Gary F. Mitchell

BACKGROUND: Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. METHODS AND RESULTS: We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P=0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models. CONCLUSIONS: Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community.

With advancing age, arterial stiffness and wave reflections increase and elevate systolic and pulse pressures. An elevated central pulse pressure is generally ascribed to increased wave reflection and portends an unfavorable prognosis. Using arterial tonometry, we evaluated central (carotid-femoral) and peripheral (carotid-brachial) pulse wave velocity, amplitudes of forward and reflected pressure waves, and augmentation index in 188 men and 333 women in the Framingham Heart Study offspring cohort who were free of clinical cardiovascular disease, hypertension, diabetes, smoking within the past 12 months, dyslipidemia, and obesity. In multivariable linear regression models, advancing age was the predominant correlate of higher carotid-femoral pulse wave velocity; other correlates were higher mean arterial pressure, heart rate, and triglycerides and walk test before tonometry (model R2=0.512, P<0.001). A similar model was obtained for carotid-brachial pulse wave velocity (model R2=0.227, P<0.001), although the increase with advancing age was smaller. Owing to different relations of age to central and peripheral stiffness measures, carotid-femoral pulse wave velocity was lower than carotid-brachial pulse wave velocity before age 50 years but exceeded it thereafter, leading to reversal of the normal central-to-peripheral arterial stiffness gradient. In this healthy cohort with a minimal burden of cardiovascular disease risk factors, an age-related increase in aortic stiffness, as compared with peripheral arterial stiffness, was associated with increasing forward wave amplitude and pulse pressure and reversal of the arterial stiffness gradient. This phenomenon may facilitate forward transmission of potentially deleterious pressure pulsations into the periphery.

M uch has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as "cf" is used when speaking of specific segments of the arterial circulation.