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Background and Aims: After assessing the risk for cardiovascular disease (CVD) based on traditional risk factors, decisions concerning lipid lowering therapy might remain uncertain. To investigate whether lipoprotein subfraction levels could aid these decisions, we assessed the association between lipoprotein subfractions and CVD, after adjustment for traditional risk factors including standard lipids., Methods: Using a case-cohort design, participants were randomly drawn from the Malmö Prevention Project (MPP), a population-based prospective study of 18,240 participants, and supplemented with additional incident CVD events (5764 participants, 1784 CVD events)., Results: Low density lipoprotein particle number (LDL-P) and individual subfractions ranging in size from very-small to large were associated with CVD (continuous p value (p cont ) < 0.001) while adjusting for age, sex, hypertension, smoking, and diabetes. After further adjustment for LDL-C, HDL-C, and triglycerides, very small LDL subfraction (b) (LDL-VS (b)) remained associated with CVD (HR = 1.23, 95% CI, 1.06 to 1.43 for top vs. bottom quartile, p cont  = 0.03). Among participants with low/intermediate risk [without diabetes and with LDL-C <3.36 mmol/L (<130 mg/dL)], the fully adjusted HR for LDL-small (top vs. bottom quartile) was 1.48 (95% CI 1.02 to 2.17, p cont  = 0.03). Among those with very-high risk (>20% 10-year risk of CVD), LDL-VS(a) and LDL-VS(b) were associated with CVD in fully adjusted models (HR = 1.37, 95% CI 1.12 to 1.67 and HR = 1.28, 95% CI 1.07 to 1.53, respectively, p cont ≤0.03)., Conclusions: Smaller LDL particles are associated with incident CVD independently of traditional risk factors, including standard lipids, in participants with low/intermediate and very-high risk, who might benefit from improved risk assessment., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: LPA encodes apolipoprotein(a), and a CCTC haplotype in the LPA locus is associated with CHD. The 4399Met variant (rs3798220) of LPA has a risk estimate for CHD similar to that of the CCTC haplotype. We asked whether co-incidence with the 4399Met variant explained the association of the haplotype with CHD., Methods: We stratified by the 4399Met variant and another LPA SNP (rs10455872) associated with CHD and tested the association between CHD and 4 SNPs that define two haplotypes associated with CHD: CCTC and CTTG., Results: For CCTC, in the presence of the rs3798220 risk allele the OR was 1.68 (95% CI: 1.05-2.68, P=0.03) versus 0.30 (95% CI: 0.06-1.59, P=0.16) with the non-risk allele. For CTTG, in the presence of the rs10455872 risk allele the OR was 1.57 (95% CI: 1.15-2.13, P=0.004) versus 1.04 (95% CI: 0.79-1.35, P=0.77) with the non-risk allele., Conclusion: The rs3798220 and rs10455872 SNPs explain the association of the CCTC and CTTG haplotypes with CHD., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women's Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers., Methods and Results: Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants. Median Lp(a) levels at baseline were 10.0, 79.5, and 153.9mg/dL for major allele homozygotes, heterozygotes, and minor allele homozygotes, respectively (P<0.0001). During the 9.9 years of follow-up, minor allele carriers (3.7%) in the placebo group had twofold higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR)=2.21, 95% CI: 1.39-3.52). Among carriers, risk was reduced more than twofold by aspirin: for aspirin compared with placebo the age-adjusted HR was 0.44 (95% CI: 0.20-0.94); risk was not significantly reduced among non-carriers (age-adjusted HR=0.91, 95% CI: 0.77-1.08). This interaction between carrier status and aspirin allocation was significant (P=0.048)., Conclusions: In the Women's Health Study, carriers of an apolipoprotein(a) variant had elevated Lp(a), doubled cardiovascular risk, and appeared to benefit more from aspirin than non-carriers.