Across 99,064 participants drawn from the UK Biobank and NHANES (2005–2018), adherence to the Alternative Mediterranean Diet (AMED) and Healthful Plant-Based Diet Index (HPDI) was associated with a 5–7% reduction in major adverse cardiovascular events (MACE) per standard-deviation increase in diet score, among individuals spanning cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3. Higher dietary inflammatory index (DII) scores moved in the opposite direction, positively tracking with MACE and all-cause mortality. Micronutrients including alpha- and beta-carotene, vitamin C, copper, iron, and magnesium independently associated with lower MACE incidence. Oxidative stress, phenotypic aging biomarkers, and inflammatory markers partially mediated these relationships, explaining 1.3–29.5% of observed associations.
The CKM syndrome framework, formalized by the American Heart Association in 2023, usefully integrates cardiometabolic and renal risk into a single staging continuum — but dietary guidance tailored to it has been sparse. This large dual-cohort analysis fills a meaningful gap. The mechanistic mediation findings — showing oxidative stress and phenotypic aging as partial pathways — add biological plausibility beyond prior observational diet-heart literature. However, critical limitations apply: dietary data in both cohorts rely on self-report (24-hour recalls in NHANES, food frequency questionnaires in UKB), introducing substantial measurement error. Observational design precludes causal inference, and residual confounding by socioeconomic or lifestyle factors remains likely. The 5–7% per-SD risk reduction is modest, though population-level impact could be meaningful given CKM syndrome's prevalence. Overall, this is confirmatory and contextually valuable — not paradigm-shifting — but reinforces actionable dietary targets for high-risk adults.
