Isolated systolic hypertension: pathophysiology, consequences and therapeutic benefits

Abstract

During recent decades the importance of perceiving isolated systolic hypertension (ISH) in cardiovascular pathophysiology has been changed from a benign condition to the major cardiovascular risk factor. Aging is per se associated with the deterioration in arterial compliance through both structural and functional changes in large arteries which mainly involves the intima and media. The observed changes result in a decrease of the lumen-to-wall ratio, the overall lumen cross-sectional area and an increase of arterial stiffness which especially involve the aorta and other elastic arteries. In addition to the structural changes in vessel walls, aging is associated with certain functional changes such as an increase in sympathetic system activity probably due to the age-related decreased sensitivity of beta-receptors. While the function of arterial wall alpha-receptors remains intact, in elderly subjects a shift towards arterial vasoconstriction can be observed. In many of the published studies the definition of ISH was based on the criterion 160/95 mm Hg or 160/90 mm Hg while in recognition of the high risk associated with systolic blood pressure (SBP) the WHO/ISH guidelines and Report of the Sixth Joint National Committee on Hypertension indicated that ISH should be diagnosed with SBP as > or =140 mm Hg and diastolic BP (DBP) as <90 mm Hg. Thus the setting down of normal values of SBP will lead to an earlier diagnosis and treatment of ISH. Several prospective studies, such as the US Hypertension Detection and Follow-up Programme, confirmed this and the Multiple Risk Factor Intervention Trial demonstrated that for any given level of DBP, higher SBP was associated with an increase in cardiovascular risk. Moreover, data from the Framingham Study show that ISH was associated not only with increased mortality but also cardiovascular morbidity. Risk of non-fatal stroke and myocardial infarction was increased three and two-times respectively in the presence of ISH. Three major up-to-date studies that included patients with ISH have been published. In concordance to the previously published SHEP and MCR trials, the most recent, the Systolic Hypertension in the Elderly Trial (SYST-EUR), demonstrated that active treatment significantly reduces the risk of stroke and all fatal and non-fatal cardiac end-points, including sudden death. Of note, these benefits were demonstrated with new anti-hypertensive classes such as dihydropiridyne calcium channel blocker (nitrendipine) and the angiotensin-converting enzyme inhibitor (enalapril). The necessity to carefully balance the benefits and risks of anti-hypertensive therapy in the elderly indicates that patients with suspected ISH should undergo careful BP measurements on at least three different occasions before the diagnosis is established and an orthostatic reaction should be evaluated. If non-pharmacological procedures fail, drug therapy should be considered, especially in elderly patients with a SBP over 160 mm Hg, since their risk of complications is markedly higher. Pharmacological treatment should also be strongly considered in patients with a SBP between 140 and 160 mm Hg with such concomitant cardiovascular risk factors as diabetes, angina pectoris, and left ventricular hypertrophy. The drug regimen should be simple, starting with a low dose of a single drug that is titrated slowly. The selection of the first-line anti-hypertensive agent should be based on a careful assessment of pathophysiological and clinical parameters in each individual geriatric patient.