More women with aortic valve (AV) stenosis tended to exhibit left ventricular (LV) hypertrophy than men, but women also reversed the hypertrophy faster immediately following valve replacement surgery. Genetic differences affecting fibrosis may be responsible for this phenomenon, according to a study published in a surgical supplement, Circulation: Surgery for Valvular Heart Disease.
Geroge Petrov, MD, of the Charite University of Medicine in Berlin, and colleagues noted that the late follow-up period after AV replacement has been studied in detail, but very few studies analyzed the early time course of regression.
"In addition, sex differences in the regression of myocardial hypertrophy and fibrosis after AV replacement have not yet been analyzed. This is astonishing, because sex differences in the manifestation of LV hypertrophy before surgery are well accepted," they wrote.
To study this phenomenon further, investigators assessed 92 patients—53 women with an average age of 72 and 39 men with an average age of 67—undergoing AV replacement between January 2007 and December 2008 to compare LV hypertrophy and its post-op regression.
Petrov and colleagues also analyzed myocardial biopsies to assess genetic differences between men and women in molecular adaptation to myocardial hypertrophy that could potentially explain the differences in LV hypertrophy regression.
The investigation found a similar number of men and women with increased LV dimensions at end-diastole and end-systole prior to surgery. Post-surgery end-diastolic dimensions decreased in both sexes, but these decreases were more notable in women then in men, 5 mm versus 2 mm, respectively.
After AV replacement, the prevalence of LV hypertrophy decreased in women at a greater rate than in men: 86 to 45 percent versus 56 to 36 percent, respectfully.
Regarding genetic findings, men exhibited a greater makeup of collagen and metalloproteinase (MMP), which were “well in agreement with higher levels of fibrous tissues in the hearts of men compared to women," and only men showed an increase in fibrous tissue gene expression.
"Higher collagen content in males could be responsible for slower regression of left ventricular hypertrophy," the authors wrote. "Linking sex differences in regression to the molecular signature of left ventricular hypertrophy may improve our understanding on the relevance of molecular changes at the time of surgery and may point to new interventions."
The researchers noted that while other studies reported sex differences in collagen architecture, little research has been performed regarding molecular analysis like those done in this study.
"Cardiac hypertrophy in patients with aortic stenosis (AS) is associated with an increase in interstitial fibrosis, which is more pronounced in male hearts," the authors wrote. "Relief of mechanical obstruction by aortic valve replacement leads to hemodynamic improvement and a substantial decrease of LV mass. Regression of LV mass occurs early after aortic valve stenosis and continues up to 10 years after surgery.
"We show for the first time that women exhibit faster regression of LV hypertrophy in the early postoperative course after aortic valve replacement compared with men," the authors wrote. “If confirmed, these results may lead to the development of strategies to slow the increase of cardiac fibrous tissue in both men and women with aortic stenosis."
Study co-author Vera Regitz-Zagrosek, MD, a professor of cardiology at the Center for Gender in Medicine and Cardiovascular Disease in Women in Berlin, concluded: "It is important to study gender differences in elderly patients. Many think that when people don't have sex hormones or have low levels, women and men are the same. This is untrue. To develop optimal treatment for both, we need studies that pre-specify gender differences as an endpoint and that have enough statistical power to look at the differences between women and men."