Association of Short-term Pain and Chronic Pain Intensity With Cardiometabolic Multimorbidity Progression: A Multistate Markov Model Analysis

BACKGROUND: The impact of pain intensity on the progression trajectories of cardiometabolic multimorbidity (CMM) is not well understood. We attempted to dissect the relationship of short-term pain (STP) and chronic pain intensity with the temporal progression of CMM. METHODS: We conducted a prospective cohort study based on the UK Biobank participants. Incident cases of cardiometabolic diseases (CMDs) were identified based on self-reported information and multiple health-related records in the UK Biobank. CMM was defined as the occurrence of at least 2 CMDs, including heart failure (HF), ischemic heart disease (IHD), stroke, and type 2 diabetes (T2D). The pain intensity was categorized into 5 levels based on pain duration and the number of sites involved, including chronic widespread pain (CWSP), chronic multilocation pain (CMLP), chronic single-location pain (CSLP), STP, and free-of-pain (FOP). Multistate models were used to assess the impact of pain intensity on the CMM trajectories from enrollment to initial cardiometabolic disease (ICMD), subsequently to CMM, and ultimately to death. RESULTS: A total of 429,145 participants were included. Over the course of a 12.8-year median follow-up, 13.1% (56,137/429,145) developed ICMD, 19.6% (10,979/56,137) further progressed to CMM, and a total of 5.3% (22,775/429,145) died. Compared with FOP, CMLP (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.06-1.17) and CWSP (HR, 1.26; 95% CI, 1.13-1.42) elevated the risk of transitioning from ICMD to CMM. STP (HR, 0.89; 95% CI, 0.82-0.96), CSLP (HR, 0.88; 95% CI, 0.82-0.95), and CMLP (HR, 0.87; 95% CI, 0.81-0.93) lowered the risk of transition from ICMD to mortality, and STP also reduced the risk of transition from enrollment to mortality (HR, 0.94; 95% CI, 0.89-0.98). The results of disease-specific transitions revealed that the influence of pain intensity varied across transitional stages. Specifically, CMLP and CWSP heightened the risk of conversion from T2D or IHD to CMM, whereas only CWSP substantially elevated the transition risk from HF to CMM. CONCLUSIONS: Our results highlighted reductions in chronic pain may mitigate both the onset and progression of CMM, potentially having an important impact on future revisions of cardiometabolic and pain-related guidelines.