Windkessel Measures Derived From Pressure Waveforms Only: The Framingham Heart Study

Background: Waveform parameters derived from pressure-only Windkessel models are related to cardiovascular disease risk and could be useful for understanding arterial system function. However, prior reports varied in their adjustment for potential confounders. Methods and Results: Carotid tonometry waveform data from 2539 participants (mean age 63±11 years, 58% women) of the Framingham Heart Study were used to derive Windkessel measures using pressure and assuming a linear model with fixed diastolic time constant (τ_dias) and variable asymptotic pressure (P_inf, median 54.5; 25th, 75th percentiles: 38.4, 64.9 mm Hg) or nonlinear model with inverse pressure-dependent τ_dias and fixed P_inf (20 mm Hg). During follow-up (median 15.1 years), 459 (18%) participants had a first cardiovascular disease event. In proportional hazards models adjusted for age, sex, total cholesterol, high-density lipoprotein cholesterol, smoking, antihypertensive medication use, diabetes mellitus, and physician-acquired systolic blood pressure, only the systolic time constant (τ_sys) derived from the nonlinear model was related to risk for cardiovascular disease events (hazard ratio=0.91 per 1 SD, 95% CI=0.84–0.99, P=0.04). When heart rate was added to the model, τ_sys (hazard ratio=0.92, CI=0.84–1.00, P=0.04) and reservoir pressure amplitude (hazard ratio=1.14, CI=1.01–1.28, P=0.04) were related to events. In contrast, measures derived from the linear model were not related to events in models that adjusted for risk factors including systolic blood pressure (P>0.31) and heart rate (P>0.19). Conclusions: Our results suggest that pressure-only Windkessel measures derived by using a nonlinear model may provide incremental risk stratification, although associations were modest and further validation is required.