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

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 the following:Twenty studies that investigated the association between OHT and future adverse events. Of these, 13 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 55 456 (47.3% 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 doubled odds of stroke or brain vessel disease. Furthermore, three of four studies found a significant association between SOHT and impaired cognition. Diastolic OHT was not found to be associated with these outcomes. The 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 that 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. 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.