Gender score development in the Berlin Aging Study II: A retrospective approach

In addition to biological sex, gender, defined as the sociocultural dimension of being a woman or a man, plays a central role in health. However, there are so far few approaches to quantify gender in a retrospective manner in existing study datasets. We therefore aimed to develop a methodology that can be retrospectively applied to assess gender in existing cohorts. We used baseline data from the Berlin Aging Study II (BASE-II), obtained in 2009-2014 from 1869 participants aged 60 years and older. We identified 13 gender-related variables and used them to construct a gender score by using primary component and logistic regression analyses. Of these, nine variables contributed to a gender score: chronic stress, marital status, risk-taking behaviour, personality attributes: agreeableness, neuroticism, extraversion, loneliness, conscientiousness, and level of education. Females and males differed significantly in the distribution of the gender score, but a significant overlap was also found. Thus, we were able to develop a gender score in a retrospective manner from already collected data that characterized participants in addition to biological sex. This approach will allow researchers to introduce the notion of gender retrospectively into a large number of studies

Health-Related Quality of Life in Premature Acute Coronary Syndrome: Does Patient Sex or Gender Really Matter?

Background-Limited data exist as to the relative contribution of sex and gender on health-related quality of life (HRQL) among patients with acute coronary syndrome (ACS). This study aims to evaluate the effect of sex and gender-related variables on long-term HRQL among young adults with ACS. Methods and Results-GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome) is a multicenter, prospective cohort study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form-12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49 years. Women reported worse HRQL than men over time post-ACS, both in terms of physical and mental functioning. Gender-related factors were more likely to be predictors of HRQL than sex. Femininity score, social support, and housework responsibility were the most common gender-related predictors of HRQL at 12 months. We observed an interaction between female sex and social support (beta=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical limitation subscale of the SAQ. Conclusions-Young women with ACS report significantly poorer HRQL than young men. Gender appears to be more important than sex in predicting long-term HRQL post-ACS. Specific gender-related factors, such as social support, may be amenable to interventions and could improve the HRQL of patients with premature ACS.CIHRHeart and Stroke Foundation of QuebecHeart and Stroke Foundation of Nova ScotiaHeart and Stroke Foundation of AlbertaHeart and Stroke Foundation of OntarioHeart and Stroke Foundation of YukonHeart and Stroke Foundation of British Columbia, CanadaJames McGill Chair at McGill Universit

Association of Chromosome 9p21 with Subsequent Coronary Heart Disease events:A GENIUS-CHD study of individual participant data

BACKGROUND:Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS:A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103,357 Europeans with established CHD at baseline from the GENIUS-CHD Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/MI), occurred in 13,040 of the 93,115 participants with available outcome data. Effect estimates were compared to case/control risk obtained from CARDIoGRAMPlusC4D including 47,222 CHD cases and 122,264 controls free of CHD. RESULTS:Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/MI among those with established CHD at baseline (GENIUS-CHD OR 1.02; 95% CI 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D OR 1.20; 95% CI 1.18-1.22; p for interaction Conclusions: In contrast to studies comparing individuals with CHD to disease free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Sex Differences in Cardiovascular Effectiveness of Newer Glucose-Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus

Background: Randomized controlled trials showed that newer glucose-lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results: Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT-2i, GLP-1RA, or dipeptidyl peptidase-4 inhibitors (Marketscan-Database: 2011–2017). We used multivariable Cox proportional hazards models with time-varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex–drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5-year follow-up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000-person-year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP-1RA (adjusted HR-women: 0.57, 95% CI: 0.48–0.68; aHR-men: 0.82, 0.71–0.95), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.83, 0.77–0.89; aHR-men: 0.85, 0.79–0.91) and SGLT-2i (aHR-women: 0.58, 0.46–0.74; aHR-men: 0.69, 0.57–0.83). A sex-by-drug interaction was statistically significant only for GLP-1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP-1RA (aHR-women: 0.81, 0.73–0.89; aHR-men: 0.80, 0.71–0.89), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.82, 0.78–0.87; aHR-men: 0.83, 0.78–0.87) and SGLT-2i (aHR-women: 0.68, 0.59–0.78; aHR-men: 0.67, 0.59–0.78) (all sex–drug interactions for adverse events P>0.05). Conclusions: Newer glucose-lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP-1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT-2i than for GLP-1RA regardless of sex

Variations in Quality of Care by Sex and Social Determinants of Health among Younger Adults with Acute Myocardial Infarction in the US and Canada

Importance: Quality of care of young adults with acute myocardial infarction (AMI) may depend on health care systems in addition to individual-level factors such as biological sex and social determinants of health (SDOH). Objective: To examine whether the quality of in-hospital and postacute care among young adults with AMI differs between the US and Canada and whether female sex and adverse SDOH are associated with a low quality of care. Design, Setting, and Participants: This retrospective cohort analysis used data from 2 large cohorts of young adults (aged ≤55 years) receiving in-hospital and outpatient care for AMI at 127 centers in the US and Canada. Data were collected from August 21, 2008, to April 30, 2013, and analyzed from July 12, 2019, to March 10, 2021. Exposures: Sex, SDOH, and health care system. Main Outcomes and Measures: Opportunity-based quality-of-care score (QCS), determined by dividing the total number of quality indicators of care received by the total number for which the patient was eligible, with low quality of care defined as the lowest tertile of the QCS. Results: A total of 4048 adults with AMI (2345 women [57.9%]; median age, 49 [interquartile range, 44-52] years; 3004 [74.2%] in the US) were included in the analysis. Of 3416 patients with in-hospital QCS available, 1061 (31.1%) received a low QCS, including more women compared with men (725 of 2007 [36.1%] vs 336 of 1409 [23.8%]; P <.001) and more patients treated in the US vs Canada (962 of 2646 [36.4%] vs 99 of 770 [12.9%]; P <.001). Conversely, low quality of post-AMI care (748 of 2938 [25.5%]) was similarly observed for both sexes, with a higher prevalence in the US (678 of 2346 [28.9%] vs 70 of 592 [11.8%]). In adjusted analyses, female sex was not associated with low QCS for in-hospital (odds ratio [OR], 1.05; 95% CI, 0.87-1.28) and post-AMI (OR, 1.07; 95% CI, 0.88-1.30) care. Conversely, being treated in the US was associated with low in-hospital (OR, 2.93; 95% CI, 2.16-3.99) and post-AMI (OR, 2.67; 95% CI, 1.97-3.63) QCS, regardless of sex. Of all SDOH, only employment was associated with higher quality of in-hospital care (OR, 0.72; 95% CI, 0.59-0.88). Finally, only in the US, low quality of in-hospital care was associated with a higher 1-year cardiac readmissions rate (234 of 962 [24.3%]). Conclusions and Relevance: These findings suggest that beyond sex, health care systems and SDOH that depict social vulnerability are associated with quality of AMI care. Taking into account SDOH among young adults with AMI may improve quality of care and reduce readmissions, especially in the US

Impact of race on the in-hospital quality of care among young adults with acute myocardial infarction

BACKGROUND: The extent to which race influences in-hospital quality of care for young adults (≤55 years) with acute myocardial infarction (AMI) is largely unknown. We examined racial disparities in in-hospital quality of AMI care and their impact on 1-year cardiac readmission. METHODS AND RESULTS: We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolling young Black and White US adults with AMI (2008–2012). An in-hospital quality of care score (QCS) was computed (standard AMI quality indicators divided by the total a patient is eligible for). Multivariable logistic regression was performed to identify factors associated with the lowest QCS tertile, including interactions between race and social determinants of health. Among 2846 young adults with AMI (median 48 years [interquartile range 44–52], 67.4% women, 18.8% Black race), Black individuals, especially women, exhibited a higher prevalence of cardiac risk factors and social determinants of health and were more likely to experience a non–ST-segment–elevation myocardial infarction than White individuals. Black individuals were more likely in the lowest QCS tertile than White individuals (40.8% versus 34.7%; P=0.003). The association between Black race and low QCS (odds ratio [OR], 1.25; 95% CI, 1.02–1.54) was attenuated by adjustment for confound-ers. Employment was independently associated with better QCS, especially among Black participants (OR, 0.76; 95% CI, 0.62–0.92; P-interaction =0.02). Black individuals experienced a higher rate of 1-year cardiac readmission (29.9% versus 20.0%; P<0.0001). CONCLUSIONS: Black individuals with AMI received lower in-hospital quality of care and exhibited a higher rate of cardiac re-admissions than White individuals. Black individuals had a lower quality of care if unemployed, highlighting the intersection of race and social determinants of health