👤 Luisa Prada

Elevated lipoprotein(a) (Lp(a)) and Lp(a)-raising genetic variants (e.g. rs3798220) are independent cardiovascular risk factors lacking preventive strategies. Given the prothrombotic properties attributed to high Lp(a), aspirin was hypothesized to confer benefit in primary prevention. We performed a systematic review and meta-analysis to evaluate the impact of aspirin on cardiovascular and bleeding outcomes in this population. MEDLINE, Web of Science and CENTRAL were searched (November 2025) for randomized and observational studies assessing aspirin use in primary prevention among individuals with Lp(a) ≥ 50 mg/dL or Lp(a)-associated genetic variants. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included myocardial infarction (MI), coronary artery disease (CAD), cardiovascular mortality, and bleeding. Random-effects meta-analyses pooled the Hazard ratios (HR) with 95% confidence intervals (CI). Certainty of evidence was assessed using GRADE. Seven studies including 6498 participants met inclusion criteria. Aspirin was not associated with a reduction in MACE (HR 0.99, 95% CI 0.79-1.24; I Aspirin was not associated with a reduction of MACE among individuals with elevated Lp(a). A potential benefit for MI requires confirmation in adequately designed and powered prospective studies. Pooled data from rs3798220-C carriers suggest a potential significant benefit that warrants further investigation REGISTRATION: PROSPERO identifier no. CRD42024520731. Show less

Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) levels-reflective of dietary LA intake, are associated with a reduced risk of type 2 diabetes. However, genetic variants in the fatty acid desaturase 1 gene (FADS1) may influence individual responses to plant-based fats. We explored whether FADS1 variants influence the relationships of LA and α-linolenic acid (ALA) intakes and nut consumption with plasma phospholipid fatty acid profiles and type 2 diabetes risk in a large-scale cohort study and a randomized controlled trial. In the EPIC-InterAct case-cohort (7,498 type 2 diabetes cases, 10,087 subcohort participants), we investigated interactions of dietary and plasma phospholipid fatty acids and nut consumption with FADS1 rs174547 in relation to incident type 2 diabetes using weighted Cox regression. In PREDIMED (492 participants in the Mediterranean Diet + Nuts intervention group, 436 participants in the control group), we compared changes in plasma phospholipid FAs from baseline to year 1. In EPIC-InterAct and PREDIMED, nut consumption was positively associated with LA plasma levels and inversely with arachidonic acid, the latter becoming stronger with increasing number of the minor rs174547 C allele (p interaction EPIC-InterAct: 0.030, PREDIMED: 0.003). Although the inverse association of nut consumption with diabetes seemed stronger in participants with rs174547 CC-genotype (HR: 0.73, 95% CI: 0.54-1.00) compared with CT (0.94, 0.81-1.10) or TT (0.90, 0.78-1.05) in EPIC-InterAct, this interaction was not statistically significant. FADS1 variation modified the effect of nut consumption on circulating FAs. We did not observe clear evidence that it modified the association between nut consumption and type 2 diabetes risk. Show less