Prognostic significance of mechanical biomarkers derived from pulse wave analysis for predicting long-term cardiovascular mortality in two population-based cohorts

Background Numerous mechanical biomarkers derived from pulse wave analysis (PWA) have been proposed to predict cardiovascular outcomes. However, whether these biomarkers carry independent prognostic value and clinical utility beyond traditional cardiovascular risk factors hasn't been systematically evaluated. We aimed to investigate the additive utility of PWA-derived biomarkers in two independent population-based cohorts. Methods PWA on central arterial pressure waveforms obtained from subjects without a prior history of cardiovascular diseases of two studies was conducted based on the wave transmission and reservoir-wave theory: firstly in the Kinmen study (1272 individuals, a median follow-up of 19.8 years); and then in the Cardiovascular Disease Risk Factors Two-Township Study (2221 individuals, median follow-up of 10 years). The incremental value of the biomarkers was evaluated by net reclassification index (NRI). Results In multivariate Cox analyses accounting for age, gender, body mass index, systolic blood pressure, fasting glucose, high-density- and low-density-lipoprotein cholesterol, and smoking, only systolic (SC) and diastolic rate constant (DC) of reservoir pressure could independently and consistently predict cardiovascular mortality in both cohorts and the combined cohort (SC: hazard ratio 1.18 [95% confidence interval 1.08-1.28, p < 0.001; DC: 1.18 [1.09-1.28], p < 0.001]. Risk prediction estimates in traditional risk prediction models were significantly more accurate when incorporating peak of reservoir pressure (NRI = 0.049, p = 0.0361), SC (NRI = 0.043, p = 0.0236) and DC (NRI = 0.054, p = 0.047). Conclusions Of all PWA-derived biomarkers, SC and DC were consistently identified as valuable parameters for incremental cardiovascular risk prediction in two large prospective cohorts.