Table 1.

Relationship of cardiovascular human aging in health to cardiovascular disease

Age-associated changes	Plausible Mechanisms	Possible relation to human disease
Cardiovascular structural remodeling
↑Vascular intimal thickness	↑Migration of and ↑matrix production by VSMC Possible derivation of intimal cells from other sources	Early stages of atherosclerosis
↑Vascular stiffness	Elastin fragmentation ↑Elastase activity ↑Collagen production by VSMC and ↑ Cross linking of collagen Altered growth factor regulation/tissue repair mechanisms	Systolic Hypertension LV wall thickening Stroke Atherosclerosis
↑LV wall thickness	↑LV myocyte size with altered Ca2+ handling ↓Myocyte number (necrotic and apoptotic death) Altered growth factor regulation Focal matrix collagen deposition	Retarded early diastolic cardiac filling ↑Cardiac filling pressure Lower threshold for dyspnea ↑Likelihood of heart failure with relatively normal systolic function
↑Left atrial size	↑Left atrial pressure/volume	↑Prevalence of lone atrial fibrillation and other atrial arrhythmias
Cardiovascular functional changes
Altered regulation of vascular tone	↓NO production/effects	Vascular stiffening; hypertension Early atherosclerosis
Reduced threshold for cell Ca2+ overload	Changes in gene expression of proteins that regulate Ca2+ handling; increased ω6ω3 PUFA ratio in cardiac membranes	Lower threshold for atrial and ventricular arrhythmia Increased myocyte death Increased fibrosis
↑Cardiovascular reserve		Lower threshold for, and increased severity of heart failure
Reduced physical activity	Learned lifestyle	Exaggerate age changes in some aspects of CV structure and function. Negative impact on atherosclerotic vascular disease, hypertension, and heart failure

Abbreviations: LV, Left ventricular; PUFA, polyunsaturated fatty acids;