Longitudinal change in ankle-brachial index and incident cardiovascular disease and all-cause mortality

Background The Ankle-Brachial Index (ABI) is associated with cardiovascular disease (CVD) and all-cause mortality. However, the impact of longitudinal ABI changes on CVD and mortality remains unclear. Purpose To investigate clinical risk factors influencing ABI variations and evaluate the predictive value of sequential ABI measurements for future CVD and all-cause mortality in a multiethnic cohort without baseline cardiovascular disease. Methods We analyzed 5,215 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent ABI measurements at two time points (2000-2002 and 2004-2005). Linear regression models were used to examine clinical factors associated with ABI changes. Cox proportional hazards models, including smooth curve fitting, were employed to assess the relationship between ABI variations and clinical outcomes. Results During a mean follow-up of 12.9 years for CVD (499 events) and 13.5 years for all-cause mortality (790 events), significant clinical factors associated with substantial ABI level changes were identified: age, smoking, interim development of chronic kidney disease (CKD) and interim development of CVD (P < 0.05 for all in multivariable model). Longitudinal ABI changes were associated with future CVD (HR=0.83 per 0.1-unit increase; 95%CI: 0.76-0.90) and all-cause mortality (HR=0.83 per 0.1-unit increase; 95%CI: 0.78-0.89). Compared to participants maintaining consistently normal ABI (1.0≤ABI<1.4), those with initially high ABI (ABI≥1.4) transitioning to normal ABI demonstrated a 187% increased CVD risk (HR=2.87, 95%CI: 1.09-7.57) and a 237% increased all-cause mortality risk (HR=3.37, 95%CI: 1.51-7.54). A non-linear U-shaped relationship was observed between ABI changes and all-cause mortality, with an inflection point at 0.163. Below this point, each 0.1-unit increase in ΔABI reduced mortality risk by 19% (HR: 0.81, 95%CI: 0.75-0.86). Conversely, beyond the inflection point, each 0.1-unit increase in ΔABI increased mortality risk by 23% (HR: 1.23, 95%CI: 0.92-1.65). Conclusion Longitudinal ABI changes are associated with traditional cardiovascular risk factors and kidney disease. ABI variations can predict future CVD and all-cause mortality in a multiethnic cohort without baseline cardiovascular disease. Particular caution is warranted when ABI transitions from high to normal values, emphasizing the necessity of comprehensive medical examination, screening, and intervention.