Concept of Extremes in Vascular Aging

Abstract

With advancing age, changes in the arterial wall contribute to what has been called vascular aging, and in some prematurely affected subjects even early vascular aging (EVA).1–5 Several years ago,1 we listed various components of EVA, including arteriosclerosis, atherosclerosis, and excess vasoconstriction, with their clinical expression: arterial stiffening and increased central pulse pressure, carotid intima media thickening and endothelial dysfunction, and increased total peripheral resistance, respectively. In this review, we focus on arteriosclerosis, ie, arterial stiffening, for several reasons: this is the most characteristic clinical feature of the aging process of the arterial system,6 its measurement has been well standardized and referenced,7,8 and an increasing number of epidemiological studies have analyzed its independent determinants.9–11 Increased pulse wave velocity (PWV) is the established hallmark of arterial stiffening and is suggested to be one of the best biomarkers available to calculate the prospective cardiovascular risk and mortality risk of an individual.9,10,12,13 EVA can be diagnosed in subjects who present an abnormally high arterial stiffness for their age and sex.In the present review, we propose the concept of supernormal vascular aging (SUPERNOVA). SUPERNOVA can be diagnosed in subjects who present an exceptionally low arterial stiffness for their age and sex. We address the issue of the metrics and definition of EVA and SUPERNOVA as 2 extremes of the distribution of vascular aging. We discuss the concept of extremes in cardiometabolic research. Further, we review the molecular basis and mechanobiology of EVA and SUPERNOVA, in parallel with their epidemiological, genetic, and epigenetic determinants. Finally, we suggest therapeutic options and insist on the need for discovering novel molecular targets for slowing arterial aging and protecting against cardiovascular complications. By choosing the wording SUPERNOVA, we referred to the life of a supernova—a large explosion that takes place at the end of a star’s life cycle. The relationship between supernova and black hole is not firmly established, but physics theory states that in a black hole, time is slowed…like aging of arteries in SUPERNOVA subjects.