It is accepted that 24-h ambulatory blood pressure (BP) monitoring (ABPM) is superior to office BP measurement in predicting cardiovascular risk.1 Individuals not taking antihypertensive medication who have persistently elevated office BP readings (>140 systolic and/or 90 mmHg diastolic) but normal BP otherwise have what is known as white coat hypertension (WCH).2 The European3 and American4 guidelines on hypertension state that a diagnosis of WCH requires such values to be observed on at least three occasion, together with average daytime or home measurements of <135/85 mmHg. Although these are the criteria3,5 most often used in studies, as shown in a recent meta-analysis,6 some authors suggest that confirmation of WCH requires two ABPM readings.

WCH, which appears to occur in at least 20% of the population with office hypertension,7,8 is the subject of heated debate with regard to its prognostic significance compared to normotension or sustained hypertension. Several studies9–15 have shown that WCH is associated with low prevalences of metabolic disturbances and target-organ damage compared to sustained hypertension, but other studies have documented more structural and functional abnormalities in target organs in white coat hypertensives than in normotensives.11,16–24 A greater tendency for individuals with WCH to go on to develop hypertension has been reported by some25 but not by others.26–28 In longitudinal studies, WCH was associated with lower mortality6 and a lower incidence of cardiovascular events than sustained hypertension,29–31 and in another study no difference was seen between WCH and normotension.30 By contrast, two other longitudinal studies32,33 found that the incidence of cardiovascular events in individuals with WCH was similar to those with hypertension and higher than in normotensives. However, in one of these studies32 many patients with WCH were diabetic and had been treated with antihypertensive medication, which does not fit the usual definition of WCH, while in the other,33 the older age of the WCH subjects compared to controls could explain their higher risk. These apparently contradictory findings may be due to differences in study populations and in the diagnostic criteria for WCH.

Two aspects of the question of the risk associated with WCH have yet to be addressed. One is that nocturnal BP values are not considered in the diagnosis of WCH. This could be important, since nocturnal BP has the highest predictive value for cardiovascular risk of all BP measures.1,34 Individuals with similar daytime BP levels may have different nocturnal BP levels, with important implications for cardiovascular risk. The second is that there may be differences between normotensives, white coat hypertensives and sustained hypertensives in terms of aortic pressure, central pressure wave and arterial wave reflection, independently of the office and ambulatory BP values used to diagnose WCH. Several studies35,36 have shown that increased pulse pressure (PP) amplification (PPA) and aortic stiffness, as well as early wave reflection, are associated with increased cardiovascular risk independently of peripheral BP.

The present study aimed to assess aortic stiffness, central pressure and arterial wave reflections in individuals with normotension, WCH and treated hypertension, matched for age, gender, body mass index (BMI) and 24-h and nocturnal BP.

The study was approved by the ethics committee of Hospital Pedro Hispano. The population of this descriptive, cross-sectional, retrospective study consisted of all individuals registered in the databases of the Hypertension Unit of the Local Health Unit of Matosinhos who between 1999 and 2014 underwent 24-h ABPM and pulse wave velocity (PWV) measurement using the Complior device and analysis of central pressure curves using the SphygmoCor device. In 2014 the database included around 19000 ABPM records, 11000 PWV measurements and 6000 central pressure curves. The present study only includes records of individuals who at the time of assessment were aged over 18 years and had normal renal function (creatinemia <1.2 mg/dl), were not diabetic, and had no history of cardiovascular events.

After selection and stratification, the final study population consisted of 175 normotensives, 315 white coat hypertensives and 691 hypertensives. Table 1 shows the characteristics of the three groups. There were no significant differences between the groups in terms of age, gender, BMI, low-density lipoprotein cholesterol (LDL-C), or 24-h or nocturnal BP. As expected, normotensives presented lower office BP levels than the other groups, while hypertensives had higher values in the two indices of arterial stiffness (PWV and ASI), which did not differ between normotensives and white coat hypertensives. Regarding parameters of central pressure, compared to normotensives and white coat hypertensives, hypertensives had higher PPc, AIx and AugP and lower PPA, and included a greater percentage with microalbuminuria. There were no significant differences in any of these parameters between normotensives and white coat hypertensives.

Figure 1 shows the distribution of 24-h and nocturnal SBP levels in the three groups. As a result of the selection criteria used, a gaussian distribution can be seen in the hypertensive group but not in the other two groups, even though the mean values of the three groups are not significantly different.

Figure 1.

Distribution of 24-h and nocturnal systolic blood pressure levels in normotensives (n=175), white coat hypertensives (n=316), and treated hypertensives (n=691), matched for age, gender, body mass index and 24-h and nocturnal blood pressure. HT: hypertensives; NT: normotensives; SBP: systolic blood pressure; WCH: white coat hypertensives.

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Figure 2 shows PWV and ASI values in the three groups, divided according to 24-h SBP: low (<120 mmHg) or high (120-129 mmHg). Higher values in hypertensives than in normotensives and white coat hypertensives were observed both for individuals with 24-h SBP <120 mmHg and with 120-129 mmHg, as also shown in Table 1 in the overall population.

Figure 2.

Pulse wave velocity and aortic stiffness index in normotensives (n=175), white coat hypertensives (n=316), and treated hypertensives (n=691), according to 24-h systolic blood pressure <120 mmHg or 120-129 mmHg. The number of individuals in each group is indicated on the corresponding column. ASI: aortic stiffness index; HT: hypertensives; NT: normotensives; PWV: pulse wave velocity; SBP: systolic blood pressure; WCH: white coat hypertensives.

*p<0.04 (significantly different from normotensives and white coat hypertensives in the same group).

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Figure 3 presents AIx and PPA values in the three groups according to 24-h SBP: low (<120 mmHg) or high (120-129 mmHg). As in Figure 2, values were higher in hypertensives than in normotensives and white coat hypertensives both for individuals with 24-h SBP <120 mmHg and with 120-129 mmHg, as was also the case in the overall population.

Figure 3.

Values of augmentation index and pulse pressure amplification calculated from the central pressure wave in normotensives (n=175), white coat hypertensives (n=316), and treated hypertensives (n=691), according to 24-h systolic blood pressure <120 mmHg or 120-129 mmHg. The number of individuals in each group is indicated on the corresponding column. AIx 75: augmentation index adjusted for heart rate of 75 bpm; HT: hypertensives; NT: normotensives; SBP: systolic blood pressure; WCH: white coat hypertensives.

*p<0.04 (significantly different from normotensives and white coat hypertensives in the same subgroup).

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The present study assessed central pressures and aortic stiffness in a population of white coat hypertensives compared to normotensives and controlled hypertensives. The groups were carefully matched for age, gender, BMI and ambulatory BP values.

Indices of aortic stiffness (PWV and ASI) and central BP and peripheral wave reflection in white coat hypertensives did not differ significantly from those of normotensives but were considerably lower than in hypertensives. WCH is a common condition, with a prevalence of over 20% of the population diagnosed as hypertensive based on office BP.7,8 However, the findings of clinical trials and meta-analyses have fueled a heated debate as to whether WCH has a benign prognosis6,9–15,26–29,31 or is associated with increased cardiovascular risk16–20,22–25,32,33 compared to normotension and sustained hypertension. Since meta-analyses34,44 that include most studies comparing ABPM with office BP demonstrate that ABPM has higher prognostic value than office BP, WCH, in which ABPM values are normal, should in theory have a relatively benign prognosis.

The reasons for the conflicting results include differences in study populations with WCH and the influence of the white coat effect and cardiovascular risk factors such as age, gender, BMI, and diabetes.45,46. Thus, in order to minimize the effect of these variables in our study, we took great care to match white coat hypertensives, normotensives and hypertensives for age, gender, BMI and ambulatory BP. Furthermore, LDL-C values did not differ between the three groups, although we cannot exclude the possibility that this was due to different rates of use of lipid-lowering drugs.

To our knowledge, only one study46 has assessed arterial wave reflections in white coat hypertensives, in which factors influencing WCH were not as rigorously controlled. In our study hypertensives, even though well controlled, presented higher indices of aortic stiffness (PWV and ASI) than white coat hypertensives and normotensives. Similarly, indices derived from the central pressure wave (PPc, PPA and AIx) were less favorable in hypertensives than in the other two groups, both in the overall population and in the 24-h systolic BP <120 mmHg and 120-129 mmHg subgroups.

Although values for indices of aortic stiffness and central hemodynamics were slightly higher in white coat hypertensives than in normotensives in our study, this tendency did not reach statistical significance. Various studies have shown that increased PP and aortic stiffness and early wave reflection are independently associated with higher cardiovascular risk.35,36 Greater aortic stiffness increases BP, PP and PWV, which in turn causes peripheral wave reflection to occur early, in systole rather than in diastole.47,48 Early wave reflection, as typically seen in aging and in hypertension, leads to increased PP in the central more than the peripheral arteries, disrupting the normal amplification of PP between the aorta and the peripheral vasculature.

Our findings suggest that white coat hypertensives have a more favorable profile in terms of aortic distensibility and central pressures than hypertensives. White coat hypertensives and normotensives had similar hemodynamics and vascular structure, with similar effects on central pressure. Lower indices of aortic stiffness (lower PWV and ASI) and lower PPc for the same brachial BP gave these two groups more favorable PPA values than in the hypertensive group.

Aortic pulse wave analysis by applanation tonometry in this study showed that normotensives and white coat hypertensives presented lower AIx and AugP than hypertensives, which suggests that wave reflections from peripheral arteries are weaker in WCH. Several studies have suggested that PPc depends, among other factors, on the strength and timing of peripheral wave reflection and duration of ventricular ejection, and that reducing pulse wave reflection could lower central SBP without significantly altering peripheral pressures.49

The most important finding of our study was that aortic stiffness and central hemodynamics in white coat hypertensives are closer to those of normotensives than to those of hypertensives, for similar age, gender distribution, BMI, and ambulatory daytime and nocturnal BP. These data contrast with those of other studies in which increased aortic stiffness was seen in WCH, either intermediate between normotensives and hypertensives51 or similar to those with masked hypertension.52 However, it should be noted that these studies did not match the groups as rigorously for variables such as age, comorbidities or daytime BP on ABPM, and the diagnostic criteria used for WCH were not standard, since some patients were under therapy.

Almost all studies assessing WCH have used only daytime BP values (<135/85 mmHg), as recommended in the international guidelines.3,5 To the best of our knowledge, this is the first study in which normal nocturnal BP (<120/70 mmHg) was a diagnostic criterion for the diagnosis of WCH. Since nocturnal BP is known to be a better predictor of cardiovascular risk,5,34,44,50 this requirement may have had the effect of making WCH appear a more benign condition.

Indices of arterial stiffness and central pressure are important markers of target organ damage and predictors of cardiovascular risk,35,36,41 and the fact that these indices were relatively normal in white coat hypertensives indicates that WCH is a benign condition, although we cannot exclude the possibility that it may confer some additional cardiovascular risk. These findings support the guidelines,3–5 which recommend vigilance but not medication, since there is insufficient evidence that it is of benefit.

Our study has certain limitations. The first is that, as in all cross-sectional studies, causal relationships are difficult to establish. The second is that the particularly rigorous matching process may have led to the selection of a population at relatively low risk, and thus not fully representative of all white coat hypertensives.

Our data suggest that for similar age, gender distribution, BMI, and 24-h and nocturnal BP, aortic stiffness, central pressures and wave reflection in white coat hypertensives are closer to those of normotensives than to treated hypertensives. This means that for those with normal 24-h and nocturnal BP, WCH may be a relatively benign condition compared to hypertension, although the possibility cannot be excluded that it may confer some additional cardiovascular risk compared to normotension.

The authors have no conflicts of interest to declare.