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Emergency medical services (EMS) activation is an integral component in managing individuals with myocardial infarction (MI). EMS play a crucial role in early MI symptom recognition, prompt transport to percutaneous coronary intervention centres and timely administration of management. The objective of this study was to examine sex differences in prehospital EMS care of patients hospitalized with Ml using data from a retrospective population-based cohort study of linked health administrative data for people with a hospital diagnosis of MI in Australia (2001-18).

Background and ObjectivesWomen have been underrepresented in cardiovascular disease clinical trials but there is less certainty over the level of disparity specifically in stroke. We examined the participation of women in trials according to stroke prevalence in the population.MethodsPublished randomized controlled trials with ≥100 participants enrolled between 1990 and 2020 were identified from ClinicalTrials.gov. To quantify sex disparities in enrollment, we calculated the participation to prevalence ratio (PPR), defined as the percentage of women participating in a trial vs the prevalence of women in the disease population.ResultsThere were 281 stroke trials eligible for analyses with a total of 588,887 participants, of whom 37.4% were women. Overall, women were represented at a lower proportion relative to their prevalence in the underlying population (mean PPR 0.84; 95% confidence interval [CI] 0.81–0.87). The greatest differences were observed in trials of intracerebral hemorrhage (PPR 0.73; 95% CI 0.71–0.74), trials with a mean age of participants p for trend = 0.201).DiscussionWomen are disproportionately underrepresented in stroke trials relative to the burden of disease in the population. Clear guidance and effective implementation strategies are required to improve the inclusion of women and thus broader knowledge of the impact of interventions in clinical trials.

This study aimed to investigate the association between individual and combinations of macronutrients with premature death, CVD and dementia. Sex differences were investigated. Data were utilised from a prospective cohort of 120 963 individuals (57 % women) within the UK Biobank, who completed ≥ two 24-h diet recalls. The associations of macronutrients, as percentages of total energy intake, with outcomes were investigated. Combinations of macronutrients were defined using k-means cluster analysis, with clusters explored in association with outcomes. There was a higher risk of death with high carbohydrate intake (hazard ratios (HR), 95 % CI upper v. lowest third 1·13 (1·03, 1·23)), yet a lower risk with higher intakes of protein (upper v. lowest third 0·82 (0·76, 0·89)). There was a lower risk of CVD with moderate intakes (middle v. lowest third) of energy and protein (sub distribution HR (SHR), 0·87 (0·79, 0·97) and 0·87 (0·79, 0·96), respectively). There was a lower risk of dementia with moderate energy intake (SHR 0·71 (0·52, 0·96)). Sex differences were identified. The dietary cluster characterised by low carbohydrate, low fat and high protein was associated with a lower risk of death (HR 0·84 (0·76, 0·93)) compared with the reference cluster and a lower risk of CVD for men (SHR 0·83 (0·71, 0·97)). Given that associations were evident, both as single macronutrients and for combinations with other macronutrients for death, and for CVD in men, we suggest that the biggest benefit from diet-related policy and interventions will be when combinations of macronutrients are targeted.

This narrative review synthesizes sex differences in guideline-directed medical therapy (GDMT) use and response among female patients with heart failure with reduced ejection fraction (HFrEF), discusses female representation in HFrEF clinical trials, and outlines future areas of investigation to reduce sex disparities in HFrEF care globally. Observational registries suggest sex-specific disparities persist in GDMT rates, and there may be key sex-specific differences in optimal dosing of GDMT in HFrEF patients. Underrepresentation of female patients in HF clinical trials is a key barrier, and sex disparities in HF clinical trial leadership may influence sex-specific knowledge generation of medical management of HFrEF patients. There are important sex-specific differences in GDMT use and response among female HFrEF patients that warrant further study. Increasing female representation in HFrEF clinical trials, diversifying HF trial leadership, and embedding sex-specific approaches in the lifecycle of research from conception to reporting are essential to decreasing sex disparities in clinical care of all HFrEF patients.

Background: Rates for recurrent coronary heart disease (CHD) events have declined in the United States. However, few studies have assessed whether this decline has been similar among women and men. Methods: Data were used from 770 408 US women and 700 477 US men Results: From 2008 to 2017, age-standardized recurrent MI rates per 1000 person-years decreased from 89.2 to 72.3 in women and from 94.2 to 81.3 in men (multivariable-adjusted P interaction by sex P interaction P interaction=0.001). All-cause mortality rates decreased from 403.2 to 389.5 in women and from 436.1 to 417.9 in men ( P interaction=0.82). In 2017, the multivariable-adjusted rate ratios comparing women with men were 0.90 (95% CI, 0.86–0.93) for recurrent MI, 0.80 (95% CI, 0.78–0.82) for recurrent CHD events, 0.99 (95% CI, 0.96–1.01) for heart failure hospitalization, and 0.82 (95% CI, 0.80–0.83) for all-cause mortality. Conclusions: Rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality in the first year after an MI declined considerably between 2008 and 2017 in both men and women, with proportionally greater reductions for women than men. However, rates remain very high, and rates of recurrent MI, recurrent CHD events, and death continue to be higher among men than women.

BackgroundDue to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D.MethodsIndividual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study.ResultsAfter a median follow-up of 2.5years (Q1 to Q3: 1.9-3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n=179) of patients who were treated with online HDF compared with 19% (n=152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86-1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92-1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes.ConclusionsTreatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions., CONVINCE study (European Union's Horizon 2020 research and innovation programme) [754803], Funding details are listed in Appendix 4. RWMV, PJB, and MLB are funded by the CONVINCE study (European Union's Horizon 2020 research and innovation programme under grant agreement No 754803).

AIMS: Data suggest that women have worse outcomes than men after coronary artery bypass grafting (CABG), but results have been inconsistent across studies. Due to the large differences in baseline characteristics between sexes, suboptimal risk adjustment due to low-quality data may be the reason for the observed differences. To overcome this limitation, we undertook a systematic review and pooled analysis of high-quality individual patient data from large CABG trials to compare the adjusted outcomes of women and men. METHODS AND RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events, MACCE). The secondary outcome was all-cause mortality. Multivariable mixed-effect Cox regression was used. Four trials involving 13 193 patients (10 479 males; 2714 females) were included. Over 5 years of follow-up, women had a significantly higher risk of MACCE [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04–1.21; P = 0.004] but similar mortality (adjusted HR 1.03, 95% CI 0.94–1.14; P = 0.51) compared to men. Women had higher incidence of MI (adjusted HR 1.30, 95% CI 1.11–1.52) and repeat revascularization (adjusted HR 1.22, 95% CI 1.04–1.43) but not stroke (adjusted HR 1.17, 95% CI 0.90–1.52). The difference in MACCE between sexes was not significant in patients 75 years and older. The use of off-pump surgery and multiple arterial grafting did not modify the difference between sexes. CONCLUSIONS: Women have worse outcomes than men in the first 5 years after CABG. This difference is not significant in patients aged over 75 years and is not affected by the surgical technique.

The COVID-19 pandemic has disrupted healthcare services around the world, which may have serious implications for the prognosis of patients with acute cardiovascular disease. We conducted a systematic review to assess the extent to which health services related to the care and management of acute cardiovascular events have been impacted during the COVID-19 pandemic. PubMed, MedRxiv, and Google Scholar were searched for observational studies published up to 12 August 2020 for studies that assessed the impact of the pandemic on the care and management of people with acute cardiovascular disease (CVD). In total, 27 articles were included. Of these, 16 examined the impact on acute coronary syndromes (ACS), eight on strokes, one on ACS and strokes, and two on other types of CVD. When comparing the COVID-19 period to non-COVID-19 periods, 11 studies observed a decrease in ACS admissions ranging between 40% and 50% and 5 studies showed a decrease in stroke admissions of between 12% and 40%. Four studies showed a larger reduction in non-ST-segment elevation myocardial infarctions compared to ST-segment elevation myocardial infarctions. A decrease in the number of reperfusion procedures, a shortening in the lengths of stay at the hospital, and longer symptom-to-door times were also observed. The COVID-19 pandemic has led to a substantial decrease in the rate of admissions for acute CVD, reductions in the number of procedures, shortened lengths of stay at the hospital, and longer delays between the onset of the symptoms and hospital treatment. The impact on patient’s prognosis needs to be quantified in future studies.

ObjectiveTo determine whether there are sex differences in the association between risk factors and incident stroke, including stroke subtypes.MethodsA total of 471,971 (56% women) UK Biobank participants without a history of cardiovascular disease were included. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded. Cox models yielded adjusted hazard ratios (HRs) and women-to-men ratios of HRs (RHRs) for stroke associated with 7 risk factors.ResultsThe incidence rate per 10,000 person-years was 8.66 (8.29–9.04) in women and 13.96 (13.44–14.50) in men for any stroke, 6.06 (5.75–6.38) in women and 11.35 (10.88; 11.84) in men for ischemic stroke, and 1.56 (1.41–1.73) in women and 2.23 (2.02–2.45) in men for hemorrhagic stroke. The association between increases in blood pressure, body anthropometry, and lipids, diabetes, and atrial fibrillation and any stroke was similar between men and women. Hypertension, smoking, and a low socioeconomic status were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26–1.47), 1.18 (1.02–1.36), and 1.17 (1.03–1.33), respectively. Diabetes was associated with a higher HR of ischemic stroke in women than men (RHR 1.25 [1.00–1.56]). Atrial fibrillation was associated with a higher HR of hemorrhagic stroke in women than men (RHR 2.80 [1.07–7.36]).ConclusionSeveral risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke remains higher among men than women.

Highlights • Socioeconomic position (SEP) impacts women’s health across the lifespan. • There are gender differences in health inequalities for self-rated, physical and mental health. • Indicators of socioeconomic position misrepresent inequities in the health status of women. • Initiatives must be tailored to socioeconomic position to ameliorate the health burden for women., The “social gradient of health” refers to the steep inverse associations between socioeconomic position (SEP) and the risk of premature mortality and morbidity. In many societies, due to cultural and structural factors, women and girls have reduced access to the socioeconomic resources that ensure good health and wellbeing when compared with their male counterparts. Thus, the objective of this paper is to review how SEP - a construct at the heart of the Social Determinants of Health (SDoH) theory - shapes the health and longevity of women and girls at all stages of the lifespan. Using literature identified from PubMed, Cochrane, CINAHL and EMBASE databases, we first describe the SDoH theory. We then use examples from each stage of the life course to demonstrate how SEP can differentially shape girls’ and women’s health outcomes compared with boys’ and men’s, as well as between sub-groups of girls and women when other axes of inequalities are considered, including ethnicity, race and residential setting. We also explore the key consideration of whether conventional SEP markers are appropriate for understanding the social determinants of women’s health. We conclude by making key recommendations in the context of clinical, research and policy development.

Aims/hypothesisPrevious meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD).MethodsPubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle–Ottawa scale was used to assess study quality.ResultsData from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29–2.63) in women and 1.84 (95% CI 1.29–2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90–1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6–8, on the Newcastle–Ottawa scale of 0–9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors.Conclusion/interpretationConsistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.

Aim To examine possible sex differences in the excess risk of myocardial infarction (MI) consequent to a range of conventional risk factors in a large-scale international cohort of patients with diabetes, and to quantify these potential differences both on the relative and absolute scales. Materials and methods Eleven thousand and sixty-five participants (42% women) with type 2 diabetes in the ADVANCE trial and its post-trial follow-up study, ADVANCE-ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non-fatal) by sex, and the women-to-men ratio of HRs (RHR). Results Over a median of 9.6 years of follow-up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c, total and LDL cholesterol, duration of diabetes, triglycerides, body mass index (BMI) and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05-2.91) for current smoking, 1.53 (1.00-2.32) for former smoking, 1.18 (1.02-1.37) for SBP, and 1.13 (95% CI, 1.003-1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1000 person-years) compared with women (5.8 per 1000 person-years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI. Conclusions In patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex-specific approaches and early interventions in women with diabetes.

BackgroundIntimate partner violence (IPV) is a significant problem with several negative health outcomes. Disasters are linked to increased IPV, but little is known about reporting of and strategies to address IPV during the COVID-19 pandemic. This review maps the IPV reporting during the pandemic and interventions to prevent and respond to IPV in 11 Western and Southern European countries.MethodsGovernment websites, news articles and pre-prints were searched using the terms ‘domestic violence’ or ‘violence’ in combination with ‘Covid’ or ‘Corona’. Embase, PubMed, Scopus and Google Scholar were searched using the terms ‘domestic violence’ and ‘partner violence’ and ‘interventions’.ResultsSix countries showed an increase in domestic violence reports (Austria, Belgium, France, Ireland, Spain and UK), two countries a drop (Italy and Portugal), two countries showed no change (The Netherlands and Switzerland) and one country did not provide comparative data (Germany). Common measures to address IPV were starting a campaign (nine countries), creating online support (seven), more funding for alternative accommodation (seven) and support (eight) and use of a code word (four).ConclusionsIPV reports or helpline calls in Western and Southern European countries in the first weeks of COVID-19 measures increased in six countries, remained the same in two countries and showed a decrease in two countries. While this review cannot ascertain the impact of the measures taken by the countries during the pandemic and beyond, this mapping provides a foundation for future research, and an opportunity to trace the efficacy of these strategies.

Aims: The association between diabetes and cognitive decline (CD) and dementia has been well-documented. This study estimated the associations between risk factors and CD/dementia, and the sex differences in these risk factors in individuals with type 2 diabetes, while accounting for the competing risk of death.\ud \ud Materials and methods: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 individuals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression.\ud \ud Results: During a median five-year follow-up, 1,827 participants (43.2% women) had CD/dementia (1,718 with CD only; 21 with dementia only; 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had a lower odds of CD/dementia than men (Odds Ratio (OR) (95% confidence interval), 0.88 (0.77, 1.00)); older age, higher total cholesterol, HbA1c , waist circumference, waist-to-height ratio, moderately increased ACR (Albumin-Creatinine Ratio), stroke/transient ischemic attack and retinal disease were each associated with greater odds of CD/dementia; higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women-to-men Ratio of Odds Ratios (ROR), 1.05 (1.00, 1.10) per 5 cm) and presence of anxiety/depression (ROR, 1.28 (1.01, 1.63)) were associated with greater OR for CD/dementia in women than men.\ud \ud Conclusions: Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms which underlie these sex differences. This article is protected by copyright. All rights reserved.

Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

Background and Aims An individual participant data (IPD) meta-analysis of four randomized controlled trials (RCTs) demonstrated that hemodiafiltration (HDF) reduced overall mortality compared to hemodialysis (HD) in patients with end-stage kidney disease (ESKD). It remains, however, difficult to translate these average results into clinical practice as absolute treatment effects may substantially differ between individuals. The aim of this study was to develop and validate a treatment effect prediction model to determine which patients would benefit the most from HDF or HD in terms of all-cause mortality. Method We used an IPD meta-analysis based on four RCTs comparing HDF with HD on mortality endpoints to derive a Royston-Parmar model for prediction of absolute treatment effect of HDF based on pre-specified patient and disease characteristics. Validation of the model with regard to model discrimination, calibration and net benefit was performed using internal-external cross validation. Results The median predicted gain in median survival was 44 (Q1-Q3: 44-46) days for every year of treatment with HDF compared to HD. The overall gain in median survival with HDF ranged from 2 to 48 months (Figure). Patients who benefited most from HDF were younger, less likely to have diabetes or a cardiovascular history and had higher serum creatinine and albumin levels. Internal-external cross validation showed adequate calibration and discrimination. Decision curve analysis indicated that prediction-based treatment allocation improved the net clinical benefit compared to treating all with patients HDF or treating all with HD. Conclusion Although overall mortality is reduced by HDF compared to HD in ESKD patients, the absolute survival gain can vary greatly between individuals. Our results indicate that the effects of HDF on survival can be predicted using a combination of readily available patient and disease characteristics, which could guide shared decision-making.

Objective To determine whether sex differences exist in the assessment of cardiovascular disease (CVD) risk scores/risk factors in primary health care. Design/Methods PubMed and EMBASE were systematically searched on 31 January 2017. Clinical trials and observational studies were included if they reported on the assessment of CVD risk score, blood pressure (BP), cholesterol or smoking status in primary health care, stratified by sex. Meta-analyses were performed, using random effects models, to determine differences between sexes, separately for adjusted and unadjusted data. Results Of 14,928 studies found in the search, 22 studies (including 4,754,782 patients) were included in the systematic review with the meta-analysis for quantitative assessment. Overall, the assessment rates of CVD risk score and risk factors were similar in women and men (CVD risk score: 30.7% vs. 35.2% [difference (95% CI): -4.5 (-5.1, -3.9)]; BP: 91.3% vs. 88.5% [2.8 (2.5, 3.0)]; cholesterol: 69.9% vs. 71.0% [-1.1 (-1.5, -0.8)]; and smoking: 85.9% vs. 86.7% [-0.8 (-1.1, -0.5)]). The pooled, adjusted likelihood of having the risk score, BP and cholesterol assessments were comparable between women and men: OR (95% CI): 0.87 (0.70, 1.07); 1.41 (0.89, 2.25); and 1.15 (0.82, 1.60), respectively. However, women were 32% less likely to be assessed for smoking (0.68 [0.47, 1.00]). There was substantial heterogeneity between studies and the risk of publication bias was moderate. Conclusion Despite the guideline recommendations, assessment of CVD risk score in primary health care was low in both sexes. Further, women were less likely to be assessed for their smoking status than men, whereas no sex discrepancies were found for BP and cholesterol assessments.

Aims/hypothesis The prevalence of diabetes and heart failure is increasing, and diabetes has been associated with an increased risk of heart failure. However, whether diabetes confers the same excess risk of heart failure in women and men is unknown. The aim of this study was to conduct a comprehensive systematic review with meta-analysis of possible sex differences in the excess risk of heart failure consequent to diabetes. Our null hypothesis was that there is no such sex difference. Methods A systematic search was conducted in PubMed for population-based cohort studies published between January 1966 and November 2018. Studies were selected if they reported sex-specific estimates of RRs for heart failure associated with diabetes, and its associated variability, which were adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratio of RRs (RRRs) for heart failure associated with diabetes. Results Data from 47 cohorts, involving 12,142,998 individuals and 253,260 heart failure events, were included. The pooled multiple-adjusted RR for heart failure associated with type 1 diabetes was 5.15 (95% CI 3.43, 7.74) in women and 3.47 (2.57, 4.69) in men, leading to an RRR of 1.47 (1.44, 1.90). Corresponding pooled RRs for heart failure associated with type 2 diabetes were 1.95 (1.70, 2.22) in women and 1.74 (1.55, 1.95) in men, with a pooled RRR of 1.09 (1.05, 1.13). Conclusions/interpretation The excess risk of heart failure associated with diabetes is significantly greater in women with diabetes than in men with diabetes. PROSPERO registration: CRD42019135246 Electronic supplementary material The online version of this article (10.1007/s00125-019-4926-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Background Preeclampsia is a disease specific to pregnancy that can cause severe maternal and foetal morbidity and mortality. Early identification of women at higher risk for preeclampsia could potentially aid early prevention and treatment. Although a plethora of preeclampsia prediction models have been developed in recent years, individualised prediction of preeclampsia is rarely used in clinical practice. Objectives The objective of this systematic review was to provide an overview of studies on preeclampsia prediction. Study design Relevant research papers were identified through a MEDLINE search up to 1 January 2017. Prognostic studies on the prediction of preeclampsia or preeclampsia-related disorders were included. Quality screening was performed with the Quality in Prognostic Studies (QUIPS) tool. Results Sixty-eight prediction models from 70 studies with 425,125 participants were selected for further review. The number of participants varied and the gestational age at prediction varied widely across studies. The most frequently used predictors were medical history, body mass index, blood pressure, parity, uterine artery pulsatility index, and maternal age. The type of predictor (maternal characteristics, ultrasound markers and/or biomarkers) was not clearly associated with model discrimination. Few prediction studies were internally (4%) or externally (6%) validated. Conclusions To date, multiple and widely varying models for preeclampsia prediction have been developed, some yielding promising results. The high degree of between-study heterogeneity impedes selection of the best model, or an aggregated analysis of prognostic models. Before multivariable preeclampsia prediction can be clinically implemented universally, further validation and calibration of well-performing prediction models is needed.

Diabetes has been associated with a greater excess risk of cardiovascular disease (CVD) in women than men. We investigated whether there are also sex differences in the association of diabetes duration and the risk of CVD.Data were used from 18,961 (40% women) individuals with type 2 diabetes, without a history of CVD, in the UK Biobank. Sex-specific incidence rates were calculated by diabetes duration. Cox proportional hazards analyses estimated multiple-adjusted sex-specific hazard ratios (HR) and women-to-men ratio of HRs (RHR).Over a median follow-up of 11 years, 1,506 (29% women) CVD events were documented. Compared with men, women had lower multiple-adjusted incidence rates of CVD per 10,000 person-years for all categories of diabetes duration. Duration of diabetes was associated with an increased risk of CVD in both sexes. A 5-year increase in diabetes duration was associated with an approximately similar excess risk of about 20% for each of the three endpoints, in both sexes.The increased risk of CVD associated with longer duration of diabetes is similar in women and men, and thus cannot explain the higher excess risk from diabetes in women in this study population.

Background: To examine the risk of incident all-cause dementia associated with reproductive factors in women, and the number of children in both sexes; and whether the effects vary by age, socioeconomic status (SES), smoking status and body mass index in the UK Biobank.Methods: A total of 273,265 women and 228,966 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia.Results: Over a median of 11.3 years follow-up, 1,680 dementia were recorded in women and 2,021 in men. Adjusted HRs (95% confidence intervals (CIs)) for dementia were 1.20 (1.08, 1.35) for menarche

OBJECTIVE Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. RESEARCH DESIGN AND METHODS Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment. RESULTS MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs. CONCLUSIONS This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.

BackgroundWomen with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.MethodsIn a population-based cohort study of individuals aged 40–75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.ResultsMen with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: − 0.74% (− 1.22; − 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (− 3.50;4.07) and: − 0.52% (− 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.ConclusionsOur findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

Obesity is associated with severe COVID‐19 outcomes, yet, it unclear whether the risk of COVID‐19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID‐19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza/pneumonia and coronary heart disease (CHD). The analyses included 502,493 individuals (54% women), of whom 410 (36% women) died of COVID‐19, 549 (36% women) died of influenza/pneumonia, and 3355 (19% women) died of CHD. A higher BMI, waist circumference, waist‐to‐hip ratio, and waist‐to‐height ratio were each associated with a greater risk of death from COVID‐19, influenza/pneumonia, and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza/pneumonia death in men. A higher BMI was associated with a stronger risk of COVID‐19 mortality in women than men; the women‐to‐men ratio of hazard ratios was 1.20 (95% confidence interval: 1.00; 1.43). This study demonstrates the role of obesity in COVID‐19 mortality and shows that the relative effects of a higher BMI on COVID‐19 mortality may be stronger in women than men. This article is protected by copyright. All rights reserved.

Background and Aim: Women have been under-represented in clinical trials areas of cardiovascular disease but there is less certainty over the level of disparity specifically in stroke and whether there is any influence of pathological subtype, age and time. We examined the participation of women in trials according to stroke prevalence in the population. Methods: Randomized controlled trials with ≥100 participants enrolled between 1990 and 2020 identified from ClinicalTrials.gov, using keywords “stroke” and “cerebrovascular accidents”, and subsequently published (identified using PubMed, Google Scholar, and Scopus) were included. To quantify sex disparites in enrolment we calculate the participation to prevalence ratio (PPR), defined as the percentage of women participating in a trial against the prevalence of women in the disease population. Results: There were 281 stroke trials eligible for analyses with a total of 588,887 participants, of whom 37.4 % were women. Overall, women were represented at a lower proportion relative to their prevalence in the underlying population (mean PPR 0.84; 95% confidence interval [CI] (0.81 to 0.87)). The greatest differences were observed in trials of hemorrhagic stroke (PPR 0.73; 95% CI 0.71 to 0.74), trials with a mean age of participants

Objective:To assess the contribution of different food groups to total salt purchases and to evaluate the estimated reduction in salt purchases if mandatory maximum salt limits in South African legislation were being complied with.Design:This study conducted a cross-sectional analysis of purchasing data from Discovery Vitality members. Data were linked to the South African FoodSwitch database to determine the salt content of each food product purchased. Food category and total annual salt purchases were determined by summing salt content (kg) per each unit purchased across a whole year. Reductions in annual salt purchases were estimated by applying legislated maximum limits to product salt content.Setting:South Africa.Participants:The study utilised purchasing data from 344 161 households, members of Discovery Vitality, collected for a whole year between January and December 2018.Results:Vitality members purchased R12·8 billion worth of food products in 2018, representing 9562 products from which 264 583 kg of salt was purchased. The main contributors to salt purchases were bread and bakery products (23·3 %); meat and meat products (19 %); dairy (12·2 %); sauces, dressings, spreads and dips (11·8 %); and convenience foods (8·7 %). The projected total quantity of salt that would be purchased after implementation of the salt legislation was 250 346 kg, a reduction of 5·4 % from 2018 levels.Conclusions:A projected reduction in salt purchases of 5·4 % from 2018 levels suggests that meeting the mandatory maximum salt limits in South Africa will make a meaningful contribution to reducing salt purchases.

BackgroundSex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different cardiometabolic consequences of adiposity in females and males. We examined whether adiposity influences cardiometabolic trait levels differently in females and males at four different life stages.MethodsData were from two generations (offspring, Generation 1 [G1] and their parents, Generation 0 [G0]) of the Avon Longitudinal Study of Parents and Children birth cohort study. Body mass index (BMI) and total fat mass from dual-energy x-ray absorptiometry were measured at mean age 9y, 15y and 18y in G1. Waist circumference was measured at 9y and 15y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15y, 18y and 25y in G1. In G0, all three adiposity measures and the same 148 traits were available at 50y.Using linear regression models, sex-specific associations of adiposity measures at each time point (9y, 15y and 18y) with cardiometabolic traits 3 to 6 years later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross- sectionally at 50y.Results3081 G1 and 4887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males at younger ages (15y-25y) and associations were more similar between the sexes or stronger in females at 50y, particularly for apolipoprotein-B-containing lipoprotein particles and lipid concentrations. For example, a 1- SD (3.8 kg/m2) higher BMI at 18y was associated with 0.36 SD (95% Confidence Interval (CI) = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females. In contrast, at 50y, a 1-SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females respectively. Sex-specific associations of DXA-measured fat mass and waist circumference were similar to findings for BMI in both generations and at all ages.ConclusionThe results of this study suggest that the adverse cardiometabolic effects of adiposity are stronger and begin earlier in the life course among males compared with females until mid life, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.

BACKGROUND: To inform the interpretation of dietary data in the context of sex differences in diet-disease relations, it is important to understand whether there are any sex differences in accuracy of dietary reporting.OBJECTIVE: To quantify sex differences in self-reported total energy intake (TEI) compared with a reference measure of total energy expenditure (TEE).METHODS: Six electronic databases were systematically searched for published original research articles between 1980 and April 2020. Studies were included if they were conducted in adult populations with measures for both females and males of self-reported TEI and TEE from doubly labeled water (DLW). Studies were screened and quality assessed independently by 2 authors. Random-effects meta-analyses were conducted to pool the mean differences between TEI and TEE for, and between, females and males, by method of dietary assessment.RESULTS: From 1313 identified studies, 31 met the inclusion criteria. The studies collectively included information on 4518 individuals (54% females). Dietary assessment methods included 24-h recalls (n = 12, 2 with supplemental photos of food items consumed), estimated food records (EFRs; n = 11), FFQs (n = 10), weighed food records (WFRs, n = 5), and diet histories (n = 2). Meta-analyses identified underestimation of TEI by females and males, ranging from -1318 kJ/d (95% CI: -1967, -669) for FFQ to -2650 kJ/d (95% CI: -3492, -1807) for 24-h recalls for females, and from -1764 kJ/d (95% CI: -2285, -1242) for FFQ to -3438 kJ/d (95% CI: -5382, -1494) for WFR for males. There was no difference in the level of underestimation by sex, except when using EFR, for which males underestimated energy intake more than females (by 590 kJ/d, 95% CI: 35, 1,146).CONCLUSION: Substantial underestimation of TEI across a range of dietary assessment methods was identified, similar by sex. These underestimations should be considered when assessing TEI and interpreting diet-disease relations.

Background It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction in women. Methods We used data from 263,295 female UK Biobank participants (mean age 56.2; SD 8.0 years) without prior cardiovascular disease. Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, age, and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels. Results After a mean follow-up of 9 years, 2,206 incident cases of MI had been recorded, including 230 events among the 57,204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with a HR (95% CI) for MI of 0.73 (0.58; 0.92). After adjusting for age this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, pill use, and the use of hormone replacement therapy. The multivariable adjusted HR for the 171,431 women (mean age 59) with undetectable levels of oestradiol, compared to those with detectable levels, was 0.97 (0.92; 1.02). Conclusion Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age, and further confounded by other cardiovascular risk factors. Figure 1 Funding Acknowledgement Type of funding source: None

Background Women have lower age-specific rates of incident coronary heart disease (CHD) than men. However, it remains unclear whether women maintain the same advantage once they have had a cardiac event. Purpose To assess whether sex differences in the rates of cardiac events and all-cause mortality among individuals without a history of CHD persist following a myocardial infarction (MI). Methods We identified 171,897 women and 167,993 men Results The age-standardized rates of MI per 1,000 person-years were 4.5 in women and 5.7 in men without a history of CHD (multivariable-adjusted hazard ratio [HR] [95% confidence interval] of female sex: 0.64 [0.62; 0.67]) and 60.2 in women and 59.8 in men with a history of MI (HR: 0.94 [0.92, 0.96]) (Figure 1). Rates of CHD events in women vs. men were 6.3 vs. 10.7 among those without CHD (HR: 0.53 [0.51, 0.54]) and 84.5 vs. 99.3 among those with MI (HR: 0.87 [0.85, 0.89]). Heart failure hospitalization rates in women vs. men were 9.3 vs. 6.6 for those without CHD (HR: 0.93 [0.90, 0.96]) and 114.9 vs. 97.9 among those with MI (HR: 1.02 [1.00, 1.04]). All-cause mortality rates in women vs. men were 63.7 vs. 59.0 among those without CHD (HR: 0.72 [0.71; 0.73]) and 311.6 vs. 284.5 among those with a MI (HR: 0.90 [0.89, 0.92]). Conclusion The women advantage against MI, CHD, heart failure and all-cause mortality is considerably attenuated following a MI, suggesting that a prior MI puts women at almost the same high-risk of subsequent events as men. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was funded by an industry/academic collaboration between Amgen Inc. and University of Alabama at Birmingham.

IntroductionSex differences in cardiometabolic risk factors and their management in type 2 diabetes (T2D) have not been fully identified. Therefore, we aimed to examine differences in cardiometabolic risk factor levels, pharmacological treatment and achievement of risk factor control between women and men with T2D.Research design and methodsCross-sectional data from the Dutch Diabetes Pearl cohort were used (n=6637, 40% women). Linear and Poisson regression analyses were used to examine sex differences in cardiometabolic risk factor levels, treatment, and control.ResultsCompared with men, women had a significantly higher body mass index (BMI) (mean difference 1.79 kg/m2 (95% CI 1.49 to 2.08)), while no differences were found in hemoglobin A1c (HbA1c) and systolic blood pressure (SBP). Women had lower diastolic blood pressure (−1.94 mm Hg (95% CI −2.44 to −1.43)), higher total cholesterol (TC) (0.44 mmol/L (95% CI 0.38 to 0.51)), low-density lipoprotein cholesterol (LDL-c) (0.26 mmol/L (95% CI 0.22 to 0.31)), and high-density lipoprotein cholesterol (HDL-c) sex-standardized (0.02 mmol/L (95% CI 0.00 to 0.04)), and lower TC:HDL ratio (−0.29 (95% CI −0.36 to −0.23)) and triglycerides (geometric mean ratio 0.91 (95% CI 0.85 to 0.98)). Women had a 16% higher probability of being treated with antihypertensive medication in the presence of high cardiovascular disease (CVD) risk and elevated SBP than men (relative risk 0.84 (95% CI 0.73 to 0.98)), whereas no sex differences were found for glucose-lowering medication and lipid-modifying medication. Among those treated, women were less likely to achieve treatment targets of HbA1c (0.92 (95% CI 0.87 to 0.98)) and LDL-c (0.89 (95% CI 0.85 to 0.92)) than men, while no differences for SBP were found.ConclusionsIn this Dutch T2D population, women had a slightly different cardiometabolic risk profile compared with men and a substantially higher BMI. Women had a higher probability of being treated with antihypertensive medication in the presence of high CVD risk and elevated SBP than men, and were less likely than men to achieve treatment targets for HbA1c and LDL levels.

ObjectiveTo investigate sex differences in prevalence, treatment and control of major cardiovascular risk factors in England.MethodsData from the Health Survey for England 2012–2017 on non-institutionalised English adults (aged ≥16 years) were used to investigate sex differences in prevalence, treatment and control of major cardiovascular risk factors: body mass index, smoking, systolic blood pressure and hypertension, diabetes, and cholesterol and dyslipidaemia. Physical activity and diet were not assessed in this study.ResultsOverall, 49 415 adults (51% women) were included. Sex differences persisted in prevalence of cardiovascular risk factors, with smoking, hypertension, overweight and dyslipidaemia remaining more common in men than in women in 2017. The proportion of individuals with neither hypertension, dyslipidaemia, diabetes nor smoking increased from 32% to 36% in women and from 28% to 29% in men between 2012 and 2017. Treatment and control of hypertension and diabetes improved over time and were comparable in both sexes in 2017 (66% and 51% for treatment and control of hypertension and 73% and 20% for treatment and control of diabetes). However, women were less likely than men to have treated and controlled dyslipidaemia (21% vs 28% for treatment and 15% vs 24% for control, for women versus men in 2017).ConclusionsImportant sex differences persist in cardiovascular risk factors in England, with an overall higher number of risk factors in men than in women. A combination of public health policy and individually tailored interventions is required to further reduce the burden of cardiovascular disease in England.

Although covid-19 is a new and emerging disease, it could be one of the best understood in terms of its sex disaggregated outcomes. This may sound surprising. Sex disaggregated data (separated for women and men) for confirmed covid-19 cases and deaths are lacking from around half of the most severely affected countries, and most countries are not routinely reporting metrics such as sex or pregnancy status for covid-19 test results, treatment, vaccine trials, or deaths. But even the fact that some countries are considering sex as an important factor in covid-19 outcomes is a significant improvement when compared with the norm of non-sex disaggregated data collection for other infectious and chronic diseases. Current covid-19 mortality and morbidity data show that women are faring better than men in terms of severity of disease course, likelihood of hospitalisation, and risk of death.1 This difference can be seen across nations and socioeconomic groups, while case numbers are similar for men and women.234 …

OBJECTIVE Diabetes has shown to be a stronger risk factor for myocardial infarction (MI) in women than men. Whether sex differences exist across the glycemic spectrum is unknown. We investigated sex differences in the associations of diabetes status and glycated hemoglobin (HbA1c) with the risk of MI. RESEARCH DESIGN AND METHODS Data were used from 471,399 (56% women) individuals without cardiovascular disease (CVD) included in the UK Biobank. Sex-specific incidence rates were calculated by diabetes status and across levels of HbA1c using Poisson regression. Cox proportional hazards analyses estimated sex-specific hazard ratios (HRs) and women-to-men ratios by diabetes status and HbA1c for MI during a mean follow-up of 9 years. RESULTS Women had lower incidence rates of MI than men, regardless of diabetes status or HbA1c level. Compared with individuals without diabetes, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were associated with an increased risk of MI in both sexes. Previously diagnosed diabetes was more strongly associated with MI in women (HR 2.33 [95% CI 1.96; 2.78]) than men (1.81 [1.63; 2.02]), with a women-to-men ratio of HRs of 1.29 (1.05; 1.58). Each 1% higher HbA1c, independent of diabetes status, was associated with an 18% greater risk of MI in both women and men. CONCLUSIONS Although the incidence of MI was higher in men than women, the presence of diabetes is associated with a greater excess relative risk of MI in women. However, each 1% higher HbA1c was associated with an 18% greater risk of MI in both women and men.

Women have lower age-specific rates of incident coronary heart disease (CHD) than men. It is unclear whether women remain at lower risk for CHD events versus men following a myocardial infarction (MI).This study assessed sex differences in recurrent MI, recurrent CHD events, and mortality among patients with MI and compared these associations with sex differences in a control group without a history of CHD.This study analyzed data for 171,897 women and 167,993 men age 21 years or older with health insurance in the United States who had a MI hospitalization in 2015 or 2016. Patients with a MI were frequency matched by age and calendar year to 687,588 women and 671,972 men without CHD. Beneficiaries were followed until December 2017 for MI, CHD (i.e., MI or coronary revascularization), and in Medicare for all-cause mortality.Age-standardized rates of MI per 1,000 person-years were 4.5 in women and 5.7 in men without CHD (hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.62 to 0.67) and 60.2 in women and 59.8 in men with MI (HR: 0.94; 95% CI: 0.92 to 0.96). CHD rates in women versus men were 6.3 versus 10.7 among those without CHD (HR: 0.53; 95% CI: 0.51 to 0.54) and 84.5 versus 99.3 among those with MI (HR: 0.87; 95% CI: 0.85 to 0.89). All-cause mortality rates in women versus men were 63.7 versus 59.0 among those without CHD (HR: 0.72; 95% CI: 0.71 to 0.73) and 311.6 versus 284.5 among those with MI (HR: 0.90; 95% CI: 0.89 to 0.92).The lower risk for MI, CHD, and all-cause mortality in women versus men is considerably attenuated following a MI.

IntroductionDiet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure.Methods and analysisA comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by self-report assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality.Ethics and disseminationAll data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences.PROSPERO registration numberCRD42019131715.

Background Sex differences in the management of cardiovascular disease have been reported in secondary care. We conducted a systematic review with meta‐analysis of systematically investigated sex differences in cardiovascular medication prescription among patients at high risk or with established cardiovascular disease in primary care. Methods and Results PubMed and Embase were searched between 2000 and 2019 for observational studies reporting on the sex‐specific prevalence of aspirin, statins, and antihypertensive medication prescription, including beta blockers, calcium channel blockers, angiotensin‐converting enzyme inhibitors, and diuretics, in primary care. Random effects meta‐analysis was used to obtain pooled women‐to‐men prevalence ratios for each cardiovascular medication prescription. Metaregression models assessed the impact of age and year on the findings. A total of 43 studies were included, involving 2 264 600 participants (28% women) worldwide. Participants’ mean age ranged from 51 to 76 years. The pooled prevalence of cardiovascular medication prescription for women was 41% for aspirin, 60% for statins, and 68% for any antihypertensive medications. Corresponding rates for men were 56%, 63%, and 69% respectively. The pooled women‐to‐men prevalence ratios were 0.81 (95% CI , 0.72–0.92) for aspirin, 0.90 (95% CI , 0.85–0.95) for statins, and 1.01 (95% CI , 0.95–1.08) for any antihypertensive medications. Women were less likely to be prescribed angiotensin‐converting enzyme inhibitors (0.85; 95% CI , 0.81–0.89) but more likely with diuretics (1.27; 95% CI , 1.17–1.37). Mean age, mean age difference between the sexes, and year of study had no significant impact on findings. Conclusions Sex differences in the prescription of cardiovascular medication exist among patients at high risk or with established cardiovascular disease in primary care, with a lower prevalence of aspirin, statins, and angiotensin‐converting enzyme inhibitors prescription in women and a lower prevalence of diuretics prescription in men.

Background Timely recognition of patients with acute coronary syndromes ( ACS ) is important for successful treatment. Previous research has suggested that women with ACS present with different symptoms compared with men. This review assessed the extent of sex differences in symptom presentation in patients with confirmed ACS . Methods and Results A systematic literature search was conducted in PubMed, Embase, and Cochrane up to June 2019. Two reviewers independently screened title‐abstracts and full‐texts according to predefined inclusion and exclusion criteria. Methodological quality was assessed using the Newcastle‐Ottawa Scale. Pooled odds ratios ( OR ) with 95% CI of a symptom being present were calculated using aggregated and cumulative meta‐analyses as well as sex‐specific pooled prevalences for each symptom. Twenty‐seven studies were included. Compared with men, women with ACS had higher odds of presenting with pain between the shoulder blades ( OR 2.15; 95% CI , 1.95–2.37), nausea or vomiting ( OR 1.64; 95% CI , 1.48–1.82) and shortness of breath ( OR 1.34; 95% CI , 1.21–1.48). Women had lower odds of presenting with chest pain ( OR 0.70; 95% CI , 0.63–0.78) and diaphoresis (OR 0.84; 95% CI , 0.76–0.94). Both sexes presented most often with chest pain (pooled prevalences, men 79%; 95% CI , 72–85, pooled prevalences, women 74%; 95% CI , 72–85). Other symptoms also showed substantial overlap in prevalence. The presence of sex differences has been established since the early 2000s. Newer studies did not materially change cumulative findings. Conclusions Women with ACS do have different symptoms at presentation than men with ACS , but there is also considerable overlap. Since these differences have been shown for years, symptoms should no longer be labeled as “atypical” or “typical.”

Background: Major differences between women and men exist in the clinical presentation, medical care, and prognosis and outcomes of stroke. We assessed the sex-specific association of major risk factors and the risk of incident stroke, including its major subtypes, among women and men. Methods: Between 2006-10, the UK Biobank recruited over 500,000 participants aged 40-69 years across the UK. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded among 471,971 (56% women) individuals without a history of cardiovascular disease at baseline. Cox regression models yielded adjusted hazard ratios (HRs), and women-to-men ratios of HRs (RHR), for stroke associated with seven risk factors. Results: The incidence rate per 10,000 person years was 8.66 (8.29; 9.04) in women and 13.96 (13.44; 14.50) in men for any stroke; 6.06 (5.75; 6.38) in women and 11.35 (10.88; 11.84) in men for ischaemic stroke, and 1.56 (1.41; 1.73) in women and 2.23 (2.02; 2.45) in men for haemorrhagic stroke. The magnitude of the relationship between increases in indices of blood pressure, body anthropometry, and lipid levels, diabetes mellitus, and atrial fibrillation and the risk of any stroke was similar between men and women. Hypertension (stage 2), current smoking, and a low socioeconomic status, respectively, were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26; 1.47), 1.18 (1.02; 1.36), and 1.17 (1.03; 1.33). Diabetes was associated with a higher HR of ischaemic stroke in women than men (RHR: 1.25 [1.00; 1.56]). Atrial fibrillation was associated with a higher HR of haemorrhagic stroke in women than men (RHR: 2.80 [1.07; 7.36]). The incidence of stroke was higher among men than women for all risk factors, except type 1 diabetes and atrial fibrillation (haemorrhagic stroke only). Conclusion: Several risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke in the presence of risk factors generally remains higher among men than women.

Diabetes is a strong risk factor for vascular disease. There is compelling evidence that the relative risk of vascular disease associated with diabetes is substantially higher in women than men. The mechanisms that explain the sex difference have not been identified. However, this excess risk could be due to certain underlying biological differences between women and men. In addition to other cardiometabolic pathways, sex differences in body anthropometry and patterns of storage of adipose tissue may be of particular importance in explaining the sex differences in the relative risk of diabetes-associated vascular diseases. Besides biological factors, differences in the uptake and provision of health care could also play a role in women’s greater excess risk of diabetic vascular complications. In this review, we will discuss the current knowledge regarding sex differences in both biological factors, with a specific focus on sex differences adipose tissue, and in health care provided for the prevention, management, and treatment of diabetes and its vascular complications. While progress has been made towards understanding the underlying mechanisms of women’s higher relative risk of diabetic vascular complications, many uncertainties remain. Future research to understanding these mechanisms could contribute to more awareness of the sex-specific risk factors and could eventually lead to more personalized diabetes care. This will ensure that women are not affected by diabetes to a greater extent and will help to diminish the burden in both women and men.

BackgroundAtrial fibrillation (AF) is a stronger risk factor for cardiovascular disease in women than men. We assessed whether there are sex differences in the effects of 43 established and novel risk factors and the risk of incident AF.MethodsData were used from the Scottish Heart Health Extended Cohort, a prospective cohort study with over 20 years of follow-up for AF incidence. Cox regression models were used to obtain the adjusted sex-specific HRs and 95% CIs, and the women-to-men ratio of HRs (RHRs), of incident AF associated with personal characteristics, smoking, physical measurements, diabetes mellitus, lipid, inflammatory, cardiac, and diet- and renal-related markers.ResultsOverall, 15 737 participants (52% women) were included. There were sex differences in the relationship between a 1 SD increase in body mass index (BMI), NT-pro-BNP, uric acid, and cystatin-C and the risk of AF. The HRs were 1.17 (95% CI 1.08 to 1.27) in women and 1.36 (95% CI 1.24 to 1.49) in men for BMI (RHR 0.86, 95% CI 0.77 to 0.97); 1.84 (95% CI 1.62 to 2.09) in women and 1.54 (95% CI 1.40 to 1.68) in men for NT-pro-BNP (RHR 1.22, 95% CI1.05 to 1.42); 1.27 (95% CI 1.14 to 1.41) in women and 1.10 (95% CI 1.00 to 1.20) in men for uric acid (RHR 1.17, 95% CI 1.01 to 1.35); and 1.22 (95% CI 1.13 to 1.32) in women and 1.07 (95% CI 0.96 to 1.18) in men for cystatin-C (RHR 1.16, 95% CI 1.05 to1.27).ConclusionHigher BMI is a stronger risk factor for AF in men whereas elevated NT-pro-BNP, uric acid and cystatin-C were more strongly associated with the risk of AF in women.