Sex Differences in Out-of-Hospital Cardiac Arrest Survival Trends.

BACKGROUND: Out-of-hospital cardiac arrest survival rates have improved over time. This study established whether improvements were similar for women and men, and to what extent resuscitation characteristics or in-hospital procedures contributed to sex differences in temporal trends. METHODS AND RESULTS: This retrospective cohort study included 3386 women and 8564 men from North Holland, the Netherlands, who experienced an out-of-hospital cardiac arrest from a cardiac cause in 2005 to 2017. Yearly rates of 30-day survival and secondary outcomes were calculated. Sex differences in temporal trends were evaluated with age-adjusted Poisson regression analysis, including interaction for sex and out-of-hospital cardiac arrest year. Resuscitation characteristics and in-hospital procedures were added to the model, and a spline at 2013 was considered. During the study period, the average 30-day survival was 24.9% in men and 15.7% in women. The 30-day survival rate increased in men (20% to 27.2%; P<0.001) but not in women (15.0% to 11.6%; P=0.40). The increase in the 30-day survival rate was 3% higher per year in men than in women (rate ratio, 1.03 [95% CI, 1.00-1.05]), with a stronger difference after 2013. Men had a larger increase in survival rate to the hospital arrival than women in 2005 to 2013, and, after 2013, an advantage over women in survival rate after hospital arrival. The sex differences were partly explained by differing trends in shockable initial rhythm (eg, adjusted rate ratio, 1.01 [95% CI, 0.99-1.03] for 30-day survival) and provision of in-hospital procedures. CONCLUSIONS: Changes in rates of 30-day survival, survival to hospital arrival, and, after 2013, survival from hospital arrival to 30 days were more beneficial in men than women. The differences in trends were partly explained by shockable initial rhythm and in-hospital procedures.

Sex and ethnic differences in unrecognized myocardial infarctions: Observations on recognition and preventive therapies from the multiethnic population-based HELIUS cohort.

Background: Epidemiological studies suggest sex differences in the prevalence and characteristics of unrecognized and recognized myocardial infarction (uMI, rMI). Despite increasingly diverse populations, observations are limited in multiethnic contexts. Gaining better understanding may inform policy makers and healthcare professionals on populations at risk of uMI who could benefit from preventive measures. Methods: We used baseline data from the multiethnic population-based HELIUS cohort (2011-2015; Amsterdam, the Netherlands). Using logistic regressions, we studied sex differences in the prevalence and proportion of uMIs across ethnic groups. Next, we studied whether symptoms, clinical parameters, and sociocultural factors were associated with uMIs. Finally, we compared secondary preventive therapies in women and men with a uMI or rMI. We relied on pathological Q-waves on a resting electrocardiogram as the electrocardiographic signature for (past) MI. Results: Overall, and in Turkish and Moroccan subgroups, the prevalence of uMIs was higher in men than women. The proportion of uMIs was similar in women (21.0%) and men (18.4%), yet varied by ethnicity. In women and men, symptoms (chest pain, dyspnea) and clinical parameters (hypertension, hypercholesterolemia), and in women also lower educational level and diabetes were associated with lower odds of uMIs. Women (0.0%) and men (3.6%) with uMI were unlikely to receive secondary preventive therapies compared to those with rMI (28.1-40.9%). Conclusions: The prevalence of uMIs was higher in men than women, and sex differences in the proportion of uMIs varied somewhat across ethnic groups. People with uMIs did not receive adequate preventative medications, posing a risk for recurrent events.

Education and age trajectories of chronic conditions: Are tests of the cumulative advantage and disadvantage hypothesis biased by underreporting?

OBJECTIVE: This study examined the impact of underreporting on tests of the cumulative advantage and disadvantage hypothesis (CAD), which predicts age-related increases in health disparities between individuals with higher and lower education. METHODS: Using the English Longitudinal Study of Ageing (ELSA), we identified underreporting by comparing self-reported hypertension and diabetes with biomedically measured hypertension (systolic blood pressure≥140 mm Hg and/or diastolic blood pressure≥90 mm Hg) and diabetes (fasting glucose level≥7 mmol/l and/or HbA1c≥6.5%). In a sample of 11,859 respondents aged 50 to 85 (54% women, 97% White), we assessed the associations between underreporting and the main analytic constructs in tests of the CAD (education, age, sex, and cohort). RESULTS: The results showed that self-reported measures underestimated the prevalence of hypertension and diabetes. Underreporting showed weak to moderate associations with the main constructs in tests of the CAD, being more pronounced in individuals with lower education, in older age, in more recent cohorts, and among men. When correcting for underreporting using biomedical measures, the overall prevalence of hypertension and diabetes increased substantially, but education differences in age trajectories of both conditions remained similar. CONCLUSIONS: Underreporting affected conclusions about the prevalence of hypertension and diabetes, but it did not affect conclusions about the CAD hypothesis for either condition.

The COVID-19 pandemic and temporal change in metabolic risk factors for cardiovascular disease: A natural experiment within the HELIUS study.

The coronavirus disease 2019 (COVID-19) pandemic, including the restrictive measures taken to reduce the spread of the virus, negatively affected people's health behavior. We explored whether the pandemic also had an effect on metabolic risk factors for cardiovascular disease (CVD) in women and men. We conducted a natural experiment, using data from 6962 participants without CVD at baseline (2011-2015) of six ethnic groups of the HELIUS study in Amsterdam, the Netherlands. We studied whether participants whose follow-up measurements were taken within the 11 months before the pandemic (control group) differed from those whose measurements were taken taken within 6 months after the first lockdown (exposed group). Using sex-stratified linear regressions with inverse probability weighting, we compared changes in baseline- and follow-up data between the control and exposed group in six metabolic risk factors: systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR). Next, we explored the mediating effect of changes in body-mass index (BMI), alcohol, smoking, depressive symptoms and negative life events at follow-up. We observed less favorable changes in SBP (+1.12mmHg for women, +1.38mmHg for men), DBP (+0.85mmHg, +0.80mmHg) and FPG (only in women, +0.12 mmol/L) over time in the exposed group relative to the control group. Conversely, changes in HbA1c (-0.65 mmol/mol, -0.84 mmol/mol) and eGFR (+1.06 mL/min, +1.04 mL/min) were more favorable in the exposed compared to the control group, respectively. Changes in SBP, DBP, and FPG were partially mediated by changes in behavioral factors, in particular BMI and alcohol consumption. Concluding, the COVID-19 pandemic, in particular behavioral changes associated with restrictive lockdown measures, may have negatively affected several CVD risk factors, in both women and men.

Psychosocial factors may serve as additional eligibility criteria for cardiovascular risk screening in women and men in a multi-ethnic population: The HELIUS study.

Cardiovascular disease (CVD) prevention strategies include identifying and managing high risk individuals. Identification primarily occurs through screening or case finding. Guidelines indicate that psychosocial factors increase CVD risk, but their use for screening is not yet recommended. We studied whether psychosocial factors may serve as additional eligibility criteria in a multi-ethnic population without prior CVD. We performed a cross-sectional analysis using baseline data of 10,226 participants of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged 40-70 years, living in Amsterdam, the Netherlands. Using logistic regressions and Akaike Information Criteria, we analyzed whether psychosocial factors (educational level, employment status, occupational level, financial stress, primary earner status, mental health, stress, depression, and social isolation) improved prediction of high CVD risk (SCORE-estimated fatal and non-fatal CVD risk ≥5%) beyond eligibility criteria from history taking (smoking, obesity, family history of CVD). Next, we compared the additional predictive value of psychosocial eligibility criteria in women and men across ethnic groups, using the area under the curve (AUC). Of our sample, 32.7% had a high CVD risk. Only socioeconomic eligibility criteria (employment status and educational level) improved high CVD risk prediction (p < .001 for likelihood-ratio tests). These increased AUCs in women (from 0.563 to 0.682) and men (from 0.610 to 0.664), particularly in Dutch, South-Asian Surinamese, African Surinamese and Moroccan women, and Dutch and Moroccan men. Concluding, socioeconomic eligibility criteria may be considered as additional eligibility criteria for CVD risk screening, as they improve detection of women and men at high CVD risk.

The contribution of smoking to differences in cardiovascular disease incidence between men and women across six ethnic groups in Amsterdam, the Netherlands: The HELIUS study.

It is unclear to what extent differences in cardiovascular disease (CVD) risk between men and women are explained by differences in smoking, and whether this contribution to risk is consistent across ethnic groups. In this prospective study, we determined the contribution of smoking to differences in CVD incidence between men and women, also in various ethnic groups. We linked baseline data of 18,058 participants of six ethnic groups from the HELIUS study (Amsterdam, the Netherlands) to CVD incidence data, based on hospital admission and death records from Statistics Netherlands (2013-2019). The contribution of smoking to CVD incidence, as estimated by the population attributable fraction, was higher in men than in women, overall (24.1% versus 15.6%) and across most ethnic groups. Among Dutch participants, however, the contribution of smoking was higher among women (21.0%) than men (16.2%). Using Cox regression analyses, we observed that differences in smoking prevalence explained 22.0% of the overall lower hazard for CVD in women compared to men. Smoking contributed minimally to the lower hazards for CVD in women among participants of Dutch (0%), Ghanaian (4.9%) and Moroccan origin (0%), but explained 28.6% and 48.6% of the lower hazards in women in South-Asian Surinamese and African Surinamese groups, respectively. While smoking prevention and cessation may lead to lower CVD incidence in most groups of men and women, it may not substantially reduce disparities in CVD risk between men and women in most ethnic groups.

Association Between Income and Risk of Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Study.

BACKGROUND: Previous studies have observed a higher out-of-hospital cardiac arrest (OHCA) risk among lower socioeconomic groups. However, due to the cross-sectional and ecological designs used in these studies, the magnitude of these inequalities is uncertain. This study is the first to assess the individual-level association between income and OHCA using a large-scale longitudinal study. METHODS: This retrospective cohort study followed 1 688 285 adults aged 25 and above, living in the catchment area of an OHCA registry in a Dutch province. OHCA cases (n=5493) were linked to demographic and income registries. Cox proportional hazard models were conducted to determine hazard ratios of OHCA for household and personal income quintiles, stratified by sex and age. RESULTS: The total incidence of OHCA per 100 000 person years was 30.9 in women and 87.1 in men. A higher OHCA risk was observed with lower household and personal income. Compared with the highest household income quintile, the adjusted hazard ratios from the second highest to the lowest household income quintiles ranged from 1.24 (CI=1.01-1.51) to 1.75 (CI=1.46-2.10) in women and from 0.95 (CI=0.68-1.34) to 2.30 (CI=1.74-3.05) in men. For personal income, this ranged from 0.95 (CI=0.68-1.34) to 2.30 (CI=1.74-3.05) in women and between 1.28 (CI=1.16-1.42) and 1.68 (CI=1.48-1.89) in men. Comparable household and personal income gradients were found across age groups except in the highest (>84 years) age group. For example, household income in women aged 65 to 74 ranged from 1.25 (CI=1.02-1.52) to 1.65 (CI=1.36-2.00). Sensitivity analyses assessing the prevalence of comorbidities at baseline and different lengths of follow-up yielded similar estimates. CONCLUSIONS: This study provides new evidence for a substantial increase in OHCA risk with lower income in different age and sex groups. Low-income groups are likely to be a suitable target for intervention strategies to reduce OHCA risk.

Cardiovascular risk profile after a complicated pregnancy across ethnic groups: The HELIUS study.

AIMS: Little is known about how pregnancy complications and cardiovascular disease (CVD) risk are associated, specifically among ethnic minorities. In this study we examined this association in women from six ethnic groups, and the potential value of pregnancy complications as eligibility criterion for CVD risk screening. METHODS: We conducted a cross-sectional study combining obstetric history from the Dutch perinatal registry with data on cardiovascular risk up to 15 years after pregnancy from the multi-ethnic HELIUS study. We included 2,466 parous women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. Associations were studied across ethnicities and predictive value of pregnancy complications for CVD risk factors above traditional eligibility criteria for CVD risk screening was assessed using Poisson regression. RESULTS: History of hypertensive disorders of pregnancy and preterm birth were associated with higher prevalence of chronic hypertension and chronic kidney disease across most groups (prevalence ratio 1.6-1.9). Gestational diabetes mellitus was associated with increased type 2 diabetes mellitus risk, particularly in ethnic minority groups (prevalence ratio 4.5-7.7). Associations did not significantly differ across ethnic groups. The prediction models did not improve substantially after adding pregnancy complications to traditional eligibility criteria for CVD risk screening. CONCLUSION: History of hypertensive disorders of pregnancy, preterm birth and gestational diabetes mellitus is associated with CVD risk factors in parous women, without evidence of a differential association across ethnic groups. However, addition of pregnancy complications to traditional eligibility criteria for CVD risk screening does not substantially improve the prediction of prevalent CVD risk factors.

Women of different ethnic backgrounds who had pregnancy complications (high blood pressure or diabetes during pregnancy, or who delivered their baby too early) have a higher risk of heart disease later in life. Screening for a high risk of heart disease is important, because interventions may help to prevent heart disease. Currently, general practitioners use several criteria to select women for screening, such as heart disease among close relatives or smoking. In our study in women in whom these 'traditional' criteria for screening were measured, the pregnancy complications did not help to find more women with a high risk. Yet, pregnancy complications may be a signal for both patients and healthcare professionals to regularly consider the need for screening. Women who had high blood pressure in pregnancy or delivered their baby too early had up to two times more often chronic hypertension or kidney disease later in life. Women who had diabetes in pregnancy, had up to eight times more type 2 diabetes later in life. Women of South-Asian Surinamese, African Surinamese and Ghanaian origin living in the Netherlands more often had pregnancy complications and cardiovascular risk factors than women with a Dutch background.

The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes-a statistical analysis plan.

BACKGROUND: South Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care. METHODS: The iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance. DISCUSSION: The iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP. ETHICS AND DISSEMINATION: The trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations. TRIAL REGISTRATION: EudraCT 2016-001,350-18 . Registered on 14 April 2016. CLINICALTRIALS: gov NCT02949739 . Registered on 31 October 2016.

Individual-level income and out-of-hospital cardiac arrest survival in men and women.

OBJECTIVE: Area-level socioeconomic factors are known to associate with chances to survive out-of-hospital cardiac arrest (OHCA survival). However, the relationship between individual-level socioeconomic factors and OHCA survival in men and women is less established. This study investigated the association between individual-level income and OHCA survival in men and women, as well as its contribution to outcome variability and mediation by resuscitation characteristics. METHODS: A cross-sectional cohort study using data from a Dutch community-based OHCA registry was performed. We included 5395 patients aged≥25 years with OHCA from a presumed cardiac cause. Household income, derived from Statistics Netherlands, was stratified into quartiles. The association between survival to hospital discharge and household income was analysed using multivariable logistic regression adjusting for age, sex and resuscitation characteristics. RESULTS: Overall women had lower household income than men (median €18 567 vs €21 015), and less favourable resuscitation characteristics. Increasing household income was associated with increased OHCA survival in both men and women in a linear manner (Q4 vs Q1: OR 1.63 95% CI (1.24 to 2.16) in men, and 2.54 (1.43 to 4.48) in women). Only initial rhythm significantly changed the ORs for OHCA survival with>10% in both men and women. Household income explained 3.8% in men and 4.3% in women of the observed variance in OHCA survival. CONCLUSION: Both in men and women, higher individual-level household income was associated with a 1.2-fold to 2.5-fold increased OHCA survival to hospital discharge, but explained only little of outcome variability. A shockable initial rhythm was the most important resuscitation parameter mediating this association. Our results do not support the need for immediate targeted interventions on actionable prehospital resuscitation care characteristics.

Gender-related factors and out-of-hospital cardiac arrest incidence in women and men: analysis of a population-based cohort study in the Netherlands.

BACKGROUND: The incidence of out-of-hospital cardiac arrest (OHCA) differs consistently between women and men. Besides sex-related (biological) factors, OHCA risk may relate to gender-related (sociocultural) factors. We explored the association of selected gender-related factors with OHCA incidence in women and men. METHODS: We combined data on emergency medical services-attended OHCA with individual-level data from all women and men aged ≥25 years living in North Holland, the Netherlands. We estimated the associations between employment status, primary earner status, living with children and marital status and the OHCA incidence with Cox proportional hazards models stratified by sex and adjusted for age and socioeconomic status. To determine if metabolic factors explain the associations, we added hypertension, diabetes mellitus and dyslipidaemia to the models. Population attributable fractions (PAF) for all gender-related factors were calculated. RESULTS: All four gender-related factors were associated with OHCA incidence (eg, unemployed vs employed; HR 1.98, 95% CI 1.67 to 2.35 in women; HR 1.60, 95% CI 1.44 to 1.79 in men). In both sexes, those unemployed, those who are not primary earners, those living without children, and married or divorced individuals had an increased OHCA risk. The PAF ranged from 4.9 to 40.3 in women and from 4.4 to 15.5 in men, with the highest PAF for employment status in both sexes. Metabolic risk factors did not explain the observed associations. CONCLUSION: Gender-related factors were associated with risk of OHCA and contributed substantially to the OHCA burden at the population level, particularly in women. Employment status contributed most to the OHCA burden.

Hypertensive Disorders of Pregnancy and Cardiovascular Disease Risk Across Races and Ethnicities: A Review.

Pregnancy is often considered to be a "cardiometabolic stress-test" and pregnancy complications including hypertensive disorders of pregnancy can be the first indicator of increased risk of future cardiovascular disease. Over the last two decades, more evidence on the association between hypertensive disorders of pregnancy and cardiovascular disease has become available. However, despite the importance of addressing existing racial and ethnic differences in the incidence of cardiovascular disease, most research on the role of hypertensive disorders of pregnancy is conducted in white majority populations. The fragmented knowledge prohibits evidence-based targeted prevention and intervention strategies in multi-ethnic populations and maintains the gap in health outcomes. In this review, we present an overview of the evidence on racial and ethnic differences in the occurrence of hypertensive disorders of pregnancy, as well as evidence on the association of hypertensive disorders of pregnancy with cardiovascular risk factors and cardiovascular disease across different non-White populations, aiming to advance equity in medicine.

Sarcopenia and its relation to protein intake across older ethnic populations in the Netherlands: the HELIUS study.

Objective: To examine the prevalence of sarcopenia and its association with protein intake in men and women in a multi-ethnic population.Design: We used cross-sectional data from the HELIUS (Healthy Life in an Urban Setting) study, which includes nearly 25,000 participants (aged 18-70 years) of Dutch, South-Asian Surinamese, African Surinamese, Turkish, Moroccan, and Ghanaian ethnic origin. For the current study, we included 5161 individuals aged 55 years and older. Sarcopenia was defined according to the EWGSOP2. In a subsample (N = 1371), protein intake was measured using ethnic-specific Food Frequency Questionnaires. Descriptive analyses were performed to study sarcopenia prevalence across ethnic groups in men and women, and logistic regression analyses were used to study associations between protein intake and sarcopenia.Results: Sarcopenia prevalence was found to be sex- and ethnic-specific, varying from 29.8% in Turkish to 61.3% in South-Asian Surinamese men and ranging from 2.4% in Turkish up to 30.5% in South-Asian Surinamese women. Higher protein intake was associated with a 4% lower odds of sarcopenia in the subsample (OR = 0.96, 95%-CI: 0.92-0.99) and across ethnic groups, being only significant in the South-Asian Surinamese group.Conclusion: Ethnic differences in the prevalence of sarcopenia and its association with protein intake suggest the need to target specific ethnic groups for prevention or treatment of sarcopenia.

Is the Association Between Education and Sympathovagal Balance Mediated by Chronic Stressors?

BACKGROUND: This study investigated whether raised chronic stress in low education groups contributes to education differences in cardiovascular disease by altering sympathovagal balance. METHODS: This study included cross-sectional data of 10,202 participants from the multi-ethnic, population-based HELIUS-study. Sympathovagal balance was measured by baroreflex sensitivity (BRS), the standard deviation of the inter-beat interval (SDNN) and the root mean square of successive differences between normal heartbeats (RMSSD). The associations between chronic stressors (work, home, psychiatric, financial, negative life events, lack of job control and perceived discrimination) in a variety of domains and BRS, SDNN and RMSSD were assessed using linear regression, adjusted for age, ethnicity, waist-to-hip ratio and pack-years smoked. Mediation analysis was used to assess the contribution of chronic stress to the association between education and sympathovagal balance. RESULTS: Modest but significant associations were observed between financial stress and BRS and SDNN in women, but not in RMSSD nor for any outcome measure in men. Women with the highest category of financial stress had 0.55% lower BRS (ms/mmHg; ß = -0.055; CI = -0.098, -0.011) and 0.61% lower SDNN (ms; ß = -0.061; CI = -0.099, -0.024) than those in the lowest category. Financial stress in women contributed 7.1% to the association between education and BRS, and 13.8% to the association between education and SDNN. CONCLUSION: No evidence was found for the hypothesized pathway in which sympathovagal balance is altered by chronic stress, except for a small contribution of financial stress in women.

The association between gender-related characteristics and type 2 diabetes risk in a multi-ethnic population: The HELIUS study.

BACKGROUND AND AIMS: Men and women have different type 2 diabetes mellitus (T2DM) risks, which have been reported across populations of different ethnicity. Where differences in T2DM risk for sex (biological) have been studied, research on gender (socio-cultural) and T2DM risk is lacking. We explored, in a multi-ethnic population, the association of six gender-related characteristics with incident T2DM over 3 years, and the mediation by known risk factors for T2DM. METHODS AND RESULTS: We included 9605 women and 7080 men of the multi-ethnic HELIUS study (Amsterdam, the Netherlands). We studied associations between gender-related characteristics and incident T2DM, using Cox regression. After a median of 3.0 years (IQR 2.0; 4.0), 198 (2.1%) women and 137 (1.9%) men developed T2DM. A lower T2DM risk was observed in those not being the primary earner (HR 0.67; 95% CI 0.47; 0.93) and a higher desired level of social support (HR 0.62; 95% CI 0.44; 0.87). Hours spent on household work, home repairs, type of employment and male- or female-dominated occupation were not associated with T2DM incidence. No evidence for effect modification by biological sex or ethnicity was found. Known risk factors of T2DM did not mediate the observed associations. CONCLUSION: Gender-related characteristics, not being the primary earner and a higher desired social support were associated with reduced T2DM risk, and this was not mediated by known risk factors for T2DM.

Harmonization of the definition of sudden cardiac death in longitudinal cohorts of the European Sudden Cardiac Arrest network - towards Prevention, Education, and New Effective Treatments (ESCAPE-NET) consortium.

BACKGROUND: The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts. METHODS: The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value. RESULTS: Consensus definitions of "definite," "possible" and "probable" SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%. CONCLUSIONS: This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information.

The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial.

BACKGROUND: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. HYPOTHESIS: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. DESIGN: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. ENTRY CRITERIA: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive). EXCLUSION CRITERIA: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. ENDPOINTS: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. INTERVENTION: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. RESULTS: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). CONCLUSION: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB APPROVAL: 16/WM/0171 TRIAL REGISTRATION: EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.

Ethnic discrimination and depressed mood: The role of autonomic regulation.

Perceived ethnic discrimination (PED) is thought to underlie increased prevalence of depressed mood in ethnic minorities. Depression is associated with increased sympathetic and decreased parasympathetic activity. We investigated a biopsychosocial model linking PED, disrupted sympathovagal balance and depressed mood. Baseline data of HELIUS, a cohort study on health among a multi-ethnic population, was used. Heart rate variability (HRV), baroreflex sensitivity (BRS), PED (evaluated with the Everyday Discrimination Scale) and presence of depressed mood (evaluated with the Patient Health Questionnaire-9) were assessed. Associations of PED, HRV/BRS and depressed mood were analyzed with linear and logistic regression analyses. Mediation of the association of PED and depressed mood by HRV/BRS was assessed in a potential outcomes model and four steps mediation analysis. Of 9492 included participants, 14.7% fulfilled criteria for depressed mood. Higher PED was associated with depressed mood (P < .001). Lower autonomic regulation indexes were associated with depressed mood (deltaR2 = 0.4-1.1%, P < .001) and at most weakly with PED (deltaR2 = 0.2-0.3%, P < .001). A very modest mediating effect by HRV/BRS in the association between PED and depressed mood was attenuated after adjustment for socioeconomic status. To conclude, we found no support for the hypothesis that autonomic regulation relevantly mediates the association between PED and depression.

Sex differences in incidence of out-of-hospital cardiac arrest across ethnic and socioeconomic groups: A population-based cohort study in the Netherlands.

BACKGROUND: Insight into the occurrence of out-of-hospital cardiac arrest (OHCA) within general populations may help to target prevention strategies. Case registries suggest that there may be substantial differences in emergency medical service (EMS)-attended OHCA incidence between men and women, but relative sex differences across ethnic groups and socioeconomic (SES) groups have not been studied. We investigated sex differences in OHCA incidence, overall and across these subgroups. METHODS: We performed a retrospective population-based cohort study, combining individual-level data on ethnicity and income (as SES measure) from Statistics Netherlands of all men and women aged ≥25 years living in one study region in the Netherlands on 01-01-2009 (n = 1,688,285) with prospectively collected EMS-attended OHCA cases (n = 5676) from the ARREST registry until 31-12-2015. We calculated age-standardised incidence rates of OHCA. Sex differences were assessed with Cox proportional hazards regression analyses, adjusted for age, ethnicity and income, in the overall population, and across ethnic and SES groups. RESULTS: The age-standardised incidence rate of OHCA was lower in women than in men (30.9 versus 87.3 per 100,000 person-years), corresponding with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.31-0.35). These sex differences in hazard for OHCA existed in all income quintiles (HR range: 0.30-0.35) and ethnic groups (HR range: 0.19-0.40), except among Moroccans (HR 0.89, 95% CI 0.51-1.57). CONCLUSION: Women have a substantial, yet lower OHCA incidence rate than men. The magnitude of these sex differences did not vary across social strata.

Gender inequality and the double burden of disease in low-income and middle-income countries: an ecological study.

INTRODUCTION: Many low-income and middle-income countries (LMIC) suffer from a double burden of infectious diseases (ID) and non-communicable diseases (NCD). Previous research suggests that a high rate of gender inequality is associated with a higher ID and NCD burden in LMIC, but it is unknown whether gender inequality is also associated with a double burden of disease. In this ecological study, we explored the association between gender inequality and the double burden of disease in LMIC. METHODS: For 108 LMIC, we retrieved the Gender Inequality Index (GII, scale 0-1) and calculated the double burden of disease, based on disability-adjusted life-years for a selection of relevant ID and NCD, using WHO data. We performed logistic regression analysis to study the association between gender inequality and the double burden of disease for the total population, and stratified for men and women. We adjusted for income, political stability, type of labour, urbanisation, government health expenditure, health infrastructure and unemployment. Additionally, we conducted linear regression models for the ID and NCD separately. RESULTS: The GII ranged from 0.13 to 0.83. A total of 37 LMIC had a double burden of disease. Overall, the adjusted OR for double burden of disease was 1.05 per 0.01 increase of GII (95% CI 0.99 to 1.10, p=0.10). For women, there was a borderline significant positive association between gender inequality and double burden of disease (OR 1.05, 95% CI 1.00 to 1.11, p=0.06), while there was no association in men (OR 0.99, 95% CI 0.95 to 1.04, p=0.75). CONCLUSION: We found patterns directing towards a positive association between gender inequality and double burden of disease, overall and in women. This finding suggests the need for more attention for structural factors underlying gender inequality to potentially reduce the double burden of disease.