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
Type 2 diabetes (T2D) is associated with an increased risk of premature death. Diet may influence long-term health outcomes among individuals with T2D, but prospective evidence on dietary patterns and mortality remains limited.
OBJECTIVES
To prospectively examine associations of eleven pre-defined or empirically-developed dietary patterns with all-cause and cause-specific mortality (e.g., cardiovascular disease [CVD] and cancer) among U.S. individuals with T2D.
METHODS
We included 7,795 participants with incident T2D in the Nurses' Health Study (1984-2016) and Health Professionals Follow-Up Study (1986-2020), who were free of CVD and cancer at diagnosis. Diet was assessed using a validated food frequency questionnaire and updated every four years. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs.
RESULTS
Over 24 years of follow-up, 3,509 deaths were confirmed, including 1,079 from CVD and 649 from cancer. Adherence to healthy dietary patterns after diagnosis (comparing the 90th with the 10th percentile of dietary pattern scores) was consistently associated with lower all-cause mortality, with multivariable-adjusted HRs ranging from 0.78 (95% CI: 0.71, 0.85) for the Planetary Health Diet to 0.92 (95% CI: 0.84, 1.01) for the Dietary Approaches to Stop Hypertension. Furthermore, greater improvements in dietary pattern adherence from pre- to post-diagnosis (comparing the 90th with the 10th percentile of change scores) were also associated with lower all-cause mortality, with HRs (95% CI) ranging from 0.63 (0.58, 0.70) to 0.92 (0.85, 1.01). A similar pattern of inverse associations with CVD mortality was also observed for these dietary scores. Additionally, the reversed Empirical Dietary Index for Hyperinsulinemia was specifically associated with lower cancer mortality.
CONCLUSIONS
Adherence to healthy dietary patterns is universally associated with better survival in individuals with T2D. These findings suggest the importance of consuming high-quality diets in the prevention of premature deaths among individuals with T2D.
Zixin Qiu, Gang Liu, Binkai Liu et al.· American Journal of Clinical...· 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
OBJECTIVE
High sodium and low potassium intake, well-established dietary risk factors for hypertension, may induce insulin resistance and increase the risk of type 2 diabetes. However, previous research based on self-reported intakes is inconclusive. We examined the association of sodium and potassium intake, assessed by multiple 24-h urine samples, with subsequent risk of developing type 2 diabetes.
RESEARCH DESIGN AND METHODS
We included 3,173 adults without major chronic diseases from three prospective cohorts. Sodium and potassium excretions were assessed using two to four 24-h urine collections per participant. We used Cox proportional hazards models to estimate hazard ratios (HR) for type 2 diabetes, adjusting for major confounding factors, including total energy intake and BMI.
RESULTS
Among 3,173 participants (mean age 62.2 ± 10.0 years, 69% women), diabetes developed in 161 over a median of 13.6 years. Risk of diabetes was 2.66 (95% CI 1.57-4.51) times higher in participants in the highest versus the lowest quartile of sodium excretion. Each 1,000 mg/day increase in sodium excretion was associated with a 32% (HR 1.32; 95% CI 1.16-1.52) higher risk of diabetes, whereas potassium excretion was not associated with diabetes risk (HR 0.87; 95% CI 0.69-1.11). Each unit increase in the sodium-to-potassium ratio was associated with a 26% higher risk of diabetes (95% CI 1.10-1.45).
CONCLUSIONS
Higher sodium intake and a higher sodium-to-potassium ratio were associated with a higher risk of type 2 diabetes. Although these findings suggest that adopting a low-sodium diet may reduce diabetes risk, the associations may partly reflect residual confounding despite comprehensive covariate adjustment.
Siwei Zhu, Xin-Yuan Zhang, R. Hamaya et al.· Diabetes Care· 0 citations
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