Mechanical factors in arterial aging: a clinical perspective

Abstract

The human arterial system in youth is beautifully designed for its role of receiving spurts of blood from the left ventricle and distributing this as steady flow through peripheral capillaries. Central to such design is "tuning" of the heart to arterial tree; this minimizes aortic pressure fluctuations and confines flow pulsations to the larger arteries. With aging, repetitive pulsations (some 30 million/year) cause fatigue and fracture of elastin lamellae of central arteries, causing them to stiffen (and dilate), so that reflections return earlier to the heart; in consequence, aortic systolic pressure rises, diastolic pressure falls, and pulsations of flow extend further into smaller vessels of vasodilated organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased stresses on small arterial vessels, particularly of brain and kidney. Clinical manifestations are a result of diastolic LV dysfunction with dyspnea, predisposition to angina, and heart failure, and small vessel degeneration in brain and kidney with intellectual deterioration and renal failure. While aortic stiffening is the principal cause of cardiovascular disease with age in persons who escape atherosclerotic complications, it is not a specific target for therapy. The principal target is the smooth muscle in distributing arteries, whose relaxation has little effect on peripheral resistance but causes substantial reduction in the magnitude of wave reflection. Such relaxation is achieved through regular exercise and with the vasodilating drugs that are used in modern treatment of hypertension and cardiac failure.