The Deep-Breath Test as a Diagnostic Maneuver for White-Coat Effect in Hypertensive Patients

Overview

Noncontrolled hypertensive patients were administered a standard deep-breath test by their usual primary care doctors at a routine office visit. Within 2 days this was followed by 24-hour ABPM with interpretation by technicians blinded to the results of the deep-breath test.

Sample, Setting, Power Calculation

The Hospital Italiano de Buenos Aires Advisory Committee on Ethics in Human Experimentation approved the study. This primary care-based study was conducted within a university-affiliated HMO serving 70,000 patients. We included adult patients with persistently uncontrolled office hypertension (>140/90 mm Hg). Pregnant women and patients having their first 2 visits to their primary care physician were excluded. We also excluded patients with suspected secondary hypertension. The study was conducted between September 2000 and May 2001.

For the deep-breath test to achieve 80 ± 15% specificity and sensitivity, we needed at least 28 patients in the least prevalent group. Because we estimated that 40% of the population would not have the white-coat effect, we aimed to recruit a total sample size of 70 patients.

Deep-Breath Test and ABPM

All office readings were done in standard conditions and were performed in the sitting position with calibrated mercury sphygmomanometers (Baumanometer; WA Baum Co., Inc., Copiague, NY) and appropriate cuff sizes.

After taking two readings before the test (basal readings), the deep-breath maneuver was done by asking the patient to breath deeply for 30 seconds. Blood pressure was recorded immediately after the test, and then after 2 minutes. We used the 24-hour ambulatory blood pressure monitoring (SpaceLab 90207) as the reference standard for ambulatory blood pressure. It was performed within 48 hours of the deep-breath test. Primary care physicians were blind to the ambulatory blood pressure monitoring, and the ambulatory blood pressure monitoring technician was also blind to the deep-breath test results. We only report patients who had an adequate ambulatory blood pressure study with more than 80% of successful readings.

Although there is variability in the definition of white-coat effect, and both systolic (SBP) and diastolic blood pressures (DBP) are typically used, we defined it in our primary analysis as the decrease of 10% or more between baseline office and daytime ambulatory SBP.

To evaluate whether the observed difference in blood pressure after the deep-breath test was an effect of time or regression to the mean, we undertook a pilot study comparing the effect of the deep-breath test versus rechecking blood pressure after 5 minutes with the patient in the sitting position. In the 20 patients evaluated in each pilot group, the difference was significant for SBP drop (16.8 ± 9.1 mm Hg for the deep-breath test vs 4.2 ± 3.1 mm Hg in the 5-minute recheck group, P < .001), but not for DBP drop (6.7 ± 5.2 vs 5.0 ± 3.9 mm Hg). With this pilot test, we can be confident that the effect of the deep-breath test on SBP was not explained by regression to the mean or just waiting 5 minutes for another reading. We also analyzed the inter-observer agreement in a subsample of 15 patients.

Statistical Considerations

We evaluated the operating characteristics of different cutoff points, or different responses to the deep-breath test, to detect the white-coat effect. We calculated the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, and likelihood ratios positive and negative for the different cutoff values of blood pressure change. We used the κ statistic to evaluate interobserver agreement. We used logistic regression analysis adjusting for age, sex, and office blood pressure to evaluate independent factors associated with the white-coat effect. All these measurements were 2-sided, with 95% confidence limits. We used descriptive statistics to present our sample characteristics. Data were analyzed with STATA version 6.0 (STATA Corporation, College Station, TX).

Patient Sample

Of the 83 subjects who completed the 24-hour ABPM, 73 had more than 80% adequate readings and were included for further analyses; excluded patients had similar age, sex, treatment, and basal blood measurements. The mean number of ABPM readings was 112, approximately 5 per hour.

The 73 patients included in the sample for analysis had a mean age of 58.7 ± 9.5 years (mean ± SD); 45% were men. Most were receiving monotherapy, and almost a third took 2 or more drugs. Medications included β-adrenergic receptor blockers in 40%, thiazides in 36%, angiotensin-converting enzyme inhibitors in 27%, calcium channel blockers in 16%, and angiotensin receptor blockers in 5% of the patients. Other demographic characteristics and risk factors are shown in Table 1.

Interobserver Agreement

In a subsample of 15 patients, there was very good interobserver agreement between the physicians in defining a positive response for SBP (defined as a decrease of >15 mm Hg of SBP). κ = 0.81 (SE = 0.2721; P = .001). The agreement was not as good for diastolic readings.

The deep-breath test reduced SBP by 15 mm Hg and DBP by about 6 mm Hg (Table 2). We found a prevalence of white-coat effect of 62% (45 of 73) in this mostly female primary care population. As reported elsewhere,7 the white-coat effect was more frequent in women than in men (72% vs 47%; P = 0.03), in older people (subjects with white-coat effect had a mean age of 60.2 vs 56.2 in those without it; P = 0.08), and in subjects with higher office SBP (persons with white-coat effect had a mean office SBP of 158.7 vs. 146.9 mm Hg in those without it, P < .001). Only 2 patients reported mild dizziness, which did not interfere with the maneuver completion. No other adverse effect was reported.

Although there was no significant difference in DBP change, the decrease in SBP was almost twice as large in patients with white-coat effect compared with those without it. This difference was highly significant (Table 3).

Limitations

Because physicians could have been aware of the effect of the deep-breath test, they might have biased the SBP decrease. It is highly unlikely that, not knowing the ambulatory blood pressure result and white-coat effect state, they could have evaluated the blood pressure change differently in patients who were later categorized as having white-coat effect or not.

Another potential limitation is that 14% of our patients were taking no antihypertensive medications, and they could have white-coat hypertension without ambulatory hypertension. An exploratory analysis, although underpowered, showed no difference in deep-breath test behavior between medicated and nonmedicated patients. This may suggest that the deep-breath test could be a useful maneuver for white-coat hypertension as well. Different drugs may exert different effects regarding breath-test response. However, our study has no power to detect differential effects on breath-test responses among different drugs.

Because the white-coat effect can lead to overtreatment of high blood pressure,27 its detection could favor the selective treatment of sustained and refractory hypertension.12 One study showed that adjustment of antihypertensive treatment based on ABPM instead of conventional blood pressure led to less intensive drug treatment with preservation of blood pressure control and inhibition of left ventricular enlargement but did not reduce the overall costs of treatment.28 High blood pressure readings in the office are the basis of the evidence that hypertension increases cardiovascular risk, and treatment decisions in the management of hypertension are mostly guided by office blood pressure readings. To date, no study has shown the safety of withholding treatment in patients with office hypertension and normal ambulatory blood pressure. The common belief that it is unnecessary to treat office hypertension in patients with “normal” ambulatory blood pressures, although attractive, is unwarranted.29 A question that remains unanswered is the clinical relevance of the white-coat effect itself.29,30

Taking this context into account, the deep-breath test could have important clinical implications. First, it may reduce overtreatment in that therapy could be guided by post-deep-breath test measurements, which are more closely related to ambulatory pressure; second, as a consequence of avoiding overtreatment, patients health-related quality of life could be improved substantially; third, this test could also lead to less resource utilization, not only in drugs but also in 24-hour ambulatory monitoring. For example, if a cut-off point of 20 mm Hg is used, 50% of patients with white-coat effect would be detected and ambulatory monitoring potentially avoided; fourth, although formal economic evaluations are needed, deep-breath test may also reduce total economic burden in hypertension management.

In conclusion, deep-breath test can be a helpful maneuver for the detection of white-coat effect. It has no major adverse effects, and it may help avoid overtreatment and unnecessary further testing procedures.