Managing White‐Coat Effect

Abstract

A 68-year-old woman was referred to the hypertension clinic for evaluation of resistant hypertension. She had been receiving antihypertensive medication for approximately 30 years. Good control had been demonstrated on 2 and 3 medications until the prior year. After that, her blood pressure was consistently elevated in the clinic despite an increasing drug regime; home blood pressure was controlled. A few years before her referral, intolerance to hydrochlorothiazide with hyponatremia had been noted, and she was placed on lisinopril and atenolol. However, her serum potassium level rose to 6.4 mEq/dL, and lisinopril was discontinued. Felodipine was added to atenolol, with office systolic blood pressure levels in the 150- and 160-mm Hg range. Hydralazine and clonidine were not effective. There was no history of diabetes mellitus or target organ damage. On evaluation, blood pressure measured by a medical assistant was 178/102 mm Hg, and levels measured by a physician were 152/98 mm Hg (both arms, supine) and 150/104 mm Hg (right arm, standing). Results of physical examination were unremarkable. The patient indicated complete adherence to her regime of felodipine 10 mg/d and atenolol 50 mg/d. Laboratory tests revealed a creatinine level of 1.1 mg (normal, 0.6–1.1 mg), a fasting glucose level of 124 mg/dL (normal, 70–125 mg/dL), and a low-density lipoprotein cholesterol level of 128 mg/dL (normal, <130 mg/dL). Findings on electrocardiography were normal. Felodipine was increased to 20 mg/d, atenolol was maintained at 50 mg/d, and furosemide 10 mg twice daily was initiated and increased to 20 mg twice daily. The patient steadfastly indicated complete adherence to her medical regimen, and a record of medication refills showed timely pickups. Systolic blood pressure levels in the clinic continued mostly in the 160-mm Hg range. Her 2-year-old home blood pressure apparatus was validated in the office, and a mean of 18 home recordings, mostly in the morning after awakening, was 112/66 mm Hg. A mean of 44 blood pressure readings taken from a 24-hour ambulatory blood pressure recording was 113/63 mm Hg. On clinic follow-up, an initial blood pressure measured by a medical assistant was 172/64 mm Hg, followed by readings of 154/74 mm Hg, 149/72 mm Hg, 148/74 mm Hg, and 152/76 mm Hg. On the continuum where blood pressure determinations are generally higher at the physician's office than at home, white-coat effect with drug-treated hypertension is probably more common than white-coat hypertension in the absence of drug treatment. White-coat effect describes an alerting reaction, either transient or persistent, observed in a majority of patients.1 Whereas the true prevalence of white-coat hypertension may be about 15%,2 in the majority of patients with true hypertension, drug treatment reduces but does not eliminate the white-coat effect.3 Fortunately, multiple blood pressure readings taken by nurses and trained clinic assistants, rather than physicians, can obviate the large amount of white-coat effect. Figure 1 depicts the impact of both observer effect and regression to the mean effect when blood pressure was measured with intra-arterial blood pressure monitors by physician and nurse observers on the opposite arms of patients whose blood pressure had stabilized. Follow-up blood pressure readings taken by both the physician and nurse were reduced approximately 10/5 mm Hg after 5 to 10 minutes. Nonetheless, blood pressure readings taken by physicians remained 10/5 mm Hg higher than those obtained by nurses, even when measurements were repeated.4 All of the hypertension treatment trials are based upon levels obtained by nurses and trained, non-physician personnel. Regression to the mean effect with repeat blood pressure assessment; observer effect comparing doctor and nurse. SBP indicates systolic blood pressure; DBP, diastolic blood pressure. aP<.005; bP<.05. Reproduced with permission from Mancia et al.4 In specialty clinic-based studies of resistant hypertension, “office resistance” was responsible for only 6% of the total resistance that was encountered after multiple blood pressure readings were obtained.5 Considering that approximately 30% of hypertensive patients may be refractory to at least 3 drugs, the experience of these clinics implies that <2% of the total number of hypertension patients will experience office resistance. Patients at another large referral center with hypertension refractory to near-maximal doses of 3 drugs, including a diuretic, underwent 24-hour ambulatory blood pressure monitoring.6 These patients were further defined as adherent to their medications, and secondary etiologies were ruled out; 19 of 49 (39%) were found to have office resistance, defined as a 24-hour ambulatory mean blood pressure <135/85 mm Hg. However, this group of 19 patients represented <1% of 2500 referrals to that hypertension unit. Nonetheless, patients refractory to ≥3 antihypertensive drugs need to be screened for medication adherence, and white-coat resistance should be considered.7 When office resistance is suspected despite 3 or 4 clinic visits at which repeated nurse- or medical assistant-administered blood pressure readings are obtained, 2 diagnostic approaches to clarify the issue are home blood pressure monitors and 24-hour ambulatory blood pressure recordings. The Seventh Report of the Joint National Commission on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)8 lists “apparent drug resistance (office resistance)” as a “clinical situation in which ambulatory blood pressure monitoring may be helpful.” Home blood pressure determinations represent an attractive, more easily obtainable, and less expensive alternative. According to a national survey, 60% of individuals who knew they had hypertension had home blood pressure devices.9 However, several obstacles need to addressed before blood pressure readings obtained at home can be considered reliable. Not every patient is a candidate. Obese individuals may not fit available cuff sizes, and patients with anxiety syndromes may overuse these devices and suffer panic attacks with secondary blood pressure elevations. Studies have shown that 40% of patients do not read the instructions, 50% of patients lack any training in measuring blood pressure, and patients frequently fabricate low numbers and omit elevated numbers.10,11 These are obstacles that can be overcome by careful selection of patients, training with regard to blood pressure technique, and the use of home devices containing memory chips. In addition to control of patient-based variables, use of reliable home blood pressure data also requires machine and protocol standards. Suitable devices are those receiving a “pass” grade from the Association for the Advancement of Medical Instrumentation or European Hypertension Society or an “A” or “B” rating from the British Hypertension Society (BHS). A Web site, www.dableducational.com, lists the most current status of home devices. A suitable monitor should also receive a validation every 1 to 2 years. Use of a Y-tube connector where simultaneous pressures are obtained with a home apparatus and a mercury manometer may be inaccurate due to rapid deceleration rates of oscillometric devices compared to optimal mercury manometer deceleration.12 A second validation option, offered by Pickering,13 involves taking a series of blood pressure measurements alternating between the office and home monitor. Up to 5 such readings are obtained, and the home device has passed the validation when a blood pressure level falls within 5 mm Hg systolic and diastolic of an immediately preceding or succeeding office reading. An explicit stepwise template of Pickering's validation protocol is being used routinely within Kaiser Permanente (KP) by medical assistants (Figure 2). A small prospective study involving 4 centers within KP (3 in southern California and 1 in Virginia) found that 71% (40/56) home machines were satisfactorily comparable to recently inspected aneroid manometers in clinic settings using this protocol. A failure rate of 28% demonstrates that home monitor readings cannot be uniformly accepted without machine validation, even when all the pertinent patient factors are addressed. Home machines older than 2 years had a higher failure rate. Patients appreciated having their machines evaluated. Stepwise validation protocol for home blood pressure (BP) apparatus, modeled after Pickering.3 An adequate home blood pressure record also requires a minimal number of suitably timed determinations. Though several small studies using disparate methodologies are difficult to compare, an analysis by Verberk and associates14 recommended a minimum of 2 blood pressure readings twice daily, morning and evening, for 3 consecutive days, discarding the first day because of training effect that skewed the readings higher. A prospective cohort home blood pressure study by Bobrie and colleagues15 relied upon 3 blood pressure readings twice daily, morning and evening, for four days15. Some have advised discarding the first of each set of three readings.16 A minimum of 6 to 8 readings17,18 for routine hypertension management, but perhaps preferably at least 14 readings, may be necessary.14,19–22 However, recent American Heart Association and European Society of Hypertension consensus has recommended a protocol of 2 to 3 morning readings and 2 to 3 evening readings every day for 7 days and to discard the readings of the first day in order to provide a minimun of 12 readings.23 Morning BP readings are advised between 6 am and 10 am, within an hour of awakening and before morning antihypertensive medication; evening BP readings are performed before bedtime. Recommendations for home blood-pressure monitoring have been made by the International Consensus Conference, the American Heart Association, the Japanese Society of Hypertension, the American Society of Hypertension, and the European Society of Hypertension.12,24–27 A patient reporting log for home blood pressures adopted by southern California KP is illustrated in Figure 3. However, it has proven difficult for many patients to fill in all of the desired blood pressures, and many times just the morning readings taken 2 or 3 times in sequence on the same morning for at least 3 days are accepted. Established by several methods, a mean home BP level <135/85 mm Hg for patients without cardiovascular comorbidities is considered controlled hypertension.15,28,29 Patient log form for reporting home blood pressure (BP) values. Is the prognosis favorable or unfavorable for patients receiving multiple antihypertensive agents with elevated office blood pressure levels and controlled home blood pressure averaging <135/85 mm Hg? Limited experience suggests a favorable prognosis. A few prospective studies have shown that patients without diabetes mellitus and lacking associated cardiovascular or renal disease who are resistant to antihypertensive therapy according to clinic blood pressure criteria with a normal ambulatory blood pressure have a low incidence of cardiovascular events.30,31 Is it necessary to identify this subset of patients by 24-hour ambulatory blood pressure monitoring? Probably not, provided a home blood pressure evaluation with all of the indicated quality parameters is undertaken.32 Home blood pressure assessment is similar to ambulatory assessment in predicting both cardiac and renal damage.14 In the Japan Home vs Office Blood Pressure Measurement Evaluation (J-HOME), patients with home resistant hypertension vs home controlled hypertension were more likely to have renal disease and hyperlipidemia.33 It is unpractical and unnecessary to subject all hypertensive patients with suspected white-coat effect to ambulatory blood pressure monitoring. The patient under discussion was suspected of having office resistant hypertension because of self-reported home blood pressure. Of interest, office resistance appeared only in the last year following more than 20 years of controlled hypertension and is not usually thought of as an etiology of acquired resistance. Increasing age and female sex are risk factors for the white-coat effect.3 Multiple follow-up nurse-administered clinic blood pressure assessments demonstrated a systolic blood pressure decrease of 20 mm Hg, but the patient's blood pressure was always elevated in the clinic setting. Her home machine was a BHS-approved instrument with a memory chip and was validated according to a protocol modified from Pickering's method. The patient's blood pressure technique was verified, and an appropriate number of home blood pressure readings, mostly taken in the morning within an hour of awakening and before her 3 morning antihypertensive medications, which included a diuretic, averaged well under 135/85 mm Hg. The Table lists the necessary features for identifying white-coat resistant (office resistant) hypertension with home blood pressure monitoring. It is important that the home monitor is validated with office equipment every 1 to 2 years.25 Office resistance is a lesser concern when several blood pressure readings are obtained by non-physicians (ie, nurses and medical assistants). Because she was referred to a specialty hypertension clinic, a 24-hour ambulatory blood pressure recording was obtained, and a mean blood pressure almost exactly that obtained via home assessment was obtained. The ambulatory blood pressure apparatus did not offer significant additional information to assist in patient management. Felodipine, furosemide, and atenolol were continued. It was decided to manage her hypertension based upon meaned sequences of at least 12 home blood pressure readings every 3 months, as templated in Figure 3, in addition to office visits at 6-month intervals. This patient probably has a good cardiovascular prognosis but will need careful follow-up. The author acknowledges Joyce M. Cheung, RN, MN, CPHQ, Director, Care Management, Kaiser Permanente, Orange County, California, for designing the nurse/medical assistant home blood pressure monitor validation protocol and the patient home blood pressure reporting log displayed in Figures 2 and 3.