AbstractBackgroundLipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of Lp(a)-lowering drugs. This study analyzes the relationship between triglycerides (TGs) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype.MethodsData from Aragon Workers Health Study (AWHS) (n = 5467), National Health and Nutrition Examination Survey III phase 2 (n = 3860), and Hospital Universitario Miguel Servet (HUMS) (n = 2079) were used for cross-sectional TG and Lp(a) relationship. Lp(a) intrasubject variation was studied in AWHS participants and HUMS patients with repeated measurements. TG-rich lipoproteins were quantified by nuclear magnetic resonance in a subsample from AWHS. Apolipoproteins B and E were quantified by Luminex in very low-density lipoprotein (VLDL) isolated by ultracentrifugation, from HUMS samples. APOE genotyping was carried in AWHS and HUMS participants. Regression models adjusted for age and sex were used to study the association.ResultsThe 3 studies showed an inverse relationship between TG and Lp(a). Increased VLDL number, size, and TG content were associated with significantly lower Lp(a). There was an inverse association between the apoE concentration in VLDL and Lp(a). No significant association was observed for apolipoprotein (apo)B. Subjects carrying the apoE2/E2 genotype had significantly lower levels of Lp(a).ConclusionOur results show an inverse relationship Lp(a)-TG. Subjects with larger VLDL size have lower Lp(a), and lower values of Lp(a) were present in patients with apoE-rich VLDL and apoE2/E2 subjects. Our results suggest that bigger VLDLs and VLDLs enriched in apoE are inversely involved in Lp(a) plasma concentration.