Dataset Information

Major lipids, apolipoproteins, and risk of vascular disease.

ABSTRACT: CONTEXT:Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE:To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS:Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes. MAIN OUTCOME MEASURES:Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values: 0.52 log(e) triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non-HDL-C, 29 mg/dL apolipoprotein AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. RESULTS:The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was 0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non-HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non-HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C. Hazard ratios for ischemic stroke were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and 1.12 (95% CI, 1.04-1.20) with non-HDL-C. CONCLUSION:Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.

SUBMITTER: Emerging Risk Factors Collaboration

PROVIDER: S-EPMC3284229 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Major lipids, apolipoproteins, and risk of vascular disease.

Di Angelantonio Emanuele E Sarwar Nadeem N Perry Philip P Kaptoge Stephen S Ray Kausik K KK Thompson Alexander A Wood Angela M AM Lewington Sarah S Sattar Naveed N Packard Chris J CJ Collins Rory R Thompson Simon G SG Danesh John J

JAMA 20091101 18

<h4>Context</h4>Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified.<h4>Objective</h4>To assess major lipids and apolipoproteins in vascular risk.<h4>Design, setting, and participants</h4>Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infar ...[more]

PMID: 19903920

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Project description:RATIONALE & OBJECTIVE:A large residual risk for atherosclerotic cardiovascular disease (ASCVD) remains in the setting of chronic kidney disease (CKD) despite treatment with statins. We sought to evaluate the associations of lipid and apolipoprotein levels with risk for ASCVD in individuals with CKD. STUDY DESIGN:Prospective cohort study. SETTINGS & PARTICIPANTS:Adults aged 21 to 74 years with non-dialysis-dependent CKD at baseline enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in 7 clinical study centers in the United States. PREDICTOR:Baseline total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), HDL-C, and apolipoprotein AI (Apo-AI) values stratified into tertiles. OUTCOME:A composite ASCVD event of myocardial infarction or ischemic stroke. ANALYTIC APPROACH:Multivariable Cox proportional hazards regression to estimate the risk for ASCVD for each tertile of lipoprotein predictor. RESULTS:Among 3,811 CRIC participants (mean age, 57.7 years; 41.8% white), there were 451 ASCVD events during a median follow-up of 7.9 years. There was increased ASCVD risk among participants with VLDL-C levels in the highest tertile (HR, 1.28; 95% CI, 1.01-1.64), Apo-B levels in the middle tertile (HR, 1.30; 95% CI, 1.03-1.64), HDL-C levels in the middle and lowest tertiles (HRs of 1.40 [95% CI, 1.08-1.83] and 1.77 [95% CI, 1.35-2.33], respectively), and Apo-AI levels in the middle and lowest tertiles (HRs of 1.77 [95% CI, 1.02-1.74] and 1.77 [95% CI, 1.36-2.32], respectively). LDL-C level was not significantly associated with the ASCVD outcome in this population (HR, 1.00 [95% CI, 0.77-1.30] for the highest tertile). LIMITATIONS:Associations based on observational data do not permit inferences about causal associations. CONCLUSIONS:Higher VLDL-C and Apo-B levels, as well as lower HDL-C and Apo-AI levels, are associated with increased risk for ASCVD. These findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipoproteins, to reduce residual risk for ASCVD among individuals with CKD.

Project description:BACKGROUND:Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD. METHODS AND FINDINGS:We conducted a genome-wide association study (GWAS) of circulating non-fasted lipoprotein lipid traits in the UK Biobank (UKBB) for low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B to identify lipid-associated single nucleotide polymorphisms (SNPs). Using data from CARDIoGRAMplusC4D for CHD (consisting of 60,801 cases and 123,504 controls), we performed univariable and multivariable MR analyses. Similar GWAS and MR analyses were conducted for high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. The GWAS of lipids and apolipoproteins in the UKBB included between 393,193 and 441,016 individuals in whom the mean age was 56.9 y (range 39-73 y) and of whom 54.2% were women. The mean (standard deviation) lipid concentrations were LDL cholesterol 3.57 (0.87) mmol/L and HDL cholesterol 1.45 (0.38) mmol/L, and the median triglycerides was 1.50 (IQR = 1.11) mmol/L. The mean (standard deviation) values for apolipoproteins B and A-I were 1.03 (0.24) g/L and 1.54 (0.27) g/L, respectively. The GWAS identified multiple independent SNPs associated at P < 5 × 10-8 for LDL cholesterol (220), apolipoprotein B (n = 255), triglycerides (440), HDL cholesterol (534), and apolipoprotein A-I (440). Between 56%-93% of SNPs identified for each lipid trait had not been previously reported in large-scale GWASs. Almost half (46%) of these SNPs were associated at P < 5 × 10-8 with more than one lipid-related trait. Assessed individually using MR, LDL cholesterol (odds ratio [OR] 1.66 per 1-standard-deviation-higher trait; 95% CI: 1.49-1.86; P < 0.001), triglycerides (OR 1.34; 95% CI: 1.25-1.44; P < 0.001) and apolipoprotein B (OR 1.73; 95% CI: 1.56-1.91; P < 0.001) had effect estimates consistent with a higher risk of CHD. In multivariable MR, only apolipoprotein B (OR 1.92; 95% CI: 1.31-2.81; P < 0.001) retained a robust effect, with the estimate for LDL cholesterol (OR 0.85; 95% CI: 0.57-1.27; P = 0.44) reversing and that of triglycerides (OR 1.12; 95% CI: 1.02-1.23; P = 0.01) becoming weaker. Individual MR analyses showed a 1-standard-deviation-higher HDL cholesterol (OR 0.80; 95% CI: 0.75-0.86; P < 0.001) and apolipoprotein A-I (OR 0.83; 95% CI: 0.77-0.89; P < 0.001) to lower the risk of CHD, but these effect estimates attenuated substantially to the null on accounting for apolipoprotein B. A limitation is that, owing to the nature of lipoprotein metabolism, measures related to the composition of lipoprotein particles are highly correlated, creating a challenge in making exclusive interpretations on causation of individual components. CONCLUSIONS:These findings suggest that apolipoprotein B is the predominant trait that accounts for the aetiological relationship of lipoprotein lipids with risk of CHD.

Project description:BackgroundA Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low-saturated fatty acid (SFA) (<7% calories) diet that contains lean beef.ObjectiveWe studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD).DesignThirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk.ResultsThere was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (-0.49 ± 0.11 and -0.37 ± 0.09 mmol/L, respectively), BOLD (-0.48 ± 0.10 and -0.35 ± 0.9 mmol/L, respectively), and BOLD+ (-0.50 ± 0.10 and -0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (-0.22 ± 0.10 and -0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets.ConclusionsLow-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.

Project description:Nuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content, but its clinical utility is uncertain.Baseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease (n=1015) over an 11-year period. After adjustment for nonlipid risk factors, hazard ratios and 95% confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration (measured in particles per liter) were 2.51 (1.91 to 3.30) for low-density lipoprotein (LDL(NMR)), 0.91 (0.75 to 1.12) for high-density lipoprotein (HDL(NMR)), 1.71 (1.38 to 2.12) for very low-density lipoprotein (VLDL(NMR)), and 2.25 (1.80 to 2.81) for the LDL(NMR)/HDL(NMR) ratio. Similarly adjusted results for NMR-measured lipoprotein particle size (measured in nanometers) were 0.64 (0.52 to 0.79) for LDL(NMR) size, 0.65 (0.51 to 0.81) for HDL(NMR) size, and 1.37 (1.10 to 1.70) for VLDL(NMR) size. Hazard ratios for NMR measures were comparable but not superior to standard lipids (total cholesterol 2.08 [1.63 to 2.67], LDL cholesterol 1.74 [1.40 to 2.16], HDL cholesterol 0.52 [0.42 to 0.64], triglycerides 2.58 [1.95 to 3.41], non-HDL cholesterol 2.52 [1.95 to 3.25], total/HDL cholesterol ratio 2.82 [2.23 to 3.58]) and apolipoproteins (B(100) 2.57 [1.98 to 3.33], A-1 0.63 [0.52 to 0.77], and B(100)/A-1 ratio 2.79 [2.21 to 3.54]). Essentially no reclassification improvement was found with the addition of the LDL(NMR) particle concentration or apolipoprotein B(100) to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors (net reclassification index 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index.In this prospective study of healthy women, cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins.

Dataset Information

Major lipids, apolipoproteins, and risk of vascular disease.

Publications

Major lipids, apolipoproteins, and risk of vascular disease.

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