However, the fact that in another study we showed the functional
relevance of the same
C allele in non-Japanese hypertensive
patients lends further support to the relevance of this polymor-
phism for cardiovascular disease in Caucasians (5).
Gian Paolo Rossi, MD, FACC, FAHA
Maurizio Cesari, MD
Achille C. Pessina, MD, PhD
Department of Clinical and Experimental Medicine
Clinica Medica 4 University Hospital
via Giustiniani, 2
1. Rossi GP, Cesari M, Zanchetta M, et al. The T
C endothelial nitric
oxide synthase genotype is a novel risk factor for coronary artery disease
in Caucasian patients of the GENICA study. J Am Coll Cardiol
2. Alvarez R, Gonzalez P, Batalla A, et al. Association between the NOS3
(-786 T/C) and the ACE (I/D) DNA genotypes and early coronary
artery disease. Nitric Oxide 2001;5:343–8.
3. Nakayama M, Yasue H, Yoshimura M, et al. T
3 C mutation in the
5Ј-ﬂanking region of the endothelial nitric oxide synthase gene is
associated with coronary spasm. Circulation 1999;99:2864 –70.
4. Jeerooburkhan N, Jones LC, Bujac S, et al. Genetic and environmental
determinants of plasma nitrogen oxides and risk of ischemic heart
disease. Hypertension 2001;38:1054 –61.
5. Rossi GP, Taddei S, Virdis A, et al. The T
C and Glu298Asp
polymorphisms of the endothelial nitric oxide gene affect the forearm
blood ﬂow responses of Caucasian hypertensive patients. J Am Coll
Cardiol 2003;41:938 –45.
Response to Renin-Angiotensin System
Antagonists in Hypertensive Black Subjects
We read with interest the study by Flack et al. (1) which appeared
in the April 2, 2003, issue of the Journal. We commend the
researchers on investigating the effects of aldosterone antagonism
in the black population, who are traditionally underrepresented in
clinical trials. However, we have some concerns regarding the
characteristics of the study subjects.
First of all, we question the investigators’ use of weight, rather
than body mass index (BMI), as an anthropometric measurement.
Data from the Framingham Heart Study indicate that higher BMI
is a major determinant of inadequate blood pressure control with
antihypertensive medications (2). Though not statistically differ-
ent, both male and female subjects in the eplerenone group had
greater body weight than did those in the losartan group. Thus, we
are curious as to whether BMI differed between treatment groups
and, if so, whether these differences may have contributed to the
disparity in results between groups.
Second, the study included participants from both the U.S. and
Africa. The investigators do not report the percentage of black
participants who were from Africa versus those from the U.S. This
information is important in conferring the applicability of the
study ﬁndings to blacks in the U.S. Differences in environmental
factors have been reported among populations of African origin,
with higher BMI and greater sodium intake reported among
American blacks compared to African blacks (3). Similar to BMI,
sodium intake is a well-known factor inﬂuencing antihypertensive
response to renin-angiotensin system antagonists (4 –6). Thus,
whether aldosterone antagonism would produce similar antihyper-
tensive effects in black Americans compared to black Africans is
Larisa M. Humma, PharmD
Patricia L. Adenekan, PharmD
University of Illinois at Chicago
College of Pharmacy
Department of Pharmacy Practice
833 S. Wood
Chicago, IL 60612
1. Flack JM, Oparil S, Pratt JH, et al. Efﬁcacy and tolerability of
eplerenone and losartan in hypertensive black and white patients. J Am
Coll Cardiol 2003;41:1148 –55.
2. Lloyd-Jones DM, Evans JC, Larson MG, O’Donnell CJ, Roccella EJ,
Levy D. Differential control of systolic and diastolic blood pressure:
factors associated with lack of blood pressure control in the community.
Hypertension 2000;36:594 –9.
3. Cooper R, Rotimi C, Ataman S, et al. The prevalence of hypertension
in seven populations of West African origin. Am J Public Health
4. Singer DR, Markandu ND, Cappuccio FP, Miller MA, Sagnella GA,
MacGregor GA. Reduction of salt intake during converting enzyme
inhibitor treatment compared with addition of a thiazide. Hypertension
5. Weir MR, Chrysant SG, McCarron DA, et al. Inﬂuence of race and
dietary salt on the antihypertensive efﬁcacy of an angiotensin-converting
enzyme inhibitor or a calcium channel antagonist in salt-sensitive
hypertensives. Hypertension 1998;31:1088 –96.
6. Houlihan CA, Allen TJ, Baxter AL, et al. A low-sodium diet poten-
tiates the effects of losartan in type 2 diabetes. Diabetes Care 2002;25:
We appreciate the questions raised by Humma and Adenekan
regarding the potential impact of body mass index (BMI) on the
blood pressure (BP)-lowering differences between eplerenone and
losartan in our recently published study. Also, the relevance of the
BP-lowering obtained in South African blacks to U.S. blacks was
There were 335 black participants in our trial; 260 (77.6%)
resided in the U.S. and 75 (22.4%) in South Africa. Black
participants were approximately evenly dispersed across treatment
groups with randomization to placebo, eplerenone, and losartan in
the following numbers (U.S. blacks/South African blacks): 1)
placebo (86/24); 2) eplerenone (83/25); and 3) losartan (91/26).
Blood pressure responses (SBP/DBP mm Hg) at 16 weeks (end of
trial) for blacks were: 1) placebo (Ϫ3.7/Ϫ4.8); 2) eplerenone
(Ϫ13.5/Ϫ10.2); and 3) losartan (Ϫ5.3/Ϫ6.0). Among South
African blacks, BP changes were: 1) placebo (Ϫ1.1/Ϫ4.1); 2)
eplerenone (Ϫ11.6/Ϫ10.1); and 3) losartan (Ϫ0.8/Ϫ3.6). The
overall rank-order of BP response was the same among U.S. and
South African blacks, although the absolute magnitude of change
JACC Vol. 42, No. 6, 2003
Letters to the Editor
September 17, 2003:1140 – 6