [95% CI, 1.09-1.74]). Risk estimates were similar in the family and population cohorts also after adjusting for lipid-lowering medication. In lipidomic profiling, high LDL -C associated with 108 lipid species, and high triacylglycerides associated with 131 lipid species in either cohort (at 5% false discovery rate; P-value range 0.038-2.3×10-56). Lipidomic profiles were highly similar for hyperlipidemic individuals in the families and the population ( LDL -C: r=0.80; triacylglycerides: r=0.96; no lipid species deviated between the cohorts). Conclusions Hyperlipidemias with family history conferred similar coronary artery disease risk as population-based hyperlipidemias. We identified distinct lipidomic profiles associated with high LDL -C and triacylglycerides. Lipidomic profiles were similar between hyperlipidemias with family history and population-ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms.

Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37-9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20-3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02-2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13-3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10-2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22-3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31-0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services. [ABSTRACT FROM AUTHOR]

Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37–9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20–3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02–2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13–3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10–2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22–3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31–0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services.

Abstract Background Heterogeneity should be carefully addressed to facilitate establishment of effective population-level blood lipid management. The primary aim of the study was to investigate gender heterogeneity in prevalence of dyslipidemia, including trends with age and associated factors in middle age rural Chinese. Methods This is a cross-sectional study based on a baseline investigation of a population-based randomized controlled trial in rural China, involving 26,378 permanent residents of age 45–69. The age-specific prevalence of dyslipidemia was estimated for men and women, and the trends of prevalence with age were compared. Logistic regression was used to explore the factors associated with prevalent risk of dyslipidemia. Results The overall prevalence of dyslipidemia was significantly higher in females than in males for borderline high and above (BHA) total cholesterol (TC ≥ 200 mg/dL), BHA triglycerides (TG ≥ 150 mg/dL) and BHA low-density lipoprotein cholesterol (LDL-C ≥ 130 mg/dL), but was lower for low high-density lipoprotein cholesterol (HDL-C

ObjectivesThe aim of this study was to determine the associations between statin use and major adverse cardiovascular and cerebrovascular events (MACCE) and amputation-free survival in critical limb ischemia (CLI) patients.BackgroundCLI is an advanced form of peripheral arterial disease associated with nonhealing arterial ulcers and high rates of MACCE and major amputation. Although statin medications are recommended for secondary prevention in peripheral arterial disease, their effectiveness in CLI is uncertain.MethodsWe reviewed 380 CLI patients who underwent diagnostic angiography or therapeutic endovascular intervention from 2006 through 2012. Propensity scores and inverse probability of treatment weighting were used to adjust for baseline differences between patients taking and not taking statins.ResultsStatins were prescribed for 246 (65%) patients. The mean serum low-density lipoprotein (LDL) level was lower in patients prescribed statins (75 ± 28 mg/dl vs. 96 ± 40 mg/dl, p < 0.001). Patients prescribed statins had more baseline comorbidities including diabetes, coronary artery disease, and hypertension, as well as more extensive lower extremity disease (all p values 130 mg/dl had increased HRs of MACCE and mortality compared with patients with lower levels of LDL.ConclusionsStatins are associated with lower rates of mortality and MACCE and increased amputation-free survival in CLI patients.

There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort. The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression. Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors, a higher eosinophil count was associated with lower HDL cholesterol and apolipoprotein A-I concentration (p < 0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p < 0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p < 0.001). In the longitudinal analysis, lipoprotein(a) was inversely associated with basophil count in men but not women (p < 0.001). Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leukogenesis. However, unlike in murine models, the remainder of these relationships is modest, which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans. Image 1 • Triglycerides are a robust predictor of total and differential leukocyte counts. • HDL cholesterol and apolipoprotein A-I are inversely associated with eosinophil count. • Apolipoprotein B is positively associated with lymphocyte count. • Total and LDL cholesterol predicts lymphocyte count in longitudinal analysis. • Lipoprotein(a) shows no longitudinal relationship with leukocyte counts. [ABSTRACT FROM AUTHOR]

Background Prevalence of cardiovascular disease risk factors and rates of atherosclerotic cardiovascular disease outcomes vary across racial/ethnic groups. This analysis examined the effects of evolocumab on LDL‐C (low‐density lipoprotein cholesterol) levels and LDL‐C goals achievement by race/ethnicity. Methods and Results Data from 15 phase 2 and 3 studies of treatment with evolocumab versus placebo or ezetimibe were pooled (n=7669). Results were analyzed by participant clinical characteristics and by self‐identified race/ethnicity. Key outcomes included percent change from baseline in LDL‐C, achievement of LDL‐C

Background Dyslipidemia guidelines recommend non‐high‐density lipoprotein cholesterol (non‐HDL‐C) and apolipoprotein B (ApoB) as additional targets of therapy and consider lipoprotein(a) a significant cardiovascular risk marker. The current analysis evaluates the effects of evolocumab on these parameters in various patient populations over time. Methods and Results Data from 7690 patients, 4943 of whom received at least 1 dose of evolocumab, in 15 phase 2 and phase 3 studies with a duration ranging from 12 weeks to 5 years were pooled based on study length, patient population, and ezetimibe or placebo comparator groups. Patients could receive intensive statin therapy but not in the statin intolerance and monotherapy studies. The effects of evolocumab on percent change from baseline for non‐HDL‐C, ApoB, and lipoprotein(a) and achievement of treatment goals for non‐HDL‐C and ApoB were examined. Compared with placebo, evolocumab at both approved dosing regimens substantially reduced mean non‐HDL‐C (Q2W dose: −49% to −56%, monthly dose: −48% to −52%), mean ApoB (Q2W dose: −46% to −52%, monthly dose: −40% to −48%), and median lipoprotein(a) (Q2W dose: −22% to −38%, monthly dose: −20% to −33%) at 12 weeks. Effects on all 3 parameters persisted over 5 years. Lipid‐lowering effects were consistent among the patient populations examined (hypercholesterolemia/mixed dyslipidemia, statin intolerance, heterozygous familial hypercholesterolemia, and type 2 diabetes mellitus). Conclusions In this pooled analysis, evolocumab substantially reduced non‐HDL‐C, ApoB, and lipoprotein(a) compared with placebo. The effect was consistent and maintained in various patient populations over 5 years.

Caveolin-3 (Cav-3) is an essential scaffolding protein for caveolae formation in cardiomyocytes and targets multiple long QT syndrome (LQTS)-associated ion channels. Mutations in CAV3 have caused an LQT3-like accentuation in late sodium current, I Na (Nav1.5). Here, we characterize a novel CAV3-V37L variant and determine whether it is the substrate for the patient's LQTS. The proband was a 39-year-old female with drug-induced, sudden cardiac arrest (SCA) with profound QT prolongation (QTc > 600 ms). Genetic testing revealed a rare CAV3-V37L variant of uncertain significance (VUS). Whole-cell patch clamp technique was used to measure I Ks , I Kr , I Na , and I Ca, L currents co-expressed with either CAV3-WT or CAV3-V37L in TSA201 cells and to measure the action potential duration (APD) in control human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) overexpressed with CAV3-WT or CAV3-V37L. CAV3-V37L did not affect Nav1.5 late current. Instead, CAV3-V37L resulted in 1) I Ca, L with slower inactivation, a 1.5 fold increase in peak I Ca, L current density and a 1.1 fold increase in I Ca, L persistent current, 2) dramatically reduced I Ks peak current density by 74.9%, 3) significantly reduced I Kr peak current density by 31.1%, and 4) significantly prolonged the APD in hiPSC-CMs. These functional validation assays enabled the promotion of CAV3-V37L from VUS status to a likely pathogenic variant. Although Nav1.5 was spared, this monogenetic insult precipitated an oligo-proteomic impact with a concomitant gain-of-function of I Ca, L and loss-of-function of both I Ks and I Kr culminating in a marked prolongation of the cardiomyocyte's action potential duration. • Cav3-V37L did not increase Nav1.5 (SCN5A) late current. • CAV3-V37L increased I Ca, L inactivation tau, peak, and persistent current. • CAV3-V37L dramatically reduced the I Ks current and reduced I Kr peak current. • CAV3-V37L reduced intensity of CAV3 on the membrane and co-localization with Cav1.2 channel. • CAV3-V37L prolonged APD50 and APD90 when overexpressed in control hiPSC-CMs. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity should be carefully addressed to facilitate establishment of effective population-level blood lipid management. The primary aim of the study was to investigate gender heterogeneity in prevalence of dyslipidemia, including trends with age and associated factors in middle age rural Chinese. Methods: This is a cross-sectional study based on a baseline investigation of a population-based randomized controlled trial in rural China, involving 26,378 permanent residents of age 45–69. The age-specific prevalence of dyslipidemia was estimated for men and women, and the trends of prevalence with age were compared. Logistic regression was used to explore the factors associated with prevalent risk of dyslipidemia. Results: The overall prevalence of dyslipidemia was significantly higher in females than in males for borderline high and above (BHA) total cholesterol (TC ≥ 200 mg/dL), BHA triglycerides (TG ≥ 150 mg/dL) and BHA low-density lipoprotein cholesterol (LDL-C ≥ 130 mg/dL), but was lower for low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL) in females than the corresponding prevalence in males. The prevalence of borderline high and above TC, TG and LDL-C all rose with age in females, but was stable or even decreased with age in males. In contrast, graphic representation of the prevalence of low HDL-C showed no striking age related trend in both genders. Risk of dyslipidemia was associated predominantly with obesity in males, but was more predominantly associated with hypertension in females. Conclusion: Heterogeneity was found in comparing the prevalence of dyslipidemia in men and women, and gender heterogeneity was found in its trend with age and associated factors in middle aged rural Chinese. The effectiveness of population-level blood lipid management and CVD primary prevention programs in China is expected to be improved if gender heterogeneity is considered. [ABSTRACT FROM AUTHOR]

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low‐density lipoprotein‐cholesterol (LDL‐C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. Material and Methods: Twelve male patients with T2DM on an intensive insulin regimen completed a 6‐week randomized, double‐blind, placebo‐controlled, proof‐of‐concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change −24.7%; P = 0.018) and fasting apoB48 serum levels (−35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (−26.4%; P = 0.006) and apoB48 AUC (−55.7%; P = 0.046), as well as plasma TG incremental AUC (−21.4%; P = 0.04) and apoB48 incremental AUC (−26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low‐density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions: In addition to the well‐known LDL‐C‐reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants. [ABSTRACT FROM AUTHOR]

Although individual lipid parameters have been frequently examined in association with asymptomatic intracranial arterial stenosis (aICAS), few population-based studies have investigated the lipid profiles associated with aICAS among Chinese adults. This study aims to characterize the lipid profiles associated with aICAS in rural-dwelling adults in China. This population-based study included 2027 persons who were aged ≥40 years and free of stroke. Data were collected via interviews, clinical examinations, and laboratory testing. We diagnosed aICAS by integrating transcranial color Doppler with magnetic resonance angiography. Data were analyzed using binary and multinomial logistic regression models. Of the 2027 participants, 154 were detected with aICAS. The multiadjusted odds ratio (95% confidence interval) of aICAS was 1.41 (0.997–2.00) for high small dense low-density lipoprotein cholesterol, 1.44 (1.02–2.04) for high lipoprotein(a), 1.71 (1.21–2.44) for low apolipoprotein A-1, 1.43 (1.00–2.04) for low high-density lipoprotein cholesterol (HDL-C), 1.61 (1.14–2.27) for high apolipoprotein B/apolipoprotein A-1 ratio, 1.95 (1.38–2.76) for high low-density lipoprotein cholesterol/HDL-C ratio, and 1.51 (1.06–2.14) for high total cholesterol/HDL-C ratio. When severity of aICAS was analyzed, high levels of lipoprotein(a), small dense low-density lipoprotein cholesterol, and lipid ratios were significantly associated with an increased likelihood of moderate-to-severe aICAS (P <.05). An increasing number of abnormal lipid measurements was associated with an increased likelihood of aICAS (P for trend <.001). These findings suggest that lipid profiles for aICAS among rural residents in China are characterized by high atherogenic cholesterol, low antiatherogenic cholesterol, and high ratios of atherogenic-to-antiatherogenic cholesterol or lipoproteins. • We explore lipids associated with asymptomatic intracranial arterial stenosis (aICAS). • Lipid profiles for aICAS are high atherogenic and low antiatherogenic lipids. • Having more abnormal lipid measurements is related to a higher likelihood of aICAS. [ABSTRACT FROM AUTHOR]

Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participants (mean age, 66±9 years; 55% women) who attended their eighth examination cycle and underwent routine echocardiography and liquid chromatography–tandem mass spectrometry–based assays for circulating ceramide concentrations. We used multivariable linear regression models to relate C16:0/C24:0 (independent variable) to the following echocardiographic measures (dependent variables; separate models for each): left ventricular mass, left ventricular ejection fraction, left atrial emptying fraction, left atrial end‐systolic volume, E/e′ (a measure of left ventricular diastolic function), and left ventricular global circumferential and longitudinal strain by speckle‐tracking echocardiography. In multivariable‐adjusted analyses, higher C16:0/C24:0 per standard deviation increment was associated with lower left ventricular ejection fraction (0.991‐fold change in left ventricular ejection fraction; P=0.0004), worse global circumferential strain (β=0.34, P=0.004), higher left atrial end‐systolic volume (β=2.48, p

Background Apolipoprotein B/apolipoprotein A‐I (apoB/apoA‐I) ratio and lipoprotein(a) (Lp[a]) are associated with aortic valve stenosis (AVS) disease progression. Clinical characteristics such as age, sex, and presence of concomitant coronary artery disease may strongly modify these associations; however, these effects have not been well defined in longitudinal studies. We set out to assess these associations between apoB/apoA‐I ratio, Lp(a), and AVS incidence in a large population study. Methods and Results We analyzed data from 17 745 participants (mean age, 59.2±9.1 years; men, 44.9%) in the EPIC‐Norfolk (European Prospective Investigation Into Cancer in Norfolk Prospective Population Study) population study in whom apoB/apoA‐I and Lp(a) levels were measured. Participants were identified as having incident AVS if they were hospitalized or died with AVS as an underlying cause. After a median follow‐up of 19.8 years (17.9–21.0 years) there were 403 (2.2%) incident cases of AVS. The hazard ratio for AVS risk was 1.30 (95% CI, 1.19–1.41; P50 mg/dL) remained an independent risk factor for AVS after adjustment for age, sex, low‐density lipoprotein cholesterol, and concomitant coronary artery disease (hazard ratio, 1.70; 95% CI, 1.33–2.19 [P

Background We asked whether, after excluding familial hypercholesterolemia, individuals with high low‐density lipoprotein cholesterol (LDL‐C) or triacylglyceride levels and a family history of the same hyperlipidemia have greater coronary artery disease risk or different lipidomic profiles compared with population‐based hyperlipidemias. Methods and Results We determined incident coronary artery disease risk for 755 members of 66 hyperlipidemic families (≥2 first‐degree relatives with similar hyperlipidemia) and 19 644 Finnish FINRISK population study participants. We quantified 151 circulating lipid species from 550 members of 73 hyperlipidemic families and 897 FINRISK participants using mass spectrometric shotgun lipidomics. Familial hypercholesterolemia was excluded using functional LDL receptor testing and genotyping. Hyperlipidemias (LDL‐C or triacylglycerides >90th population percentile) associated with increased coronary artery disease risk in meta‐analysis of the hyperlipidemic families and the population cohort (high LDL‐C: hazard ratio, 1.74 [95% CI, 1.48–2.04]; high triacylglycerides: hazard ratio, 1.38 [95% CI, 1.09–1.74]). Risk estimates were similar in the family and population cohorts also after adjusting for lipid‐lowering medication. In lipidomic profiling, high LDL‐C associated with 108 lipid species, and high triacylglycerides associated with 131 lipid species in either cohort (at 5% false discovery rate; P‐value range 0.038–2.3×10−56). Lipidomic profiles were highly similar for hyperlipidemic individuals in the families and the population (LDL‐C: r=0.80; triacylglycerides: r=0.96; no lipid species deviated between the cohorts). Conclusions Hyperlipidemias with family history conferred similar coronary artery disease risk as population‐based hyperlipidemias. We identified distinct lipidomic profiles associated with high LDL‐C and triacylglycerides. Lipidomic profiles were similar between hyperlipidemias with family history and population‐ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms.

Background Although acute coronary syndromes (ACS) are a major cause of morbidity and mortality, relationships with biologically active lipid species potentially associated with plaque disruption/erosion in the context of their lipoprotein carriers are indeterminate. The aim was to characterize lipid species within lipoprotein particles which differentiate ACS from stable coronary artery disease. Methods and Results Venous blood was obtained from 130 individuals with de novo presentation of an ACS (n=47) or stable coronary artery disease (n=83) before coronary catheterization. Lipidomic measurements (533 lipid species; liquid chromatography electrospray ionization/tandem mass spectrometry) were performed on whole plasma as well as 2 lipoprotein subfractions: apolipoprotein A1 (apolipoprotein A, high‐density lipoprotein) and apolipoprotein B. Compared with stable coronary artery disease, ACS plasma was lower in phospholipids including lyso species and plasmalogens, with the majority of lipid species differing in abundance located within high‐density lipoprotein (high‐density lipoprotein, 113 lipids; plasma, 73 lipids). Models including plasma lipid species alone improved discrimination between the stable and ACS groups by 0.16 (C‐statistic) compared with conventional risk factors. Models utilizing lipid species either in plasma or within lipoprotein fractions had a similar ability to discriminate groups, though the C‐statistic was highest for plasma lipid species (0.80; 95% CI, 0.75–0.86). Conclusions Multiple lysophospholipids, but not cholesterol, featured among the lipids which were present at low concentration within high‐density lipoprotein of those presenting with ACS. Lipidomics, when applied to either whole plasma or lipoprotein fractions, was superior to conventional risk factors in discriminating ACS from stable coronary artery disease. These associative mechanistic insights elucidate potential new preventive, prognostic, and therapeutic avenues for ACS which require investigation in prospective analyses.

We aimed to investigate blood lipid and lipoprotein profiles in patients with dyslipidemia receiving hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) after 8 weeks of omega-3 fatty acid ethyl esters (Omega-3) treatment, using high-performance liquid chromatography with highly-sensitive gel filtration columns. In this phase 4, randomized, open-label study, patients with dyslipidemia receiving statins were randomized 1:1 to Omega-3 treatment (oral Omega-3 2 g twice daily) or Control (no Omega-3). Primary endpoint was change in mean particle size of low-density lipoprotein (LDL) and small dense LDL (cholesterol monitoring) in the specific 20-lipoprotein fraction assay. Secondary endpoints included changes in lipids, apolipoproteins, and lipoprotein concentrations in fasting blood. Changes were compared between treatments using analysis of covariance, adjusted by baseline fasting triglycerides and age. Fifty-three patients were randomized (Omega-3, n = 24; Control, n = 29). The difference in LDL particle size between Omega-3 and Control groups was significant at week 8 (p = 0.0040). Differences in least squares mean change in concentration from baseline to week 8 between Omega-3 and Control groups were significant for total cholesterol (p = 0.0009), LDL-C (p = 0.0442), non-high-density lipoprotein cholesterol (p = 0.0009), and remnant lipoprotein-cholesterol (p = 0.0396). Differences were significant for apolipoproteins AI, AII, B, B-48, B-100, CII, CIII, and CII/III, but not apolipoprotein E. Significant increases in LDL particle sizes and significant decreases in blood lipid, lipoprotein and apolipoprotein concentrations were observed with Omega-3 compared with Control. Omega-3 may improve blood lipid profile and increase LDL particle size, resulting in an anti-atherogenic profile. Image 1 • Dyslipidemia patients received omega-3 fatty acid ethyl esters or no treatment. • Low-density lipoprotein (LDL) particle sizes increased in treated patients. • Blood lipid concentrations decreased in treated patients. • Lipoprotein and apolipoprotein concentrations decreased in treated patients. • Serum lipid profile and LDL particle size may improve in treated patients. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that elevated cholesterol results in increased white blood cell counts in mouse models. However, there is insufficient evidence to support this in humans. The objective of the study was to investigate the relationship of plasma lipids with white blood cell counts (basophils, eosinophils, monocytes, neutrophils and lymphocytes) in the Multi-Ethnic Study of Atherosclerosis. The analysis included 2873 Multi-Ethnic Study of Atherosclerosis participants with a complete white blood count and differential analysis. The cross-sectional association of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels with different white blood cell counts was analyzed by multivariable linear regression. After adjusting for sociodemographic and confounding factors including red blood cell counts, platelet counts, use of lipid-lowering medication, cardiovascular disease risk factors and other lipid measures, and multiple testing correction, a one–standard deviation increment in total cholesterol and low-density lipoprotein cholesterol was associated with 2.8% and 2.3% lower total white blood cell counts, 3.7% and 3.0% lower monocyte counts, and 3.4% and 2.7% lower neutrophil counts (all P <.01). The same increment in logarithm-transformed triglyceride levels was associated with 2.3% higher total white blood cell counts and 4.5% higher lymphocyte counts (both P <.001). Similar results were obtained after excluding participants taking lipid-lowering medication. A one–standard deviation increase in high-density lipoprotein cholesterol was associated with a 1.5% lower white blood cell count (P =.018) but was not significantly associated with changes in any individual cell type. While significant associations were observed between plasma lipid levels and white blood cell populations, the heterogeneous and modest nature of these relationships makes it hard to support the hypothesis that lipids are in the causal pathway for leukogenesis in humans. [ABSTRACT FROM AUTHOR]

Background The relation between tea consumption and age‐related changes in high‐density lipoprotein cholesterol (HDL‐C) concentrations remains unclear, and longitudinal human data are limited. The aim of current study was to examine the relation between tea intake and longitudinal change in HDL‐C concentrations. Methods and Results Baseline (2006) tea consumption was assessed via a questionnaire, and plasma HDL‐C concentrations were measured in 2006, 2008, 2010, and 2012 among 80 182 individuals (49±12 years of age) who did not have cardiovascular diseases or cancer, or did not use cholesterol‐lowering agents both at baseline (2006) and during the follow‐up period (2006–2012). The associations between baseline tea consumption and rate of change in HDL‐C concentrations were examined using generalized estimating equation models. Tea consumption was inversely associated with a decreased rate of HDL‐C concentrations (P‐trend

BackgroundOur objective was to identify the determinants of high‐density lipoprotein cholesterol efflux capacity (HDL‐CEC) changes in patients with coronary artery disease who participated in a lifestyle modification program aimed at increasing physical activity levels and improving diet quality. Methods and ResultsA total of 86 men with coronary artery disease aged between 35 and 80 years participated in a 1‐year lifestyle modification program that aimed to achieve a minimum of 150 minutes of aerobic physical activity weekly and improve diet quality. HDL‐CECs were measured before and after the 1‐year intervention using 3H‐cholesterol–labeled J774 and HepG2 cells. Visceral, subcutaneous, and cardiac adipose tissue levels were assessed before and after the intervention using magnetic resonance imaging. Lipoprotein particle size and concentrations were measured by proton nuclear magnetic resonance spectroscopy and a complete lipoprotein‐lipid profile was obtained. At baseline, the best correlate of HDL‐CECs were apolipoprotein AI (R2=0.35, P

Elevated oxidized low-density lipoprotein (ox-LDL) and cell adhesion molecules are associated with inflammation and atherosclerosis. The role of exercise in circulating ox-LDL, enzyme mediators, and cell adhesion molecules are not clearly understood in obesity. As a randomized controlled design, 27 obese (BMI > 30 kg/m²) sedentary men (N = 13) and women (N = 14) were randomly assigned to either an exercise (N = 15) or a control (N = 12) group. The exercise group performed a 60-min supervised treadmill exercise at moderate intensity (70 % of HRmax) for 3 days per week for 4 weeks, while the control group did not exercise. Overnight fasting blood samples were collected before and after the study period to analyze serum lipids, lipoprotein-cholesterol, ox-LDL, 12- and 15-lipoxygenases, myeloperoxidase (MPO), and soluble vascular cell adhesion molecules-1 and intercellular adhesion molecule-1. Moderate- intensity exercise training lowered both ox-LDL (from 44.76 ± 1.99 to 38.51 ± 1.99 U/L, p = 0.032) and MPO (from 31.48 ± 2.20 to 23.09 ± 2.20 ng/mL, p = 0.010), without significantly altering body weight, other parameters of serum lipids and lipoproteins, or soluble cell adhesion molecules. Moderate intensity exercise training reduced the levels of ox-LDL and MPO, indicating a reduced risk for developing CVD and additional protection to the possible metabolic complications associated with obesity. [ABSTRACT FROM AUTHOR]

BackgroundConsumption of almonds or dark chocolate and cocoa has favorable effects on markers of coronary heart disease; however, the combined effects have not been evaluated in a well‐controlled feeding study. The aim of this study was to examine the individual and combined effects of consumption of dark chocolate and cocoa and almonds on markers of coronary heart disease risk. Methods and ResultsA randomized controlled, 4‐period, crossover, feeding trial was conducted in overweight and obese individuals aged 30 to 70 years. Forty‐eight participants were randomized, and 31 participants completed the entire study. Each diet period was 4 weeks long, followed by a 2‐week compliance break. Participants consumed each of 4 isocaloric, weight maintenance diets: (1) no treatment foods (average American diet), (2) 42.5 g/d of almonds (almond diet [ALD]), (3) 18 g/d of cocoa powder and 43 g/d of dark chocolate (chocolate diet [CHOC]), or (4) all 3 foods (CHOC+ALD). Compared with the average American diet, total cholesterol, non–high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol after the ALD were lower by 4%, 5%, and 7%, respectively (P

BackgroundLevels of LDL (low‐density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid‐related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (

The apolipoprotein E-deficient ( apoE-/-) mouse model has advanced our understanding of cardiovascular disease mechanisms and experimental therapeutics. This spontaneous model recapitulates aspects of human atherosclerosis, and allows for the development of dissecting abdominal aortic aneurysms (AAAs) when combined with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar to mice, they would develop dissecting AAAs. We created rats with a 16-bp deletion of the apoE gene using transcription activator-like effector nucleases. We imaged the suprarenal aorta for 28 days after implantation of miniosmotic pumps that infuse angiotensin II (AngII, 200 ng/kg/min). Blood pressure (BP), serum lipids and lipoproteins, and histology were also analyzed. These rats did not develop pathological aortic dissection, but we did observe a decrease in circumferential cyclic strain, a rise in BP, and microstructural changes in the aortic medial layer. We also measured increased serum lipids with and without administration of a high-fat diet, but did not detect atherosclerotic plaques. Chronic infusion of AngII did not lead to the formation of dissecting AAAs or atherosclerosis in the rats used in this study. While reduced amounts of atherosclerosis may explain this resistance to dissecting aneurysms, further investigation is needed to fully characterize species-specific differences. [ABSTRACT FROM AUTHOR]

BackgroundCurrent recommendations for lipoprotein(a) (Lp[a]) focus on the control of other risk factors, including lowering low‐density lipoprotein cholesterol (LDL‐C), with little evidence to support this approach. Identifying interactions between Lp(a) and other risk factors could identify individuals at increased risk for Lp(a)‐mediated disease. Methods and ResultsWe used a case‐only study design and included 939 participants (median age=49 years, interquartile range 46–53, women=33.1%) from the GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond‐Premature Acute Coronary Syndrome (GENESIS‐PRAXY) study, a multicenter prospective cohort study of premature acute coronary syndrome. There was a higher prevalence of elevated Lp(a) levels (>50 mg/dL; 80th percentile) in PRAXY participants as compared to the general population (31% versus 20%; P2.5 mmol/L, indicating a synergistic interaction (adjusted odds ratio 1.51; 95% CI 1.08–2.09; P=0.015). The interaction with high Lp(a) was stronger at increasing LDL‐C levels (LDL‐C >3.5, adjusted odds ratio 1.87; LDL‐C >4.5, adjusted odds ratio 2.72). In a polytomous logistic model comparing mutually exclusive LDL‐C categories, the interaction with high Lp(a) became attenuated at LDL‐C ≤3.5 mmol/L (odds ratio 1.16; 95% CI 0.80–1.68, P=0.447). Other risk factors were not associated with high Lp(a). ConclusionsIn young acute coronary syndrome patients, high Lp(a) is more prevalent than in the general population and is strongly associated with high LDL‐C, suggesting that Lp(a) confers greater risk for acute coronary syndrome when LDL‐C is elevated. Individuals with high Lp(a) and LDL‐C >3.5 mmol/L may warrant aggressive LDL‐C lowering.

Acyl-CoA:cholesterol acyltransferase 2 (ACAT2) generates cholesterol esters (CE) for packaging into newly synthesized lipoproteins and thus is a major determinant of blood cholesterol levels. ACAT2 is expressed exclusively in the small intestine and liver, but the relative contributions of ACAT2 expression in these tissues to systemic cholesterol metabolism is unknown. We investigated whether CE derived from the intestine or liver would differentially affect hepatic and plasma cholesterol homeostasis. We generated liver-specific (ACAT2L−/L−) and intestine-specific (ACAT2SI−/SI−) ACAT2 knockout mice and studied dietary cholesterol-induced hepatic lipid accumulation and hypercholesterolemia. ACAT2SI−/SI− mice, in contrast to ACAT2L−/L− mice, had blunted cholesterol absorption. However, specific deletion of ACAT2 in the intestine generated essentially a phenocopy of the conditional knockout of ACAT2 in the liver, with reduced levels of plasma very low-density lipoprotein and hepatic CE, yet hepatic-free cholesterol does not build up after high cholesterol intake. ACAT2L−/L− and ACAT2SI−/SI− mice were equally protected from diet-induced hepatic CE accumulation and hypercholesterolemia. These results suggest that inhibition of intestinal or hepatic ACAT2 improves atherogenic hyperlipidemia and limits hepatic CE accumulation in mice and that depletion of intestinal ACAT2 is sufficient for most of the beneficial effects on cholesterol metabolism. Inhibitors of ACAT2 targeting either tissue likely would be beneficial for atheroprotection.

Background--SR-B1 (scavenger receptor class B type 1), encoded by the gene SCARB1, is a lipoprotein receptor that binds both high-density lipoprotein (HDL) and low-density lipoprotein. We reported that SR-B1 is also a receptor for lipoprotein (a) (Lp(a)), mediating cellular uptake of Lp(a) in vitro and promoting clearance of Lp(a) in vivo. Although genetic variants in SCARB1 are associated with variations in HDL level, no SCARB1 variants affecting Lp(a) have been reported. Methods and Results--In an index subject with high levels of HDL cholesterol and Lp(a), SCARB1 was sequenced and demonstrated a missense mutation resulting in an S129L substitution in exon 3. To follow up, 2 cohorts (GeneSTAR, the family-based Genetic Study of Atherosclerosis Risk [n=543], and CCHS, the population-based Copenhagen City Heart Study [n=5835]) were screened for combined HDL cholesterol and Lp(a) elevations. Subjects with the extreme phenotype (HDL >80 mg/dL and Lp(a) >100 nmol/L in GeneSTAR, n=8, and >100 mg/dL in CCHS, n=9) underwent sequencing of SCARB1 exons; 15 of 18 from the combined population demonstrated genetic variants, including rare or uncommon missense or splice site mutations in 9 and homozygous synonymous variants in 6. Functional studies with 4 of the SCARB1 variants (c.386C>T, c.631-14T>G, c.4G>A, and c.631-53mC>T & c.726+55mCG>CA) showed decreased receptor function in vitro. Conclusions--Human SCARB1 gene variants are associated with a new lipid phenotype, characterized by high levels of both HDL cholesterol and Lp(a). SCARB1 exonic variants often result in diminished function of translated SR-B1 via reduced binding/intracellular transport of Lp(a). [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is associated with chronic cardiovascular disease. However, the effect of dyslipidemia on acute ischemic stroke is unclear. We hypothesized that dyslipidemia could contribute to early neurological deterioration (END) after ischemic stroke.Methods: A total of 410 acute ischemic stroke patients who were admitted to our stroke center within 24 hours after ictus were consecutively included in this study. END was defined as any new neurological symptoms/signs or any neurological worsening occurring during the admission and/or within 3 weeks after the index stroke. Multivariable logistic regression was used to examine the independent association between lipid indices and END.Results: Mean age was 68.2 ± 13.3 years, 241 (58.8%) were male, and 78 (19.0%) experienced END. Almost END occurred within 3 days after admission (n = 70, 89.7%), and the majority of END was stroke progression (n = 68, 87.1%). In univariate analysis, high-density lipoprotein (HDL)-cholesterol levels (per 1 mmol/L; odds ratio [OR] .37; 95% CI .17-.80; P = .012) and apolipoprotein B (apoB)/apoA-I ratio (per 1 increase; OR 3.71; 95% CI 1.48-9.29; P = .005) were associated with END. In the multivariable analysis, adjusted ORs of END for the highest quartile of HDL-cholesterol and apoB/apoA-I ratio were .42 (95% CI .19-.94; P = .034) and 2.37 (95% CI 1.02-5.53; P = .045), respectively. The ratio of apoB/apoA-I was associated with END in large artery atherosclerosis stroke but not in other stroke subtypes.Conclusions: Independent association of low HDL-cholesterol and high apoB/apoA-I ratio with END warrants further research to investigate if correction of the lipid profile during the acute period of ischemic stroke could reduce the risk of END. [ABSTRACT FROM AUTHOR]

Background: Persons with spinal cord injury (SCI) often have low levels of physical activity, which predispose to increased adiposity and decreased high density lipoprotein cholesterol (HDL-C) concentrations, and, generally, normal low density lipoprotein cholesterol (LDL-C) concentrations. In spite of the mixed lipoprotein profile, the SCI population has been reported to have an elevated risk of cardiovascular-related morbidity and mortality. Nuclear magnetic resonance spectroscopy may permit a more precise quantification of lipoprotein particle (P) species, enabling a more accurate inference of risk for cardiovascular disease (CVD) in the SCI population. Methods: Fasting blood samples were obtained on 83 persons with chronic SCI and 62 able-bodied (AB) subjects. Fasting plasma insulin (FPI), triglycerides (TG), and P number and size of VLDL (very low density lipoprotein), LDL, and HDL subclasses were determined. AB and SCI subjects were stratified based on HDL-C (i.e., Low <40 and Normal ≥40 mg/dl): AB-Normal (n = 48), AB-Low (n = 14), SCI-Normal (n = 49), and SCI-Low (n = 34). Factorial analyses of variance were performed to identify group differences in lipoprotein measurements. Pearson correlations were performed between the number of P by lipoprotein subclass, size, FPI, and TG. Results: The SCI-Normal group was not significantly different from the AB-Normal group for body composition, FPI, TG or LP-IR and had negligible differences in the lipoprotein P profile, except for fewer number and smaller size of HDL-P. The SCI-Low group had a similar lipoprotein profile to that of the AB-Low group, but with a lipid P composition associated with a heightened atherogenic risk and greater tendency toward insulin resistance by the Lipoprotein-Insulin Resistance (LP-IR) score. In the SCI-Low group, the decreased number and reduced size of lipoprotein P were more prevalent and may be associated with increased waist circumference (i.e., abdominal adiposity), relatively elevated TG values (compared to the other subgroups), and an underlying subclinical state of insulin resistance. Conclusions: Prolonged sitting and restricted physical activity in individuals with SCI had the most profound effect on the HDL-C and its lipoprotein P subclasses, but not on LDL-C, however its P subclasses were also unfavorably affected but not to the same degree. The quantification of lipoprotein P characteristics may be a potent tool for the determination of risk for CVD in persons with SCI. [ABSTRACT FROM AUTHOR]

Aims: LDL cholesterol (LDL-C) is the current lipid standard for cardiovascular disease (CVD)-risk assessment in type 1 diabetes. Apolipoprotein B (apoB) may be helpful to further stratify CVD risk. We explored the association between apoB and pulse wave velocity (PWV) to determine if apoB would improve CVD-risk stratification, especially in type 1 diabetes adolescents with borderline LDL-C (100-129 mg/dL). We hypothesized that type 1 diabetes adolescents with borderline LDL-C and elevated apoB (≥90 mg/dL) would have increased PWV compared to those with borderline LDL-C and normal apoB (<90 mg/dL), and that apoB would explain more of the variability of PWV than alternative lipid indices. Methods: Fasting lipids, including apoB, were collected in 267 adolescents, age 12-19 years, with diabetes duration >5 years and HbA1c 8.9 ± 1.6 %. Triglyceride to HDL-C ratio (TG/HDL-C) and nonHDL-cholesterol (nonHDL-C) were calculated. PWV was measured in the carotid-femoral segment. Results: ApoB, nonHDL-C and TG/HDL-C correlated with PWV ( p < 0.0001). ApoB, nonHDL-C and TG/HDL-C remained significantly associated with PWV in fully adjusted models. In adolescents with borderline LDL-C ( n = 61), PWV was significantly higher in those with elevated apoB than in those with normal apoB (5.6 ± 0.6 vs. 5.2 ± 0.6 m/s, p < 0.01) and also remained significant after adjustment for CVD-risk factors ( p = 0.0002). Moreover, in those with borderline LDL-C, apoB explained more of the variability of PWV than nonHDL-C and TG/HDL-C. Conclusion: Elevated apoB is associated with increased arterial stiffness in type 1 diabetes adolescents. Measurement of apoB in addition to LDL-C may be helpful in stratifying CVD risk in type 1 diabetes adolescents, especially in those with borderline LDL-C. [ABSTRACT FROM AUTHOR]

The effect of severity of liver cirrhosis, an alcoholic and non-alcoholic genesis, on the results of serum lipids and lipoproteins was evaluated. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-Ch), and low-density lipoprotein cholesterol (LDL-Ch) were measured in the sera of 59 patients suffering from alcoholic cirrhosis and 34 patients with non-alcoholic cirrhosis. The level of serum triglycerides depends on the severity of liver damage in alcoholic liver cirrhosis, being the highest in Child-Pugh score B. The severity of liver damage significantly affects the HDL-Ch and LDL-Ch levels in cirrhosis of non-alcoholic origin, reaching the highest value for LDL-Ch and the lowest for HDL-Ch in score C. It should not be generalized that the levels of lipids and lipoproteins in liver cirrhosis progressively diminished with the deterioration of liver function. The serum HDL-Ch and LDL-Ch may be considered as markers of severity of liver damage in non-alcoholic cirrhosis, but the triglycerides only in disease of alcoholic origin. [ABSTRACT FROM AUTHOR]

The current study examined the effects of niacin and a single bout of aerobic exercise on plasma glucose, insulin, and C-peptide in sedentary, nondiabetic postmenopausal women. As a crossover design, 17 participants underwent four different trials: rest during the no-niacin condition (R), exercise during the no-niacin condition (E), rest during the with-niacin condition (RN), and exercise during the with-niacin condition (EN). All participants took 1,000 mg/day of extended-release niacin for 4 weeks during the with-niacin conditions (RN and EN). The exercise treatment consisted of a single bout of treadmill walking at 60% heart rate reserve until 400 kcal were expended. Blood samples were collected at 24 hours after each trial and analyzed for changes in plasma glucose, insulin, and C-peptide. A two by two analysis of variance was used to examine the changes in dependent variables, and the Bonferroni adjustment was employed as the post hoc test. The level of statistical significance was set at P,0.05. There was no significant interaction between exercise and niacin, nor was there a main effect of exercise for changes in glucose, insulin, or C-peptide. However, there was a significant main effect for niacin as mean glucose, insulin, and C-peptide values significantly increased with niacin; glucose increased 10.6% (P=0.001), from 95.03±10.67 mg/dL to 105.07±13.56 mg/dL; insulin increased 61.8% (P=0.001), from 16.98±12.49 μU/mL to 27.48±14.84 μU/mL; and C-peptide increased 46.1% (P=0.001), from 1.65±0.75 ng/mL to 2.41±0.97 ng/mL. Although niacin was generally well tolerated, given its adverse effects on glucose, insulin, and C-peptide profiles, the use of niacin should be done so with caution and under medical supervision. [ABSTRACT FROM AUTHOR]

Background Previous research has suggested that vitamin D and sunlight are related to cardiovascular outcomes, but associations between sunlight and risk factors have not been investigated. We examined whether increased sunlight exposure was related to improved cardiovascular risk factor status. Methods Residential histories merged with satellite, ground monitor, and model reanalysis data were used to determine previous-year sunlight radiation exposure for 17,773 black and white participants aged 45+ from the US. Exploratory and confirmatory analyses were performed by randomly dividing the sample into halves. Logistic regression models were used to examine relationships with cardiovascular risk factors. Results The lowest, compared to the highest quartile of insolation exposure was associated with lower high-density lipoprotein levels in adjusted exploratory (-2.7 mg/dL [95% confidence interval: -4.2, -1.2]) and confirmatory (-1.5 mg/dL [95% confidence interval: -3.0, -0.1]) models. The lowest, compared to the highest quartile of insolation exposure was associated with higher systolic blood pressure levels in unadjusted exploratory and confirmatory, as well as the adjusted exploratory model 2.3 mmHg [95% confidence interval: 0.8, 3.8]), but the not adjusted confirmatory model (1.6 mg/dL [95% confidence interval: -0.5, 3.7]). Conclusions The results of this study suggest that higher long-term sunlight exposure has an association with lower high-density lipoprotein levels. However, all associations were weak, thus it is not known if insolation may affect cardiovascular outcomes through these risk factors. [ABSTRACT FROM AUTHOR]

Background: The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days). Results: Analysis of data with mixed-model methods (EMMAX, GEMMA, GenABEL) and PLINK showed a low positional concordance between trait-associated regions (TARs) for serum lipids at 45 and 190 days. Besides, the proportion of phenotypic variance explained by SNPs at these two time points was also substantially different. The four analyses consistently detected two regions on SSC3 (124 Mb, CHOL and LDL at 190 days) and SSC6 (135 Mb, CHOL and TRIG at 190 days) with highly significant effects on the porcine blood lipid profile. Moreover, we have found that SNP variation within SSC3, SSC6, SSC10, SSC13 and SSC16 TARs is associated with the expression of several genes mapping to other chromosomes and related to lipid metabolism. Conclusions: Our data demonstrate that the effects of genomic determinants influencing lipid concentrations in pigs, as well as the amount of phenotypic variance they explain, are influenced by age-related factors. [ABSTRACT FROM AUTHOR]

There is clear evidence of the effects of sex and age on the prevalence of cardiovascular disease. We investigated the interactions of dietary omega (n)-3 polyunsaturated fatty acids (PUFA), sex, and age on plasma lipids and lipoproteins in the offspring of C57BL/6 mice exposed to high, medium, or low n-3 PUFA at weaning and 16 weeks postweaning. There was an increase in plasma triglycerides from weaning to 16 weeks in male and female offspring; however, the high n-3 PUFA group showed a reduction in triglycerides in both sexes at 16 weeks. High n-3 PUFA caused an increase in plasma LDL-cholesterol from weaning to 16 weeks in male offspring; however, the LDL particle size was significantly larger in the high n-3 PUFA group. Plasma from male mice showed higher cholesterol efflux compared to females; high n-3 PUFA increased cholesterol efflux. Thus the effects of n-3 PUFA are age and sex dependent. [ABSTRACT FROM AUTHOR]