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

AIMS: 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 AND RESULTS: Study inclusion criteria included: (i) any observational/interventional studies of participants aged ≥18 years (ii) that 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-19 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 (OR/HR), with 95% confidence interval. Twenty studies (n = 61 669; 47.3% women) were eligible, of which 13 were included in the meta-analysis (n = 55 456; 47.3% women). Median interquartile range (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 two studies (HR: 1.39, 1.05-1.84), and near doubled odds of stroke/cerebrovascular disease (OR: 1.94, 1.52-2.48). The lack of association with other outcomes may be due to weak evidence or low statistical power. CONCLUSION: 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.