Abstract Body (Do not enter title and authors here): Background: Poor sleep and physical inactivity are lifestyle-related behaviors that impact cardiometabolic health, but there is limited insight into their combined association with cardiometabolic markers.

Aims: This study investigated the joint association of device-measured sleep patterns (regularity and duration) and daily step counts with cardiometabolic biomarkers.

Methods: Harmonized individual participant data of 12,223 adults (mean±SD age:54.6±9.5 years; 54.8% female) from the pooled Prospective Physical Activity, Sitting and Sleep consortium (ProPASS), comprising six cohorts with thigh-worn accelerometry data were analysed. Sleep regularity was assessed using the validated Sleep Regularity Index (SRI, range 0-100), quantifying day-to-day sleep consistency. We used generalized linear models to examine cross-sectional joint associations between sleep patterns, regularity (SRI tertiles ≤75.8, low; 75.8-84.5, medium; >84.5, high) and duration (<7h, short; 7-8h, adequate; >8h, long), and daily step counts (step tertiles <8488, low; 8488-11601, medium; >11601, high steps/day) with a composite cardiometabolic health score and individual biomarkers, including BMI, waist circumference, total cholesterol, HDL cholesterol, triglycerides, and HbA1c.

Results: Lower sleep regularity, deviation from adequate sleep, along with lower step counts were adversely associated with the composite cardiometabolic health risk score. Compared to optimal sleep patterns (SRI>84.5 or 7-8h/day) and high step groups, low sleep regularity and short sleep duration were separately associated with the least favourable composite cardiometabolic health (z-score [95%CI] 0.32 [0.28,0.37] and 0.25 [0.21,0.29], respectively) among participants with low volume of steps. Low sleep regularity and low daily steps were jointly associated with higher BMI (2.98 [2.67,3.29] kg/m²), waist circumference (8.61 [7.81,9.4] cm), total cholesterol (0.15 [0.08,0.23] mmol/L), and lower HDL levels (0.17 [0.14,0.2] mmol/L), regardless of sleep duration. For short/long sleep duration and low daily step count, such associations were only evident in BMI and waist circumference.

Conclusions: Our findings suggest that the potential deleterious associations of irregular or inadequate sleep duration with cardiometabolic health outcomes may be exaggerated by lower daily step counts. Future studies should examine the prospective joint association of sleep patterns and physical activity on cardiometabolic health.