Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies

Background: Whether orthostatic hypotension (OH) is a risk factor for cardiovascular morbidity and death is uncertain. Currently available evidence derives from non-homogeneous and partly ambiguous studies.

Objective: We aimed at assessing the relationship between OH and death or major adverse cardiac and cerebrovascular events (MACCEs) by integrating results of previous studies.

Methods: We performed a meta-analysis of prospective observational studies reporting on the association between prevalent OH, mortality, and incident MACCE, published from 1966 through 2013. Mantel-Haenszel pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for all-cause death were assessed as the primary endpoint at the longest follow-up; incident coronary heart disease (CHD), heart failure (HF), and stroke were assessed as secondary endpoints. We also performed post hoc subgroup analyses stratified by age and a meta-regression analysis.

Results: We identified a total of 13 studies, including an overall population of 121 913 patients, with a median follow-up of 6 years. Compared with the absence of OH, the occurrence of OH was associated with a significantly increased risk of all-cause death (RR 1.50; 95% CI 1.24-1.81), incident CHD (RR 1.41; 95% CI 1.22-1.63), HF (RR 2.25; 95% CI 1.52-3.33), and stroke (RR 1.64; 95% CI 1.13-2.37). When analysed according to age, pooled estimates of RR (95% CI) for all-cause death were 1.78 (1.25-2.52) for patients <65 years old, and 1.26 (0.99-1.62) in the older subgroup.

Conclusion: Orthostatic hypotension is associated with a significantly increased risk of all-cause death, incident CHD, HF, and stroke.