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It is estimated that hypertension affects one billion people globally.1 In the United States, one in three Americans have elevated blood pressure (BP). Hypertension is responsible for 62% of cerebrovascular events and 49% of ischemic heart disease events. It is directly associated with 7.1 million deaths, making it the most common cause of death in the world. Despite these sobering statistics, 30% of adults in the United States are still unaware that they have hypertension, more than 40% are not being treated, and 65% have blood pressure levels that are above goal.2 Blood pressure increases with age such that the lifetime risk of developing hypertension among normotensive persons older than 55 years is 90%.3 The prevalence of hypertension in older women and men is 78% and 64%, respectively. The prevalence of hypertension will continue to grow due to a burgeoning population of senior citizens and an increase in factors that predispose patients to hypertension, such as obesity, diabetes, sedentary lifestyle, and dietary indiscretion.

Large observational studies demonstrate that the risk of death due to ischemic heart disease and stroke increases steeply beginning at blood pressure levels as low as 115/75 mm Hg.4Hypertension and blood pressure in the high-normal range (systolic BP [SBP] of 130 to 139 mm Hg and diastolic BP [DBP] of 85 to 89 mm Hg diastolic) are associated with a more than twofold increase in cardiovascular disease risk compared with BP <120/80 mm Hg. The importance of hypertension as a risk factor is illustrated by the high concordance between high blood pressure and first heart attack (69% have hypertension), first stroke (77% have hypertension), and heart failure (HF; 74% have hypertension). Correspondingly, lowering BP results in a cardiovascular risk reduction that is blood pressure dependent. A reduction in SBP as small as 2-mm Hg reduces the risk of death from ischemic heart disease or other vascular causes by 7% and from stroke by 10%.4 These data highlight the importance of effective treatment of hypertension.


Blood pressure is the mathematical product of peripheral vascular resistance (PVR) and cardiac output (CO), the latter defined as the product of heart rate and stroke volume (Table 3-1). Hypertension is the result of increased CO and/or increased PVR. The same factors that normally regulate BP can be responsible for the development of hypertension. Aberrations in the normal function of neurohormonal systems such as the renin-angiotensin system (RAS) or sympathetic nervous system (SNS), abnormal neuronal mechanisms, defects in peripheral autoregulation, and disturbances in sodium, calcium, and natriuretic hormones have all been implicated in the pathophysiology of hypertension. Hypertension is usually multifactorial; consequently, multiple antihypertensive drugs targeting these mechanisms are often necessary to sufficiently control BP.5

TABLE 3-1 Pathophysiology of Hypertension

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