What is the clinical evidence from this study?

Study design: Cohort. Population: Isolated systolic hypertension (n=4714). Intervention: Orthostatic hypertension vs. Normal orthostatic response. Primary outcome: All-cause mortality at 17 years (fully adjusted) (HR 1.27, 95% CI 1.06-1.53, p=0.0096).

February 25, 2019Open Access

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

Key Result

Orthostatic hypertension was associated with a 27% increased risk of long-term all-cause mortality at 17 years compared to a normal orthostatic response in older adults with isolated systolic hypertension (HR 1.27, 95% CI 1.06-1.53, p=0.0096).

Study Design

Type

Cohort (n=4,714)

Blinding

Double-blind

Multicenter

Yes

Structured PICO

Does orthostatic hypertension increase the risk of all-cause mortality in older adults with isolated systolic hypertension?

Population

4,714 older adults (aged 60 years and older) with isolated systolic hypertension, followed for up to 17 years to assess the association of orthostatic hypertension with mortality.

Exposure

Orthostatic hypertension (defined as an SBP increase by ≥15 mm Hg upon standing after 1 minute).

Comparator

Normal orthostatic response (changes in SBP between hypertensive and hypotensive categories).

Outcome

All-cause mortality at 4.5 years and 17 years following randomization.hard clinical

Orthostatic hypertension is an easily detectable clinical sign that independently predicts long-term all-cause mortality in older adults with isolated systolic hypertension.

Main Result

Hazard Ratio: 1.27 (95% CI 1.06–1.53)

p-value: p=0.0096

Limitations

Retrospective nature (post-hoc analysis not specified during the design of SHEP)
Inclusion of only older patients with isolated systolic hypertension who were otherwise healthy
Use of diuretic-based stepped-care therapy
Lack of information on 24-h ambulatory blood pressure
Lack of measurement of orthostatic changes during the years after randomization
No information on non-fatal events, pharmacologic therapy, and other interventions at 17 years following randomization

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.

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