By Michael H. Crawford, MD, Editor

SYNOPSIS: Patients presenting with white-coat hypertension were selected from a large, multicenter ambulatory blood pressure outcome study and compared to matched control subjects. Investigators found that the risk of cardiovascular events over a 10-year follow-up was similar between the two groups.

SOURCES: Franklin SS, Thijs L, Asayama K, et al. The cardiovascular risk of white-coat hypertension. J Am Coll Cardiol 2016;68:2033-2043.

Mancia G, Grassi G. The heterogeneous nature of white-coat hypertension. J Am Coll Cardiol 2016;68:2044-2046.

The association of white-coat hypertension with cardiovascular risk is unclear. Thus, investigators from the International Database on Ambulatory Blood Pressure in relation to the Cardiovascular Outcome compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with white-coat hypertension and 653 control subjects. The study subjects were from 11 randomly recruited population cohorts with validated outcome data, which totaled 12,752 subjects. Ambulatory hypertension was defined as daytime levels of > 135/85 mmHg, and white-coat hypertension was defined as >140 mmHg at the office visit with normal daytime ambulatory blood pressure. The controls were age and cardiovascular risk matched. The prevalence of white-coat hypertension among those normotensive on ambulatory daytime blood pressure was 11%. The white-coat subjects tended to be older, male, and to have higher cardiovascular risk. All subjects were categorized as either low risk (up to two risk factors, not including age or hypertension) or high risk (three or more risk factors, diabetes, or prior cardiovascular events). During a median follow-up of 10.5 years, 70 white-coat subjects and 48 normotensives experienced a cardiovascular event. In low-risk subjects, there was no significant increase in events in the white-coat compared to the normotensive group (494 in each group; hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.66-1.72; P = 0.80), whereas in the high-risk subjects (159 in each group) the white-coat subjects experienced more events (HR, 2.06; 95% CI, 1.10-3.84; P = 0.023). However, in subjects < 60 years of age, white-coat hypertension did not increase cardiovascular events in either risk group. The authors concluded that the risk of cardiovascular events in white-coat hypertension subjects is comparable to age and risk-adjusted normotensive controls.

COMMENTARY

Research on white-coat hypertension has suffered from small numbers of subjects, low cardiovascular event rates, and failure to account for the cardiovascular risk of the subjects. Thus, this study of 11 relatively large databases, which accounts for the subject risk profile and has a median follow up of 10 years, is of interest. The authors made the following points based on the results: 1) After adjusting for age, the white-coat effect was not influenced by the subjects’ cardiovascular risk, or, more precisely, only in older subjects with high cardiovascular risk profiles did the white-coat effect increase observed events; 2) In subjects with low risk profiles or < 60 years of age, the white-coat effect did not increase cardiovascular events, and this represented 86% of the white-coat population in this study; 3) The magnitude of the white-coat effect on blood pressure was not related to the event rate. Also, the authors speculated that in older patients at high risk for cardiovascular events, isolated systolic hypertension may have been missed because they were subject to only one day of ambulatory blood pressure monitoring and two manual blood pressure measurements on the same visit. If this is the case, then white-coat hypertension is entirely benign. Thus, in the older high-risk subject suffering from white-coat hypertension, more attention should be paid to identifying isolated systolic hypertension and perhaps treating it. Finally, the authors hypothesized that the mechanism of white-coat hypertension is a hyperactive, sympathetic response to perceived stress. If so, one would expect a rise in heart rate as well, but this is not observed in white-coat hypertension. In addition, one would expect the reaction to diminish with age, but the observation is that it is more common among older patients, so the mechanism of this phenomenon is not clear.

There are limitations to this study. Despite the large number of total subjects, only 11% presented with white-coat hypertension, and there were a low number of events over a decade of follow-up, which reduces the power of the study. Also, there was considerable heterogeneity between the 11 sites. For example, the incidence of white-coat hypertension ranged from 3-38% of the study population at each site. In addition, there was no information on subsequent anti-hypertensive drug therapy, which could have affected event rates. Finally, there were no data on blood pressure after the baseline visit, so we don’t know if the natural history of white-coat measurements or whether the development of persistent hypertension occurred in some subjects. The latter has been shown in some prior studies. At this time, we should be reassured that white-coat hypertension is a largely benign phenomenon that should not be overtreated, but in the older subjects at high risk of cardiovascular disease, we need to be sure we aren’t missing isolated systolic or masked hypertension.