Association of Estrogen Receptor β Gene Polymorphisms With Left Ventricular Mass and Wall Thickness in Women

Peter, Inga; Shearman, Amanda M.; Vasan, Ramachandran S.; Zucker, Deborah; Schmid, Christopher H.; Demissie, Serkalem; Cupples, L. Adrienne; Kuvin, Jeffrey T.; Karas, Richard H.; Mendelsohn, Michael E.

doi:10.1016/j.amjhyper.2005.05.023

Cited by 65 publications

(45 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, it could be speculated that the presumably low levels of endogenous estradiol in our female and the presumably low levels of testosterone in our mainly elderly male study population may be partly responsible for the observed higher susceptibility of female hearts for hypertrophic stimuli, i.e., adiposity. Additional explanatory effects could be interactions between the signaling effects of estrogen and aldosterone receptors (39,40); however, in the largest study, sex-related differences of serum aldosterone on left ventricular geometry were independent of menopausal status and BMI (41).…”

Section: Left Ventricular Mass In Diabetesmentioning

confidence: 99%

Sex-Specific Determinants of Left Ventricular Mass in Pre-Diabetic and Type 2 Diabetic Subjects

et al. 2007

View full text Add to dashboard Cite

OBJECTIVE -Obesity and hypertension are regarded as the most important determinants of left ventricular mass in the community. Little is known about sex-specific influences of obesity, hypertension, and other risk factors on left ventricular mass in pre-diabetic or diabetic subjects.RESEARCH DESIGN AND METHODS -We examined how body composition, blood pressure, and other factors are related to left ventricular structure in elderly subjects (mean age 62 years, 88% of women postmenopausal) with pre-diabetes (impaired fasting glucose or impaired glucose tolerance; n ϭ 112) and diabetes with (n ϭ 181) and without (n ϭ 213) overt cardiovascular disease (CVD).RESULTS -Neither microalbuminuria nor physical activity was significantly associated with left ventricular mass. In pre-diabetic as well as diabetic subjects with CVD, mainly BMI and fat mass, particularly in women, were correlated with left ventricular mass. In the diabetic group without overt CVD, fat mass was only slightly correlated with left ventricular mass. In the latter group waist-to-hip-ratio, and, only in men, systolic blood pressure, glucose, and A1C were moderately correlated with left ventricular mass. Multiregression analysis over all groups again revealed fat mass as the main determinant of left ventricular mass in women. In women but not men obesity was associated with a significantly increased prevalence of concentric left ventricular hypertrophy.CONCLUSIONS -In pre-diabetic and diabetic elderly subjects fat mass is the major determinant of left ventricular mass in women but not in men. These results may partly explain sex differences in CVD mortality in obese elderly diabetic subjects and underscore the need for activities focused on weight reduction. Diabetes Care 30:946 -952, 2007L eft ventricular hypertrophy is independently associated with congestive heart failure and cardiovascular mortality (1-3). Diabetes is also known as an important risk factor for cardiovascular morbidity and mortality, and this association is partly mediated by its effect on left ventricular structure. Traditionally, hypertension and obesity have been regarded as the most important etiological factors in the development of left ventricular hypertrophy in the community (4 -8). Diabetes and impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), the latter being regarded as a preclinical stage of diabetes, are also recognized as independent risk factors for the development of left ventricular hypertrophy (9 -11). However, the role of the traditional etiological risk factors in prediabetic or diabetic subjects is unknown. In patients with more advanced stages of diabetes, in particular, it has been speculated that the traditional risk factors for left ventricular hypertrophy may have a lesser influence on left ventricular mass because of other mechanisms that may become more important (12). Furthermore, although it is known that in the general population cardiac adaptations to obesity and hypertension are sex-specific (7,8) and, in addition, influences of di...

show abstract

Section: Left Ventricular Mass In Diabetesmentioning

confidence: 99%

Sex-Specific Determinants of Left Ventricular Mass in Pre-Diabetic and Type 2 Diabetic Subjects

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Several studies have shown sex differences in cardiac structure. [21][22][23] For example, in animal models of pressure overload, females did develop more hypertrophy than males. 21 Furthermore, an association between estrogen gene polymorphism and LVM has been reported.…”

Section: Effects Of Bp and Time On Lvhmentioning

confidence: 99%

BP Control and Left Ventricular Hypertrophy Regression in Children with CKD

Kupferman

Friedman

Cox

et al. 2014

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.

show abstract

“…4 The 2 functional isoforms, ER␣ and ER␤, are expressed in the myocardium. 5 Receptor-mediated effects of estrogens on cardiomyocyte biology are injury or stimulus dependent, 4,6 which, in turn, implicates activation of distinct, sex-dependent, signaling pathways and gene expression programs. 7 We described recently a sex-specific dimorphism in cardiac adaptation in response to deoxycorticosterone acetate (DOCA)-salt and showed that this response was independent of blood pressure.…”

mentioning

confidence: 99%

Estrogen Receptor-β Signals Left Ventricular Hypertrophy Sex Differences in Normotensive Deoxycorticosterone Acetate-Salt Mice

et al. 2011

View full text Add to dashboard Cite

Abstract-We found earlier that deoxycorticosterone acetate-salt treatment causes blood pressure-independent left ventricular hypertrophy, but only in male mice. To test the hypothesis that the estrogen receptor-␤ (ER␤) protects the females from left ventricular hypertrophy, we treated male and female ER␤-deficient (ER␤ Ϫ/Ϫ ) mice and their male and female littermates (wild-type [WT]) with deoxycorticosterone acetate-salt and made them telemetrically normotensive with hydralazine. WT males had increased (ϩ16%) heart weight/tibia length ratios compared with WT females (ϩ7%) at 6 weeks. In ER␤ Ϫ/Ϫ mice, this situation was reversed. Female WT mice had the greatest heart weight/tibia length ratio increases of all of the groups (ϩ23%), even greater than ER␤ Ϫ/Ϫ males (ϩ10%). Echocardiography revealed concentric left ventricular hypertrophy in male WT mice, whereas ER␤ Ϫ/Ϫ females developed dilative left ventricular hypertrophy. The hypertrophic response in female ER␤ Ϫ/Ϫ mice was accompanied by the highest degree of collagen deposition, indicating maladaptive remodeling. ER␤ ϩ/ϩ females showed robust protective p38 and extracellular signal-regulated kinase 1/2 signaling relationships compared with other groups. Calcineurin A␤ expression and its positive regulator myocyte-enriched calcineurin-interacting protein 1 were increased in deoxycorticosterone acetate-salt female ER␤ Ϫ/Ϫ mice, yet lower than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, which could be blocked by estradiol and an ER␤ agonist. We conclude that a functional ER␤ is essential for inducing adaptive p38 and extracellular signal-regulated kinase signaling, while reducing maladaptive calcineurin signaling in normotensive deoxycorticosterone acetate female mice. Our findings address the possibility of sex-specific cardiovascular therapies. Key Words: estrogen receptor-␤, heart Ⅲ hypertrophy Ⅲ fibrosis Ⅲ calcineurin Ⅲ p38 MAPK Ⅲ ERK1/2 F emales seem to be relatively protected from cardiovascular disease on the basis of animal and human studies; estrogens could play a role. 1-3 Clinical trials using estrogens for improving cardiovascular health were disappointing, perhaps because of poor estrogen receptor (ER) isoform selectivity and specificity. 4 The 2 functional isoforms, ER␣ and ER␤, are expressed in the myocardium. 5 Receptor-mediated effects of estrogens on cardiomyocyte biology are injury or stimulus dependent, 4,6 which, in turn, implicates activation of distinct, sex-dependent, signaling pathways and gene expression programs. 7 We described recently a sex-specific dimorphism in cardiac adaptation in response to deoxycorticosterone acetate (DOCA)-salt and showed that this response was independent of blood pressure. 8 Male mice developed left ventricular hypertrophy (LVH) that was linked to activation of a calcineurin-dependent pathway, which increased proinflammatory and profibrotic responses. In contrast, female DOCA mice maintained their initial physiological adaptive cardiac phenotype despite mineralocorticoid and...

show abstract

Association of Estrogen Receptor β Gene Polymorphisms With Left Ventricular Mass and Wall Thickness in Women

Abstract: Background: Left ventricular (LV) hypertrophy is a significant risk factor for cardiovascular disease. Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure.

Cited by 65 publications

References 48 publications

Sex-Specific Determinants of Left Ventricular Mass in Pre-Diabetic and Type 2 Diabetic Subjects

Sex-Specific Determinants of Left Ventricular Mass in Pre-Diabetic and Type 2 Diabetic Subjects

BP Control and Left Ventricular Hypertrophy Regression in Children with CKD

Estrogen Receptor-β Signals Left Ventricular Hypertrophy Sex Differences in Normotensive Deoxycorticosterone Acetate-Salt Mice

Contact Info

Product

Resources

About