Sex differences in heart failure Lam, Carolyn S P; Arnott, Clare; Beale, Anna L ...
European heart journal,
12/2019, Letnik:
40, Številka:
47
Journal Article
Recenzirano
Odprti dostop
Abstract
The overall lifetime risk of heart failure (HF) is similar between men and women, however, there are marked sex differences in the landscape of this condition that are both important and ...under-recognized. Men are predisposed to HF with reduced ejection fraction (HFrEF), whereas women predominate in HF with preserved ejection fraction (HFpEF). Sex differences are also notable in the penetrance of genetic cardiomyopathies, risk factors, e.g. breast cancer which may be associated with cancer treatment-induced cardiomyopathy, as well as sex-specific conditions such as peripartum cardiomyopathy (PPCM). This review outlines the key sex differences with respect to clinical characteristics, pathophysiology, and therapeutic responses to HF treatments. Finally, we address important differences in the prognosis of HF. A central hypothesis is that the higher risk of HFrEF in men compared to women may be attributable to their predisposition to macrovascular coronary artery disease and myocardial infarction, whereas coronary microvascular dysfunction/endothelial inflammation has been postulated to play a key role in HFpEF and maybe the common link among HF syndromes that women are predisposed to Takotsubo cardiomyopathy, PPCM, and breast cancer radiotherapy-induced cardiomyopathy. Under-pinning current sex disparities in HF, there is a paucity of women recruited to HF clinical trials (20–25% of cohorts) and thus treatment guidelines are predominantly based on male-derived data. Large gaps in knowledge exist in sex-specific mechanisms, optimal drug doses for women and sex-specific criteria for device therapy.
Consistent epidemiological data demonstrate that patients with heart failure with preserved ejection fraction (HFpEF) are more likely to be women than men. Exploring mechanisms behind this sex ...difference in heart failure epidemiology may enrich the understanding of underlying HFpEF pathophysiology and phenotypes, with the ultimate goal of identifying therapeutic approaches for the broader HFpEF population. In this review we evaluate the influence of sex on the key domains of cardiac structure and function, the systemic and pulmonary circulation, as well as extracardiac factors and comorbidities that may explain the predisposition of women to HFpEF. We highlight the potential role of factors exclusive to or more prevalent in women such as pregnancy, preeclampsia, and iron deficiency. Finally, we discuss existing controversies and gaps in knowledge, as well as the clinical importance of known sex differences in the context of the potential need for sex-specific diagnostic criteria, improved risk stratification models, and targeted therapies.
There has been intense interest in the role of the gut microbiome in human health and a broad range of diseases in recent years. In the context of cardiovascular disease, gut dysbiosis (defined as a ...change in the gut microbiome and the gut-epithelial barrier) has been linked to disturbances in blood pressure (BP) regulation. These findings build upon our understanding of the complex pathophysiology of essential hypertension. There are clear sex differences in the epidemiology of hypertension, with distinct trends in BP across the life-course in men and women. To date, a role for the gut microbiome in contributing to the sex differences in BP is yet to be clearly established. The purpose of this review is to summarise the current literature regarding how the gut microbiome differs between men and women and to investigate whether sex-determined differences in the gut microbiome influence the response to factors such as diet, obesity and inflammation. Finally, we will explore evidence for the possible interaction between sex-specific factors, including sex hormones and pregnancy, with the gut in the context of hypertension pathophysiology.
Background
Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently ...contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors.
Methods and Results
We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF (
P
=0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so (
P
=0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day;
P
=0.016).
Conclusions
We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.
Background Women have higher vascular stiffness with aging. The aim of this study was to characterize sex differences in vascular and ventricular structure and function, and to investigate the impact ...on the primary outcome in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). Methods and Results Data from the Americas cohort of the TOPCAT trial were analyzed. Patients with echocardiography (n=654) were compared according to sex, and achievement of the primary end point (a composite of death from cardiovascular causes and heart failure hospitalization) assessed. Echocardiography revealed higher arterial, systolic, and diastolic ventricular elastance and worse ventricular-vascular coupling in women. Women had better overall survival and heart failure hospitalization outcomes (hazard ratio 0.74, 95% CI 0.57-0.98, P=0.034), however, determinants of achievement of the primary outcome differed between the sexes. Pulse pressure was a key determinant of outcome in women (hazard ratio 1.04, 95% CI 1-1.09, P=0.034) whereas in men heart rate (hazard ratio 1.61, 95% CI 1.02-2.52 per 10 mm Hg increase, P=0.04) and B-type natriuretic peptide (hazard ratio 1.01, 95% CI 1-1.02 per 10 ng/mL increase P=0.02) were associated with poorer outcome. Conclusions Outcomes in patients with heart failure with preserved ejection fraction appear to be differentially influenced by key physiological factors that vary according to sex. In women, ventricular-vascular stiffening was the most significant determinant of outcome, whereas in men overall survival was influenced by heart rate and B-type natriuretic peptide; this highlights key sex differences in the pathophysiology and outcomes of heart failure with preserved ejection fraction and warrants further exploration. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT00094302.
Abstract
Arrhythmias are the most common cardiac complications occurring in pregnancy. Although the majority of palpitations in pregnancy may be explained by atrial or ventricular premature ...complexes, the full spectrum of arrhythmias can occur. In this article, we establish a systematic approach to the evaluation and management of arrhythmias in pregnancy. Haemodynamically unstable arrhythmias warrant urgent cardioversion. For mild cases of benign arrhythmia, treatment is usually not needed. Symptomatic but haemodynamically stable arrhythmic patients should first undergo a thorough evaluation to establish the type of arrhythmia and the presence or absence of structural heart disease. This will ultimately determine the necessity for treatment given the potential risks of anti-arrhythmic pharmacotherapy in pregnancy. We will discuss the main catalogue of anti-arrhythmic medications, which have some established evidence of safety in pregnancy. Based on our appraisal, we provide a treatment algorithm for the tachyarrhythmic pregnant patient.
Regional or diffuse fibrosis is an early feature of hypertrophic cardiomyopathy (HCM) and is related to poor prognosis. Previous studies have documented low-grade inflammation in HCM. The aim of this ...study was to examine the relationships between circulating inflammatory markers and myocardial fibrosis, systolic and diastolic dysfunction, and the degree of cardiac hypertrophy in HCM patients.
Fifty HCM patients were recruited while 20 healthy subjects served as the control group. Seventeen inflammatory cytokines/chemokines were measured in plasma. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac phenotypes. Tumour necrosis factor (TNF)-α, interleukin (IL)-6 and serum amyloid P (SAP) were significantly increased in HCM patients compared to controls. IL-6, IL-4, and monocyte chemotactic protein (MCP)-1 were correlated with regional fibrosis while stromal cell-derived factor-1 and MCP-1 were correlated with diffuse fibrosis. Fractalkine and interferon-γ were associated with left ventricular wall thickness. The above associations remained significant in a linear regression model including age, gender, body mass index and family history. TNF-α, IL-6, SAP, MCP-1 and IL-10 were associated with parameters of diastolic dysfunction. White blood cells were also increased in HCM patients and correlated with diffuse fibrosis and diastolic dysfunction. However the associations between parameters of systemic inflammation and diastolic dysfunction were weakened in the linear regression analysis.
Systemic inflammation is associated with parameters of the disease severity of HCM patients, particularly regional and diffuse fibrosis. Modifying inflammation may reduce myocardial fibrosis in HCM patients.
Background
Hypertensive disorders of pregnancy, gestational diabetes, and having a small‐for‐gestational‐age baby are known to substantially increase a woman's risk of cardiovascular disease. Despite ...this, evidence for models of care that mitigate cardiovascular disease risk in women with these pregnancy‐related conditions is lacking.
Methods and Results
A 6‐month prospective cohort study assessed the effectiveness of a multidisciplinary Women's Heart Clinic on blood pressure and lipid control in women aged 30 to 55 years with a past pregnancy diagnosis of hypertensive disorders of pregnancy, gestational diabetes, or a small‐for‐gestational age baby in Melbourne, Australia. The co‐primary end points were (1) blood pressure <140/90 mm Hg or <130/80 mm Hg if diabetes and (2) total cholesterol to high‐density lipoprotein cholesterol ratio <4.5. The study recruited 156 women with a mean age of 41.0±4.2 years, 3.9±2.9 years from last delivery, 68.6% White, 20.5% South/East Asian, and 80.5% university‐educated. The proportion meeting blood pressure target increased (69.2% to 80.5%,
P
=0.004), with no significant change in lipid targets (80.6% to 83.7%,
P
=0.182). Systolic blood pressure (−6.9 mm Hg 95% CI, −9.1 to −4.7,
P
<0.001), body mass index (−0.6 kg/m
2
95% CI, −0.8 to −0.3,
P
<0.001), low‐density lipoprotein cholesterol (−4.2 mg/dL 95% CI, −8.2 to −0.2,
P
=0.042), and total cholesterol (−4.6 mg/dL 95% CI, −9.1 to −0.2
P
=0.042) reduced. Heart‐healthy lifestyle significantly improved with increased fish/olive oil (36.5% to 51.0%,
P
=0.012), decreased fast food consumption (33.8% to 11.0%,
P
<0.001), and increased physical activity (84.0% to 92.9%,
P
=0.025).
Conclusions
Women at high risk for cardiovascular disease due to past pregnancy‐related conditions experienced significant improvements in multiple cardiovascular risk factors after attending a Women's Heart Clinic, potentially improving long‐term cardiovascular disease outcomes.
Registration
URL:
https://www.anzctr.org.au
; Unique identifier: ACTRN12622000646741.
Objective To investigate the association of aircraft noise with risk of stroke, coronary heart disease, and cardiovascular disease in the general population. Design Small area study. Setting 12 ...London boroughs and nine districts west of London exposed to aircraft noise related to Heathrow airport in London. Population About 3.6 million residents living near Heathrow airport. Risks for hospital admissions were assessed in 12 110 census output areas (average population about 300 inhabitants) and risks for mortality in 2378 super output areas (about 1500 inhabitants). Main outcome measures Risk of hospital admissions for, and mortality from, stroke, coronary heart disease, and cardiovascular disease, 2001-05. Results Hospital admissions showed statistically significant linear trends (P<0.001 to P<0.05) of increasing risk with higher levels of both daytime (average A weighted equivalent noise 7 am to 11 pm, LAeq,16h) and night time (11 pm to 7 am, Lnight) aircraft noise. When areas experiencing the highest levels of daytime aircraft noise were compared with those experiencing the lowest levels (>63 dB v ≤51 dB), the relative risk of hospital admissions for stroke was 1.24 (95% confidence interval 1.08 to 1.43), for coronary heart disease was 1.21 (1.12 to 1.31), and for cardiovascular disease was 1.14 (1.08 to 1.20) adjusted for age, sex, ethnicity, deprivation, and a smoking proxy (lung cancer mortality) using a Poisson regression model including a random effect term to account for residual heterogeneity. Corresponding relative risks for mortality were of similar magnitude, although with wider confidence limits. Admissions for coronary heart disease and cardiovascular disease were particularly affected by adjustment for South Asian ethnicity, which needs to be considered in interpretation. All results were robust to adjustment for particulate matter (PM10) air pollution, and road traffic noise, possible for London boroughs (population about 2.6 million). We could not distinguish between the effects of daytime or night time noise as these measures were highly correlated. Conclusion High levels of aircraft noise were associated with increased risks of stroke, coronary heart disease, and cardiovascular disease for both hospital admissions and mortality in areas near Heathrow airport in London. As well as the possibility of causal associations, alternative explanations such as residual confounding and potential for ecological bias should be considered.
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