Editorial Commentary
High Prevalence of White-Coat Hypertension in Spanish
Resistant Hypertensive Patients
William J. Elliott
See related article, pp 898 –902
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hypertensive population. Both white-coat phenomena (effect
and hypertension) would be expected to be more common in
resistant hypertension than in the general hypertensive population, because neither typically responds well to antihypertensive drug therapy.
In this issue of Hypertension, de la Sierra et al6 present
interesting analyses of data from their large registry of
Spanish patients who had 24-hour ABPM performed and
were recruited from primary care and specialty clinics since
2004. They carefully gathered data from ⬎68 000 hypertensive patients and determined that 12.2% had resistant hypertension. More interestingly, 37.5% of these 8295 patients had
relatively normal 24-hour ambulatory blood pressures, so
their elevated clinic pressures could be explained by the
white-coat effect, and the remaining 62.5% had “true resistant
hypertension.” With the exception of younger age, the latter
group had a higher prevalence of each and every cardiovascular risk factor that was examined compared with those who
displayed the white-coat effect. In addition, the latter group
was more likely to display the “early morning surge” in blood
pressure, which has been associated (at least in epidemiological
studies) with an increased risk of stroke (49%), acute myocardial
infarction (39%), and cardiovascular death (29%).7
These data are important because of the large number of
included patients, the difficulties involved in gathering similar nationwide data from both primary care and specialty
sites (particularly in the United States), and the validation of
previous knowledge about the increased risk factor burden
and disturbed circadian blood pressure variation in true
resistant hypertensives (drawn from much smaller populations, many with inherent selection biases). The authors’
estimate of the prevalence of resistant hypertension is much
lower than that garnered from the American Society of
Hypertension Registry Initiative, which has a growing database of 265 000 unique hypertensive patients, primarily from
North Carolina, South Carolina, Florida, and Georgia (the
“Stroke Belt,” where hypertension, uncontrolled hypertension, and its sequelae were once more common than other
regions in the United States). Approximately 33% of patients
with uncontrolled hypertension in this database were taking ⱖ3
antihypertensive medications per day.8 The question thus arises
as to whether differences in the prevalence of resistant hypertension could be regional (because of diet, prevalence of hypertension, or access to medical care).9 It also reinforces other data
suggesting that the white-coat effect may be more common in
Italy and Spain compared with Northern Europe and North
America. Only a very large effort using a standardized protocol
would be able to properly address these issues.
esistant hypertension is a major public health challenge
both in the United States and worldwide. Although
various authors use different definitions, a recent scientific
statement from the American Heart Association Professional
Education Committee of the Council for High Blood Pressure
Research1 defined resistant hypertension as blood pressure
either controlled by ⱖ4 antihypertensive medications or
ⱖ140/90 mm Hg, despite 3 antihypertensive medications of
different classes, at near-maximal US Food and Drug Administration–approved doses, one of which is a diuretic. Some
authors add a minimum duration of 3 months of such
treatment; others insist that the medications must be “appropriately chosen,” the patient adherent, and/or the patient
referred by a physician to a hypertension center. Patients with
resistant hypertension are of great public health importance,
because they have a higher risk of future cardiovascular and
renal events, greater healthcare expenditures, a higher prevalence of secondary hypertension and target organ damage,
and are, by definition, “difficult to control.”1,2 Most reports of
the prevalence of resistant hypertension come from tertiary
referral centers2,3 or from clinical trials that implemented a
stepwise sequence of medications to control blood pressure4,5; ⬇15% to 20% of all hypertensives in these reports
would be classified as “resistant.”
A major confounder in the office diagnosis of resistant
hypertension is the “white-coat effect,” defined as a persistently increased blood pressure in the medical office compared with home (or better) 24-hour ambulatory blood pressure monitoring (ABPM).3 In the United States, the
distinction between the white-coat effect and white-coat
hypertension is important, because one criterion for the latter
diagnosis (which is required for reimbursement of 24-hour
ABPM), according to the Centers for Medicare and Medicaid
Services, is the lack of target organ damage. The procedure is
currently not covered for Medicare beneficiaries who have
target organ damage, even if their 24-hour ambulatory blood
pressure monitor shows an unequivocal white-coat effect.
The exact prevalence of the white-coat effect varies, but the
usual range in large studies is 18% to 33% across the general
The opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
From the Division of Pharmacology, Pacific Northwest University of
Health Sciences, Yakima, WA.
Correspondence to William J. Elliott, Division of Pharmacology,
Pacific Northwest University of Health Sciences, 200 University Pkwy,
Yakima, WA 98901. E-mail [email protected]
(Hypertension. 2011;57:889-890.)
© 2011 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.111.170118
889
890
Hypertension
May 2011
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The data of de la Sierra et al6 also shed some new light on
the large group (37% in this report) of patients who would
have been classified as “resistant hypertensives” if ABPM
had not been performed (as is often the case in the United
States). It is still controversial as to how much effect, if any,
the white-coat effect has on prognosis10 and whether such
patients should be spared more intensive treatment and
investigation. The multivariate analyses of de la Sierra et al6
indicate that the risk factor burden of resistant hypertensive
patients with the white-coat effect is lower than that of
patients without it. However, it is unlikely that the differences
in risk factor profile are sufficient to discriminate between
these diagnoses; in addition, ABPM is the only way to obtain
information about the circadian pattern of blood pressure.
These data are consistent with the call from many outside the
United States to use ABPM more, for both initial diagnosis
and assessment of therapy. One hopes that de la Sierra et al6
will enlighten us further in future publications reporting on
factors that led to intensification of treatment after ABPM, its
results in BP control, and long-term cardiovascular and renal
outcomes (and associated healthcare expenditures) in their 2
large cohorts. It is tempting to predict that ABPM might be
economically justified, perhaps even in the United States, if
future costs for “extra” medications and clinic visits could be
avoided, without increasing the risk of very expensive hospitalizations in the group displaying the white-coat effect.
Sources of Funding
None.
Disclosures
In the last 12 months, W.J.E. has been the principal investigator of
an investigator-initiated research grant (to his institution) from and a
consultant to Forest Research Institute, as well as on the speakers’
bureau for Forest Laboratories. He has been a consultant to NicOx,
Inc (since out of business in the United States), and BoehringerIngelheim and has received honoraria and royalties from Elsevier.
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High Prevalence of White-Coat Hypertension in Spanish Resistant Hypertensive Patients
William J. Elliott
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Hypertension. 2011;57:889-890; originally published online March 28, 2011;
doi: 10.1161/HYPERTENSIONAHA.111.170118
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