Sex differences in response to chronic heart failure therapies

Ghali, Jalal K.; Lindenfeld, JoAnn

doi:10.1586/14779072.6.4.555

Cited by 21 publications

(7 citation statements)

References 97 publications

(73 reference statements)

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“…71 Women are reported to have potentially benefit more from ARBs and men from ACEIs. 72 Users of hormone therapy had less MH and a better clinical course in HF studies than non-users. 73 At present, there is no therapeutic exploitation of this potential approach.…”

Section: Discussionmentioning

confidence: 99%

Sex and Gender Differences in Myocardial Hypertrophy and Heart Failure

Regitz‐Zagrosek

Oertelt‐Prigione

Seeland

et al. 2010

Circ J

163

103

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EpidemiologyHeart failure (HF) is one of the leading hospital discharge diagnoses in the modern world and has enormous implications with respect to cardiovascular mortality and morbidity, to individual quality of life experiences and societal resource utilization. The number of patients with HF is continuously increasing. Approximately 10% of 70-year-olds are affected, with an increasing prevalence after that age. HF patients have a life expectancy of approximately 5 years, similar to patients with malignant disease. Women with HF are older than their male counterparts and more likely to exhibit a non-ischemic cause of the disease. 1 The population-based Framingham study suggests that the prognosis in women is significantly better than in men after the onset of HF. 2 However, despite the higher mortality in men, given the overall longer lifespan of women, total numbers of HF deaths are higher in women. The incidence of HF increases dramatically in the female population over 55 years, further compensating the sex differences in mortality. This also appears to account for the stronger correlation between age and mortality observed in women. In fact, in men the NYHA class at baseline is the strongest predictor of mortality, whereas in women it is age. African-Americans might have a higher incidence of HF than Caucasians, with men affected more frequently than females.Major risk factors in both sexes are: age, presence of diabetes, anemia, elevated blood pressure, presence of AF, myocardial hypertrophy (MH) and prior myocardial infarction. Distribution of risk factors differs between the sexes. Women more frequently exhibit hypertension 1,3 and diabetes mellitus. 1,3 Hypertension contributes to the population attributable risk for HF in women to a greater extent than in men. 4 Obesity, diabetes, and impaired glucose carry a greater risk in women and inhibit or impair myocardial metabolism more severely in women than in men. 5-7 Men are more likely to suffer from preexisting coronary heart disease 1,8 and dilated cardiomyopathy (DCM). In the Euro HF survey, systolic HF was found predominantly in men whereas women presented with HF with preserved ejection fraction (EF) or diastolic HF. 9-11 Both systolic and diastolic HF carry a poor prognosis, with astonishingly small differences. 12 MH is a major risk factor for HF and is a negative prognostic sign in itself. Interestingly, women are better protected against the development of MH than men. However, even though MH appears later in women than it does in men at a given hemodynamic load, once established, it is more malign in women. 13 Left ventricular (LV) mass has been presented as the strongest independent mortality predictor in females. Sex and Gender Differences in Myocardial Hypertrophyand Heart Failure Vera Regitz-Zagrosek, MD; Sabine Oertelt-Prigione, MD; Ute Seeland, MD; Roland Hetzer, MDHeart failure (HF) is a leading cause of cardiovascular mortality and morbidity in the Western world. It affects men at younger age than women. Women have more frequently diast...

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Section: Discussionmentioning

confidence: 99%

Sex and Gender Differences in Myocardial Hypertrophy and Heart Failure

Regitz‐Zagrosek

Oertelt‐Prigione

Seeland

et al. 2010

Circ J

163

103

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“…For instance, men may experience more benefits from ACEIs, such as a reduction in hospitalizations and mortality, while women may have more benefits from ARBs as described previously [60]. Women develop digitalis toxicity and experience ACEI side effects more often than men [61].…”

Section: Issues Related To Pharmacological Management In Womenmentioning

confidence: 99%

Disparities in Heart Failure and other Cardiovascular Diseases among Women

McSweeney

Pettey

Lefler

et al. 2012

Womens Health (Lond Engl)

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This article reviews literature pertinent to cardiovascular disparities in women, focusing primarily on heart failure (HF). It provides an in-depth look at causes, biological influences, self-management and lack of adherence to HF-treatment guidelines in women. Disparities in treatment of causative factors of HF, such as myocardial infarction and hypertension, contribute to women having poorer HF outcomes than men. This article discusses major contributing reasons for nonadherence to medication regimes for HF in women, including advanced age at time of diagnosis, likelihood of multiple comorbidities, lack of social support and low socioeconomic status. Limited inclusion of women in clinical trials and the scarcity of gender analyses for HF and other cardiovascular diseases continues to limit the applicability of research findings to women.

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“…This progress in knowledge remains relatively ignored as we have little information regarding translation of these experimental findings to female-specific therapy for LVDD and HF with preserved ejection fraction [11], [12]. In fact, retrospective analyses of large trials suggest that the effects of ACE-inhibitors may be less pronounced in women than in men receiving treatment for hypertension and heart failure [26], [27], [28], [29].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Cardiac Renin Angiotensin System in Oophorectomized and Estrogen-Replete mRen2.Lewis Rats

et al. 2013

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The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17) or sham-operation (Sham; n = 13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 β-estradiol (E2, 36 µg/pellet, 60-day release, n = 8) or vehicle (OVX-V, n = 9) for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang) II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1–7) content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R). E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1–7) mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.

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Sex differences in response to chronic heart failure therapies

Cited by 21 publications

References 97 publications

Sex and Gender Differences in Myocardial Hypertrophy and Heart Failure

Sex and Gender Differences in Myocardial Hypertrophy and Heart Failure

Disparities in Heart Failure and other Cardiovascular Diseases among Women

Characterization of the Cardiac Renin Angiotensin System in Oophorectomized and Estrogen-Replete mRen2.Lewis Rats

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