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CV Events and Mortality in White Coat Hypertension
Study Questions:
What is the impact of untreated white coat hypertension (WCH) and treated white coat hypertension (WCE or white coat effect) on risk of cardiovascular (CV) events and all-cause mortality?
Methods:
The authors conducted a systematic review and meta-analysis using PubMed and EMBASE, without language restriction, from inception to December 2018. Two investigators reviewed observational studies with ≥3 years of follow-up evaluating the CV risk of WCH or WCE compared with normotension. Twenty-seven studies comprised 25,786 participants with untreated WCH or treated WCE and 38,487 with normal blood pressure (BP) followed for a mean of 3-19 years. Six studies were population based, 11 recruited participants from outpatient clinics, and 10 included patients who were referred for ambulatory BP monitoring (ABPM) or to a specialized hypertension clinic. Eighteen studies assessed out-of-office BP with ABPM, seven with home BP monitoring, and two with both methods. To diagnose WCH or WCE, 15 studies used a daytime out-of-office BP threshold of <135/85 mm Hg, seven used a 24-hour threshold of <130/80 mm Hg, and five used a different threshold (such as 125/80 mm Hg) or combined both thresholds. Twenty-five studies incorporated antihypertensive medication in the models, and all adjusted for ≥2 additional covariates among smoking status, lipid levels, diabetes mellitus, body mass index, kidney function, and left ventricular hypertrophy.
Results:
Mean study-specific participant age ranged from 43 to 72 years (median, 56 years) with a mean follow-up of 3-19 years (median, 8 years). Compared with normotension, untreated WCH was associated with an increased risk for CV events (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.03-2.00), all-cause mortality (HR, 1.33; 95% CI, 1.07-1.67), and CV mortality (HR, 2.09; 95% CI, 1.23-4.48); the risk of WCH was attenuated in studies that included stroke in the definition of CV events (HR, 1.26; 95% CI, 1.00-1.54). No significant association was found between treated WCE and CV events (HR, 1.12; 95% CI, 0.91-1.39), all- cause mortality (HR, 1.11; 95% CI, 0.89-1.46), or CV mortality (HR, 1.04; 95% CI, 0.65-1.66). The findings persisted across several sensitivity analyses.
Conclusions:
Untreated WCH, but not treated WCE, is associated with an increased risk for CV events and all-cause mortality. Out-of-office BP monitoring is critical in the diagnosis and management of hypertension.
Perspective:
The increased use of out-of-office BP monitoring (ambulatory and home BP) to supplement and more accurately base treatment options and BP targets has led to several different BP phenotypes with different prognostic implications. These BP phenotypes that require a combination of in-office and out-of-office BP readings include masked hypertension (normal in-office but elevated out-of-office BP), and WCH (elevated in-office and normal out-of-office). Patients with WCH have been shown to be at modestly increased CV risk compared to true normotensives in several prior studies. This meta-analysis confirmed this finding. However, it is important to note that while included studies may have adjusted for several covariates (age, body mass index), the individual prior studies included in this meta-analysis did not correct for BP differences.
Despite having BP levels within a categorically defined “normal” range, individuals with WCH are well-known to typically have slightly higher home BP values (5-10 mm Hg) than true normotensives. This likely explains most or all of the apparent increase in CV risk. Thus, WCH can often be considered a state of “prehypertension” or “elevated BP” (using the new terminology) – a condition well-known to be linked to higher CV risk.
Finally, the current American College of Cardiology/American Heart Association/multisociety Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults now defines stage I hypertension as a BP level in the clinic, home, and daytime ambulatory monitoring >130/80 mm Hg. All previous studies that assessed the risk of WCH used the diagnosis of hypertension in the clinic as a BP >140/90 mm Hg. Therefore, the new guidelines have completely changed the relevance of all prior studies as well as the current meta-analysis results regarding WCH.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Hypertension, Smoking
Keywords: Ambulatory Care Facilities, Antihypertensive Agents, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Body Mass Index, Diabetes Mellitus, Hypertension, Hypertrophy, Left Ventricular, Lipids, Masked Hypertension, Metabolic Syndrome, Prehypertension, Primary Prevention, Smoking, Stroke, White Coat Hypertension, Vascular Diseases
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