Chronic low-grade inflammation associated with higher risk and earlier onset of cardiometabolic multimorbidity in middle-aged and older adults: a population-based cohort study

Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40-69 years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37 months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19 months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM.