Lipoprotein(a) and LDL-C are independently associated with CVD risk. At LDL-C levels below <2.5 mmol/L, the risk associated with elevated Lp(a) attenuates in a primary prevention setting.

Background and aimsLipoprotein(a) (Lp[a]) is a strong genetic risk factor for cardiovascular disease (CVD). The American Heart Association has prioritised seven cardiovascular health metrics to reduce the burden of CVD: body mass index, healthy diet, physical activity, smoking status, blood pressure, diabetes and cholesterol levels (together also known as ideal cardiovascular health). Our objective was to determine if individuals with high Lp(a) levels could derive cardiovascular benefits if characterized by ideal cardiovascular health.MethodsA total of 14,051 participants of the EPIC-Norfolk study were stratified according to the cardiovascular health score (based on the number of health metrics with an ideal, intermediate or poor status). Of them, 1732 had a CVD event during a mean follow-up of 11.5 years. Cox proportional hazards models were used to describe the association between the cardiovascular health score and Lp(a) level or genotype (as estimated by the rs10455872 variant) with the risk of CVD.ResultsWe observed little or no differences in serum Lp(a) levels across the seven cardiovascular health metric categories. Among participants with high serum Lp(a) levels ≥50 mg/dl), those in the highest (i.e. healthiest) cardiovascular health score category (10–14) had an adjusted hazard ratio for cardiovascular disease of 0.33 (95% CI = 0.17–0.63, p = 0.001) compared to participants in the lowest (i.e. unhealthiest) cardiovascular health score category(0–4). Similar results were obtained when we replaced Lp(a) with rs10455872.ConclusionsAlthough Lp(a) levels are only slightly influenced by cardiovascular health metrics, an ideal cardiovascular health could substantially reduce CVD risk associated with high Lp(a) levels or genotype.

Objective-Carriers of the PCSK9 (proprotein convertase subtilisin/kexin 9) R46L genetic variant (rs11591147) are characterized by low levels of low-density lipoprotein cholesterol and a decreased risk of cardiovascular disease. We studied the impact of the R46L variant on lipoprotein size and composition. Approach and Results-Lipoprotein size and composition were measured by nuclear magnetic resonance spectroscopy in 2373 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. DiscussionOur study shows that carriers of the PCSK9 R46L variant are characterized by lower levels of NMR-measured atherogenic lipoproteins and subfractions compared with noncarriers. The most prominent differences based on percentage change between carriers and noncarriers were observed with IDL-P (−18%) and medium VLDL-P (−16%; Figure). The most prominent differences based on change in SD between carriers and noncarriers were observed with apolipoprotein B ( who have reported a 15% reduction in LDL-C in carriers of the PCSK9 R46L variant in the ARIC study (Atherosclerosis Risk in Communities). The effect on other parameters of the lipoprotein-lipid profile was comparable, with in both studies significant lower levels of total cholesterol and no effect on high-density lipoprotein cholesterol.In a cross-sectional study of 52 healthy subjects, PCSK9 levels were found to correlate with total cholesterol, nonhigh-density lipoprotein cholesterol, LDL-C, triglycerides, and VLDL-P and LDL-P concentrations. 4 In a subsequent multivariable regression analysis, PCSK9 levels were only related to LDL-P concentration. Interestingly, in an analysis that included the 3 LDL subfractions, PCSK9 was only associated with IDL-P. The R46L variant examined in our study has been shown to be associated with lower levels of PCSK9, 5 and therefore, we expected a similar effect on NMR lipoprotein subfractions. Our study suggests that there is not only an association between PCSK9 and IDL-P but also with other lipoprotein particles. The effect of the R46L variant on lipoproteins in our study seemed to be comparable with the results of Chasman et al, 6 who showed a significant effect of the single-nucleotide polymorphism on large LDL-P, total LDL-P, small LDL-P, IDL-P, LDL-C, total VLDL-P, and small VLDL-P. Other groups also documented the effect of different single-nucleotide The relationship between LDL-C and CVD risk is strong and consistent, but evidence suggest that LDL-P concentrations could be more closely associated with CVD risk than LDL-C. 12 Because of a possible discordance between LDL-C and LDL-P concentrations, patients with LDL-C levels on target could be at increased CVD risk attributable to high LDL-P levels. 13 The American Association of Clinical Chemistry has suggested to strive for a LDL-P concentration treatment goal of <1100 nmol/L 14 or an equivalent LDL-C level of <100 mg/dL in patients at high CVD risk according to the National Cholesterol Education Program Adult Treatment Panel III. 15As w...

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The existing evidence supports the claim that non-HDL-C is superior to LDL-C in CVD risk estimation.

ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

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