Association of orthostatic hypertension with mortality in the Systolic Hypertension in the Elderly Program

Abstract

We examined the association of orthostatic hypertension with all-cause mortality in the active treatment and placebo randomized groups of the Systolic Hypertension in the Elderly Program (SHEP). SHEP was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the effect of chlorthalidone-based antihypertensive treatment on the rate of occurrence of stroke among older persons with isolated systolic hypertension (ISH). Men and women aged 60 years and above with ISH defined by a systolic blood pressure (SBP) of 160 mm Hg or higher and diastolic blood pressure lower than 90 mm Hg were randomized to chlorthalidone-based stepped care therapy or matching placebo. Among 4736 SHEP participants, 4073 had a normal orthostatic response, 203 had orthostatic hypertension, and 438 had orthostatic hypotension. Compared with normal response, orthostatic hypertension was associated with higher all-cause mortality at 4.5 and 17 years in analyses adjusted for age, gender, treatment, SBP, and pulse pressure (PP, HR 1.87, 95% CI 1.30-2.69, p = 0.0007; HR 1.40, 95% CI 1.17-1.68, p = 0.0003, respectively). These associations remained significant after additional adjustment for risk factors and comorbidities (HR 1.43, 95% CI 0.99-0.08, p = 0.0566 at 4.5 years, and HR 1.27, 95% CI 1.06-1.53, p = 0.0096 at 17 years). The increased risk of all-cause mortality associated with orthostatic hypertension was observed in both the active and placebo groups without significant interaction between randomization group and the effect on mortality. Orthostatic hypertension is associated with future mortality risk, is easily detected, and can be used in refining cardiovascular risk assessment.

Fig. 1

Factors associated with all-cause mortality at 17 years. Hazard ratios and 95% confidence intervals derived from a Cox regression model adjusting for demographic and clinical variables

Fig. 2

All-cause mortality at 4.5 and 17 years among patients with orthostatic hypertension as compared to normal response by randomization group (active treatment or placebo). Hazard ratios and 95% confidence intervals adjusted for age, sex, and systolic blood pressure, and pulse pressure (top) and adjusted for serum creatinine, diabetes, BMI, smoking status, left ventricular failure, HDL cholesterol, and randomization to active treatment, as well as age, gender, and baseline SBP and PP (bottom)