Chapter 2

• Prehypertension: systolic pressure of 120–139 mm Hg or diastolic pressure of 80–89 mm Hg.
• Stage 1 hypertension: systolic pressure of 140–159 mm Hg or diastolic pressure of 90–99 mm Hg.
• Stage 2 hypertension: systolic pressure of at least 160 mm Hg or diastolic pressure of at least 100 mm Hg.

Hypertension is a major public health problem in the United States and many countries worldwide. Prevalence of hypertension in the United States remains unchanged in the past decade at 30%, while prevalence of resistant hypertension (failure to achieve blood pressure [BP] control despite three or more medications) has almost doubled in recent years from 16% to 28%. When the risk is calculated over lifetime, the burden of hypertension in middle-aged men and women is enormous. Eight to nine out of 10 normotensive women or men over the age of 55 are expected to develop hypertension in the next 20 years. Thus, complete understanding of basic pathophysiologic mechanisms and treatment strategies is one crucial step in improving hypertension control.

Pathophysiology of primary hypertension is complex and heterogeneous. At least one or more of the mechanisms involved in BP regulation, such as vascular, neural, renal, and hormonal mechanisms, contribute to development of primary hypertension. Accordingly, therapy often requires more than one antihypertensive agent or approach to tackle hypertension in the majority of patients.

Systemic vascular resistance and cardiac output are two major determinants of BP. Thus, augmented peripheral vasoconstriction at the level of resistance vessels may lead to hypertension in the presence of normal cardiac output. More recently, large arterial stiffness has been shown to contribute to elevated systolic BP. In many epidemiologic studies, systolic BP increases with age both in men and women. However, after the fifth decade of life, systolic BP continues to increase while diastolic BP starts to fall, causing the pulse pressure to widen. Normally, elasticity of aorta helps absorb pressure during systole, and the elastic recoil of the aorta helps maintain BP during diastole. The loss of aortic elasticity causes BP to rise excessively during systole and decrease markedly during diastole. Furthermore, the aortic pulse wave travels at much faster speed in the stiff artery, and the reflected wave from the peripheral sites further amplifies the systolic BP in the central aorta. Although diastolic BP is traditionally thought to be the most important predictor of cardiovascular risk, it is an important risk factor only for the younger population. For hypertensive patients above the age of 60, systolic BP and pulse pressures are much more important in predicting long-term cardiovascular outcomes.

Neural control of BP also plays an important role in development of hypertension. Overactivity of the sympathetic nervous system has been identified in patients with uncomplicated essential hypertension, and many conditions predispose to hypertension such as obesity, renal failure, and obstructive sleep apnea. Sympathetic overactivity contributes to hypertension by stimulating increase in cardiac output while producing peripheral vasoconstriction. Activation of β1...

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