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Epidemiologic studies such as the National Health and Nutrition Examination Surveys have shown that the overall prevalence of hypertension in noninstitutionalized individuals above the age of 65 is between 50% and 70%. The prevalence is highest among African-Americans relative to whites and Mexican-Americans. Unlike the younger hypertensive population in which there is a male predominance, there is no marked gender difference in the overall prevalence of hypertension in the elderly. Moreover, the age-associated increase in the prevalence of isolated systolic hypertension appears to be greater for women than for men.

Pathophysiology

Many age-related changes in physiology contribute to the increase in blood pressure. Lifestyle factors, such as diet, obesity, and physical activity, and the presence of comorbidities are also important contributors. A multitude of pathophysiologic mechanisms interact in the dynamic and complex regulation of arterial blood pressure. The maintenance of blood pressure homeostasis and the provision of adequate cerebral perfusion in the response to such hypotensive stimuli as volume depletion, upright posture, vasodilating medications, or a meal is an important physiologic challenge facing the aging individual.

As is the case in younger individuals, the etiology of essential hypertension in older humans is not known. An increase in peripheral vascular resistance is one pathognomonic feature of hypertension in the elderly. Several mechanisms contribute to the increase in peripheral vascular resistance. Table 40.2 summarizes those mechanisms that appear to be associated with aging and are discussed in detail here. A rational approach to therapy of hypertension in older individuals requires an understanding of this pathophysiologic context. Although not all the following mechanisms have been convincingly proven to be primary age-associated changes (i.e., independent of the effects of disease or lifestyle factors), they may be important contributors to hypertension in the elderly. It is also quite possible that the age-associated increase in blood pressure is secondary to age-related disease or lifestyle factors, because in some populations the increase in blood pressure with aging is either absent or less marked.

An age-associated increase in arterial vascular stiffness has been demonstrated, particularly in the larger arteries. Several alterations in vessel structure contribute to the decrease in distensibility, such as an increase in smooth muscle cell size and number, an increase in medial collagen deposition, and a decrease in elastin content. Arterial compliance and stroke volume are the major determinants of pulse pressure. Because stroke volume does not vary significantly with age, the decline in arterial compliance produces an increase in pulse pressure, which contributes to a disproportionate increase in systolic pressure. This finding may account for the age-associated increase in the prevalence of isolated systolic hypertension, as well as an increase in pulse pressure. Another consequence of the decrease in arterial compliance with aging is an increase in arterial pulse wave velocity. The increase in arterial pulse wave velocity has been shown to lead to an early return of wave reflection, which alters the aortic pressure wave contour, increasing the pressure in late systole. The wave reflection further accentuates the increase in pulse pressure between central and peripheral arteries.

In addition to changes in vascular structure, the dynamic regulation of vascular tone by the autonomic nervous system, as well as by the vascular endothelium, is an important determinant of peripheral vascular resistance. A decrease in baroreceptor sensitivity with age has been described, perhaps as a manifestation of the decrease in arterial distensibility already discussed.

The decline in baroreceptor sensitivity alters the central nervous system (CNS) control of sympathetic nervous system (SNS) outflow, resulting in two important manifestations. First, having an insensitive baroreceptor means that a larger change in blood pressure is needed to activate the baroreceptor and produce the appropriate compensatory response. Attenuated baroreceptor sensitivity is believed to contribute to the greater blood pressure variability in older individuals.

Second, attenuated baroreceptor sensitivity results in enhanced SNS activity for a given level of arterial blood pressure. Many studies have demonstrated an age-associated increase in the activity of the SNS measured by an increase in plasma norepinephrine levels, rates of norepinephrine release determined from tracer kinetics studies, and muscle sympathetic nerve activity.

The increase in the rate of norepinephrine release would be expected to result in increased cardiovascular adrenergic responses if it were not for the corresponding downregulation of adrenergic receptor function. Indeed, there is evidence to suggest an age-associated decrease in adrenergic responsiveness for β-adrenergic receptor chronotropic, inotropic, and vascular responses, as well as for α-adrenergic vasoconstrictor responses.

As a result of the decrease in arterial α-adrenergic receptor response, it appears that overall arterial α-adrenergic tone is similar in older normotensive compared with younger normotensive subjects and that an increase in peripheral vascular resistance cannot be accounted for solely by age-associated changes in SNS function. Hypertensive older individuals, however, have been characterized by having greater arterial α-adrenergic receptor responsiveness relative to their level of SNS activity in comparison to older normotensive subjects.

Another important modulator of vascular tone is the vascular endothelium, which synthesizes a number of vasoactive substances. Endothelial-derived relaxing factor (EDRF) is a potent vasodilator that has been extensively investigated since being identified as nitric oxide. Several studies have demonstrated that there is an age-associated decrease in EDRF-mediated vasocilation, and there may also be endothelial dysfunction with hypertension. Impaired function of this important regulator of vasodilator tone could lead to an increase in peripheral vascular resistance if not met by appropriate compensatory alterations in other vasoactive systems. The extent to which impaired endothelial function contributes to an increase in blood pressure in aging remains to be defined.

Several age-associated changes in renal function (e.g., decreased renal blood flow and glomerular filtration rate) combine to result in an age-associated inability to rapidly excrete a sodium load. The net result of these alterations is a tendency for sodium retention by the aging kidney and an increase in total body sodium. It has been observed that a greater proportion of older hypertensives demonstrate an increase in mean arterial blood pressure in response to challenge with a sodium load or demonstrate sodium sensitivity. These renal changes in sodium balance may contribute to the increased prevalence for sodium sensitivity among older individuals.

The renin-angiotensin system represents another blood pressure regulatory system that may be altered with advancing age. The evidence in this instance is for an age-associated decline in plasma renin activity. There is a corresponding low prevalence of older hypertensives with high renin levels. The decrease in plasma renin activity may be related to a decrease in the number of glomeruli, as well as an increased delivery of sodium to the macula densa.

Several studies have identified an age-associated impairment in glucose tolerance. Decreased sensitivity to the peripheral effects of insulin on carbohydrate metabolism, or insulin resistance, with aging may contribute to the decline in glucose tolerance. Insulin resistance and an associated increase in fasting insulin levels have been shown to be a characteristic of some hypertensive groups, including older hypertensives. Although a mechanistic causal link between insulin resistance and hypertension has not yet been identified, if such a mechanism exists, an age-associated decline in insulin sensitivity could contribute to hypertension. However, based on the results of a study performed to determine predictors of insulin sensitivity, it appears that age is not an independent predictor of insulin sensitivity after accounting for the confounding effects of higher body mass index and blood pressure. Thus, although there is a clear association between blood pressure and insulin resistance and many older hypertensives are insulin resistant, there are no data to indicate that an age-associated decline in insulin sensitivity independently contributes to hypertension in older adults.

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