Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis Anna Angelousi a , Nicolas Girerd b , Athanase Benetos c , Luc Frimat d , Sylvie Gautier c , Georges Weryha a , and Jean-Marc Boivin b Objective: Several studies have suggested that orthostatic hypotension may be an independent predictor of cardiovascular or cerebrovascular risk and all-cause mortality, particularly in a geriatric population. In 1996, a consensus defined orthostatic hypotension as a SBP fall at least 20 mmHg and/or a DBP fall at least 10 mmHg within 3 min of standing. Methods: Pubmed and Cochrane database were searched up to October 2013 in order to identify prospective studies evaluating, in adult populations, the association between orthostatic hypotension as defined by the 1996 consensus and clinical outcome. Meta-regression was performed when sufficient data were available. Results: A total of 28 prospective studies were found eligible for inclusion in this systematic review. Nine prospective studies found an association between orthostatic hypotension and various cardiovascular events such as coronary disease, heart failure, and arrhythmias. No association was found between orthostatic hypotension and the risk for strokes and falls in the majority of the prospective included studies. Insufficient data were available to perform a meta-analysis for strokes and falls. The meta-analysis of seven prospective studies found that orthostatic hypotension is associated with a significant increased risk for overall mortality [pooled hazard ratio in random-effects model ¼ 1.36 (1.13–1.63), P < 0.001)]. Conclusion: This meta-analysis provides evidence that orthostatic hypotension is associated with a 36% increase in the risk of overall mortality. A systematic review of the literature suggests that orthostatic hypotension is also associated with a higher risk for cardiovascular events. Insufficient data are available to enable a precise assessment of the association of orthostatic hypotension with strokes and falls. Keywords: cardiovascular risk, cognitive decline, coronary disease, dementia, falls, mortality, orthostatic hypotension, strokes, white matter lesions hyperintensities Abbreviations: CBV, cerebrovascular disease; CI, confidence interval; COH, consensus orthostatic hypotension; DOH, diastolic orthostatic hypotension; FTD, frontotemporal dementia; HTA, hypertension; MCI, mild cognitive decline; MI, myocardial infarction; NOH, neurogenic orthostatic hypotension; OHT, orthostatic hypertension; ONT, orthostatic normotensive; OR, odds ratio; PD, Parkinson disease; SD, standard deviation; SOH, systolic orthostatic hypotension INTRODUCTION O rthostatic hypotension is a multifactorial disorder, often asymptomatic, with a nonnegligible preva- lence ranging from 5–11% among middle-aged patients to 20% or more in the frail elderly [1,2]. According to a widely used consensus guideline established in 1996 by the American Autonomic Society and the American Academy of Neurology, orthostatic hypotension is defined as a decrease in SBP of at least 20 mmHg and/or a decrease in DBP of at least 10 mmHg within 3 min of standing up [3,4]. Traditionally, the cause of orthostatic hypotension has been classified as neurogenic in the context of chronic autonomic failure such as Parkinson’s disease, multiple system atrophy and pure autonomic failure, or among patients with polyneuropathy (diabetes or autonomic disorders, i.e. Sjogren’s disease). Nonneurogenic ortho- static hypotension is largely attributable to medications such as vasodilators, diuretics, and tricyclic antidepressants [5]. It is generally believed that patients with orthostatic hypotension are particularly vulnerable to falls, and to cardiovascular complications due to the acute drop of Journal of Hypertension 2014, 32:000–000 a Department of Endocrinology, Ho ˆ pital de Brabois, CHU, Vandœuvre-le ` s-Nancy, b Clinical Investigation Center-Inserm CIC9501, Lorrain du Coeur et des Vaisseaux Louis Mathieu, Nancy, c Department of Geriatrics and d Department of Nephrology, Ho ˆ pital de Brabois, CHU, Vandœuvre-le ` s-Nancy, France Correspondence to Anna Angelousi MD, 6 Rue Andromachis, 12135 Athens, Greece. Tel: +00302105742648 and þ00306978167876: e-mail: a.angelousi@gmail.com Received 27 September 2013 Revised 1 April 2014 Accepted 1 April 2014 J Hypertens 32:000–000 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0000000000000235 Journal of Hypertension www.jhypertension.com 1 Original Article