Response to Gender Differences in Left Ventricular Hypertrophy Regression
Escobar and Barrios1 raise several interesting and important issues regarding our recent article demonstrating greater risk reduction with losartan- than atenolol-based therapy in women with ECG-LVH in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) Study.2 First, they question how it is possible that women have lesser event rates than men despite greater regression of ECG-LVH in men than in women.1 The lower cardiovascular (CV) morbidity and mortality among women in the LIFE Study are in line with expectations from all of the previous epidemiological studies and large clinical trials that have examined gender differences in CV outcomes. Paralleling and contributing to these findings, women in the LIFE Study had significantly lower Framingham risk scores and less pre-existing cerebrovascular and coronary heart disease.2 Although it is possible that lesser reductions in ECG-LVH in women may have contributed to a narrowing of the observed gender differences in CV event rates in the LIFE Study,2,3 it would appear that any potential impact of lesser regression of LVH in women on outcomes was inadequate to overcome the greater burden of other CV risk factors and increased CV risk in men. Unfortunately, the relative contribution of gender differences in LVH regression induced by aggressive antihypertensive treatment to differences in outcomes cannot be further analyzed in the LIFE Study population, because there was no untreated control group. However, our observation that lower in-treatment ECG indices of LVH were associated with lower event rates, without significant gender differences, indicates that LVH regression is beneficial in women and men.4
Although data on gender differences in regression of LVH were not presented in our recent article,2 the question of whether different ECG criteria influence whether men or women have greater regression of LVH in response to blood pressure reduction is an interesting one. In the LIFE Study, women had lesser reduction of ECG-LVH by both Sokolow-Lyon voltage and Cornell voltage-duration product criteria.3 In addition, women had more residual echocardiographic LV hypertrophy despite ≈5 years of intensive antihypertensive therapy in the LIFE Study, as reported recently.5 In addition to the possible gender differences in behavior of ECG-LVH criteria cited by Escobar and Barrios,1 discrepancies between our findings and those noted by the authors in their letter could also reflect differences between the study populations or designs, as well as the much smaller size of the cited studies (n=97 and n=276) as compared with the LIFE Study (n=9193).
I.O. has received grant support from Merck and has received honoraria from several pharmaceutical companies within the last 2 years in fields other than hypertension. R.B.D. has received grant support and honoraria from Merck and has served as a consultant for Merck and Novartis. P.M.O. has received grant support from Merck.
Escobar C, Barrios V. Gender differences in left ventricular hypertrophy regression. Hypertension. 2008; 51: e58.
Os I, Franco V, Kjeldsen SE, Manhem K, Devereux RB, Gerdts E, Hille DA, Lyle PA, Okin PM, Dahlöf B, Oparil S. Effects of losartan in women with hypertension and left ventricular hypertrophy. Results from the Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension. 2008; 51: 1103–1108.
Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Dahlöf B. Gender differences in regression of electrocardiographic left ventricular hypertrophy in response to antihypertensive therapy: the LIFE Study. J Am Coll Cardiol. 2003; 19: 230A. Abstract.
Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, Snapinn S, Harris KE, Aurup P, Edelman JM, Wedel H, Lindholm LH, Dahlöf B. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and prediction of major cardiovascular events: the LIFE Study. JAMA. 2004; 292: 2343–2349.
Gerdts E, Okin PM, de Simone G, Cramariuc D, Wachtell K, Boman K, Devereux RB. Gender differences in left ventricular structure and function during antihypertensive treatment. The Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension. 2008; 51: 1109–1114.