Combined variations in sleep, physical activity, and nutrition and the risk of major adverse cardiovascular events

AIMS: Sleep, physical activity, and nutrition (SPAN) are major lifestyle behaviours that influence cardiovascular disease risk. We examined the multi-behaviour associations of SPAN with risk of major adverse cardiovascular events (MACE) and its subtypes (myocardial infarction (MI), heart failure (HF), and stroke). METHODS AND RESULTS: This prospective cohort analysis included 53 242 participants from the UK Biobank (median age: 63.0 years; 56.8% male). Wearable-measured sleep (h/day) and moderate to vigorous physical activity (MVPA; min/day) were calculated using a machine learning-based algorithm, and diet was assessed using a 10-item diet quality score (DQS). Major adverse cardiovascular event risk was estimated across 27 joint tertile combinations of SPAN behaviours, and dose-response associations of SPAN with MACE were examined using a composite score (0-100). Synergistic relationships were examined using the relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Over the 8.0-year follow-up, 2034 MACE events occurred, including 932 MI, 584 strokes, and 518 HF events. Compared with the lowest tertile for all SPAN behaviours, the optimal SPAN combination of 8.0-9.4 h/day sleep, 42-104 min/day MVPA, and a DQS of 32.5-50.0 was associated with a 57% lower risk of MACE (HR: 0.43; 95% CI: 0.30, 0.62). A median SPAN score (52.8) was associated with a 41% lower risk of MACE (HR: 0.59; 95% CI: 0.49, 0.70). The median SPAN score corresponded to an HR of 0.53 (0.38, 0.75) for HF, 0.65 (95% CI: 0.50, 0.84) for MI, and 0.52 (95% CI: 0.38, 0.71) for stroke. A minimum combined variation of an additional 11 min/day of sleep, 4.5 min/day MVPA, and 3 DQS points was associated with 10% lower MACE risk (HR: 0.90; 0.88, 0.94). No synergistic interaction was observed between the SPAN behaviours and MACE (RERI = 0.003; 95% CI: -0.03, 0.04; AP = 0.4%; 95% CI: -6 to 7%; S = 1.03; 95% CI: -3.32, 5.29). CONCLUSION: Modest differences in combined SPAN behaviour levels were associated with meaningful reductions in MACE risk.