AJH 2004; 17:523 528 Frequent Nurse Visits Decrease White Coat Effect in Stage III Hypertension Grazia Maria Guerra-Riccio, Dante Marcelo Artigas Giorgi, Fernanda Marciano Consolin-Colombo, José Augusto Soares Barreto-Filho, Heno Ferreira Lopes, Ana Lúcia Rego Fleury Camargo, and Eduardo Moacyr Krieger Arterial hypertension is a public health problem and patient adherence to treatment is challenging. This study tested whether frequent nurse visits provide additional benefits to antihypertensive treatment. Every 30 days, a pharmacist visited these patients to deliver antihypertensive drugs and perform a pill count. Nurses visited group A (48 patients) every 15 days and group B (52 patients) every 90 days. Ambulatory blood pressure (BP) monitoring was performed 15 and 180 days after randomization. At randomization, groups A and B had the same clinical systolic (191 5 v 186 3 mm Hg) and diastolic BP levels (122 3 v 117 4 mm Hg), respectively. After 90 days, BP declined more in group A than in group B (35 5/19 3 v 27 5/9 3 mm Hg). At 180 days, the difference increased because the reduction persisted in group A but decreased in group B (36 6/21 4 v 17 4/10 2 mm Hg). The mean ambulatory BP monitoring values were similar in both groups at 15 and 180 days. However, the attenuation of the clinic daytime BP difference was larger in group A than in group B (systolic, 13 4 v 3 4 mm Hg; diastolic 11 3 v 4 3mm Hg). The patients with clinic daytime differences decreased more in group A (systolic, 16 to 10; diastolic, 20 to 14) than in group B (systolic, 19 and 20; diastolic, 22 and 22). These data indicate that frequent nurse visits significantly attenuate the white coat effect (clinic daytime BP difference). Am J Hypertens 2004;17:523 528 2004 American Journal of Hypertension, Ltd. Key Words: Hypertension, adherence of patient, attention of patient, ambulatory blood pressure monitoring. Evidence exists indicating that patient adherence to antihypertensive regimens is essential to obtain blood pressure (BP) control in hypertension. 1 Unfortunately, up to 50% of patients undergoing antihypertensive treatment are nonadherent after 1 year, 2 and 85% are nonadherent after 5 years. 3,4 The nonadherence to hypertensive regimens is complex and involves different factors: chronic conditions and patient perception of the disease, the complexity and cost of the medical regimen, adverse effects of the medication, and also the behavior of health care providers. 5 According to a recent review, 6 during the past four decades only 19 intervention studies have been published that used a randomized, controlled design with both adherence and clinical outcomes measured and with a 6-month or longer follow-up. Approximately one half of these procedures showed a positive impact on adherence. Therefore, new strategies are necessary to predict and improve patient adherence to hypertensive regimens in pharmacologic and nonpharmacologic treatment, especially the greater use of nurses and other health care professionals working on the health care team. The main objective of this study was to analyze whether frequent visits (every 15 days) by a nurse result in additional benefits in controlling BP when compared with patients receiving visits every 90 days in patients with stage III hypertension under antihypertensive treatment for 6 months. A pharmacist was included in the professional health care team to assure the delivery of medication to all patients. Special attention was focused on the white coat effect, defined as the difference between clinic and average daytime BPs, which has been attributed to increased tension and induced by the measurement of BP by a physician and less so when measured by a nurse. 7 Because the additional benefit produced by frequent nurse visits during antihypertensive treatment could, in part, result from the attenuation of the white coat effect, in addition to clinic BP Received September 16, 2003. First decision November 12, 2003. Accepted February 9, 2004. From the Hypertension Unit Heart Institute (InCor HC. FMUSP), Faculty of Medicine of the University of São Paulo, São Paulo SP, Brazil. This study was supported by grants from Fundação de Amparo á Pesquisa do Estado de São Paulo (FAPESP) and Fundação Zerbini São Paulo, Brazil. Address correspondence and reprint requests to Dr. Eduardo Moacyr Krieger, Hypertension Unit Heart Institute (InCor HC. FMUSP), Faculty of Medicine of the University of São Paulo, Av Dr Enéas de Carvalho Aguiar, 44, Cerqueira Cesar, São Paulo, SP-Brazil 05403-000; e-mail: edkrieger@incor.usp.br 2004 by the American Journal of Hypertension, Ltd. Published by Elsevier Inc. 0895-7061/04/$30.00 doi:10.1016/j.amjhyper.2004.02.007
524 NURSE VISITS DECREASE WHITE COAT HYPERTENSION AJH June 2004 VOL. 17, NO. 6 we used ambulatory BP monitoring (ABPM) in our study to evaluate the white coat effect. Methods Subjects The study population included 100 patients, both sexes, with primary hypertension who were treated at the Hypertension Unit of the Heart Institute (InCor) of the Medical School of the University of São Paulo, Brazil, during a 6-month period. The patients were randomized in two groups. Group A was comprised of 48 patients, 26 women and 22 men, with a mean age of 54 10 years; 17 were white and 31 were not white, with a mean body mass index of 30.7 6 kg/m 2. This group had a nurse visit every 15 days (12 nurse visits). Group B was comprised of 52 patients, 21 women and 31 men, with a mean age of 53 9 years; 21 were white and 31 were not white, with a mean body mass index of 30.6 5 kg/m 2. This group was selected to receive nurse visits every 90 days (2 nurse visits). The same nurse was responsible to BP measurement in patients of groups A and B. During the time of the study, the patients had regular physician visits (every 3 months). Both groups received the same attention from the physicians who make the necessary adjustment on the therapy on an individual basis not knowing to which group the patient belongs. Therefore, the major difference between group A and B was the number of nurse visits. The Ethics Committee of the Heart Institute of the University of São Paulo School of Medicine approved the study protocol, and written informed consent for participation was obtained from all subjects. FIG. 1. Clinic systolic and diastolic blood pressures for group A (gray columns) and groupb (black columns) measured on the day of randomization (0) and during the study period (total of 180 days). Study Protocol At the first nurse interview (day 0: randomization), a questionnaire was used to obtain information related to general data, habits, history of disease, other risk factors for cardiovascular disease, and prescribed medications. This questionnaire was used only to characterize the adherence behavior and the risk factors at the beginning the study, but was not used to evaluate modifications of behavior during the study. Body weight and height were measured. Three consecutive measurements of BP were taken after the patient had rested for 5 min in the supine position. The patients were instructed to return to visit the nurse according to the randomization schedule. At each return, the nurse gave patients the necessary reinforcement about adherence to the therapy and took new BP measurements. Also on this day (day 0: randomization), patients had a first interview with the pharmacist who supplied them every month with the exact number of tablets necessary for each 30-day period, gave instructions on the correct use of the medications, its possible side effects, and performed a pill count. The medication delivered to the patient was free. To quantify the effect of the special attention to BP control of the hypertensive patients, we compared the level of systolic and diastolic BP measurements. These were used as a baseline (obtained on the day of randomization; Fig. 1). We used the BP of both groups at the 90- and 180-day follow-up and compared them with that at baseline and between groups, at office and ambulatory BP monitoring at 15 and 180 days. Blood pressure was measured at every nurse visit with an appropriate-sized cuff (standard and obesity fitted cuff) and mercury sphygmomanometer; values were recorded by using the first and fifth phases of 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). Three measurements were collected with patients in the supine position, three values were used as the clinic BP. Ambulatory BP monitoring was recorded at 15 and 180 days of follow-up for 24 h with a noninvasive ABPM (Space Labs 90207 monitor; Space Labs, Redmond, WA) with an appropriate-sized cuff. The monitor was placed on the nondominant arm and was set to take BP readings every 10 min during the day and every 20 min at night. Statistical Analysis Data were analyzed by using the Statistical Analysis System (SAS Institute Inc., Cary, NC) statistical package. The size of sample was considered adequate for statistical analyses and no dropout occurred during the study. The Pearson 2 test was used to compare both groups regarding the proportions of homogeneity; the Student t test was used to compare both groups regarding the referring averages to the quantitative data. For the systolic BP, diastolic BP, and heart rate variables, the average behavior during evaluation conditions in the two groups was ana-
AJH June 2004 VOL. 17, NO. 6 NURSE VISITS DECREASE WHITE COAT HYPERTENSION 525 Table 1. Biochemical and echocardiograph values at the control period in group A (12 nurse visits n 48) and groupb (2 nurse visits, n 52) Variables A B Glycemia (mg/dl) 104.3 2.47 103 1.8 Creatinine (mg/dl) 1.3 0.07 1.2 0.2 Uric acid (mg/dl) 7.1 0.41 6.4 0.31 Cholesterol (mg/dl) 206 5.85 198 5.68 Triglycerides (mg/dl) 155 10.7 144 9.49 Sodium (meq) 140 0.33 140 0.33 Potassium (meq) 4.2 0.07 4.1 0.07 IV septum (mm) 12.2 0.3 12 0.27 Posterior wall (mm) 12 0.3 12 0.25 Diastolic diameter (mm) 51 1.0 51 0.98 Election fraction (%) 0.68 0.01 0.68 0.01 LV mass index (g/m 2 ) 164 9.1 152 6.26 IV interventricular. lyzed by repeated-measures ANOVA. Multivariate analyses and the Student t test were performed to determine differences in the white coat effect (clinic pressure daytime ABPM) observed in both groups. Values of P.05 were considered significant. Data are presented as mean SEM. Results No significant differences were observed between group A (12 nurse visits) and group B (2 nurse visits) regarding age, sex, race (Methods), and biochemical and echocardiographic data (Table 1). The antihypertensive therapies were similar in the randomization period, with nonsignificant differences between groups A and B: diuretics (87% v 98%), angiotensin-converting enzyme inhibitors (ACEIs) (75% v 75%), -adrenergic antagonists (56% in group A and 98% in group B), and calcium channel antagonists (54% in group A and 38% in group B). At 180 days, the antihypertensive agents were still similar with no significant differences between groups A and B: diuretics (83% v 90%), ACEIs (62% v 65%), -adrenergic antagonists (62% in group A and 61.0% in group B), and calcium channel antagonists (58.3% in group A and 36.5% in group B). Evolution of Arterial BP Fig. 1 depicts systolic and diastolic BP values on the day of randomization (point zero) and the values observed during the 180 days of follow-up. The systolic and diastolic BP levels at randomization were similar in both groups. A significant reduction in BP was detected in both groups during the observation period. This can be better observed in Fig. 2 by the differences in systolic and diastolic BPs obtained comparing the values during treatment with those during the control period. Patients in group A (white column) already exhibited a significant decrease in systolic and diastolic BPs at the first observation after randomization (day 15). Sequential analysis showed a progressive decline in BP reaching its maximum at 90 days and 135 days. In group B (black columns), both systolic and diastolic BPs also had a significant decrease at the first evaluation (day 90). Although the BP levels at day 180 were still low when compared with those at baseline, the degree of reduction tended to be smaller for systolic BP. The differences between both groups are depicted in Fig. 2B. The decrease in systolic BP was statistically larger in group A than in group B at day 90 ( 35 5mm Hg v 27 5 mm Hg), and at 180 days, the difference was still larger ( 36 6mmHgv 17 4 mm Hg). The decrease in diastolic BP was also greater in group A than in group B at both 90 days ( 19 3mmHgv 9 3 mm Hg) and at 180 days ( 21 4mmHgv 10 2mm Hg). The interaction between time of treatment and treatment group was still significant even after the adjustment for gender (P.008) or -blocker treatment (P.007). Also, no differences were observed between groups A and B regarding adherence as measured by the pill count. Differences in Clinical and Daytime Average BP (ABPM) The mean values of daytime systolic BP/diastolic BP (daytime and nighttime) obtained with ABPM were similar in both groups when analyzed after 15 days and remained unchanged after 180 days of treatment (Table 2). In group A, the values between the first and the second measurement were slightly but not significantly smaller for systolic BP and diastolic BP in the daytime ( 3 2.5 mm Hg and 2 1.6 mm Hg) and nighttime ( 3.6 3.3 mm Hg and 3.8 2 mm Hg). The differences for group B were also not significant but tended to be smaller: for systolic BP and diastolic BP daytime ( 1.5 2.3 mm Hg and 1.2 1.4 mm Hg) and nighttime ( 1 3mmHg and 1 2 mm Hg). White Coat Effect The clinic daytime difference for systolic BP decreased at 180 days compared with that at 15 days in group A (23 3mmHgv 10 3 mm Hg). The same was observed for diastolic BP (19 2mmHgv8 2mm Hg). For group B, the white coat effect had a minor decrease for systolic BP (25 3mmHgto22 3 mm Hg) and for diastolic BP (18 2mmHgto14 2mm Hg). The decrease in white coat effect observed at 15 and 180 days was significantly larger in group A than in group B, both for systolic BP ( 13 4mmHgv 3 4 mm Hg) as well as for diastolic BP ( 11 3mmHgv 4 3 mm Hg) as shown in Fig. 3. Another indication that, for the patients in group A, the white coat effect (clinic daytime BP difference) was more intensively attenuated than in group B was provided by the individual analysis identifying patients with differences
526 NURSE VISITS DECREASE WHITE COAT HYPERTENSION AJH June 2004 VOL. 17, NO. 6 FIG. 2. Influence of 180 days of treatment expressed as the absolute differences for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in relation to values measured at the control period (A). Comparison between groupa and groupb after 90 and 180 days of treatment (B). *P.05. greater than 20 mm Hg for systolic BP and greater than 10 mm Hg for diastolic BP in the two tests (15 and 180 days). For systolic BP, the number dropped from 16 to 10 in 30 patients in group A, but the number remained similar (19 and 20 in 34 patients) in group B. The same was observed for diastolic BP: the number decreased from 20 to 14 in group A but remained the same (22) in group B in the two tests. Discussion The main finding of this study was the demonstration that frequent nurse visits for the hypertensive patient undergoing antihypertensive treatment represent an effective contribution to BP control when BP was evaluated by the clinic method. Both groups had similar high levels of BP and antihypertensive therapy before starting the protocol at the time of randomization and both had the same attention by physician staff and had a significant decrease in systolic and diastolic BP during the observation period. Patients enrolled in group A (12 nurse visits) exhibited better BP control than group B patients (only 2 nurse visits). Furthermore, the reduction in BP observed in group B at 180 day was lower than that measured at 90 days, suggesting a small loss of therapeutic response. Therefore, our data suggest, that the frequency of the Table 2. Ambulatory SBP and DBP measured 15 days (first test) and 180 days (second test) after onset of the antihypertensive evaluation Group Days A Daytime B A Nighttime B 15 days 143 3/91 3 145 4/92 2 134 4/81 3 129 3/78 2 180 days 139 3/88 2 143 3/91 2 130 5/77 2 129 3/77 2 SBP systolic blood pressure; DBP diastolic blood pressure. Means SE in mm Hg.
AJH June 2004 VOL. 17, NO. 6 NURSE VISITS DECREASE WHITE COAT HYPERTENSION 527 FIG. 3. Attenuation of the clinic daytime blood pressure differences (white coat effect) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) observed after 15 days and 180 days of treatment in groupa (n 37) and groupb (n 39).*P.05. reinforcement provided by the nurse visits affected the reduction in BP during a 6-month period of antihypertensive treatment when BP was measured with the sphygmomanometric method. Evidence exists that the inclusion of nurses in the health care team increases the compliance of patients on treatment for hypertension. 8 When nurse practitioners and physicians served as primary care providers with the same authority, the diastolic values was significantly lower for nurse practitioners patients (82 v 85 mm Hg). 9 However, our study was the first to demonstrate the influence of frequent nurse visits in hypertensive patients receiving standard physician care. The additional benefit on the antihypertensive treatment produced by frequent nurse visits detected by clinic BP was not confirmed by ABPM. Both groups had similar reductions in daytime BP. However, group A had a greater attenuation of the white coat effect than group B, quantified both by the absolute difference between clinic and ambulatory BP and by the number of patients with clinic daytime difference greater than 20 mm Hg for systolic BP and 10 mm Hg for diastolic BP. It seems, therefore, that the major consequence of frequent nurse visits was the habituation to sphygmomanometric measurement producing a greater attenuation of the white coat effect. This result is somewhat different from that described by the Mancia group, 10 who found that the white coat effect measured directly with continuous BP monitoring remained unchanged for several weeks. The clinical significance of the white coat effect and white coat hypertension when ambulatory BP is normal but clinic BP is increased is still controversial. The condition seems not to be an innocent phenomenon because it tends to coexist with metabolic risk factors and predicts total and cardiovascular mortality. 11 Alteration in organ structure and function and increased metabolic risk factors have been associated with the white coat effect. 12,13 However, other studies have concluded that the magnitude of the white coat effect may not be a clinically relevant finding with no correlation to the severity of hypertension on the degree of cardiac hypertrophy. 14,15 More recently, Parati et al 16 showed that the antihypertensive treatment actually attenuates the clinic daytime differences in BP, but that the attenuation of the white coat effect has no substantial value in predicting the regression of ventricular hypertrophy. Reduction of the white coat effect after a short period of antihypertensive treatment has already been reported in other studies. 17 19 To our knowledge, the present study is the first to demonstrate that frequent nurse visits can increase the degree of attenuation of the white coat effect on antihypertensive treatment. Unfortunately, we have no data to evaluate the clinical significance of this finding in our patients. Perspectives One limitation of our study is that the modification caused by frequent nurse visits, maintaining the same medical attention and the same antihypertensive treatment, was assessed only by BP reduction with no analyses of other variables such as lifestyle modifications. The major contribution of the present study was the demonstration that the additional benefit to hypertension treatment was detected by clinical BP and not by ABMP measurement. Although frequent nurse visit improved BP control, properly designed studies are necessary to establish its cost effectiveness. The decrease of the white coat effect raise another important question not addressed in our study or completely understood in the literature: What is the real clinical relevance of reduction the white coat effect? References 1. Garfield FB, Caro JJ: Compliance and hypertension. Curr Hypertens Rep 1999;1:502 506. 2. Bittar N: Maintaining long-term control of blood pressure: the role of improved compliance. Clin Cardiol 1995;18:III12 III16. 3. Juncos LI: Patient compliance and angiotensin-converting enzyme inhibitors in hypertension. J Cardiovasc Pharmacol 1990;15(Suppl 3):22 25.
528 NURSE VISITS DECREASE WHITE COAT HYPERTENSION AJH June 2004 VOL. 17, NO. 6 4. Caro JJ, Speckman Jl: Existing treatment strategies: does noncompliance make a differences. J Hypertens 1998;16(Suppl 7):31 34. 5. Hill MN, Bone LR, Kim TM, Miller DJ, Dennison CR, Lenine DM: Barriers to hypertension care and control in young urban black men. Am J Hypertens 1999;12:951 958. 6. Dunbar-Jacob J, Mortimer-Stephens MK: Treatment adherence in chronic disease. J Clin Epidemiol 2001;54:S57 S60. 7. Mancia G, Zanchetti A: White-coat hypertension: misnomers, misconceptions and misunderstandings. What should we do next? J Hypertens 1996;14:1049 1052. 8. Benkert R, Buchholz S, Poole M: Hypertension outcomes in a urban nurse-managed center. J Am Acad Nurse Pract 2001;13:84 89. 9. Mundinger MO, Kane RL, Lenz ER, Totten AM, Tsai WY, Cleary PD, Friedewald WT, Siu AL, Shelanski ML: Primary care outcomes in patients treated by nurse practitioners or physicians: a randomized trial. JAMA 2000;283:59 68. 10. Mancia G, Parati G, Pomidossi G, Grassi G, Casadei R, Zanchetti A: Alerting reaction and rise in blood pressure during measurement by physician and nurse. Hypertension 1987;9:209 215. 11. Strandberg TE, Salomaa V: White coat effect, blood pressure and mortality in men: prospective cohort study. Eur Heart J 2000;21: 1714 1718. 12. Kuvajima I, Suzuki J, Fujisawa A, Kuramoto K: Is white-coat hypertension innocent? Structure and function of the heart in the elderly. Hypertension 1993;22:826 831. 13. Cerasola G, Cottone S, Nardi E, D Ignoto G, Volpe V, Mule G, Carollo C: White-coat hypertension and cardiovascular risk. J Cardiovasc Risk 1995;2:545 549. 14. Gosse P, Bougaleb M, Egloff P, Lemetayer P, Clementy J: Clinical significance of white-coat hypertension. J Hypertens 1994;12(Suppl 8):S43 S47. 15. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Reboldi G: Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension 1994;24:793 801. 16. Parati G, Ulian L, Sampieri L, Palatini P, Villani A, Vanasia A, Mancia G: Attenuation of the white-coat effect by antihypertensive treatment and regression of target organ damage. Hypertension 2000;35:614 620. 17. Parati G, Omboni S, Mancia G: Difference between office and ambulatory blood pressure and response to antihypertensive treatment. J Hypertens 1996;14:791 797. 18. Myers MG, Reeves RA: White coat phenomenon in patients receiving antihypertensive therapy. Am J Hypertens 1991;4:844 884. 19. Morimoto S, Takeda K, Oguni A, Kido H, Harada S, Moriguchi J, Itoh H, Nakata T, Sasaki S, Nakagawa M: Reduction of white coat effect by cilnidipine in essential hypertension. Am J Hypertens 2001;14:1053 1057.