Nocturnal Blood Pressure in Treated Hypertensive African Americans Compared to Treated Hypertensive European Americans1

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1 Nocturnal Blood Pressure in Treated Hypertensive African Americans Compared to Treated Hypertensive European Americans1 Lee A. Hebert,2 Garima Agarwal, Stephanie E. Ladson-Wofford, Max Reif, Leena Hiremath, Sharon G. Carlton, N. Stanley Nahman, Jr., Michael E. Falkenhain, and Anil Agarwal L.A. Hebert, G. Agarwal. SE. Ladson-Wofford, L. Hiremath, S.G. Canton. N.S. Nahman, Jr.. ME. Falkenhain, A. Agarwal. Department of Internal Medicine, The Ohio State University, Columbus. OH M. Reif, Department of Internal Medicine, University of Cincinnati, Cincinnati. OH (J. Am. Soc. Nephrol. 199#{243}; 7: ) ABSTRACT Previous studies have shown that African Americans (blacks) tend to have higher nocturnal blood pressure than European Americans (whites). The study presented here was undertaken to determine whether treatment of hypertension influences nocturnal blood pressure differently in blacks than in whites. To answer this question, this study measured nocturnal blood pressure by ambulatory blood pressure monitoring (ABPM) in treated hypertensive blacks and whites whose daytime blood pressures were comparable. Inclusion criteria for this study were: diagnosis of essential hypertension, absence of renal failure, and documentation of antihypertensive therapy, diabetic status, proteinuria status, and body weight. All of the black patients in our programs who underwent ABPM and met the above criteria were included in this study. White patients were included on the basis of having the same inclusion criteria as blacks and showing, by ABPM, daytime mean arterial pressure (MAP) in the same range as that of the blacks selected for this study. The results of nocturnal blood pressure were unknown to the investigators when the patients were selected forthis study. In the blacks (N = 62) and whites (N = 72) selected for study, the mean daytime (0600 to 2200 h) MAP was 107 ± 1 SE mm Hg for both the black and white cohorts. To assess nocturnal blood pressure, the period from 0100 to 0500 h was chosen because it likely encompassed an interval of sleep, which is associated with the nadir of nocturnal blood pressure. This interval was termed t Received January Accepted April 27, Correspondence to Dr. LA. Hebert. Ohio State University Medical Center Upham Drive, Room N210 Means Hall, Columbus, OH &6673/ $03.0O/0 Journal of the American Society of Nephrology Copyright 1996 by the American SocIety of Nephrology 0100 to 0500 h, middle night. Mean middle night MAP was 97 ± 12 mm Hg in blacks versus 90 ± 14 mm Hg in whites (P < 0.006, unpaired t test). The greater middle night MAP in blacks compared with whites was a result of the higher diastolic pressure in blacks (80± 11 mmhg)versuswhites(75± 11 mmhg)(p= 0.003). Mean middle night systolic blood pressure was numerically higher in blacks than whites (131 ± 18 mm Hg versus 128 ± 17 mm Hg), but this difference did not achieve statistical significance. The higher middle night blood pressure in blacks versus whites could not be explained by differences between the groups in daytime MAP, age, gender, body weight, serum creatinine level, proteinuria, diabetic status, or greater use of short-acting antihypertensive agents in blacks versus whites. It was concluded that when treated hypertensive blacks and whites are matched for the same daytime blood pressure, blacks tend to have significantly higher nocturnal blood pressure than whites. The magnitude ofthis difference suggests that it could contribute importantly to the greater target-organ damage that is seen in hypertensive blacks compared with hypertensive whites. Key Words: Blacks, ambulatory blood pressure monitoring. hypertension T here is abundant evidence that hypertensive ASrican Americans (blacks) are more likely to experience hypertension-related target-organ injury than hypertensive European Americans (whites) ( 1,2). The reasons for this difference are not clear. Blacks are known to have a higher prevalence and severity of hypertension, and a higher prevalence of diabetes. However, adjusting for these influences shows that blacks still have a significantly higher incidence of hypertension-related target-organ damage than whites ( 1 ). The above observations have led to the suggestion that blacks are constitutiveby more vulnerable to hypertension-induced injury than whites. However, the studies that have examined the relationship between blood pressure bevel and hypertensioninduced injury have used clinic blood pressure measurements, which are taken during the daytime. Recent studies have suggested that target-organ injury resulting from hypertension may be more closely related to nocturnal than daytime blood pressure (3-8), particularly in white women (8). Furthermore, most studies show that blacks tend to have higher nocturnal blood pressure than whites (9-14). Thus, it 2130 Volume 7 - Number

2 Hebert et al is possible that the greater risk of target-organ damage in blacks, compared with whites, is related to higher nocturnal blood pressure in blacks. However, the previous studies showing higher nocturnal blood pressure in blacks than in whites primarily compared normotensive or untreated mildly hypertensive blacks and whites. It is possible that, once hypertension is established and treated, the difference between blacks and whites in nocturnal blood pressure either disappears or is obliterated by antihypertensive therapy. The study presented here tested this hypothesis by examining ABPM in treated hypertensive blacks and whites who achieved the same level of daytime blood pressure METHODS Patient control. Population The patients in this study were tested by ABPM by The Ohio State University Nephrobogy Program or the University of Cincinnati Hypertension Program. Most of the patients underwent ABPM to assess the degree of blood pressure control. Some were studied by ABPM specifically for this study. The inclusion criteria for the black patients in this study were as follows: 1. Diagnosis of essentiat hypertension. This was based on untreated systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg that was not explained by secondary causes of hypertension. 2. Absence of renatfallure. Renal failure is associated with increased nocturnal blood pressure ( 1 ). To enter the study presented here, serum creatinine concentration had to be < 1.6 mg/dl in men and < 1.3 mg/dl in women. Patients with proteinuria > 2+ by dipstick or 24-h proteinuria > 1.0 gm were also excluded from this study. 3. Known status with respect to diabetes. Diabetes is cornmon in hypertensive populations and is associated with increased nocturnal blood pressure ( 1 ). Thus, it was necessary to define the diabetic status of our study population. Diabetes was defined as a fasting glucose bevel> 140 mg/dl, or the need for insulin or oral hypoglycemic agents to control blood glucose. 4. Adequate ABPM study. This is described below. The white patients selected for this study were selected after the black cohort had been selected. The inclusion criteria for the white patients of this study were as follows: 1. The same entry criteria as that of the black patients, described above. 2. An ABPM record showing a mean daytime MAP (see below) within the range of that of the black patients selected for the study. This criterion was used in an effort to match blacks and whites with respect to daytime MAP. Analysis of the ABPM Record The standard format of the Space Labs Model ABPM monitor (Redmond, WA) defines daytime as 0600 to 2200 h, and nighttime as 2200 to 0600 h. In this study, we also defined daytime as 0600 to 2200 h. However, nocturnal blood pressure was taken as the interval h to 0500 h, which we termed middle night blood pressure. The rationabe for using the middle night interval rather than the standard nighttime interval is that we wished to study blood pressure during sleep, which is the nadir of nocturnal blood pressure ( 1 5). The standard nocturnal interval often includes a period of nonsleep. Thus, an interval shorter than the standard nocturnal interval is recommended for the study of blood pressure during sleep (15). The ABPM device was programmed to measure blood pressure every 30 mm during the daytime (0600 to 2200 h) and hourly during the nighttime (2200 to 0600 h). An adequate ABPM study was defined as: At beast 90% of the scheduled ABPM measurements was recorded. At beast three of the five scheduled measurements between 0100 h and 0500 h was recorded. MAP was determined by the algorithm of the Space Labs ABPM device. The program for data analysis allows for calculation of extrapolated data points, one for each missed 2-h period. If the gap between valid measurements exceeds 4 h, no extrapolation is calculated. The algorithm of the Space Labs device uses arbitrary parameters to exclude individual blood pressures that are inexplicably high or low. A further programmed editing function evaluates and tests values that appear to deviate excessively from neighboring measurements. These values are deleted. To reduce motion artifacts, the patients were instructed to straighten their arm and, if possible, remain motionless when the ABPM device was activated to measure blood pressure. Data Analysis All mean values are expressed ± 1 SE. The statistical tests used are discussed in relationship to the data. RESULTS Table 1 shows the key clinical characteristics of the black and white cohorts of this study. As can be seen, the groups were comparable with respect to age, weight, serum creatinine level, prevalence of diabetes, and absence of heavy proteinuria. However, there was a significantly higher percentage of females in the black cohort, compared with the white cohort. Table 2 shows the primary results of the ABPM testing in the blacks and whites of this study. As can be seen, the mean daytime MAP was the same for blacks and whites. Mean daytime systolic pressure, diastolic blood pressure, and pulse rate also were not different between blacks and whites. By contrast, mean middle night MAP was significantly higher in blacks than whites. This difference was primarily the result of a higher middle night diastolic blood pressure. Middle night pulse rate was not different between blacks and whites. To assess whether the differences between blacks and whites in daytime versus middle night blood pressure could be explained by the higher percentage of women in the black cohort compared with the white cohort, we compared daytime versus middle night systolic, diastolic, and MAP in black men versus black women. There were no significant differences between the black men and women in these parameters. Thus, the higher middle night blood pressure in blacks than in whites is not the result of a higher proportion of Journal of the American Society of Nephrology 2131

3 Nocturnal Blood Pressure in African Americans TABLE 1. Clinical characteristicsa Age % Female Weight (Ibs) 5Cr (mg/dl) Diabetes b (%) Blacks (N = 62) 51.4 ± C 176 ± ± Male (N = 20) 51.7 ± ± ± Female (N = 42) 51.3 ± ± Whites (N = 72) 51.9 ± ± ± Male (N = 40) 50.4 ± ± ± Female (N = 32) 53.9 ± ± ± a Dipstick proteinuria value was 1 + or less in 131 of 134 patients. Two black women and one white man had dipstick proteinuria values of 2+. 5Cr, serum creatinine. b Defined as fasting blood glucose concentration >140 mg/dl or requiring insulin or oral hypoglycemic agents to control blood glucose. C p _o.ooo compared with whites by chi-squared testing. None of the above other differences between blacks and whites of the same gender is statistically significant. TABLE 2. Daytime and middle night ambulatory blood pressure monitoring (ABPM) results MAP Daytime (0600 to 2200 h) ABPM Mid die Night (010 0 to 0500 h) ABPM SYSb DIAC Pulsed MAP SYS DIA Pulse Blacks 107±1 143±2 90±1 83±2 97±2e 131±2 80±V 72±2 Male 108±2 143±3 92±2 69±3 983g 130±4 82±2 69±2 Female 107±2 143±2 89±2 84±2 96±2 131±3 79±2 73±3 Whites 107±1 142±2 88±1 79±2 91±2 129±2 75±1 69±1 Male 109±1 144±2 90±1 79±2 89±2 128±2 76±2 69±2 Female 104±2 139±2 85±2 79±3 92±2 129±4 73±2 68±2 a Mean Arterial Pressure, mm Hg as estimated by the Space Labs ABPM algorithm. b Systolic Blood Pressure, mm Hg. C Diastolic Blood Pressure, mm Hg. d Beats/mm. e p comparing blacks with whites by unpaired f test. I p = comparing blacks with whites by unpaired f test. 0 = comparing black men with white men by unpaired ttest. h p _0.015 comparing black women with white women by unpaired ttest. women in the black cohort, compared with the white cohort. Table 3 shows the proportion of blacks that experienced a nocturnal dip ( 10%) in blood pressure or pulse rate. As can be seen, blacks are numerically less likely than whites to experience a nocturnal decrease in blood pressure. However, these differences achieved statistical significance only for MAP. Table 4 shows the antihypertensive medication used by the blacks and whites of the study. As can be seen, a higher proportion of blacks than whites used calcium channel blockers. We also assessed the extent to which antihypertensive medications with a short duration ofaction were used in blacks compared with whites. The medications used in our patients that were regarded as having short duration of action were clonidine tablets, minoxidib, hydrabazine, prazosin, labetabol, metoprobol, and captopril. All other antihypertensive medications were regarded as long-acting medications. As can be seen, the percentage of black patients using short-acting medications was not different from that of white patients. Thus, the higher nocturnal blood pressure in blacks than in whites cannot be explained by the greater use in blacks of medications with antihypertensive effects that might have dissipated at the time of the middle night blood pressure measurements. Relatively few of the study patients were receiving a single antihypertensive agent at the time of the ABPM study. Thus, it was not possible to determine whether certain classes of antihypertensive agents were better than others in reducing nocturnal blood pressure. DISCUSSION The study presented here shows that when treated hypertensive blacks and whites are matched for daytime blood pressure, blacks have higher middle night MAP than whites. The higher middle night MAP in blacks is not explained by differences between the groups in age, gender, weight, serum creatinine, proteinuria, prevalence of diabetes, or greater use of short-acting antthypertensive medications in blacks. Other studies suggest that differences in quality of sleep between blacks and whites also cannot explain the higher nocturnal blood pressure in blacks ( 14). In the study presented here, there was greater use of calcium channel blockers in the blacks than in the 2132 Volume 7 - Number

4 Hebert et al TABLE 3. Frequency Of Dippersa Dipp ers, % of In dicated cohort MAP SYS DIA Pulse Blacks 42b 37 55C 4 Male Female Whites Male Female a Defined as a 10% or greater decrease in MAP, systolic blood pressure (SYS), diastolic blood pressure (DIA). or Pulse (pulse rate beats/mm) from daytime to middle night for each of the parameters. b p comparing blacks with whites by chi-squared testing with Yates correction. C p = comparing blacks with whites by chi-squared testing with Yates correction. TABLE 4. Antihypertensive therapy: % of blacks and whites receiving the given class of drug Diuretic p-blockers CCB ACEb Others SAC Blacks d Whites a Calcium channel blocker. b ACE inhibitor. C Short-acting antihypertensive agents (see text). d p _0.005 comparing blacks with whites by chi-squared testing using the Yates correction. whites. Nevertheless, it is unlikely that differences in antthypertensive regimens between blacks and whites can account for the higher nocturnal blood pressure in the black patients because the antihypertensive regimens were equally effective in controlling the daytime blood pressures of blacks and whites. The differences in middle night blood pressure between blacks and whites may be constitutive. Nevertheless, differences in environmental factors such as alcohol intake or smoking, both of which tend to increase the amplitude of diurnal I nocturnal blood pressure variation ( 1 ) would also play a role. The influence of these factors on the ABPM studies in our patients was not assessed. In any event, hypertensive blacks as a group manifest higher nocturnal blood pressure than hypertensive whites, and this difference is not obliterated by standard antihypertensive therapy. The higher middle night MAP in blacks, compared with whites, is primarily the result of higher middle night diastolic pressure in blacks. Middle night systolic blood pressure was numerically higher in blacks than whites but this difference did not achieve statistical significance. The study presented here did not evaluate the dinical significance of higher middle night blood pressure in blacks than in whites. However, there is considerable evidence, primarily from cross-sectional studies, that patients with higher nocturnal blood pressure are more likely to have greater left ventricular hypertrophy, central nervous system vascular injury, and progression of renal disease (3-6,16,17). The magnitude of the differences in middle night blood pressure between blacks and whites was 5 mm Hg difference in diastolic pressure and 7 mm Hg difference in MAP. Differences of this magnitude measured during the daytime have shown significant differences in outcome in both interventional and observational studies ( 1 8, 1 9). Thus, the differences in nocturnal blood pressure noted in the study presented here could contribute importantly to the higher levels of target organ injury that is seen in hypertensive blacks compared with hypertensive whites. ACKNOWLEDGMENT This study was supported in part by National Institutes of Health Grants DK MO 1 RR and a grant from Marion Merrell Dow. REFERENCES 1. Pickering TG: Hypertension in blacks. Curr Opin Nephrob Hypertens 1994;3:207-2!2. 2. Hebert LA, Cody LU, Slivka AP. Sedmak DD. Hypertension-induced kidney, heart, and central nervous system disease. In: Mandal AK, Jennette JD, Eds. Diagnosis and Management of Renal Disease and Hypertension, 2nd Ed. Durham, NC: Carolina Academic Press; 1994: Kobrin I, Oigman W, KumarA, et at.: Diurnal variation of blood pressure in elderly patients with essential hypertension. J Am Geriatr Soc 1984;32: Verdecchia P, Schillaci G, Guerrieri M, et at.: Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1 990;8 1: O Brien E, Sheridan J, O Malley K: Dippers and nondippers. Lancet 1988;2: Pickering TG, James GD: Determinants and consequences of the diurnal rhythm of blood pressure. Am J Hypertens 1993:6: 166S-!69S. 7. Verdecchia P, Porcellati C, Schilbaci G, et al.: Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension (Dallas)!994;24: Verdecchia P, Schilaci G, Gatteschi C, et at.: Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events. Circulation 1993;88: Rowlands DB, DeGiovanni J, McLeay RAB, Watson RDS, Stallard TJ, Littler WA: Cardiovascular response in black and white hypertensives. Hypertension (Dallas) 1992;4: Harshfiebd GA, Alpert BS, Willey ES, Somes GW, Murphy JK, Dupaul LM: Race and gender influence ambulatory blood pressure patterns of adolescents. Hypertension (Dallas) 1 989; 14: Prisant LM, Thompson WO. Bottini PB, Carr AA, Rhoades R: Racial aspects of ambulatory blood pressure. J Hum Hypertens : Fume MT, Teeger 5, Lang RM, Bednarz J, Sarebi P, Murphy MB: Diurnal blood pressure variation and cardiac mass in American blacks and whites and South African blacks. Am J Hypertens 1992;5: Chaturvedi N, McKeigue PM, Marmot MG: Resting and ambulatory blood pressure differences in Afro-Carthbeans and Europeans. Hypertension (Dallas) 1993;22: Gretler DD: Ethnic differences in circadian hemodynarnic profile. Am J Hypertens!993;7: van Ittersum FJ, Ijzerman RG, Stehouwer CDA, Donker AJM: Analysis of twenty-four-hour ambulatory blood pressure monitoring: What time period to assess blood Journal of the American Society of Nephrology 2133

5 Nocturnal Blood Pressure in African Americans pressures during waking and sleeping? J Hypertens 1995; 13: Shimada K, Kawamoto A, Matsubayashi K, Nishinaga M, Kimura 5, Ozawa T: Diurnal blood pressure variations and silent cerebrovascubar damage in elderly patients with hypertension. J Hypertens 1992; 10: Rizzoni D, Muiesan ML, Montani G, Zulu R, Calebich 5, Agabiti-Rosei E: Relationship between initial cardiovascular structural changes and daytime and nighttime blood pressure monitoring. Am J Hypertens 1992:5: MacMahon S. Peto R, Cutler J, et at.: Blood pressure, stroke, and coronary heart disease. Part 1. Prolonged differences in blood pressure: Prospective observational studies corrected for the regression dilution bias. Lancet 1990;335: Collins R, Peto R, MacMahon 5, et at.: Blood pressure, stroke, and coronary heart disease. Part 2, short-term reductions in blood pressure: Overview of randomised drug trials in their epidemiobogicab context. Lancet 1990; 335: Volume 7 - Number