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Chapter Summary

This chapter discusses the pathophysiology of the aging processes in relation to the cardiovascular system. Epidemiological studies demonstrate that the impact of conventional cardiovascular risk factors (eg, diabetes, hypertension, dyslipidemia, lifestyle factors, etc.) on the prevalence of cardiovascular and cerebrovascular diseases are dwarfed by the magnitude of effect of advanced aging in relation to these diseases. Both cell autonomous and cell nonautonomous mechanisms of aging contribute to the pathogenesis of these diseases, including age-related oxidative stress, mitochondrial dysfunction, NAD+ depletion and dysregulation of sirtuin-regulated pathways, impaired proteostasis and autophagy, low-grade sterile inflammation, and cellular senescence (see Fuster and Hurst’s Central Illustration). Emerging experimental evidence also supports the existence and significance of diverse secreted/circulatory factors derived from distal organs that modulate cardiac and vascular aging processes (including endocrine regulation). Emerging understanding of cardiac and vascular aging processes can enable the identification of novel targets for therapeutic intervention to reverse the deleterious consequences of cardiovascular aging and to improve cardiovascular and cerebrovascular health in older adults.

eFig 82-01 Chapter 82: Cardiovascular Disease and Ageing: Cellular and Molecular Mechanisms


Significant increases in expected lifespan in previous decades have led to the rapid growth of the older population (aged ≥65 years) across the world and in the United States.1 In 2015, 617.1 million people (9% of the total world population) were aged 65 and older. By 2050, this number will increase to 1.6 billion (17% of the total world population).1 In 2016, 19.2% of the population of the European Union was aged 65 or over and it is projected that by 2050, a quarter of the European Union’s total population will be comprised of older individuals. In the United States, the population aged 65 and over is projected to reach 83.7 million by 2050, almost double its estimated population of 43.1 million in 2012.1 Governments and other stakeholders (healthcare systems, policymakers, nongovernmental organizations, funding agencies, clinicians, and researchers) have realized the importance of reducing the prevalence of chronic disease and disability associated with aging, to prevent a substantial strain on healthcare resources and the economy.

The famous 17th-century physician Thomas Sydenham (1624–1689), known as the “English Hippocrates,” observed, “a man is as old as his arteries.” Modern cardiovascular medicine concurs: Diseases of the circulatory system are the leading causes of morbidity, serious long-term disability, and mortality among older adults in the developed world.2,3 Cardiovascular and cerebrovascular diseases account for approximately one-third of all deaths in the United States at the age of 65 and nearly two-thirds at the age of 85.4 Addressing age-related cardiovascular and cerebrovascular diseases is of critical importance because the annual cost to care for these older patients are projected to more than double over the next 30 years.5

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