By Michael H. Crawford, MD, Editor

SYNOPSIS: In a long-term, fixed-drug therapy of hypertension study, masked uncontrolled and white coat uncontrolled hypertension exhibited poor reproducibility over four years. This calls into question studies showing higher rates of adverse outcomes with one baseline blood pressure assessment used to categorize patients.

SOURCE: Mancia G, Facchetti R, Cuspidi C, et al. Limited reproducibility of MUCH and WUCH: Evidence from the ELSA study. Eur Heart J 2020;41:1565-1571.

Recent outcome studies of hypertension management have focused on masked uncontrolled hypertension (MUCH), where only office blood pressure (BP) is controlled (not home BP), and white coat uncontrolled hypertension (WUCH), where only home BP is controlled. In some studies, both have shown an increase in cardiovascular outcomes. The authors of these studies almost always only measured ambulatory BP once. Thus, the long-term reproducibility of MUCH and WUCH is unclear.

Accordingly, Mancia et al interrogated the European Lacidipine Study on Atherosclerosis (ELSA), a comparison of the effect of a calcium channel blocker to a beta-blocker on carotid intima-media thickness (CIMT) over an average of four years. The authors examined the annual assessments of office and ambulatory BP measurements for the stability of MUCH and WUCH. Only patients with at least two annual measurements were included, resulting in 1,664 subjects studied. At baseline, the prevalence of patients with white coat hypertension was 13%. After one year of treatment, the prevalence of MUCH was 18%, WUCH 21%, and controlled hypertension 45%. These relative prevalences remained constant throughout the four-year study, but there were large shifts of patients from one category to another. Only 34-41% of MUCH patients maintained this classification one or more years later, while 38-45% of WUCH patients maintained this classification. Controlled hypertension (office and ambulatory) was more consistent (46-57% persistence), as was uncontrolled hypertension (61-68%). The most common category shift for MUCH patients was to uncontrolled hypertension. Few patients among 918 with complete datasets with MUCH or WUCH maintained these classifications throughout (5% and 6%, respectively). These properties did not vary with the type of randomized treatment. The authors concluded that both MUCH and WUCH exhibit poor reproducibility over time on a constant drug regimen. This calls into question the prognostic value of these classifications if measured only once.

COMMENTARY

The original definition of masked and white coat hypertension came from observations in untreated patients. Outcome studies demonstrated that white coat hypertension was associated with persistent hypertension later in life. However, long-term outcomes are unclear, as is whether white coat hypertension needs to be treated pharmacologically. Masked hypertension has been associated with a higher risk of sustained hypertension, diabetes, and organ damage, which is almost as high as sustained hypertension. Masked hypertension is common. The incidence in the Hypertension Optimal Treatment (HOT) study was 25%; in the Spanish hypertension registry, it was 30%. Mancia et al recorded a rate of 18%. Also, masked hypertension has been reported in up to 16% of presumably healthy individuals, especially young people with borderline office blood pressures. However, the effect of pharmacologic treatment of isolated masked hypertension is unclear. The Mancia et al study takes these concepts into a pharmacologic hypertension treatment trial, which concerned the comparative effects of two classes of drugs on atherosclerosis measured by CIMT. The patients were put on fixed doses of lacidipine or atenolol for four years without regard for blood pressure control after the initial titration phase to a diastolic BP < 95 mmHg. This created an opportunity to study the reproducibility of MUCH and WUCH independent of drug therapy. Mancia et al demonstrated poor reproducibility of both, which was independent of the drug therapy. Patients with completely controlled or completely uncontrolled hypertension demonstrated significantly better reproducibility. Other shorter studies with measurements in two-month intervals have shown better reproducibility of these four subgroups. Hypertension is a long game, so clinicians need long-term reproducibility to assess outcomes. In MUCH patients, the most common category change was to completely uncontrolled. Considering the poor outcomes reported in other studies, it would seem that MUCH should be treated. It is less clear what to do with WUCH.

One of the strengths of the Mancia et al study was the use of standardized office and high-quality ambulatory BP measurements rather than home BP. However, other studies have shown the variability in ambulatory BP measurements is high. Weaknesses of this study included the lack of data on drug adherence and annual measurements of BP rather than more frequent assessments. Also, the authors reported no outcome data, probably because there were few events in ELSA. Pending future research, it seems patients who report high home BPs (but who record normal office BP) would be ideal candidates for ambulatory BP studies during therapy.