Atherosclerosis confers an illness burden on the general population larger than that associated with any other disease process. With advancing age, the incidence and prevalence of coronary, cerebral, and peripheral arterial disease (PAD) and aneurysmal formation are higher and their severity is more pronounced. Thus, cardiovascular disease (CVD) outcomes are worse in older compared to younger adults. Although age is the most powerful independent risk factor for CVD, the mechanisms by which aging predisposes to atherogenesis are only now becoming elucidated, as are specific strategies to optimally prevent and treat atherosclerotic disease in older adults.
Research to date, spanning from basic science to epidemiology, suggests that aging potentiates atherosclerosis through a combination of factors (Figure 75-1). First, specific biological changes associated with aging increase vulnerability to atherosclerosis. Second, increasing age lengthens the time of exposure to known CV risk factors and modifies their effects. Finally, older individuals have increased comorbidities, which may contribute to or exacerbate the severity of atherosclerosis, particularly conditions that create or maintain a proinflammatory biologic milieu.
Schematic view of the intersection and overlap between aging and atherosclerosis.
The clinical manifestations of atherosclerotic disease are more varied and severe in older compared to younger adults. Multiple etiologic factors have variable effects on the aging vasculature over a lifetime (Figure 75-2). Thus, vascular aging plays a primary and prominent role in predisposing older individuals to atherogenesis. This chapter highlights how vascular aging, in addition to both traditional and nontraditional risk factors, can enhance and accelerate the development of atherosclerosis in older adults.
Contributors to the development of atherosclerosis interact with vascular aging to increase the variability and severity of disease manifestation in older age.
It is a common misconception that vascular aging is synonymous with the development of atherosclerosis. Although the majority of individuals older than 60 years have clinically significant (>75%) coronary stenoses on autopsy, at least 25% of this age group will have only mild or no significant coronary plaque burden. Yet, age-associated vascular changes, and the cellular and molecular factors that underlie their development, do increase the vulnerability of older arteries to atherogenesis (Table 75-1).
Table 75-1 Common Underlying Pathologies of Vascular Aging and Atherosclerosis |Favorite Table|Download (.pdf)
Table 75-1 Common Underlying Pathologies of Vascular Aging and Atherosclerosis
- NOS uncoupling
- ↓Total and free NO
- ↑Adhesion molecule expression
- Endothelial cell senescence
- Progenitor cell senescence
- ↑Susceptibility to sheer stress
- ↑MMP levels and activity
- ↑Adhesion molecule expression
- ↑Nitrite and nitrate
- ↑ACE activity
- ↑AT-II activity
- ↑SMC proliferation
- SMC senescence
- ↑Thickness (from SMC proliferation and matrix deposition)
- ↑Luminal diameter
- Basement membrane permeability