Aldosterone Contributes to Blood Pressure Variance and to Likelihood of Hypertension in Normal-Weight and Overweight African Americans

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1 nature publishing group articles See reviewer commentary page 1234 Aldosterone Contributes to Blood Pressure Variance and to Likelihood of Hypertension in Normal-Weight and Overweight African Americans Srividya Kidambi 1,2, Jane M. Kotchen 1, Shanthi Krishnaswami 1, Clarence E. Grim 1 and Theodore A. Kotchen 1 Background Hypertension and obesity are highly prevalent among African Americans (AAs). We have previously reported that both plasma aldosterone (PA) and body mass index (BMI) are higher in hypertensive than in normotensive AAs. This study evaluates the relative contributions of adiposity and PA to hypertension in AAs. Methods A total of 466 AAs (50% hypertensive, 51% women) were evaluated in a Clinical Research Center by stratifying them into three subgroups based on BMI (normal weight, overweight, and obese). Anthropometric measurements, ambulatory blood pressure (BP), fasting glucose, insulin, 24-h urine sodium and potassium, creatinine clearance, standing PA and plasma renin activity (PRA) were measured. Insulin resistance was estimated by the homeostasis model assessment. Results Compared to normotensives, hypertensives had higher BMI, waist circumference (WC), and were more insulin resistant (P 0.01). When stratified by BMI, hypertensives in each BMI strata had higher PA (P 0.05) and lower PRA (P 0.01) compared to normotensives. Compared to normotensives, WC was greater in overweight and obese hypertensives, but not in normal-weight hypertensives. In the overall sample, age, WC, PA, and PRA were the major contributors to BP variance and to hypertension. Among normal-weight subjects, PA and PRA significantly predicted BP and the odds ratio for hypertension, whereas WC had no predictive value. Conclusions PA, but not WC, is associated with BP and likelihood of hypertension in normal-weight AAs, whereas both WC and PA are predictive of hypertension in overweight and obese individuals. This suggests that aldosterone antagonists may be useful for the treatment of hypertension among AAs, regardless of BMI. Am J Hypertens 2009; 22: American Journal of Hypertension, Ltd. Hypertension and obesity frequently coexist. In the United States, a consistent rise in the prevalence of both hypertension and obesity has occurred in recent decades among all ethnic groups. Between and , hypertension prevalence increased in normal-weight, overweight, and obese National Health and Nutrition Examination Survey participants, 1 suggesting that increased rates of obesity do not entirely account for the increase in prevalence of hypertension. Compared with whites, hypertension and obesity are more frequent in African Americans (AAs). Almost two-thirds of AAs are either obese or overweight, and hypertension rates reach 40 50% (refs. 2,3). Obesity, particularly centripetal obesity, is considered a harbinger of hypertension, and it has been suggested that insulin resistance mediates the relationship between obesity and hypertension. 4 However, we have 1 Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; 2 Department of Medicine, Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin, USA. Correspondence: Srividya Kidambi (skidambi@mcw.edu) Received 20 April 2009; first decision 14 May 2009; accepted 25 July 2009; advance online publication 17 September doi: /ajh American Journal of Hypertension, Ltd. recently shown that blood pressure (BP) levels correlate with measures of adiposity in normotensive, but not in untreated hypertensive AAs, 5 suggesting that the relationship between adiposity and BP differs in normotensive and hypertensive individuals. We and others have recently reported that plasma aldosterone (PA) is associated with BP, waist circumference (WC), and insulin resistance, raising the possibility that aldosterone contributes to obesity-related hypertension. 6 Consistent with this hypothesis, previous reports suggest an association between aldosterone and obesity, unrelated to plasma renin activity (PRA), in both normotensive adults and in patients with essential hypertension As an extension of our earlier reports in the same subjects, 6,11,12 this study was undertaken to delineate the relationships among measures of adiposity, aldosterone, insulin resistance, and BP in AAs. Specifically, to determine whether insulin resistance and aldosterone are exclusively associated with obesity-related hypertension, we evaluated their relationship with BP levels and likelihood of hypertension among various body mass index (BMI) strata (i.e., normal weight, overweight, and obese). AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER december

2 articles Aldosterone and Blood Pressure in African Americans Methods AA subjects between the ages of 18 and 55 years were recruited from a variety of community resources and health-care providers within the Milwaukee area. Subjects were defined as AAs based on self-identification, birth in the continental United States, both parents reported as being AAs, and English as the native language. All subjects were initially evaluated during a screening outpatient visit and were considered to have hypertension if standardized outpatient measurement of systolic BP was 140 mm Hg, diastolic BP was 90 mm Hg, or if they were taking antihypertensive medications. Pregnant subjects and subjects with secondary hypertension, diabetes mellitus, serum creatinine concentrations >2.2 mg/dl ( µmol/l), BMI >36 kg/m 2, chronic debilitating illness, and substance abuse (including alcohol) were excluded. Before further study, subjects taking antihypertensive and lipid-lowering medications discontinued these agents for at least 1 and 4 weeks, respectively. Subjects were then admitted to an in-patient General Clinical Research Center and placed on a weightmaintaining diet containing 150 meq sodium and 80 meq potassium per day. Twenty-four-hour urine sodium, potassium, creatinine, and albumin excretion rates were measured on days 1 2; consequently they are more a reflection of the subjects usual diets rather than the protocol diet. No subjects were taking nonsteroidal anti-inflammatory agents at the time of study. Written informed consent was obtained from all subjects, and the Froedtert Memorial Lutheran Hospital/Medical College of Wisconsin institutional review board approved the protocol. BPs were measured over a 24-h period with an Accutracker (Suntech Medical Instruments, Research Triangle Park, NC) every 30 min during the day (0600 to 2000 hours) and every 60 min during the night (2000 to 0600 hours). Standardized anthropometric measurements included height, weight, WC, and skinfold thickness. WC was taken at a narrowest point between umbilicus and superior iliac spine. Subscapular, suprailiac, biceps, and triceps, skinfold thicknesses were measured with a standard protocol using a Lange skinfold caliper. All skinfolds were measured three times and averaged. Based on these measurements, percent total body fat was calculated with gender-specific formulas using the Durnin and Womersley equation. 13 Subjects were categorized as normal weight (BMI 24.9 kg/m 2 ), overweight (BMI kg/ m 2 ), or obese (BMI 30 kg/m 2 ). Peripheral venous blood was collected after an overnight fast for measurement of serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, glucose, insulin, and creatinine. PRA and PA concentrations were measured in the midmorning after subjects had been supine for 60 min followed by standing for 10 min. Serum glucose was measured with an automated glucose oxidase enzymatic assay. Insulin was measured by using a commercially available double antibody, equilibrium radioimmunoassay. Serum cholesterol was measured using a colorimetric enzymatic procedure and HDL-C was measured in a same-day assay after selective precipitation of the low-density lipoprotein cholesterol fraction. Triglycerides were measured by an enzymatic procedure based on the conversion of triglycerides to glycerol and its subsequent conversion to dihydroxyacetone phosphate and hydrogen peroxide. Low-density lipoprotein cholesterol was calculated using Friedwald s formula. In addition, peripheral venous blood was also collected for measurement of serum concentrations of sodium and potassium. Urine was collected for 24 h to measure sodium, potassium, creatinine, and albumin excretion. Serum and 24-h sodium and potassium were measured by ion-selective electrode (Olympus, Center Valley, PA), which employs crown ether membrane electrodes. Serum and urine creatinine were measured by autoanaylzer (Olympus 5400; Olympus, Irving, TX), and urine albumin was measured by radioimmunoassay (Pharmacia-Upjohn, Somerset, NJ). PRA was measured by a modification of the method of Sealey and Laragh, with the use of angiotensin-i antisera kindly provided by Dr Sealey (Cornell University Medical Center, New York, NY). 14 PA concentrations were measured by radioimmunoassay with a commercially available assay kit (Coata-Count Aldosterone; Siemens Medical Solutions Diagnostics, Los Angeles, CA). In our laboratory, the interassay coefficients of variation for the commercially available low- and highaldosterone pools are 10.2 and 9.2%, respectively. The respective intra-assay coefficients of variation are 5.1 and 4.4%. Insulin resistance was calculated with the homeostasis model assessment of insulin resistance index, a web-based program made available by Oxford University. 15 The degree of insulin resistance is related to the height of the index. Homeostasis model assessment of insulin resistance index correlates well with the euglycemic clamp technique in both normotensive and hypertensive individuals. Statistical methods. Continuous variables were reported as means ± s.e.m. BPs, PRA, PA/PRA ratio, serum insulin, insulin resistance (homeostasis model assessment of insulin resistance), total cholesterol HDL-C, triglycerides, and 24-h urine potassium were log-transformed to achieve normal distribution for statistical analyses. Plasma glucose and PA were skewed and did not achieve normal distribution by any transformation methods. Differences in the distributions of all selected phenotypes between groups of interest were determined either by Student s t-test or by Wilcoxon rank sum test depending upon the distribution of variables. The differences in the proportion of women for each group comparison were tested by χ 2 test. Age-adjusted partial correlations of 24-h BPs were identified by Pearson or Spearman correlation analysis where appropriate. One-factor analysis of covariance was carried out to test for the differences of selected phenotypes between hypertensives and normotensives within each BMI category after taking age in to account. To identify the risk factors of 24-h BPs and to assess the magnitude and strength of association of related variables with hypertension, backward-stepwise multiple linear and logistic regression analyses, respectively, were performed, by including the demographic, anthropometric, and metabolic variables that are presumed to have an etiologic effect on the development of BP. These included age, gender, BMI, WC, percent body fat, insulin resistance, 24-h urine potassium and sodium, 1304 december 2009 VOLUME 22 NUMBER 12 AMERICAN JOURNAL OF HYPERTENSION

3 Aldosterone and Blood Pressure in African Americans articles creatinine clearance, PA and PRA. Collinear diagnostic was evaluated using variance inflation factor. Testing for two-way interactions of the variables did not yield any statistical significance and hence only the main effects are shown. A P value of <0.05 was considered significant. All analyses were performed using SAS software version 9.1 (SAS Institute, Cary, NC). Results A total of 466 (51% women) subjects with mean age of 43 years were studied (Table 1). Fifty percent of the subjects were hypertensive. Overall, compared to normotensive subjects, hypertensives were older, had significantly higher BMI, WC, and percent body fat (P 0.01). Hypertensives were also more insulin resistant (P = 0.005), had higher total cholesterol (P = 0.01), low-density lipoprotein cholesterol (P = 0.03), and triglycerides (P = 0.004). In addition, PA was higher (P < 0.001), and PRA was lower (P < 0.001) in the hypertensives. Consequently, the PA/PRA ratio was higher in the hypertensives (P < 0.001). Twenty-four-hour sodium excretion, creatinine excretion, and albumin excretion did not differ between normotensive and hypertensive subjects; however, potassium excretion was lower in hypertensives (P = 0.02). Overall, including normotensive and hypertensive subjects, systolic BP positively correlated with BMI (r = 0.23, P < 0.001), WC (r = 0.38, P < 0.001), insulin resistance (r = 0.14, Table 1 Characteristics of normotensive and hypertensive subjects (mean ± s.e.m.) Variable Normotensive (n = 233) Hypertensive (n = 233) Age (years) 42 ± ± 0.4*** Female (%) Mean 24-h systolic/diastolic blood pressure (mm Hg) 116 ± 1/69 ± ± 1/86 ± 1*** BMI (kg/m 2 ) 27.4 ± ± 0.3*** Waist circumference (cm) 87 ± 1 93 ± 1*** Percent body fat (%) 30.2 ± ± 0.6** Insulin resistance (HOMA IR ) 1.46 ± ± 0.06** Total cholesterol (mg/dl) 174 ± ± 3** HDL cholesterol (mg/dl) 46 ± 1 47 ± 1 LDL cholesterol (mg/dl) 109 ± ± 3* Triglycerides (mg/dl) 89 ± ± 5** Plasma aldosterone (ng/dl) 6.1 ± ± 0.4*** PRA (ng/ml/h) 2.0 ± ± 0.2*** Plasma aldosterone/pra ratio 12.8 ± ± 3.0*** 24-h urine sodium (meq/24 h) 195 ± ± 6 24-h urine potassium (meq/24 h) 51 ± 2 45 ± 1* Albumin (mg/24 h) 24 ± 2 24 ± 2 Creatinine clearance (ml/min) 145 ± ± 3 BMI, body mass index; HDL, high-density lipoprotein; HOMA IR, homeostasis model assessment of insulin resistance; LDL, low-density lipoprotein; PRA, plasma renin activity. Significance between normotensives and hypertensives: *P 0.05; **P 0.01; ***P P < 0.001), and PA (r = 0.24, P < 0.001); BPs were inversely correlated with PRA (r = 0.22, P < 0.001). When normotensive and hypertensive subjects were considered separately, in both groups, BPs were positively correlated with WC (r = 0.30, P < and r = 0.15, P < 0.05, respectively) whereas BP correlated positively with PA (r = 0.18, P < 0.01) only in hypertensive subjects. PA was also significantly correlated with WC (r = 0.13, P < 0.01) in the overall sample, but not with BMI. All subjects were divided into three subcategories (normal weight, overweight, and obese) based upon the BMI. Twentyfour percent of subjects were of normal weight, 39% were overweight, and 37% were obese. The proportion of females increased from 43 to 60% with increasing BMI (P < 0.01). Actual BP levels and the prevalence of hypertension also increased with increasing BMI strata (P < 0.001). Additionally, WC, percent body fat, fasting insulin, insulin resistance, and triglycerides increased, and HDL-C decreased with increasing BMI (P < 0.05). However, BP level, the prevalence of hypertension, and insulin resistance did not differ among the three BMI strata after adjustment for WC. PA concentrations were higher in obese subjects (8.2 ± 0.5 ng/dl) than in overweight (6.7 ± 0.4 ng/dl), or normal-weight subjects (6.8 ± 0.5 ng/dl), although this difference was not statistically significant. To determine whether distinguishing hypertension-related characteristics could be identified regardless of BMI, anthropometric and metabolic variables were compared in normotensive and hypertensive subjects within each of the three BMI strata (Table 2). Among obese individuals, a higher percentage of females were normotensive than hypertensive (69 vs. 54%, P = 0.06), whereas females accounted for slightly <50% of normal-weight and overweight hypertensives. Although, BMI and percent body fat did not differ between normotensives and hypertensives within each BMI category, hypertensives had a significantly higher WC in the overweight and obese groups (P < 0.01). Among normal-weight subjects, WC did not differ significantly between normotensives and hypertensives. PA concentrations were significantly higher (P 0.05) and PRA was significantly lower (P 0.05) among hypertensives in each BMI strata. Within each of the three BMI groups, comparing hypertensive and normotensive subjects, there were no differences of plasma glucose, insulin, insulin resistance, HDL-C, or 24-h urine sodium excretion. In the overweight and obese BMI groups, potassium excretion rates were lower in hypertensive than in normotensive subjects (P < 0.05). Total cholesterol and triglyceride concentrations were higher in obese hypertensives than in obese normotensives (P 0.01). Tables 3 and 4 present results of the backward stepwise multiple linear and logistic regression analyses for the significant predictors of systolic BP level (estimates and r 2 ) and hypertension (odds ratio and 95% confidence interval) with selected correlates. In the overall sample, BMI (either as a continuous or as a categorical variable), percent body fat, insulin resistance, and gender failed to show any effect on BP or hypertension, independent of WC. In addition, creatinine clearance did not have an independent effect on BP or likelihood of hypertension. Variables that dropped out of the model in certain AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER 12 december

4 articles Aldosterone and Blood Pressure in African Americans Table 2 Comparisons of characteristics between normotensive and hypertensive subjects within each BMI stratum (age-adjusted means ± s.e.m.) Variable Normal weight (n = 114) Overweight (n = 182) Obese (n = 170) NT (n = 72) HT (n = 42) NT (n = 91) HT (n = 91) NT (n = 70) HT (n = 100) Female (%) h systolic/diastolic BP 113 ± 1/68 ± ± 2/86 ± ± 1/69 ± ± 1/84 ± ± 2/69 ± ± 1/88 ± 1 (mm Hg) Waist circumference (cm) 79 ± 1 80 ± 1 87 ± 1 91 ± 1* 95 ± ± 1*** BMI (kg/m 2 ) 22.6 ± ± ± ± 0.2* 32.5 ± ± 0.2 Percent body fat (%) 25 ± 1 25 ± 2 30 ± 1 33 ± 1* 38 ± 1 36 ± 1 Insulin resistance 1.1 ± ± ± ± ± ± 0.1 (HOMA IR ) Total cholesterol (mg/dl) 176 ± ± ± ± ± ± 4** HDL cholesterol (mg/dl) 54 ± 2 51 ± 3 48 ± 2 48 ± 1 39 ± 1 42 ± 2 LDL cholesterol (mg/dl) 104 ± ± ± ± ± ± 4 Triglycerides (mg/dl) 87 ± 5 90 ± 6 92 ± ± 9 88 ± ± 7** Plasma aldosterone 6.0 ± ± 0.8* 5.8 ± ± 0.6** 6.1 ± ± 0.7*** (ng/dl) PRA (ng/ml/h) 2.1 ± ± 0.4* 1.9 ± ± 0.2** 1.9 ± ± 0.4* Plasma aldosterone/ 14.4 ± ± 5.2** 11.0 ± ± 2.9*** 13.4 ± ± 5.2*** PRA ratio 24-h urine sodium 167 ± ± ± ± ± ± 11 (meq/24 h) 24-h urine potassium 46 ± 2 46 ± 3 53 ± 3 44 ± 3* 53 ± 3 45 ± 2* (meq/24 h) Creatinine clearance 132 ± ± ± ± 5* 144 ± ± 5 (ml/min) Albumin excretion (mg/24 h) 23 ± 3 23 ± 4 22 ± 3 24 ± 3 26 ± 4 26 ± 3 BMI, body mass index; BP, blood pressure; HDL, high-denstiy lipoprotein; HOMA IR, homeostasis model assessment of insulin resistance; HT, hypertensive; LDL, low-density lipoprotein; NT, normotensive; PRA, plasma renin activity. Significance between normotensives and hypertensives within each BMI group: *P 0.05; **P 0.01; ***P Table 3 Contributors to 24-h systolic blood pressure variance, determined by backward stepwise multiple linear regression analyses Predictor Overall Normal weight Overweight Obese β r 2 β r 2 β r 2 β r 2 Intercept (β 0 ) Age ** ns ns * Waist *** ** * circumference Plasma *** * ** *** aldosterone PRA *** ** ** ns ns 24-h sodium ns ns ns ns ns ns ** excretion 24-h potassium excretion ns ns ns ns ns ns * r 2 values presented are partial r 2 values. r reflects % variance in blood pressure explained by the model with 1-unit increase in the predictor. β, standardized estimate; PRA, plasma renin activity. *P **P ***P december 2009 VOLUME 22 NUMBER 12 AMERICAN JOURNAL OF HYPERTENSION

5 Aldosterone and Blood Pressure in African Americans articles Table 4 Contributors to hypertension, determined by backward stepwise logistic regression analyses Predictor Overall, Normal weight, Overweight, Obese, Age 1.11 ( )*** 1.12 ( )** 1.11 ( )** 1.13 ( )*** Waist circumference 1.06 ( )*** ns 1.11 ( )** 1.11 ( )*** Plasma aldosterone 2.43 ( )*** 2.29 ( )* 2.62 ( )** 3.24 ( )** PRA 0.59 ( )*** 0.63 ( )* 0.55 ( )*** ns 24-h sodium excretion ns ns 0.84 ( )** 1.30 ( )** 24-h potassium excretion ns ns ns 0.08 ( )*** Odds ratio is the increase in odds for hypertension with 1-unit increase in the predictor. CI, 95% confidence interval. *P **P ***P Odds ratios Age WC PA PRA Predictors Obese Overweight Normal Figure 1 Odds ratio for hypertension, by body mass index group. K_excre, 24-h potassium excretion; Na_excre, 24-h sodium excretion; PA, plasma aldosterone; PRA, plasma renin activity; WC, waist circumference. strata but remained significant in other groups are represented as not significant; however, the presented coefficients are from the model without these variables. In the overall sample, age, WC, PA, and PRA accounted for 23.2% of the variance in BP (Table 3). These same variables were also associated with a significantly increased odds ratio of having hypertension (Table 4 and Figure 1). When stratified by BMI strata, WC had no predictive value in subjects with normal BMI. In this subgroup, PA and PRA significantly predicted the BP level and odds ratio for hypertension. PA was the strongest positive correlate of BP (r 2 = or 6.6%) whereas PRA change was associated with lower BP (r 2 = or 9.6%). In overweight and obese individuals, age, WC, and PA significantly contributed to the predictability of BP and to the odds of hypertension. In normal-weight, overweight, and obese hypertensives, each 1 ng/dl increase of PA increased the odds of hypertension by 2.29, 2.62, and 3.24, respectively. In addition, 24-h urinary sodium and potassium excretion were also associated with BP level and hypertension among obese group subjects. Discussion We have previously reported that PA is higher and PRA is lower in hypertensive than in normotensive AAs, and that indices of adiposity correlate with BP in normotensive, but not in hypertensive Na_Excre K_Excre subjects. 5,11 The present report extends these observations by demonstrating that PA independently contributes to BP variance and to hypertension prevalence among normal-weight, overweight, and obese AAs. Among overweight and obese subjects, WC and age were also independent contributors to BP variance and hypertension. Additionally, among normal-weight subjects, BP was inversely related to PRA whereas a change in WC was not associated with BP by backward stepwise regression analyses. In contrast, among obese subjects, BP was not related to PRA; however, increase in WC or a 24-h urine sodium excretion was associated with increase in BP while increase in 24-h urine potassium was associated with lower BP. BMI did not have an independent relationship with BP after controlling for WC, consistent with previous observations indicating that hypertension is more closely related to android or visceral obesity than to overall BMI. 4 The mechanism of visceral obesity-related hypertension is often attributed to insulin resistance, although the association of hypertension with insulin resistance has been less consistent in AAs than in Caucasians In this study, although BP levels were correlated with insulin resistance, these associations were not significant after statistical adjustment for WC and PA. Similarly, among AA and Hispanic women, but not men, Foy et al. recently reported a significant relationship between visceral adipose tissue and hypertension that is unrelated to insulin resistance. 17 These observations raise the possibility that hypertension related to visceral obesity may be mediated by aldosterone rather than by insulin resistance per se, at least in AAs. Although the stimulus for increased aldosterone production, despite low PRA, remains a matter of conjecture, recent reports suggest that adipokines or lower nitric oxide may directly stimulate aldosterone production. 19 Whatever the mechanism for its increased production, our results raise the possibility that aldosterone contributes to hypertension in both obese and nonobese AAs. In this study, BP levels and the prevalence of hypertension were related to sodium excretion. Consistent with this hypothesis, obese individuals and subjects with the metabolic syndrome tend to be relatively salt sensitive Further, among nonobese AAs, hypertension also tends to be salt sensitive. 24 Consistent with a role for aldosterone in the pathogenesis of obesity-related hypertension, the mineralocorticoid AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER 12 december

6 articles Aldosterone and Blood Pressure in African Americans antagonist, eplerenone, has been shown to attenuate sodium retention and hypertension associated with the development of obesity in dogs fed a high-fat diet. 25 In addition to a high prevalence of hypertension, AAs experience a high rate of hypertension-related end-organ disease at relatively young ages. Aldosterone has been associated with endothelial dysfunction, left ventricular hypertrophy, cardiovascular disease, cerebro vascular disease, and chronic kidney disease through its effects on proliferation of vascular smooth muscle, fibrosis, inflammation, and tissue remodeling. 26 Consequently, we speculate that aldosterone, in conjunction with a high salt intake, may also contribute to end-organ disease in AAs. This study has several limitations. All subjects were studied off antihypertensive medications; however, due to safety concerns, these medications were discontinued only 1 week before study. Fifty-five percent of the hypertensive subjects had been on prior antihypertensive therapy. Of those that had been on therapy, 62% had been on a single agent, and the frequency of the use of different classes of antihypertensive agents was as follows: diuretics, 43%; calcium antagonists, 41%; angiotensin-converting enzyme inhibitors, 27%; β-blockers, 5%; angiotensin receptor blockers, 5%; α-blockers, 2%. Notably, none of the hypertensives had been on spironolactone, an agent with a relatively long biological half-life. Average 24-h systolic BP was slightly higher among previously treated than among untreated hypertensives (P < 0.05). Overall, only three hypertensive and three normotensive subjects had been on lipid-lowering medications, and these agents were discontinued at least 1 month before study. Based on the measurement of WC, we suggest that hypertension in overweight and obese subjects is related to visceral obesity; however, WC is an insensitive surrogate for visceral obesity in AAs. 27 Finally, because this is a cross-sectional study, we cannot conclude that adiposity, insulin resistance, and/or aldosterone predicts the subsequent development of hypertension. In summary, in these AAs, aldosterone contributed to BP and hypertension in normal-weight, overweight, and obese subjects. These results suggest that mineralocorticoid antagonists may be effective antihypertensive therapies, regardless of BMI. WC was associated with BP and hypertension only in overweight and obese subjects, whereas BMI and insulin resistance had no significant, independent relationship to either BP or hypertension. The relevance of these observations to other ethnic groups remains to be determined. 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