Abstract
PURPOSE: Cardiovascular disease (CVD) and chronic pain substantially affect menopausal women. However, evidence is scarce regarding how the course of pain over time-specifically, whether it is persistent and affects multiple body sites-influences the future risk of CVD in this population. This study aimed to investigate the longitudinal association between these novel pain phenotypes and incident CVD, and to evaluate the mediating roles of depressive symptoms and body mass index (BMI). PATIENTS AND METHODS: This prospective analysis included 4,890 postmenopausal women from the China Health and Retirement Longitudinal Study (CHARLS). Pain status (location, intensity) and CVD were assessed at baseline (2013) and follow-up (2018). Persistent pain was defined as pain reported at both time points. We used regression models to examine the association between pain patterns and incident CVD, and mediation analysis to quantify the contribution of depressive symptoms and BMI. RESULTS: At baseline (cross-sectional), pain presence, intensity, and multisite distribution were associated with higher CVD prevalence. Over five years (longitudinal), persistent pain phenotypes predicted incident CVD after adjustment: general persistent pain (OR = 1.05, 95% CI: 1.00-1.08, p = 0.012), persistent low back pain (OR = 1.08, 95% CI: 1.03-1.13, p = 0.001), and persistent multisite pain (OR = 1.06, 95% CI: 1.00-1.11, p = 0.020). Depressive symptoms mediated 21.6% of the association for persistent pain; for persistent low back pain, depressive symptoms (14.5%) and BMI (5.4%) were significant mediators. CONCLUSION: Among postmenopausal women, long-standing and multisite pain is associated with higher future CVD risk. A modest portion of these associations was statistically accounted for by depressive symptoms and, for low back pain, BMI. Assessing pain persistence and distribution may help identify women who could benefit from integrated appraisal of pain, mood, and metabolic health.