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Updated: Feb 3, 2026

In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Hypertension Treatment Effects on Orthostatic Hypotension and Its Relationship With Cardiovascular Disease
Stephen P Juraschek1,2, Lawrence J Appel1,2, Edgar R Miller2
1From the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.P.J., K.J.M., L.A.L.).
Insights
Orthostatic hypotension (OH) is not a contraindication for blood pressure treatment in hypertensive chronic kidney disease patients. Lowering blood pressure goals does not increase OH risk, but certain medications may be associated with it.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- Orthostatic hypotension (OH) is often incorrectly viewed as a reason to avoid blood pressure (BP) treatment.
- Limited evidence exists regarding the impact of BP management strategies on OH in patients with chronic kidney disease (CKD).
Purpose of the Study:
- To investigate the influence of intensive versus standard BP goals and initial medication choice on the incidence of OH in the African American Study of Kidney Disease and Hypertension (AASK) trial.
- To determine if OH or its association with cardiovascular disease (CVD) events is modified by BP goal or medication.
Main Methods:
- The AASK trial randomized participants with hypertensive CKD to intensive (mean arterial pressure ≤92 mm Hg) or standard (mean arterial pressure 102-107 mm Hg) BP goals.
- Participants received initial treatment with ramipril, metoprolol, or amlodipine. OH was assessed using the consensus definition (≥20 mm Hg systolic or ≥10 mm Hg diastolic drop).
- Outcomes included congestive heart failure, stroke, CVD events, and all-cause mortality over a median follow-up of 4 years.
Main Results:
- An intensive BP goal did not affect standing BP or increase OH incidence.
- Metoprolol use was associated with a higher risk of systolic OH compared to ramipril and amlodipine.
- OH was independently associated with increased risks of stroke, nonfatal CVD, and composite CVD events.
Conclusions:
- Lowering BP goals in hypertensive adults with CKD is safe and should not be deterred by concerns about OH.
- While metoprolol may increase OH risk, the overall association between OH and CVD events was not altered by BP goal or medication choice in this cohort.
Abstract:
Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ≤92 mm Hg) or standard (mean arterial pressure, 102-107 mm Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52 864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm Hg, 95.5±14.2 mm Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15-2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09-3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80-13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21-4.30), and any CVD event (HR, 2.12; 95% CI, 1.12-3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.
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