White-Coat Hypertension: Pathophysiological and Clinical Aspects: Excellence Award for Hypertension Research 2020

Abstract

Few issues of modern cardiovascular medicine have been as controversial as the relationship between white-coat hypertension (WCH), that is, a common condition in which office blood pressure is elevated while out-of-office blood pressure (ambulatory blood pressure or home blood pressure) is normal. While earlier studies showed no increased risk of cardiovascular events in WCH compared with the normotensive state, more recent studies have changed this conclusion by showing that an increased cardiovascular risk represents a trait of this hypertensive phenotype. The present article will review a number of issues related to WCH, that is, its definition, pathophysiological background, clinical alterations, and prognostic significance. This will be done by considering the available evidence published during the last decades, with special focus on the data collected in PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni)-a research project performed with a cross-sectional and longitudinal design, which has provided a series of novel clinical information on WCH throughout the years. The final part of the article will discuss the therapeutic implications of the abovementioned evidence, as well as some controversial or still undefined issues related to WCH, whose investigation will be an important goal to pursue by future research.

Keywords: antihypertensive treatment; blood pressure; cardiovascular risk factors; goals; medicine; prognosis; therapeutics.

Figure 1.

Metabolic variables in normotensive (N), white-coat hypertensive (WCH), and sustained hypertensive (SH) subjects of the PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni) population, that is, a sample of about 2100 subjects representative of the citizenship of Monza—a town in the northeast outskirt of Milan—for age decades (25–74 years), sex, and socioeconomic status. Participation rate was 64% of the sample of 3200 subjects. The N status was established by office, 24-h, and home BP normality. WCH was diagnosed by office BP elevation (≥140 mm Hg systolic or 90 mm Hg diastolic) with a normal 24-h or home BP (<125/79 mm Hg or <132/82 mm Hg, respectively). SH was diagnosed by elevation of all 3 BP values. *P<0.05, statistical significance between groups. BMI indicates body mass index; Chol, cholesterol; DM, diabetes mellitus; HDL, high-density lipoprotein; IFG, impaired fasting glucose; and MS, metabolic syndrome. Data derived from Mancia et al.

Figure 2.

Increase in incidence (top) and adjusted risk (bottom) of new-onset sustained hypertension (SH), new-onset echocardiographic left ventricular hypertrophy (LVH), new-onset diabetes mellitus (DM), and a new-onset impaired fasting glucose (IFG) state in the PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni) population sample 10 y after the initial survey. Data from normotensive (N), white-coat hypertensive (WCH), and limited to new LVH, DM, and IFG, from SH subjects. New LVH was identified by a left ventricular mass index >99 g/m² in women and >114 g/m² in men according to the body surface area; IFG was identified by a blood glucose ≥100 mg/dL, DM by a blood glucose ≥126 mg/dL or antidiabetic drug treatment and SH by addition of out-of-office to office BP elevation. Risk and P refer to age- and sex-adjusted data. Adj OR indicates adjusted odds ratio; and OR, odds ratio. Data derived from Mancia et al.^–

Figure 3.

Cumulative incidence (Kaplan-Meier curves) of cardiovascular (CV; upper left) and total mortality (lower left) in normotensive (NT), white-coat hypertensive (WCH), and sustained hypertensive (SH) subjects of the PAMELA study (Pressioni Arteriose Monitorate e Loro Associazioni.) In the left panel, numbers refer to absolute and percent fatal events. The right panels show the corresponding hazard ratio (HR), having NT as reference. HR (and 95% CI) data are shown unadjusted, adjusted for age and sex, and after further adjustment for metabolic variables, smoking, previous CV events, antihypertensive treatment, etc (full). n refers to the number and percentage showing an event during the follow-up. Data derived from Mancia et al.

Figure 4.

Twenty four–hour and home systolic (S) and diastolic (D) blood pressure (BP) values in normotensive (N) and white coat hypertensive (WCH) subjects from the PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni) population. Bottom, Left, Prevalence (%) of nocturnal hypertension in N and WCH. Bottom, Right, SBP variability in N, WCH, and sustained hypertension (SH) of the PAMELA study. P refers to data adjusted for age and sex. Twenty-four-hour BP variability was calculated as the variability value that survived the elimination of the oscillatory variability components (day-night and prepostprandial) identified by the Fourier analysis, which was termed residual or erratic variability. Data derived from Mancia et al, Cuspidi et al, and Mancia et al.

Figure 5.

Reduction of office and 24-h systolic blood pressure (SBP) in the hypertensive patients of the ELSA trial (European Lacidipine Study on Atherosclerosis) treated with antihypertensive drugs for 4 y. SBP was measured at narrow intervals during the initial titration phase and then at intervals of 6 mo. Grey histograms refer to sustained hypertensive patients and white histograms to white-coat hypertensive (WCH). The right panels show the relationship between the treatment-induced reduction of office or 24-h SBP and the corresponding baseline values. White points indicate WCH patients and grey points, sustained hypertensive (SH) patients. Statistical significance between groups are shown by the following symbols: *P<0.05, ΔP<0.01, † and ‡P<0.0001 vs control. WCH indicates white-coat hypertension. Data derived from Mancia et al.

Figure 6.

Percentage of patients with white-coat uncontrolled hypertension (WUCH) at the first set of office and ambulatory blood pressure (BP) measurements who, ≥1 y later, maintained the same status (white color) or became uncontrolled hypertensives (no office and 24-h BP control, dark grey), masked hypertensives (no 24-h BP control, black) or controlled hypertensives (both office and 24-h BP control, light grey). Histograms below the circles show how often WUCH was detected during the treatment period, that is, 1, 2, 3 or all 4 times BP measurements were made (yearly intervals). Data derived from Mancia et al.