Author + information
- John M. Flack, MD, MPHa ()
- Scott L. Krause, BSN,
- Suzanne Oparil, MD,
- J.Howard Pratt, MD and
- Elijah Saunders, MD
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 raised.
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 (−3.7/−4.8); 2) eplerenone (−13.5/−10.2); and 3) losartan (−5.3/−6.0). Among South African blacks, BP changes were: 1) placebo (−1.1/−4.1); 2) eplerenone (−11.6/−10.1); and 3) losartan (−0.8/−3.6). The overall rank-order of BP response was the same among U.S. and South African blacks, although the absolute magnitude of change did appear to differ. Nevertheless, we believe that our reported findings are relevant to U.S. blacks given the same rank-order of BP responses within each group as well as the fact that the majority of black participants were from the U.S.
We agree with Drs. Humma and Adenekan that dietary sodium intake and body size may potentially confound BP changes to pharmacological agents. We (1)and others (2,3)have shown that higher levels of dietary sodium intake attenuates the BP lowering effect of antihypertensive agents, especially drugs working primarily on the renin-angiotensin-aldosterone-kinin system. The study participants in our trial were not counseled to restrict dietary sodium intake nor was urinary sodium excretion measured. Thus, the effect of dietary sodium by region, ethnic group, or drug treatment cannot be determined. Conversely, it is plausible that high levels of dietary sodium may have attenuated the BP lowering effect of losartan moreso than eplerenone.
We also agree that body size can influence BP change to pharmacological interventions. In fact, this is an underrecognized factor influencing treatment responses (4,5). The body weights (weighted for the proportions of men and women) in the losartan and eplerenone groups, respectively, were 91.9 kg and 88.7 kg, which corresponds to a difference of 3.2 kg. When BMI levels are compared, no difference existed between the eplerenone and losartan groups in men and only a very small difference in women. Median BMI levels in women randomized to eplerenone and losartan, respectively, were 32.1 and 33.8 kg/m2; in men, median BMI rates for the same two groups were 29.7 and 29.6 kg/m2, respectively. We do not believe that these very slight differences in body size account for the BP response differences between eplerenone and losartan that we reported.
In conclusion, the questions raised are certainly important. However, we do not believe the relatively modest body size differences, as determined by any metric, explains our results to any significant degree. Finally, assuming that high levels of dietary sodium intake importantly influenced BP responses, our data suggest that eplerenone lowers BP more robustly in American and South African blacks than does losartan in high-sodium-consuming hypertensives.
- American College of Cardiology Foundation