Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease

Author:

Juraschek Stephen P.1,Hu Jiun-Ruey2,Cluett Jennifer L.1,Ishak Anthony M.13,Mita Carol4,Lipsitz Lewis A.15,Appel Lawrence J.6,Beckett Nigel S.7,Coleman Ruth L.8,Cushman William C.9,Davis Barry R.10,Grandits Greg11,Holman Rury R.8,Miller Edgar R.6,Peters Ruth121314,Staessen Jan A.1516,Taylor Addison A.17,Thijs Lutgarde18,Wright Jackson T.19,Mukamal Kenneth J.1

Affiliation:

1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

2. Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut

3. Healthcare Associates, Beth Israel–Lahey Health System, Boston, Massachusetts

4. Countway Library, Harvard University, Boston, Massachusetts

5. Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research and Harvard Medical School, Boston, Massachusetts

6. Johns Hopkins University, Baltimore, Maryland

7. Guy’s and St Thomas’ NHS Foundation Trust, London, England

8. Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, England

9. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis

10. Department of Biostatistics and Data Science, Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston

11. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis

12. The George Institute for Global Health, Sydney, Australia

13. Department of Biomedical Sciences, University of New South Wales, Sydney, Australia

14. School of Public Health, Imperial College London, London, England

15. Research Association Alliance for the Promotion of Preventive Medicine, Mechelen, Belgium

16. Biomedical Research Group, Faculty of Medicine, University of Leuven, Leuven, Belgium

17. Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas

18. Sint-Franciscuscollege, Heusden-Zolder, Belgium

19. Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, Ohio

Abstract

ImportanceThere are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.ObjectiveTo determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.Data SourcesIndividual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.Study SelectionRandomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments.Data Extraction and SynthesisIndividual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach.Main Outcomes and MeasuresMain outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less.ResultsThe 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension).Conclusions and RelevanceIn this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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