Orthostatic hypertension is an accessible, low-cost marker of cardiovascular risk

This editorial refers to ‘Orthostatic hypertension and major adverse events: a systematic review and meta-analysis’, by Z. Pasdar et al., https://doi.org/10.1093/eurjpc/zwad158. Orthostatic hypertension (OHT) is understudied and underrecognized. In fact, OHT is not even defined or commented upon in international hypertension guidelines.1,2 While no specific blood pressure (BP) threshold is consistently used, studies examining OHT typically define OHT as an increase in systolic blood pressure (SBP) ≥ 20 mmHg and/or an increase in diastolic blood pressure (DBP) ≥ 10 mmHg when moving from a supine to upright position.3–5 The mechanisms underlying OHT are thought to include baroreceptor reflex abnormalities, exaggerated adrenergic response to changes in cardiac loading conditions (i.e. decreased preload in the setting of vascular pooling), and endothelial dysfunction.3 Given the possible mechanistic connections between OHT and cardiovascular disease (CVD), a better understanding of its clinical implications is important. In this issue, Pasdar et al.6 demonstrate a consistent association between OHT and key cardiovascular/cerebrovascular outcomes through a systematic review and meta-analysis of available data. Studies eligible for inclusion were observational (prospective and cross-sectional) and interventional studies, which assessed the association between systolic and/or diastolic OHT and at least one of the following outcomes: all-cause mortality, incident coronary heart disease (CHD), heart failure (HF), stroke, falls, or neurocognitive decline. Studies were limited to adults and were conducted in inpatient as well as outpatient settings—both community-dwelling adults and those living in nursing/residential facilities were included. For this analysis, 378 studies were identified with 20 ultimately included, comprising 61 669 participants (47% women) from 12 countries. Of the included studies, one was a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) and the remainder were observational. Participant characteristics varied, but most studies focused on older adults (80% of studies in adults >40 years), and only one excluded individuals with baseline hypertension. Study quality was assessed using the Newcastle–Ottawa Scale, and studies that the authors identified as relatively homogeneous—based on the study population, design, outcome, and context—were pooled for analysis. Analyses were considered adjusted if they at minimum adjusted for age (although all analyses adjusted for additional factors). Random-effects meta-analyses were conducted using the Cochrane Collaboration statistical software package. Pasdar et al.6 report an association between systolic OHT and all-cause mortality in both studies, which provided unadjusted (n = 5) and adjusted (n = 7) hazard ratios (HRs) [unadjusted 1.44 (1.01, 2.06), P = 0.05; adjusted 1.21 (1.05, 1.40), P = 0.007]. There were no associations between diastolic OHT and mortality or OHT and mortality when the definition of OHT included DBP (SBP ≥ 20 mmHg and/or DBP ≥ 10 mmHg). They also found significant associations between systolic OHT and CVD death [adjusted HR: 1.39 (1.05, 1.84), P = 0.02] and stroke/cerebrovascular disease [unadjusted OR: 1.94 (1.52, 2.48), P < 0.001]. There were no significant associations between OHT and incident HF or incident myocardial infarction, and in their review of studies unable to be pooled, they found no, or inconsistent, associations between OHT and a number of secondary outcomes (e.g. left ventricular hypertrophy, cognitive decline, and coronary artery disease). There are some important limitations to this meta-analysis. There was substantial heterogeneity in some of the primary analyses (i.e. unadjusted all-cause mortality and systolic OHT had a high statistical heterogeneity, I2 = 86%), limiting the interpretation of the findings. In addition, for some outcomes, the associations are presented unadjusted (e.g. systolic OHT and stroke), which likely overestimates the reported effect size. Unfortunately, young people were frequently excluded in the analysed studies, which limits the generalizability of these findings to this important population. And while this meta-analysis showed associations between systolic OHT and a number of important CVD outcomes, it remains unclear if treating OHT would reduce CVD risk or prevent disease. Nonetheless, this analysis provides compelling evidence for the consideration of OHT, specifically systolic OHT, as a marker of increased CVD/cerebrovascular risk. Indeed, there is evidence that individuals with OHT are more likely than those without OHT to have a number of other abnormal BP phenotypes associated with increased CVD risk, such as masked hypertension, extreme nocturnal dipping, increased BP variability, and increased morning BP surge.3 Of note, these BP phenotypes are defined using ambulatory BP monitoring, which can be inaccessible, costly, intrusive, and challenging to obtain repeatedly over time. On the other hand, orthostatic vital signs can be easily collected at routine clinic visits. Professional societies such as the European Society of Hypertension, the American Heart Association, and the American College of Cardiology ought to consider including a definition of OHT in their hypertension guidelines to help guide future studies in this area. Further studies are needed to refine the optimal thresholds for OHT, to clarify how to implement in-clinic measurement of orthostatic vital signs, and to determine if OHT can identify individuals who would benefit from further testing and/or interventions including ambulatory BP monitoring. Given the high, and rising, mortality rates attributable to hypertension, innovative and low-cost interventions that can identify and treat at-risk individuals are of critical importance.7

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