Mechanisms and Subclinical Consequences of Aortic Stiffness

The number of published articles on PubMed with arterial stiffness or aortic stiffness in the title during the past 20 years exceeds 4000 articles published, with more than one-half published in the past 5 years (see Figure). The studies published on the topic of arterial stiffness span the full translational continuum from basic mechanistic studies in cell and animal models to small experimental studies in humans and large observational cross-sectional and prospective studies relating arterial stiffness to subclinical target organ damage or clinical cardiovascular disease (CVD) events. The reason for this rapidly growing area of investigation is likely attributed to the strong body of evidence indicating that arterial stiffness, specifically aortic stiffness as measured by the reference standard carotid-femoral pulse wave velocity (CFPWV), is a robust predictor of clinical CVD events in adults even after adjusting for blood pressure (BP) and other conventional CVD risk factors. In addition, several prospective cohort studies suggest that elevated CFPWV precedes the development of incident hypertension in middle-aged adults, consistent with the idea that aortic stiffness may be causal in the genesis of hypertension with aging in humans rather than a subclinical consequence. In 2015, the American Heart Association published a comprehensive Scientific Statement addressing the nomenclature, methodologies, utility, limitations, and gaps in knowledge related to arterial stiffness to inform the research community of the state of field and help guide future directions for investigation, including identifying targets for intervention. Because the putative mechanisms that contribute to the development of aortic stiffness remain elusive, the current review article will focus on the recent advances during the past 2 to 3 years describing some novel mechanisms that contribute to elevated aortic stiffness that may be therapeutic targets for intervention. Then, a few of the most exciting recent investigations about the subclinical negative consequences of aortic stiffness on the brain and kidney will be discussed.