disease identified by the epidemiologists. If the variable is perceived as beneficial or deleterious with respect to cardiovascular structure or function, those with extreme measures are considered to be aging “successfully” or “unsuccessfully,” respectively.“Unsuccessful” aging in this context is not synonymous with having clinical disease, as individuals with defined overt or occult clinical disease have been excluded from consideration a priori. Instead, unsuccessful aging, ie, falling within the poorest category with respect to the measure viewed as deleterious, may be viewed as a risk factor for future clinical cardiovascular disease. In this regard, unsuccessful aging is a manifestation of the interaction of the vascular aging process and specific aspects of vascular disease pathophysiology. Thus, gerontologists and epidemiologists have become part of a joint effort in the quest to define why aging confers enormous risk for cardiovascular disease.

The central thesis of this review is that quintessential clinical cardiovascular diseases of older persons and ageassociated changes in cardiovascular structure and function, heretofore not defined as disease, become intertwined and interdependent. The role of specific age-associated changes in cardiovascular structure and function in this age–disease interaction has formerly been, and largely continues to be, unrecognized by those who shape medical policy. Thus, specific aspects of cardiovascular aging have remained outside the bailiwick of clinical cardiology, and, until recently, have not been considered in most epidemiological studies of cardiovascular disease. Our main goal is to promote a new research frontier by defining our current understanding of the age-associated changes in cardiac and vascular structure and function that occur in apparently healthy persons and how these are relate to the risk of subsequent cardiovascular disease occurrence. This goal is pursued in this and the additional two articles of this series that will occur in subsequent issues of Circulation1, 2 to provoke thought regarding the new and important research efforts to design basic experiments that elucidate these mechanisms and clinical trials that evaluate strategies aimed at reducing or preventing those aspects of aging, such as age-associated increases in large vessel lumen, wall thickening, and stiffness, that occur in apparently healthy persons but confer risk for overt clinical cardiovascular disease.