Cardiac and Arterial Target Organ Damage in Adults with Elevated Ambulatory and Normal Office Blood Pressure

Epidemiologic studies have established that hypertension, detected by clinical blood pressure measurement, is a major contributor to cardiovascular mortality and morbidity (1, 2). Although this relation is highly significant in large populations, only a weak relation exists between blood pressure and likelihood of cardiovascular complications (3). In addition, the factors predisposing normotensive patients to cardiovascular complications have only been partially elucidated. One possible explanation is that office blood pressure readings, on which the existing epidemiologic data are based, may not consistently reflect the overall blood pressure load imposed on the heart and arterial tree because of the wide variations in blood pressure that occur during normal activity. It is now generally accepted that 24-hour ambulatory blood pressure is more closely associated with target organ damage and future cardiovascular events than isolated blood pressure readings taken in the clinic (4-6). However, a close correlation between clinic blood pressure and left ventricular mass has been reported when multiple readings in well-standardized conditions are done (7, 8). Ambulatory blood pressure may be higher or lower than clinic blood pressure, and attention has been focused on white coat hypertension (elevated clinic blood pressure with normal ambulatory blood pressure) (9-11). However, the converse, logically implicit phenomenon of elevated ambulatory blood pressure but normal clinic blood pressurewhich may be termed white coat normotension (12)has been reported in a small series (13) but has not been studied in a large population sample. We sought to 1) determine the prevalence of white coat normotension in large community and clinic samples and 2) to evaluate cardiac and vascular structure in patients classified as having sustained normotension or sustained hypertension according to both clinic and ambulatory blood pressure measurements and in patients classified as having white coat normotension. Methods Patients The study sample was recruited from the Hypertension Center of the New York Hospital-Cornell Medical Center and from ongoing longitudinal work site-based studies (14, 15). Normotensive persons (age range, 30 to 66 years) were recruited by sampling at defined work sites (n=295); 35 of the patients with sustained hypertension were drawn from the clinical population attending the Hypertension Center and 29 were drawn from the same work sites as normotensive participants. Participants recruited from work sites were enrolled, as described elsewhere (14), by blood pressure screening and subsequent stratification into sex and age groups in which 60% of patients had diastolic blood pressure less than 85 mm Hg and 40% of patients had diastolic pressure of 85 mm Hg or greater. We excluded persons with blood pressure greater than 160/95 mm Hg, those with clinically overt cardiovascular disease, and those who were unwilling to temporarily stop drug therapy. At the Hypertension Center, we recruited consecutive patients with mild hypertension (according to Joint National Committee [JNC] criteria) who were willing to unergo ambulatory blood pressure monitoring and ultrasonography when the laboratories could accommodate them. Normotensive patients had no history of treatment with antihypertensive medications; hypertensive patients either were previously untreated or had not been receiving antihypertensive and other cardioactive drugs for at least 3 weeks and as long as 6 years before study entry. Although the clinic was a smoke-free environment, current smokers were not specifically instructed not to smoke before the examination. All patients were free of clinical evidence of coronary artery or cerebrovascular disease. The presence of valvular disease was excluded by Doppler echocardiography. A total of 234 patients had sustained normotension on the basis of normal clinic blood pressure (<140/90 mm Hg) and awake ambulatory blood pressure (<134/90 mm Hg). The latter partition values were chosen because they represented the 90th percentiles of mean daytime systolic and diastolic blood pressure recordings in normal volunteers (16) and were subsequently shown to be useful in identifying patients with white coat hypertension who had little or no target organ damage (10, 11). Sixty-four patients had sustained hypertension (clinic blood pressure 140 mm Hg systolic or 90 mm Hg diastolic; awake ambulatory blood pressure 134 mm Hg systolic or 90 mm Hg diastolic). White coat normotension was identified in 61 patients who had average clinic blood pressure less than 140/90 mm Hg diastolic and awake ambulatory blood pressure of 134 mm Hg or more systolic or 90 mm Hg or more diastolic. Patients with secondary forms of hypertension were excluded. All patients underwent standard blood laboratory analyses, which included a lipid profile and determination of plasma renin activity. Informed consent was obtained under protocols approved by the Committee on Human Rights in Research of Cornell University Medical College. Blood Pressure Clinic blood pressure readings were taken by a physician or a nurse on three or more occasions by using an appropriate-sized arm cuff and a mercury sphygmomanometer; values were recorded by using the first and fifth phases of the Korotkoff sounds and were rounded to the nearest 2 mm Hg. As recommended by the fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V) (17), clinic blood pressure was determined by taking multiple measurements during at least two different visits, separated by at least 2 weeks, that did not include the first visit; these values were averaged to determine the clinic blood pressure. The schedule was set up so that the patients usually waited 10 to 15 minutes before their blood pressure was measured in the supine position. In the same study period, ambulatory blood pressure was recorded by having each patient wear a noninvasive ambulatory blood pressure recorder (Space Labs 90207 monitor [Space Labs, Redmond, Washington] with an appropriate-sized cuff) for 24 hours. The monitor was placed on the nondominant arm and was set to take blood pressure readings every 15 minutes during the day and every 30 minutes at night. After each reading, patients recorded their activity and location to allow calculation of 24-hour ambulatory blood pressure while awake, during sleep, at work, and at home. Methods used to validate these readings have been reported elsewhere from this laboratory (16). Echocardiography All patients underwent M-mode and two-dimensional echocardiography. The echocardiographs were equipped with 2.5-MHz and 3.5-MHz imaging transducers. The research technician who performed the echocardiography was aware of patients' enrollment source (work site or Hypertensive Center) but not their blood pressure status. Most of the studies were done by using an Acuson 128 echocardiograph (Mountain View, California). Researchers who were blinded to patients' clinical characteristics took left ventricular measurements from two-dimensionally guided M-mode tracings according to recommendations of the American Society of Echocardiography (18) or from linear measurements derived from the two-dimensional study if the M-mode tracings were technically inadequate (19). Measurements were performed on up to six echocardiographic cycles by using a digitizing tablet and were averaged. Left ventricular mass was calculated by using the Penn convention and was adjusted for body surface area (20). Left ventricular hypertrophy was considered present if the left ventricular mass index (left ventricular mass/height 2.7) exceeded 49.7 g/m 2.7 in men or 47.2 g/m 2.7 in women (21-23). Relative wall thickness, a measure of left ventricular geometry, was calculated as (2 posterior wall thickness)/end-diastolic dimension. Fractional shortening, ejection fraction, stroke volume, cardiac output, and total peripheral resistance were calculated by using standard formulas. Carotid Ultrasonography All patients underwent imaging of both carotid arteries with a Biosound Genesis II system (Esaote Biomedica, Florence, Italy) or an Acuson ultrasonography system equipped with 7.0-MHz to 7.5-MHz imaging transducers, as described elsewhere (15). The patient lay in the supine position with mild hyperextension of the neck to allow optimal visualization of the common carotid artery, carotid bulb, and extracranial internal and external carotid arteries on both sides. Multiple projections were used to identify any irregularity in the vessel walls. Discrete carotid atherosclerosis was defined as the presence of localized plaque, at least 50% greater in thickness than the surrounding wall, on any segment of the arteries (24). A two-dimensionally guided M-mode tracing of the distal common carotid artery, about 1 cm proximal to the carotid bulb, was obtained and was recorded on half-inch super VHS videotape with a simultaneous electrocardiogram. The videotape was subsequently reviewed by researchers who were blinded to patient characteristics, and suitable frames for measurements were obtained by using a frame-grabber (Imaging Technology, Inc., Woburn, Massachusetts), interfaced with a high-resolution (640 480 pixel) video monitor, and stored on diskettes. A reader who was blinded to patient characteristics and blood pressures took carotid measurements from the stored images by using a mouse-driven computer program (ARTSS, Cornell University Research Foundation, New York, New York) after calibration for depth and time. Measurements were obtained from several cycles and were averaged. The intimal-medial thickness of the far wall of the distal common carotid artery was measured at end-diastole. Standard wall thickness measurements were never obtained at the level of a discrete plaque. End-diastolic and peak systolic internal dimensions of the artery were determined by continuous tracing of the