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

Abstract 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.