Added: Wilhelm Haag - Date: 01.10.2021 15:05 - Views: 43349 - Clicks: 8611
Despite ificant progress in the care of patients suffering from cardiovascular disease, there remains a persistent sex disparity in the diagnosis, management, and outcomes of these patients. These sex disparities are seen across the spectrum of cardiovascular care, but, are especially pronounced in acute cardiovascular care. The spectrum of acute cardiovascular care encompasses critically ill or tenuous patients with cardiovascular conditions that require urgent or emergent decision-making and interventions. In this narrative review, the disparities in the clinical course, management, and outcomes of six commonly encountered acute cardiovascular conditions, some with a known sex-predilection will be discussed within the basis of underlying sex differences in physiology, anatomy, and pharmacology with the goal of identifying areas where improvement in clinical approaches are needed.
The lack of consideration of sex as an essential biological variable in both preclinical and clinical studies has crucial downstream consequences on the development of therapeutic targets in CVD. Sex is a critical and easily addressable factor influencing healthcare disparities.
Historically, CVD was considered to be a male-predominant disease, likely due to extrapolation from early trials that had a high proportion of male participants. Women with AMI are more likely to present with dissimilar symptoms to men, delay to presentation, and have increased comorbidities and increased incidence of myocardial infarction with non-obstructive coronary arteries MINOCA.
However, these differences in the cardiovascular profile of women do not fully explain the higher early mortality and lower long-term survival. Women with AMI often have a lower prevalence of hypercholesterolaemia and peripheral vascular disease compared to men. Oestrogen improves vascular function, reduces atherosclerosis, ischaemia—reperfusion injury and impacts cardiovascular health by direct effects on the vascular cells and cardiomyocytes, as well as, indirect effects mediated systemically through altered autonomic and renal function. Summary schematic of potential mechanisms by which sex steroids affect cellular functions.
At the genetic level, the basic difference between females and males are the presence of XX chromosomes in females and XY in males. The genes on these chromosomes direct the development of reproductive organs, affect gene transcription of functions related other physiological systems and can alter expression of genes on some autosomes.
Sex steroids are produced from the gon. These sex steroids can diffuse into the cell to bind to cellular receptors which migrate to the nucleus to affect gene transcription, as well, as bind to surface receptors that affect ion channel function and initiate a cascade of alling pathways that direct cell function or indirectly affect gene transcription.
Despite advances in cardiovascular care, there exists a ificant sex disparity in management and outcomes of AMI. However, even after adjusting for demographics and cardiovascular risk profile women were noted to have an excess mortality suggesting that underlying basic physiological parameters that differ between female and males are not considered in diagnostic and treatment guidelines. Wilkinson et al. There is a risk of physicians underestimating the cardiovascular risk in women.
In a study using data from the Myocardial Ischemia National Audit Project MINAPimplementing the provision of guideline-indicated care was noted to reduce excess mortality and potentially avoidable deaths. It is conceivable that the lower adherence to guideline therapy could partly be attributed to a higher incidence of MINOCA in women.
The of studies reporting sex-differences in risk factors and outcomes from AMI has grown in recent years. In light of the of the various studies, it is likely that sex differences in AMI mortality are potentially modifiable through improved concordance with guideline-indicated care. In addition, improved outcomes for women with AMI will result from better understanding of physiological factors influencing development and risk for disease, as well as elimination of bias in guidelines based on male models of disease.
Inclusion of pregnancy-associated complications including preeclampsia, preterm delivery, and gestational diabetes as risk enhancers in the assessment of atherosclerotic CVD should be standard practice. Risk stratification scores used in the emergency department and in-hospital to assess the need for angiography in patients presenting with NSTEMI should include female-specific risk factors.
The first step in minimizing negative effects of bias is increasing awareness of implicit stereotypes and being motivated to counteract them to ensure that bias does not influence behaviour. In a series of studies that spanned data collected from towomen presenting with STEMI had higher rates of acute heart failure, left ventricular dysfunction, and CS even after adjusting for age, type of MI and baseline characteristics.
Both randomized controlled trials RCT and real-world data from registries and hospitals have consistently demonstrated women with CS tend to be older, with a higher prevalence of hypertension, diabetes, and other comorbidities.
In both female and male patients presenting with AMI-CS, the majority of infarcts involved the anterior ventricular wall. Coronary angiography, PCI, and surgical revascularization rates were similar in both men and women. The lack of sex differences in treatment and in the 1, 6-months and 1-year outcomes are consistent in several contemporary studies.
In a Dutch multicentre registry of CS patients, Velders et al. Studies analysing sex disparities in AMI-CS using the NIS database noted that women had a higher in-hospital mortality compared to men on multivariate analysis which extended to all racial and ethnic groups. This difference might reflect a higher cardiovascular risk profile and a prehospital delay for women than men. Female patients with OHCA tend to be older with more comorbidities, have a higher probability of being in non-public locations, less often have witnessed arrests, more often have a non-shockable rhythm, and a lower probability of receiving resuscitation efforts during prehospital care than men.
A higher early mortality in men is accentuated by Women sex with monkey h in Louisville sc higher predilection for smoking and hyperlipidaemia leading to a higher risk for CAD and poorer outcomes after CA. Much of the literature suggests that low testosterone levels are associated with increased CVD. Additional studies are required to better understand the complex effects of testosterone on the cardiovascular system.
Women have increased chest wall compliance compared to men making chest compressions and resuscitation efforts easier and more effective. It is concerning to see sex-discrepancies in the use of TTM. There needs to be increased awareness and earnest efforts by the medical community to close this sex-based gap in order to improve survival and neurological recovery in women post-CA. The association of sex with mortality from OHCA is controversial. Some studies report improved survival in females,while others noted a lower survival in males.
Efforts to lower the incidence and mortality of CA in women needs to begin right from the level of primary preventive care that should focus at aggressively managing and reducing cardiovascular risk factors and comorbidities. Early diagnosis and timely revascularization with adherence to guideline-recommended medications for secondary prevention might help lower the incidence of CA in women. Increasing awareness of CVD in women, prehospital care and a strict adherence to guideline-recommended in-hospital management could mitigate the sex disparities in mortality and improve survival in women with CA.
Clinical and demographic factors underlying the sex disparities are likely to be complex and the pre-hospital and clinical factors predisposing to sex disparities in neurological outcomes are unknown. The lower mortality in men noted in that study is contradictory to most of the other studies which noted female sex to be associated with better survival. Studies have shown racial, ethnic, and regional disparities in OHCA. In a meta-analysis, Zhang et al. There is an urgent need to identify causes and barriers to eliminate the sex disparities in post-CA care.
The lay public associates CA with male sex, thereby risking a delay or total absence of CA recognition in females in situations of a collapse. Such lack of knowledge should be addressed in CPR training. Public health measures aimed at increasing bystander CPR for women and early referral of eligible women for internal defibrillator placement Women sex with monkey h in Louisville sc be undertaken.
Acute decompensated heart failure ADHF is the most common presentation of heart failure HF and bodes a poor prognosis. Furthermore, women are less likely to have CAD which is more frequently associated with HFrEF,atrial fibrillation, chronic obstructive pulmonary disease, or smoking; and to have a similar prevalence of diabetes mellitus. Women have smaller ventricular chambers, higher LV elastance, and higher ejection fraction compared to age-matched men. On a cellular level, sex differences exist due to the combined genetic effects of the sex chromosomes and in steroid hormones.
Oestrogen, through production of endothelium-derived nitric oxide promotes vasodilatation, the hormone also increases expression of heat shock proteins, acts as an antioxidant, and alters inflammation through cytokines associated with immune function. Additionally, many genes encode inflammatory responses in cardiac tissue leading to enhanced inflammatory pathways are up-regulated in the female myocardium.
Telomere length in the presence of the disease is better preserved in females than males, an effect that suggests that the telomere length required for the onset of HF may occur later in life in women than in men. Prognostic value NT-proBNP by determining in-hospital mortality and HF readmission in all HF phenotypes is well known,but sex differences in its prognostic value is still in question.
Baseline levels of NT-proBNP levels are higher in women than men indicating a need for age and sex-specific levels in clinical guidelines. Women Women sex with monkey h in Louisville sc more than two-thirds of patient with HFpEF. The reason because of which women are overrepresented in this phenotype of HF is complex and multifold. First, as mentioned in Section 2.
Second, myocardial metabolic response to obesity is modulated by sex. Female sex independently predicts greater fatty acid metabolism and relates to inefficiency in fatty acid metabolism. Furthermore, higher global prevalence of obesity in women, obesity and metabolic syndrome contribute to development of HFpEF in women compared to men. Third, the higher prevalence of autoimmune disorders and an overall stronger immune response compared to inflammation in women may contribute to the progression of HFpEF. There is an important overlap between atrial fibrillation and heart failure.
Risk factors include advanced maternal age, pre-eclampsia, and multiple gestations. Given the myriad of differences, women have an increased risk of developing adverse drug reactions and these adverse events are generally more serious in women than in men, due in part to different pharmacokinetics and pharmacodynamics properties between men and women, leading to up to 2. These factors can contribute to a longer duration of action of lipophilic drugs and higher peak plasma concentrations of hydrophilic drugs in women.
On the other hand, it is also seen that women with HFrEF are less often treated with guideline-directed medical therapy, are less often admitted to cardiology wards, have a lower frequency of assessment of LV function,and also continue to receive suboptimal treatment for, compared with men, with no obvious explanation for these disparities.
Lastly, the use of guideline-directed cardiac resynchronization therapy CRT and implantable cardioverter-defibrillator use was associated with substantially increased survival in eligible men and women with HFrEF. Female patients are underrepresented in the population of MCS patients and, when they are supported, left ventricle assist device LVAD implantation is more often under emergency circumstances.
SCAD is defined as an epicardial coronary artery dissection that is not associated with atherosclerosis or trauma and not iatrogenic.
Data on men with SCAD are scarce, though one study reports that men may present at a slightly younger age than women mean age, The natural history of disease progression in SCAD is multifaceted and is affected by hormonal influences, arteriopathies, genetic factors, and systemic inflammatory diseases; precipitated by environmental factors and stressors. It is thought that hormones and unique pregnancy-related complications like gestational hypertension and preeclampsia contribute.
In addition, there is a higher use of fertility treatments and hormone replacement therapy in patients with SCAD than in general population. Patients with pregnancy-associated SCAD have a more severe clinical presentation than those patients with non-pregnancy-associated SCAD, often with multivessel dissections and acute heart failure.
In addition to the underlying diseases, SCAD is also precipitated by emotional and physical stressors. Vigorous physical exercises such as weightlifting and body building, have been described as the most common SCAD precipitants in men. All patients present with elevated troponins and chest discomfort.
This disparity is driven by the fact that women present more often with symptoms like shortness of breath, fatigue, back pain and headaches, and have non-traditional cardiovascular risk factors. In a landmark study, researchers found that women under the age of 55 who experienced ACS type symptoms were seven times more likely to be misdiagnosed and discharged from the emergency department compared to their male counterparts presenting with identical symptoms with a non-diagnostic EKG being one main of the criteria for discharging.
Angiographically, type 1 SCAD variant is defined by a double lumen appearance and type 2 is characterized by diffuse stenosis of varying severity with changes in the arterial caliber. Other imaging techniques like cardiac MRI and coronary CT angiography can also be useful to differentiate between ischaemic diseases like dissection from non-ischaemic diseases.
Coexistence of SCAD and TTC has been reported in five case reports and one retrospective case series until today, including a totality of 14 patients. Although American and European guidelines for the management of ACS advocate an early invasive strategy with revascularization of culprit lesions instead of conservative therapy alone, conservative management is the mainstay for management. In the setting of underlying weak architecture of the coronary arteries in SCAD due to underlying arteriopathies as well as smaller coronary vessel diameter, greater tortuosity compared to men, studies have uniformly demonstrated that PCI increases risk of complications and renders poor outcomes by causing iatrogenic dissection and extension of dissections.
Management of SCAD during pregnancy requires multidisciplinary approach by including the cardiology and obstetric service to encompass maternal care as well as foetal wellbeing. Maintaining a strong suspicion to avoid missing a diagnosis and early diagnostic angiography to avoid iatrogenic dissection, keeping into foetal radiation exposure and finally aiming for conservative management if there is no evidence of ongoing ischaemia or infarction, haemodynamic instability, or particularly high-risk anatomy are key components of pregnancy-associated SCAD management.
Takotsubo cardiomyopathy also known as stress cardiomyopathy, apical ballooning syndrome or broken heart syndrome, was first described in Japan in is characterized by transient systolic and diastolic left ventricular dysfunction accompanied with different wall motion abnormalities. There is a female to male ratio in some studies,but, in Japan, TTC is more prevalent among men. Male sex, Killip class 3—4 on admission, and diabetes mellitus were identified as independent predictors of long-term mortality in TTC patients.
In summary, there remain persistent sex disparities in the care and management of patients with acute cardiac conditions Figure 2. In general, for all conditions, female patients typically receive less frequent guideline-directed care and have poor short- and long-term outcomes. Though ificant success has been achieved in decreasing the in-hospital mortality in most acute cardiac emergencies, it is crucial to Women sex with monkey h in Louisville sc to address easily identifiable risk factors and to use the information regarding sex differences in physiology and pharmacology to guide treatment strategies Figure 3 and Table 1.
Furthermore, there are limited data on the clinical outcomes Women sex with monkey h in Louisville sc patients undergoing gender reasment, and the heterogeneous timing for initiation of treatments, and types of treatments affecting the sex hormonal milieu present a challenging but crucial next steps in this field. Studies in cardiovascular medicine, specifically acute cardiovascular care, will benefit from additional preclinical studies of acute cardiovascular conditions, enrolment of similar proportion of men and women in clinical trials, sex-specific reporting of trial outcomes, and consideration of sex-hormones as effect-modifiers in healthcare delivery.
Gaps in care in acute cardiovascular conditions. Influence of sex chromosomes in cardiovascular disease presentation, response to treatment and outcomes. The sex chromosomes direct development of some organs prior to the development of the reproductive organs and production of sex steroids hormones. The sex steroid hormones oestrogen and testosterone are present in both females and males, albeit in different proportions, and their concentrations changes with age from birth to puberty to reproductive senescence.
The collective effect of the sex chromosome and hormones influence cellular regulatory pathways that influence organ structure and function, metabolism, and response to stress and reparative functions. Environmental, cultural, life style factors which contribute to the psychosocial construct of gender influence biology.
Insufficient knowledge of sex differences in physiology and pathophysiology limit development of sex-specific care and treatment guidelines. Investigations into sex differences in physiological and pharmacological mechanisms, reporting clinical trial data by sex, identifying modifiable behaviours, and embedding concepts of sex differences into science and medical curricula will reduce sex disparities in treatment and outcomes.
Women tend to be older with a higher prevalence of hypertension, diabetes, metabolic syndrome, and a lower prevalence of hypercholesterolaemia and smoking. Women tend to be older with a higher prevalence of hypertension and diabetes. Women tend to be older with comorbidities like hypertension, obesity, and kidney disease with higher prevalence of HFpEF. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. Age- and gender-specific differences in the prognostic value of CT coronary angiography.
Heart ; 98 : — Google Scholar. Eur Heart J ; 39 : — Circulation ; : e56 — e Sex disparities in acute kidney injury complicating acute myocardial infarction with cardiogenic shock. ESC Heart Fail ; 6 : — Utilization of palliative care for cardiogenic shock complicating acute myocardial infarction: a year national perspective on trends, disparities, predictors, and outcomes. J Am Heart Assoc ; 8 : e Intravascular ultrasound, optical coherence tomography, and fractional flow reserve use in acute myocardial infarction.Women sex with monkey h in Louisville sc
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