Systolic and diastolic blood pressures are important predictors of clinical cardiovascular events and targets of clinical and preventive treatment. The arterial blood pressure waveform between these two extremes throughout the cardiac cycle adds information to systolic and diastolic blood pressure regarding cardiovascular risk. This waveform is the net result of the forward and backward pressure waves. Functional and structural changes of the arterial system have an impact on the wave reflections during the cardiac cycle, with particular patterns indicative of different levels of arterial elasticity (1/stiffness). The radial artery pulse contour can be registered noninvasively by radial artery tonometry. One method of extracting information from the pulse contour uses a modified Windkessel model to estimate arterial elasticity in the pool of large arteries (LAE) and in the pool of small arteries (SAE), based on analysis of the diastolic portion of the pulse waveform. The systolic portion of the waveform may contain additional information about arterial elastic behavior. The modified Windkessel model was utilized in a prospective observational cohort initially free of clinical cardiovascular disease, the Multi-ethnic Study of Atherosclerosis (MESA, n=6336, average age 62). Arterial elasticity was lower at greater ages. Lower SAE was related to higher incident hypertension and clinical cardiovascular disease (hazard ratios least vs. highest SAE quartile 2.85 and 2.16) independent of blood pressure, smoking, blood lipids, and level of coronary artery calcification in MESA after median 5.8 years of followup. The associations of LAE and SAE with clinical cardiovascular disease strengthened with addition of events in MESA since the initial submission, leading to a 11% Net Reclassification Index beyond Framingham risk prediction. We propose to remeasure LAE and SAE in MESA (average age 72) to assess 1) whether 10- year change in LAE and SAE adds to prediction of clinical events in MESA, beyond the baseline level of SAE, 2) to examine and compare the predictive ability of alternate measures derived from the digitized radial artery pulse waveform, and 3) to better understand mathematical and statistical properties of estimates of the waveform and of arterial elasticity, with a goal to improve reliability of the estimates. Findings from this study will contribute information about how functional changes in the arterial system over late middle age into elderly years add to the systolic and diastolic blood pressure in prediction of coronary heart disease risk. Assessing LAE and SAE twice over 10 years is a conservative test of whether their trajectories are related to disease outcomes beyond the processes of aging. The slope of arterial elasticity could potentially be helpful in the selection of therapy to slow the loss of vascular integrity, which we hypothesis will reduce disease. PUBLIC HEALTH RELEVANCE: Project Narrative Atherosclerosis and cardiovascular disease are major public health concerns and remain major causes of death in the United States. Functional problems in the arterial system are detectable through analysis of the blood pressure levels throughout the cardiac cycle, as detailed in the radial artery pulse waveform. The proposed study will provide empirical findings of functional arterial status in relation to subclinical and clinical events, as well as gather an maintain a library of over 11000 digitized pulse waveforms for analysis of any proposed new or existing measure of functional arterial status in relation to clinical cardiovascular events.