The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels

Francesco Paneni, MD, PHD; Candela Diaz Cañestro, MSC; Peter Libby, MD, PHD; Thomas F. Lüscher, MD; Giovanni G. Camici, PHD


J Am Coll Cardiol. 2017;69(15):1952-1967. 

In This Article

Abstract and Introduction


Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients. Next, the authors summarize the current understanding of the mechanisms implicated in cardiovascular aging, and the potential for targeting novel pathways implicated in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling, and genomic instability. Lastly, the authors consider critical aspects of vascular repair, including autologous transplantation of bone marrow-derived stem cells in elderly patients.


Age dominates risk factors for cardiovascular disease (CVD).[1,2] Indeed, the advent of contemporary treatments for acute coronary syndromes and stroke have helped to extend life expectancy.[3] Although an enormous success from an individual perspective, the resultant demographic shift presents one of the greatest challenges for the social and health care systems worldwide.[4] The population over 65 years of age will double from 12% in 2010 to 22% in 2040.[2] Indeed, by 2020, the number of people 60 years of age and older will surpass the number of children below 5 years of age. The pace of population aging around the world is increasing dramatically, particularly in low- and middle-income countries (e.g., Chile, China, Iran, and Russia).

Although aging presents an array of disorders,[5] CVD carries the greatest burden for the older population, their care givers, and health systems.[6] Coronary heart disease (CHD) associates strongly with age, and is the leading cause of death in Europe and the United States.[7–9] The prevalence of CVD increases in people >65 years of age, especially in those >80 years of age, and will increase by ~10% over the next 20 years.[2] From 2010 to 2030, an additional 27 million people will have hypertension, 8 million will have CHD, 4 million will have stroke, and 3 million will have heart failure due to the rapid accumulation of elders.[2]

Increased CVD prevalence also interplays with frailty, a condition of increased vulnerability to stressors. A meta-analysis that included 54,250 elderly patients associated CVD with an odds ratio (OR) of 2.7 to 4.1 for prevalent frailty and an OR of 1.5 for incident frailty in those without frailty at baseline.[10] Current projections predict an increase in expenditures for CHD and heart failure of ~200% over the next 20 years, with stroke expected to contribute the largest relative increase in annual medical costs of 238%.[2] These considerations highlight the urgency of understanding why age contributes crucially to the development of CVD in order to enable us to cope with the aging of the population. This review provides clinical and experimental evidence to support the established link between aging and CVD.