Dataset Information

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

ABSTRACT: Aims: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke.

Methods: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure.

Results: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke.

Conclusions: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

SUBMITTER: Joshi R

PROVIDER: S-EPMC7707881 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

Joshi Roshni R Wannamethee S Goya SG Engmann Jorgen J Gaunt Tom T Lawlor Deborah A DA Price Jackie J Papacosta Olia O Shah Tina T Tillin Therese T Chaturvedi Nishi N Kivimaki Mika M Kuh Diana D Kumari Meena M Hughes Alun D AD Casas Juan P JP Humphries Steve S Hingorani Aroon D AD Schmidt A Floriaan AF

European journal of preventive cardiology 20200129 15

<h4>Aims</h4>Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke.<h4>Methods</h4>Triglyceride-containing sub-fraction measures were available in 11,560 p ...[more]

PMID: 31996015

Similar Datasets

Project description:The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain) and two progenitor strains SHR-Lx (n = 13) and BXH2/Cub (n = 18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains.

Project description:CONTEXT:Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE:To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION:Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION:Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS:Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION:Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

Project description:BackgroundLipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an inflammatory enzyme expressed in atherosclerotic plaques, is a therapeutic target being assessed in trials of vascular disease prevention. We investigated associations of circulating Lp-PLA(2) mass and activity with risk of coronary heart disease, stroke, and mortality under different circumstances.MethodsWith use of individual records from 79 036 participants in 32 prospective studies (yielding 17 722 incident fatal or non-fatal outcomes during 474 976 person-years at risk), we did a meta-analysis of within-study regressions to calculate risk ratios (RRs) per 1 SD higher value of Lp-PLA(2) or other risk factor. The primary outcome was coronary heart disease.FindingsLp-PLA(2) activity and mass were associated with each other (r=0.51, 95% CI 0.47-0.56) and proatherogenic lipids. We noted roughly log-linear associations of Lp-PLA(2) activity and mass with risk of coronary heart disease and vascular death. RRs, adjusted for conventional risk factors, were: 1.10 (95% CI 1.05-1.16) with Lp-PLA(2) activity and 1.11 (1.07-1.16) with Lp-PLA(2) mass for coronary heart disease; 1.08 (0.97-1.20) and 1.14 (1.02-1.27) for ischaemic stroke; 1.16 (1.09-1.24) and 1.13 (1.05-1.22) for vascular mortality; and 1.10 (1.04-1.17) and 1.10 (1.03-1.18) for non-vascular mortality, respectively. RRs with Lp-PLA(2) did not differ significantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA(2) mass. Adjusted RRs for coronary heart disease were 1.10 (1.02-1.18) with non-HDL cholesterol and 1.10 (1.00-1.21) with systolic blood pressure.InterpretationLp-PLA(2) activity and mass each show continuous associations with risk of coronary heart disease, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA(2) mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids.FundingUK Medical Research Council, GlaxoSmithKline, and British Heart Foundation.

Dataset Information

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

Publications

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets