A newly developed circadian imbalance index (CII) and risk of cardiovascular-kidney-metabolic disease in the UK biobank

Background To examine the association between combined circadian imbalance related traits and cardiovascular-kidney-metabolic (CKM) disease risk, and their potential interaction with night shift work. Methods This study included 191,764 UK Biobank participants without major chronic diseases who were actively working at baseline (2006–2010). Several factors indicative of a propensity for circadian misalignment were combined to create the circadian imbalance index (CII), with each factor (evening chronotype, sleep ≥ 9 or ≤ 6 hours/day, high neuroticism (score ≥ 7), caffeinated coffee consumption 0 or ≥ 5 cups/day, and vitamin D < 50 nmol/L) contributing one point if present, yielding a composite scale ranging from 0 to 5. CKM outcome (type 2 diabetes, cardiovascular diseases, chronic kidney diseases) identified by ICD codes, self-reports, or death records. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the multivariable (MV)-adjusted association between the CII and CKM risk, including effect modification by night shift work. Results During a median follow-up of 13.5 years (through 2022), 16,907 incident CKM cases were identified. Among participants with European ancestry, for highest versus lowest (0–1) CII, the MV-adjusted risk of CKM was 1.95 (95%CI: 1.70–2.23; P _trend <0.001). A significant positive relationship between CII and CKM risk was also observed in participants of Asian (HR = 2.03, 95%CI, 1.07–3.86; P _trend =0.02), but not African ancestry (HR = 1.43, 95%CI, 0.67–3.06; P _trend =0.66). Risks were higher in shift and night workers than day workers. Among Europeans, the HR for highest CII combined with current night shift work was 2.22 (95%CI, 1.95–2.53), with significant additive interaction ( P  < 0.05). Conclusions In this large prospective study, circadian imbalance index (CII) was associated with higher CKM risk in Europeans and Asians. Among Europeans, high CII plus night shift work posed the greatest risk. Maintaining low CII may help prevent CKM, especially in night shift workers.