Orthostatic hypertension and major adverse events: A systematic review and meta-analysis

Introduction
The role of orthostatic hypertension (OHT) in cardiovascular disease (CVD) and mortality is unclear. We aimed to determine if this association exists through a systematic review and meta-analysis.

Methods
Study inclusion criteria included: (i) any observational/interventional studies of participants aged ≥18 years (ii) which assessed the relationship between OHT and (iii) at least one outcome measure – all-cause mortality (primary outcome), coronary heart disease, heart failure, stroke/cerebrovascular disease, or neurocognitive decline. MEDLINE, EMBASE, Cochrane, clinicaltrials.gov and PubMed were independently searched by two reviewers (inception-19th April 2022). Critical appraisals were conducted using the Newcastle-Ottawa Scale. Random-effects meta-analysis was performed using a generic inverse variance method, and narrative synthesis, or pooled results were presented as an odds or hazards ratio (HR/OR), with 95% confidence interval.

Results
Twenty studies (n = 61669; 47.3% women) were eligible, of which thirteen were included in the meta-analysis (n = 55456; 47.3% women). Median (IQR) follow-up for prospective studies was 7.85 (4.12, 10.83) years. Eleven studies were of good quality, eight fair and one poor. Relative to orthostatic normotension (ONT), systolic OHT (SOHT) was associated with a significant 21% greater risk of all-cause mortality (HR:1.21,1.05-1.40), 39% increased risk of CVD mortality based on 2 studies (HR:1.39, 1.05-1.84) and near doubled odds of stroke/cerebrovascular disease (OR:1.94, 1.52-2.48). Lack of association with other outcomes may be due to weak evidence or low statistical power.

Conclusions
Patients with SOHT may have higher mortality risk relative to those with ONT and increased odds of stroke/cerebrovascular disease. Whether interventions can reduce OHT and improve outcomes should be explored.

Issue Section: Full Research Paper
Lay Summary
Orthostatic hypertension (OHT) is defined as an arbitrary rise in upper (systolic) and/or lower (diastolic) blood pressure readings on standing. We performed a thorough literature search and combined the evidence of impact of OHT on future adverse events, including death, heart attack, heart failure, stroke, falls and impaired cognition. We found:

Twenty studies which investigated the association between OHT and future adverse events. Of these, eleven were eligible to be included in the combined evidence (meta-analysis). This formed a total sample of 61,669 participants (47.3% women), of which 41,315 (51.8% women) were included in the meta-analysis.

Systolic OHT (SOHT) was associated with a significant 21% increased risk for death from any cause, a 39% greater risk of death due to heart and blood vessel disease and near doubling of stroke or brain vessel disease. Furthermore, three of four studies found a significant association between SOHT and impaired cognition. Diastolic OHT (DOHT) was not found to be associated with these outcomes. Lack of association with other outcomes investigated may be due to weak evidence.

Eleven studies were of good quality, eight fair and one poor. Differences in study design, study criteria and study populations mean the results need interpreting with caution. Future robust studies can build on this evidence to assess if treatment to reduce OHT would improve future outcomes.