Cardiac Benefits with Hypertension Treatment Vary by Gender

By Todd Neale
NEW YORK, 5 july 2008--In patients receiving treatment for hypertension, women have less improvement in left-ventricular hypertrophy than men, a post hoc analysis revealed.
Among patients taking either losartan (Cozaar) or atenolol (Tenormin), women had significantly less reduction of left ventricular hypertrophy using two sets of criteria -- the Cornell product (P<0.001) and Sokolow-Lyon voltage (P=0.005) -- compared with men, Peter Okin, M.D., of Weill Cornell Medical College here, and colleagues reported in the July issue of Hypertension: Journal of the American Heart Association.
The gender differences remained after adjusting for several variables, including baseline severity of hypertrophy and blood pressure changes.
There are well-established gender differences in the electrocardiographic criteria for left-ventricular hypertrophy, the researchers said, although whether these differences are also found in the magnitude of regression of the condition during treatment for hypertension had been unclear.
So the researchers evaluated improvements in left-ventricular hypertrophy in 9,193 patients from the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, a prospective, double-blind, randomized study that showed that treatment with losartan was associated with a greater reduction in hypertrophy and a lower rate of diabetes compared with atenolol.The LIFE study included patients ages 55 to 80 who had a systolic blood pressure of 160 to 200 mm Hg and a diastolic pressure of 95 to 115 mm Hg. Patients were given 50 mg of either losartan or atenolol.
Through a mean follow-up of 4.8 years, there were no gender differences in the change in systolic blood pressure.
There were, however, significant differences between the sexes in changes in diastolic blood pressure starting at four years and continuing through the end of the study, with women having slightly less change in pressure than men.
The researchers assessed changes in electrocardiographic left ventricular hypertrophy using both gender-adjusted Cornell product and Sokolow-Lyon voltage criteria throughout the five-year study.
Left ventricular hypertrophy was defined as >2,440 mm.ms using Cornell product criteria or >38 mm using Sokolow-Lyon voltage criteria.
Above-average regression of hypertrophy was defined as a reduction ³236 mm.ms or ³3.5 mm using the respective criteria.
Women had significantly less regression according to both Cornell product (-149 versus -251 mm.ms) and Sokolow-Lyon voltage (-3.0 versus -4.8 mm) criteria (P<0.001 for both).
After adjusting for baseline severity of hypertrophy, baseline levels of and changes in blood pressure, hypertension medication, age, and other baseline gender differences, the disparity between the sexes in degree of regression remained (P<0.001 for the Cornell product and P=0.005 for the Sokolow-Lyon voltage).
Women were 32% (P<0.001) and 15% (P=0.003) less likely to have above-average regression by Cornell product and Sokolow-Lyon voltage criteria, respectively.
The disparity in regression grew larger as the study progressed (P<0.001 for both criteria).
Also over time, women had less reduction in left ventricular mass in relation to height than men (P=0.01).
The prevalence of left ventricular hypertrophy decreased by a greater percentage in men than in women using both Cornell product (-19% versus 14.7%) and Sokolow-Lyon voltage (-14.9% versus -6.1%) criteria (P<0.001 for both).
The authors acknowledged some limitations, including the fact that the patients were at particularly high risk with moderate-to-severe hypertension.
Also, they said, the patients were selected for elevated measures of hypertrophy and some of the regression may have been a return to the mean.
Furthermore, ambulatory blood pressure readings may have given a more exact measure of the effect of treatment.
Finally, they said, the relative severity of hypertrophy in women varied depending on which of the two criteria were used.
In an accompanying editorial, Enrico Agabiti-Rosei, M.D., and Massimo Salvetti, M.D., of the University of Brescia in Italy, said that the study findings might partially explain why the risk of cardiovascular events increases more in women than in men as they age.
However, they said, they advised a careful interpretation of the results, "which are the result of a post hoc analysis."
They noted that the prevalence of electrocardiographic left ventricular hypertrophy is low in primary care.
"Therefore, caution is advisable in extrapolating the results observed in this highly selected, high-risk population to hypertensive patients who are encountered in everyday clinical practice."
The study was supported in part by grants from Merck, maker of losartan.
Dr. Okin received grant support from Merck. His co-authors have potential conflicts of interest with Merck, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Leo, Nycomed, Novartis, Pfizer, sanofi-aventis, and Sankyo.
The editorialists made no disclosures.
Primary source: Hypertension: Journal of the American Heart AssociationSource reference:Okin P, et al "Gender differences in regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy" Hypertension 2008; 52: 100-106. Additional source: Hypertension: Journal of the American Heart AssociationSource reference: Agabiti-Rosei E, Salvetti M "Gender differences in the regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy" Hypertension 2008; DOI: 10.31161/HYPERTENSIONAHA.108.111948.