Prognostic value of peripheral endothelial function on major adverse cardiovascular events above traditional risk factors

Aims: This study aims to identify whether adding peripheral microvascular dysfunction (PMED), a marker of atherosclerosis to established risk scores has an incremental prognostic value for major adverse cardiovascular events (MACE). Methods and results: This is a retrospective study of patients who underwent measuring peripheral arterial tonometry from 2006 to 2020. The optimal cut-off value of the reactive hyperaemia index (RHI) that had maximal prognostic value associated with MACE was calculated. Peripheral microvascular endothelial dysfunction was defined as the RHI lower than the cut-off. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, and vascular disease were determined to calculate the CHA2DS2-Vasc score. The outcome was MACE defined as myocardial infarction, heart failure hospitalization, cerebrovascular events, and all-cause mortality. A total of 1460 patients were enrolled (average age 51.4 ± 13.6, 64.1% female). The optimal cut-off value of the RHI was 1.83 in the overall population and in females and males was 1.61 and 1.8, respectively. The risk of MACE during 7 [interquartile range (IQR): 5,11] years of follow-up was 11.2%. Kaplan-Meier analysis showed that lower RHI is associated with worse MACE-free survival (P < 0.001). Multivariate Cox proportional hazard analysis, controlling for classic cardiovascular risk factors or risk scores such as CHA2DS2-Vasc and Framingham risk score revealed that PMED is an independent predictor of MACE. Conclusion: Peripheral microvascular dysfunction predicts cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events. Lay summary: We conducted a retrospective study of patients who underwent peripheral arterial tonometry to, first, identify the optimal cut-off value in predicting major adverse cardiovascular events and, second, evaluate the incremental prognostic value of peripheral microvascular dysfunction over conventional risk assessment models. Key findings: The optimum cut-off value of RHI in predicting MACE was 1.83 in the overall population and males, while it was lower in females (1.6). Integrating PMED status into previously established risk scores (CHA2DS2-Vasc score and Framingham risk score) significantly improves the prognostic stratification of patients at risk of MACE.