BACKGROUND AND AIMS
All apolipoprotein B-containing lipoproteins are established causal factors for coronary artery disease (CAD). This study aimed to identify robust proteomic signatures of low-density lipoprotein (LDL), triglyceride-rich lipoproteins (TRL), and lipoprotein(a) [Lp(a)] and to evaluate whether these signatures illuminate biological processes underlying differences in per-particle atherogenicity.
METHODS
Plasma proteins associated with LDL, TRL, and Lp(a) concentrations were identified using multivariable-adjusted regression across 2918 proteins in a primary prevention cohort based on UK Biobank (n=35,269), and findings were corroborated using one-sample Mendelian randomization. Proteins consistently identified by both approaches were summarized into lipoprotein-specific multi-protein scores and associated with incident CAD (n=1599 events) using Cox regression. High-dimensional mediation analysis quantified the proportion of lipoprotein-associated CAD risk explained by proteomic alterations. Findings were replicated in the Multi-Ethnic Study of Atherosclerosis (n=5915).
RESULTS
Requiring concordance between observational and Mendelian randomization analyses (both Bonferroni-adjusted P<0.05), 30 proteins were identified as associated with LDL, 471 with TRL, and 53 with Lp(a). The TRL and Lp(a) signatures were distinct from the LDL signature yet overlapped substantially with each other (36 shared proteins), with common enrichment in inflammatory pathways. After adjustment for potential confounders and measured lipoprotein concentrations, the multi-protein scores for TRL (hazard ratio per 1-SD [HRSD], 1.16; 95% confidence interval [95%CI]: 1.08-1.24) and Lp(a) (HRSD, 1.09; 95%CI: 1.03-1.15), but not LDL (HRSD, 0.95; 95%CI: 0.89-1.02), were associated with incident CAD. Mediation analysis was consistent with immune activation and vascular remodeling markers mediating TRL-associated CAD risk (proportion mediated, 62%) and, in part, Lp(a)-associated risk (14%).
CONCLUSIONS
Beyond arterial lipid deposition, TRL and Lp(a) converge on inflammatory and vascular remodeling pathways that, under the assumptions of observational mediation analysis, may explain their excess per-particle atherogenicity compared with LDL.
J. Morze, E. Björnson, Michael Y. Mi et al.· European Heart Journal· 0 citations
Background: Current dietary guidelines are largely based on evidence from the general population, and data on dietary patterns and survival after myocardial infarction (MI) remain limited. We evaluated post-MI adherence to multiple healthy dietary patterns, as well as changes in adherence from before to after MI diagnosis, in relation to mortality among MI survivors. Methods: We included 3,277 women from the Nurses’ Health Study and 2,618 men from the Health Professionals Follow-up Study who survived a non-fatal MI. The mean age at MI diagnosis was 68.2 (standard deviation, 10.2) years. Diet was assessed using validated food frequency questionnaires and updated every two to four years. We calculated post-MI adherence scores for eight healthy patterns: the Alternate Healthy Eating Index (AHEI), the Healthy Eating Index-2015 (HEI-2015), the Alternate Mediterranean Diet Score (AMED), the Dietary Approaches to Stop Hypertension (DASH), the healthful Plant-Based Diet Index (hPDI), the reversed empirical dietary inflammatory pattern (rEDIP), the reversed empirical dietary index for hyperinsulinemia (rEDIH), and the reversed empirical dietary index for insulin resistance (rEDIR). The main outcome was total mortality, with cardiovascular disease (CVD) mortality and recurrent non-fatal MI as secondary outcomes. Results: During 15.7 years of follow-up after MI, 3,858 deaths (65.4%) were documented, including 1,639 CVD deaths (42.5% of deaths). Comparing the highest with the lowest quintile, higher post-MI dietary scores were consistently associated with lower total mortality, with the hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.60–0.74) for AHEI, 0.73 (0.65–0.81) for HEI-2015, 0.66 (0.59–0.75) for AMED, 0.77 (0.69–0.86) for DASH, 0.74 (0.66–0.83) for hPDI, 0.77 (0.68–0.86) for rEDIP, 0.73 (0.65–0.83) for rEDIR, and 0.71 (0.64–0.80) for rEDIH. Similar inverse associations were observed for CVD mortality and recurrent non-fatal MI. Improved AHEI adherence from before to after MI was associated with lower mortality (HR: 0.86; 95% CI: 0.76–0.97), whereas decreased adherence to most patterns was associated with higher mortality. Conclusions: Among individuals who survived MI, adherence to post-MI dietary patterns emphasizing higher diet quality was associated with better long-term survival. These findings support dietary guidance focusing on overall diet quality for the secondary prevention of deaths among MI survivors.
L. Ma, Yang Hu, Gang Liu et al.· Circulation· 0 citations
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