AJH 1999;12:555–562 The Renin-Angiotensin System and Blood Pressure Differences Between Blacks and Whites Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 Jiang He, Michael J. Klag, Lawrence J. Appel, Jeanne Charleston, and Paul K. Whelton Although blacks have lower plasma renin activity 29.6 U/L, respectively). Renin activity was compared to whites, the corresponding differences significantly and inversely associated with systolic in serum angiotensin converting enzyme (ACE) and diastolic BP in both the blacks and the whites. levels have not been well studied. Furthermore, ACE levels, however, were inversely associated few studies have examined the relationship of with BP in the blacks but positively associated renin activity and ACE levels to blood pressure with BP in the whites (P 5 .02 for interaction on (BP) in blacks. We addressed these questions in a diastolic BP), even after adjustment for age, cross-sectional study conducted in 110 blacks and gender, body mass index (BMI), alcohol 183 whites who were not on antihypertensive consumption, and heart rate. The corresponding medications. Three BP readings were obtained interaction between ACE level and race on systolic during a clinic visit. Plasma renin activity was BP was of borderline significance (P 5 .06). These assayed by radioimmunoassay and serum ACE results suggest that levels of ACE are similar in levels were measured by spectrophotometry. Mean blacks and whites but their association with BP is systolic and diastolic BP were 122.6 and 77.9 mm possibly reflecting underlying ethnic differences in Hg in the blacks, and 123.4 and 77.9 mm Hg in the regulation of BP. Am J Hypertens 1999;12:555–562 whites, respectively. Plasma renin activity was © 1999 American Journal of Hypertension, Ltd. significantly lower in the blacks compared to the whites (0.92 v 1.26 ng/mL/h, respectively, P < .05), KEY WORDS: Hypertension, blood pressure, renin but ACE levels were similar in both groups (28.8 v activity, angiotensin converting enzyme, blacks. lacks have a higher risk of hypertension possibilities, including differences in the function of compared to their counterparts who are the renin-angiotensin system, have been suggested.6–8 white.1–3 Moreover, hypertension develops The first study to compare the renin-angiotensin at an earlier age and causes more severe system in black and white hypertensives was con- Btarget organ damage in blacks than in whites.4,5 Al- ducted in 1964.9 In that study, Helmer found that 30% though the underlying mechanisms for this racial dif- of blacks with hypertension had no detectable plasma ference in the risk of hypertension are unclear, several renin activity.9 Furthermore, he demonstrated that Received February 11, 1998. Accepted November 30, 1998. Maryland Affiliate Grant-in-Aid (MDBG1195), and partially by a From Department of Epidemiology, Tulane University School Outpatient General Clinical Research Center grant 5M01RR00722 of Public Health and Tropical Medicine, New Orleans, Louisiana from the National Institutes of Health. Dr. He was supported by a (JH, PKW); and the Welch Center for Prevention, Epidemiology, training grant 5T32HL07024-21 from the National Heart, Lung and and Clinical Research (MJK, LJA), Department of Medicine (MJK, Blood Institute, National Institutes of Health. LJA), Department of Epidemiology (MJK, LJA, JC), Department Address correspondence and reprint requests to Dr. Jiang He, of Health Policy and Management (MJK), Johns Hopkins Univer- Department of Epidemiology, Tulane University School of Public sity Medical Institutions, Baltimore, Maryland. Health and Tropical Medicine, 1430 Tulane Avenue SL18, New This study was supported by an American Heart Association- Orleans, LA 70112-2699; e-mail: [email protected] © 1999 by the American Journal of Hypertension, Ltd. 0895-7061/99/$20.00 Published by Elsevier Science, Inc. PII S0895-7061(99)00030-8 556 HE ET AL AJH–JUNE 1999–VOL. 12, NO. 6 even after the stimulus of a low-salt diet and diuretic ing cigarette smoking, alcohol consumption, and therapy, suppression of renin was still present in black physical activity were also assessed by questionnaire. patients with hypertension.10 Most,11–15 but not Three BP measurements were obtained in the sitting all,16–18 subsequent studies have confirmed that renin position at a single visit using the Hawksley random- activity is lower in both hypertensive and normoten- zero modification of the standard mercury sphygmo- sive blacks compared to whites. However, few studies manometer.25 BP was measured after the individual have examined the relationship between renin activity had been seated for 5 min at rest. Participants were and blood pressure (BP) in blacks. instructed not to eat or smoke for at least 30 min Another feature of hypertension in blacks is that before their BP measurements. The first and fifth Ko- they have a poorer response to therapy with angioten- rotkoff sounds were recorded as systolic and diastolic sin converting enzyme (ACE) inhibitors compared to BP, respectively. Means of three BP measurements whites. This has been demonstrated in many clinical were used for the analyses. A 30-sec heart rate was Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 trials.19–21 Although a greater tendency toward also recorded. Body height and weight were measured plasma volume expansion and parallel lower renin and body mass index (BMI) was calculated as an activity have been proposed as possible underlying indicator of obesity.26 reasons to explain these differences in the response to Each participant collected a 24-h urinary specimen. ACE inhibitors, racial differences in serum ACE levels Detailed instructions for collection of the specimen, as and their relationship to BP have not been well stud- well as specially prepared urinary containers, were ied. Elevated ACE activity has been reported in pa- mailed to the participants before their study visit. The tients with essential and renovascular hypertension.22 participants were instructed to collect their urinary The objectives of the present study were to compare specimens the day before their clinic visit. No effort plasma renin activity and serum ACE levels in blacks was made to regulate the participants’ diet or physical and whites; to examine the cross-sectional relationship activity during the collection and no preservative was of these variables with BP; and to determine whether added to the collection vessel. However, special atten- the associations differed by race. tion was paid to obtaining a complete 24-h urinary specimen. Participants were instructed to fast over- METHODS night before their clinic visit. Blood was drawn into a Study Participants Study participants were re- chilled EDTA vacutainer with the patient in the sitting cruited from those who were screened for possible position immediately after the BP measurements. The participation in the Trials of Hypertension Prevention, blood sample was immediately placed in an ice bath phase 1 (TOHP-1) at the Baltimore clinical center.23,24 for 10 min and then centrifuged at 0°C. Plasma was 2 Between September 1987 and October 1988, 463 men separated and stored at 70°C until the assay for and women aged 30–54 years participated in TOHP-1 plasma renin activity was conducted. An additional screening visits at the Baltimore clinical center. Most blood sample was withdrawn into a vacutainer for of the study participants were identified through a measurement of serum angiotensin converting en- work-site screening program conducted at the Social zyme. Security Administration and Health Care Financing Laboratory Measurements Plasma renin activity Administration headquarters located in western Balti- was assayed using a radioimmunoassay that measures more. Participants with a history of cardiovascular the amount of angiotensin I generated by incubating disease were excluded from the study. Of the 463 trial 100 mL plasma at 37°C with endogenous angiotensino- screenees, 377 (81.4%) took part in a follow-up study, gen and phenylmethyl sulfonyl fluoride to inhibit an- which was conducted between November 1994 to Sep- giotensinases and angiotensin I-converting enzyme. tember 1995. Of these, 363 had a clinic visit in which Plasma renin activity was expressed as nanograms of BP, a fasting blood specimen, and a 24-h collection of angiotensin I per milliliter per hour.27 Serum ACE was urine were obtained. Seventy study participants who determined by spectrophotometer using the method were taking antihypertensive medication at the fol- described by Lieberman.28 One unit of ACE is defined low-up examination were excluded from the current as the nanomoles of hippuric acid formed per minute analysis. The remaining 110 blacks and 183 whites at 37°C under standard assay conditions. Urinary so- were included in this analysis. Forty-three of them had dium and potassium were analyzed by flame photom- $ hypertension defined as a systolic BP 140 mm Hg etry. All assays were performed by SmithKline $ and/or a diastolic BP 90 mm Hg. Beecham Clinical Laboratories, Owings Mills, MD. Data Collection Medical history, including personal Statistical Analysis To correct for differences in so- history of hypertension and current use of antihyper- dium intake among participants and to normalize the tensive medication (during the previous 2 months), distribution of plasma renin activity, a renin index was evaluated by questionnaire. Health habits includ- was calculated as the natural logarithm of the ratio of AJH–JUNE 1999–VOL. 12, NO. 6 RENIN-ANGIOTENSIN SYSTEM AND HYPERTENSION 557 were examined in the hypertensive and normotensive participants separately. Regression coefficients associ- ated with a difference of one standard deviation in the independent variables were reported both for the overall group and for the blacks and the whites sepa- rately. The presence of interaction was determined by interpreting the product of two independent variables in linear regression models.