Advertisement
Canadian Journal of Cardiology

Sex, Gender, and Cardiovascular Health in Canadian and Austrian Populations

  • Author Footnotes
    ‡ These authors contributed equally to this work as first authors.
    Zahra Azizi
    Footnotes
    ‡ These authors contributed equally to this work as first authors.
    Affiliations
    Centre for Outcomes Research and Evaluation, McGill University Health Centre Research Institute, Montréal, Québec, Canada
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally to this work as first authors.
    Teresa Gisinger
    Footnotes
    ‡ These authors contributed equally to this work as first authors.
    Affiliations
    Gender Medicine Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna, Austria
    Search for articles by this author
  • Uri Bender
    Affiliations
    Centre for Outcomes Research and Evaluation, McGill University Health Centre Research Institute, Montréal, Québec, Canada
    Search for articles by this author
  • Carola Deischinger
    Affiliations
    Gender Medicine Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna, Austria
    Search for articles by this author
  • Valeria Raparelli
    Affiliations
    Department of Translational Medicine, University of Ferrara, Ferrara, Italy

    Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada
    Search for articles by this author
  • Colleen M. Norris
    Affiliations
    Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada

    Heart and Stroke Strategic Clinical Networks, Alberta Health Services, Edmonton, Alberta, Canada
    Search for articles by this author
  • Karolina Kublickiene
    Affiliations
    Section for Renal Medicine, Department of Clinical Intervention, Science, and Technology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
    Search for articles by this author
  • Maria Trinidad Herrero
    Affiliations
    Department of Human Anatomy and Psychobiology, Universidad de Murcia, Murcia, Spain
    Search for articles by this author
  • Khaled El Emam
    Affiliations
    Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada

    Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

    Replica Analytics, Ottawa, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    § These authors contributed equally to this work as last authors.
    Alexandra Kautzky-Willer
    Footnotes
    § These authors contributed equally to this work as last authors.
    Affiliations
    Gender Medicine Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna, Austria
    Search for articles by this author
  • Author Footnotes
    § These authors contributed equally to this work as last authors.
    Louise Pilote
    Correspondence
    Corresponding author: Dr Louise Pilote, Center for Outcomes Research and Evaluation, Division of Clinical Epidemiology and General Internal Medicine, McGill University Health Centre Research Institute, 5252 Boulevard de Maisonneuve, Montréal, Québec H3A 1A1, Canada. Tel.: +1-514-934-1934, ext 44722; fax: +1-514-843-1676.
    Footnotes
    § These authors contributed equally to this work as last authors.
    Affiliations
    Centre for Outcomes Research and Evaluation, McGill University Health Centre Research Institute, Montréal, Québec, Canada

    Divisions of Clinical Epidemiology and General Internal Medicine, McGill University Health Centre Research Institute, Montréal, Québec, Canada
    Search for articles by this author
  • for the GOING-FWD Investigators
  • Author Footnotes
    ‡ These authors contributed equally to this work as first authors.
    § These authors contributed equally to this work as last authors.
Published:March 27, 2021DOI:https://doi.org/10.1016/j.cjca.2021.03.019

      Abstract

      Background

      Evidence differentiating the effect of biological sex from psychosociocultural factors (gender) in different societies and its relation to cardiovascular diseases is scarce. We explored the association between sex, gender, and cardiovascular health (CVH) among Canadian (CAN) and Austrian (AT) populations.

      Methods

      The Canadian Community Health Survey (CCHS) (n = 63,522; 55% female) and Austrian Health Interview Survey (AT-HIS) (n = 15,771; 56% female) were analyzed in a cross-sectional survey design. The CANHEART/ATHEART index, a measure of ideal CVH composed of 6 cardiometabolic risk factors (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension; range 0-6; higher scores reflecting better CVH) was calculated for both databases. A composite measure of psychosociocultural gender was computed for each country (range 0-1, higher score identifying characteristics traditionally ascribed to women).

      Results

      Median CANHEART 4 (interquartile range 3-5) and CAN gender scores 0.55 (0.49-0.60) were similar to median ATHEART 4 (3-5) and AT gender scores 0.55 (0.46-0.64). Although higher gender scores (CCHS: β = −1.33, 95% confidence interval [CI] −1.44 to −1.22; AT-HIS: β = −1.08, 95% CI −1.26 to −0.89)) were associated with worse CVH, female sex (CCHS: β = 0.35, 95% CI (0.33-0.37); AT-HIS: β = 0.60, 95% CI (0.55-0.64)) was associated with better CVH in both populations. In addition, higher gender scores were associated with increased prevalence of heart disease compared with female sex. The magnitude of this risk was higher in Austrians.

      Conclusions

      These results demonstrate that individuals with characteristics typically ascribed to women reported poorer cardiovascular health and higher risk of heart disease, independently from biological sex and baseline CV risk factors, in both countries. Female sex exhibited better CV health and a lower prevalence of heart disease than male in both populations. However, gender factors and magnitude of gender impact varied by country.

      Résumé

      Contexte

      L’évidence différenciant l'effet du sexe biologique des facteurs psychosocioculturels (genre) dans différentes sociétés et sa relation avec les maladies cardiovasculaires reste rare. Nous avons exploré l'association entre le sexe, le genre et la santé cardiovasculaire (SCV) parmi les populations canadienne (CAN) et autrichienne (AT).

      Méthodes

      L'Enquête sur la Santé dans les Collectivités Canadiennes (ESCC) (n = 63 522; 55 % de femmes) et l'Enquête autrichienne par entretien sur la santé (AT-HIS) (n = 15 771; 56 % de femmes) ont été analysées dans le cadre d'une enquête transversale. Les indices CANHEART/ATHEART représentent une mesure de la SCV idéale composée de 6 facteurs de risque cardiométabolique (tabagisme, activité physique, consommation de fruits et légumes, surpoids/obésité, diabète et hypertension; intervalle de 0 à 6; des scores plus élevés reflétant une meilleure SCV) a été calculé pour les deux bases de données. Une mesure composite du genre psycho-socio-culturel a été calculée pour chaque pays (intervalle 0-1, un score plus élevé identifiant les caractéristiques traditionnellement attribuées aux femmes).

      Résultats

      Les scores médians associés au CANHEART 4 (intervalle interquartile 3-5) et au genre dans la population CAN 0,55 (0,49-0,60) étaient similaires aux scores médians associés à l'ATHEART 4 (3-5) et au genre dans la population AT 0,55 (0,46-0,64). Bien que des scores liés au genre plus élevés (ESCC: β = 1,33, intervalle de confiance [IC] à 95 % -1,44 à -1,22; AT-HIS: β = 1,08, IC à 95 % -1,26 à -0,89) aient été associés à une moins bonne SCV, le sexe féminin (ESCC: β = 0,35, IC à 95 % (0,33-0,37); AT-HIS: β = 0,60, IC à 95% [0,55-0,64]) a été associé à une meilleure SCV dans les deux populations. En outre, des scores plus élevés liés au genre étaient associés à une prévalence accrue des maladies cardiaques par rapport au sexe féminin. L'ampleur de ce risque était plus élevée chez les Autrichiens.

      Conclusions

      Ces résultats démontrent que les personnes présentant des caractéristiques typiquement attribuées aux femmes présentaient une moins bonne santé cardiovasculaire et un risque plus élevé de maladie cardiaque, indépendamment du sexe biologique et des facteurs de risque CV de base, dans les deux pays. Les femmes présentent une meilleure santé cardiovasculaire et une plus faible prévalence de maladies cardiaques que les hommes dans les deux populations. Cependant, les facteurs liés au sexe et l'ampleur de l'impact du sexe variaient selon le pays.
      Cardiovascular diseases (CVD) continue to represent the leading cause of mortality and morbidity among women and men worldwide.
      • Virani Salim S
      • Alonso A
      • Benjamin Emelia J
      • et al.
      Heart disease and stroke statistics—2020 update: a report from the American Heart Association.
      While the importance of sex differences (biological characteristics in females and males) in the prevention, diagnosis, and treatment of CVD are being increasingly recognised, the impact of sociocultural gender has yet to be determined.
      • Norris CM
      • Yip CYY
      • Nerenberg KA
      • et al.
      State of the science in women's cardiovascular disease: a Canadian perspective on the influence of sex and gender.
      • Regitz-Zagrosek V
      • Oertelt-Prigione S
      • Prescott E
      • et al.
      Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes.
      • Bartz D
      • Chitnis T
      • Kaiser UB
      • et al.
      Clinical advances in sex-and gender-informed medicine to improve the health of all: a review.
      Sociocultural gender refers to psychosociocultural roles, behaviours and identities. It influences people's perception of themselves and their interaction with each other and contributes to the distribution of power in different societies.
      • Bartz D
      • Chitnis T
      • Kaiser UB
      • et al.
      Clinical advances in sex-and gender-informed medicine to improve the health of all: a review.
      • Pelletier R
      • Khan NA
      • Cox J
      • et al.
      Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
      • Pelletier R
      • Ditto B
      • Pilote L
      A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
      • Lippa R
      • Connelly S
      Gender diagnosticity: a new bayesian approach to gender-related individual differences.
      • Johnson JL
      • Greaves L
      • Repta R
      Better science with sex and gender: a primer for health research.
      • Carothers BJ
      • Reis HT
      Men and women are from Earth: examining the latent structure of gender.
      • Unger RK
      Toward a redefinition of sex and gender.

      Canadian Institutes of Health Research. Online training modules: integrating sex & gender in health research. Available at: https://cihr-irsc.gc.ca/e/49347.html. Accessed March 24, 2021.

      • Phillips SP
      Defining and measuring gender: a social determinant of health whose time has come.
      World Health Organisation. A conceptual framework for action on the social determinants on health
      Biological differences between the sexes such as anatomic and physiologic variations in coronary arteries and the autonomic nervous system alter the development and progression of CVD.
      • Huxley VH
      Sex and the cardiovascular system: the intriguing tale of how women and men regulate cardiovascular function differently.
      For example, smoking has been shown to have more adverse effect on females than on males, possibly owing to a difference in nicotine metabolism. Indeed, females who smoke have a 25% higher risk of ischemic heart disease than males.
      • Huxley RR
      • Woodward M
      Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies.
      ,
      • Peters SA
      • Huxley RR
      • Woodward M
      Smoking as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes.
      Sociocultural gender also contributes to sex differences observed in cardiovascular health, including lifestyle behaviours, such as exercising, and accessibility to cardiac rehabilitation.
      • Spence JD
      • Pilote L
      Importance of sex and gender in atherosclerosis and cardiovascular disease.
      • Izadnegahdar M
      • Singer J
      • Lee MK
      • et al.
      Do younger women fare worse? Sex differences in acute myocardial infarction hospitalization and early mortality rates over ten years.
      • Sozzi FB
      • Danzi GB
      • Foco L
      • et al.
      Myocardial infarction in the young: a sex-based comparison.
      • Kawase K
      • Kwong A
      • Yorozuya K
      • et al.
      The attitude and perceptions of work-life balance: a comparison among women surgeons in Japan, USA, and Hong Kong China.
      • Winham SJ
      • de Andrade M
      • Miller VM
      Genetics of cardiovascular disease: importance of sex and ethnicity.
      Females are more likely to follow a healthy diet compared with males,
      • Forouzanfar MH
      • Afshin A
      • Alexander LT
      • et al.
      Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.
      but they are less physically active.
      • Lee SK
      • Khambhati J
      • Varghese T
      • et al.
      Comprehensive primary prevention of cardiovascular disease in women.
      ,
      • Shiroma EJ
      • Lee IM
      Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity.
      The rise in incidence of premature acute coronary syndrome, especially in females in recent decades, can be attributed to changes in family dynamics and social and institutional roles. Nevertheless, few studies differentiate biological sex from sociocultural gender with respect to cardiovascular risk.
      • Pelletier R
      • Khan NA
      • Cox J
      • et al.
      Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
      ,
      • Pelletier R
      • Ditto B
      • Pilote L
      A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
      ,
      • Lacasse A
      • Pagé MG
      • Choinière M
      • et al.
      Conducting gender-based analysis of existing databases when self-reported gender data are unavailable: the GENDER Index in a working population.
      • Norris CM
      • Murray JW
      • Triplett LS
      • Hegadoren KM
      Gender roles in persistent sex differences in health-related quality-of-life outcomes of patients with coronary artery disease.
      • Chida Y
      • Steptoe A
      Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence.
      • Peterson PN
      JAHA Spotlight on Psychosocial Factors and Cardiovascular Disease.
      • White-Williams C
      • Rossi LP
      • Bittner VA
      • et al.
      Addressing social determinants of health in the care of patients with heart failure: a scientific statement from the American Heart Association.
      As such, whether the effects of sex and gender differ based on country of residence remains to be determined.
      In this study, we therefore sought to untangle the impact of sociocultural gender from biological sex in their association with cardiovascular health of Canadian and Austrian populations.

      Methods

      Study design

      This cross-sectional survey study is part of the Gender Outcomes International Group: to Further Well-Being Development (GOING-FWD) which is a 5-country multidisciplinary consortium that was co-funded by the Canadian Institutes of Health Research, and GENDER-NET Plus (http://gender-net-plus.eu/joint-call/funded-projects/going-fwd/). The overarching aims of the consortium are to integrate sex and gender aspects in health research and to evaluate their impact on outcomes in noncommunicable diseases including CVD.
      Data from 2 independent community health surveys administered in 2014 in Canada and Austria were analysed (Supplemental Appendices S1 and S2). The Canadian Community Health Survey (CCHS 2014; n = 63,522) is a cross-sectional survey that collected population-level information on social determinants of health, health status, and health care resource utilisation in the Canadian population. This survey began in 2001, and data have been collected annually since 2007. The Austria Health Interview Survey (AT-HIS 2014; n = 15,771) was conducted as part of European Health Interview Survey series to gather comparable statistical health data (ie, population health status, health determinants, health care use and access, and sociodemographic information) from various European countries.

      The GOING-FWD methodology to merge data from the Canadian and Austrian surveys

      The GOING-FWD systematic multistep approach for retrospective studies was used to identify gender-related variables and outcomes in both databases as well as to analyse the data. Briefly, gender-related factors were identified with the use of the Women Health Research Network's gender framework (ie, gender identity, gender roles, gender relationships, and institutionalised gender),
      • Johnson JL
      • Greaves L
      • Repta R
      Better science with sex and gender: a primer for health research.
      and comparable outcomes were subsequently selected. A retrospective data harmonisation was performed according to the Maelström Research guidelines,
      • Fortier I
      • Raina P
      • van den Heuvel ER
      • et al.
      Maelstrom Research guidelines for rigorous retrospective data harmonization.
      and finally, based on the data structure of the 2 survey databases, final analyses were performed locally and results were compared.

      Gender score construction

      After the identification of gender-related variables in both databases and their harmonisation, the Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome (GENESIS-PRAXY) methodology was used to generate a composite measure of gender.
      • Pelletier R
      • Khan NA
      • Cox J
      • et al.
      Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
      ,
      • Pelletier R
      • Ditto B
      • Pilote L
      A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.

      Outcome measurements

      The primary end points of this study were the cardiovascular health of the population using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART)/ATHEART indices and prevalence of overt heart disease. To measure the cardiovascular health of the population, we used the previously published CANHEART health index.
      • Maclagan LC
      • Park J
      • Sanmartin C
      • et al.
      The CANHEART health index: a tool for monitoring the cardiovascular health of the Canadian population.
      This index is a measure of cardiovascular health, composed from the sum of the ideal metrics for 6 cardiometabolic health factors and behaviours (ie, smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes and hypertension), which range from 0 (worst) to 6 (best or ideal cardiovascular health). With our data, we determined the CANHEART index and used a similar method to synthesise an index to measure the cardiovascular health of the Austrian population (ATHEART) (Table 1).
      Table 1Definitions of ideal cardiovascular health in Canadian and Austrian populations (CANHEART and ATHEART indices)
      CANHEART: Canadian populationATHEART: Austrian population
      SmokingNonsmoker or former daily or occasional smoker who has quit more than 12 monthsNonsmoker or former daily or occasional smoker who has quit more than 12 months
      Overweight/obesityBMI < 25 kg/m2BMI < 25 kg/m2
      Leisure physical activityEnergy expenditure ≥ 1.5 kcal/kg/d equivalent to ≥ 30 min walking per dayNumber of days doing leisure physical activity for ≥ 10 min, > 3 days per week
      Fruit and vegetable consumption≥ 5 times per day≥ 1 time per day
      DiabetesNo self-reported diabetes diagnosed by health professionalNo self-reported diabetes diagnosed by health professional
      HypertensionNo self-reported HTN diagnosed by health professionalNo self-reported HTN diagnosed by health professional
      BMI, body mass index; CANHEART, Cardiovascular Health in Ambulatory Care Research Team; HTN, hypertension.
      Heart disease in the Canadian health survey was a self-reported measure of chronic heart disease diagnosed by a health care professional, whereas in the Austrian population health survey it was defined as having history of coronary heart disease or angina pectoris in the past 12 months.

      Statistical analysis

      Descriptive statistics were reported as mean ± SD for continuous variables and n (%) for categoric variables. To ensure statistical power for all analysis, a case analysis (pairwise deletion) approach was used for dealing with missing data.
      The detailed methodology of calculating the gender score has been reported in our previous publication.
      • Pelletier R
      • Khan NA
      • Cox J
      • et al.
      Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
      ,
      • Pelletier R
      • Ditto B
      • Pilote L
      A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
      In this novel method, principal component analysis (PCA), was used to choose from a large number of relevant psychosocial variables extracted from the CCHS and AT-HIS databases. The PCA method helps reduce dimensionality and facilitate data compression to select the unique set of covariates to use in the predictive model. Details of the method are reported in Supplemental Tables S1 and S2. Ultimately, components that accounted for a cumulative variance of more than 60% of the data were selected. Factor loadings (correlation between original variables and factors) with values of 0.4 or more were used to select the best set of variables. The optimised set of gender-related variables from the selected components in the PCA (Supplemental Tables S1 and S2) were then used to create a multivariable logistic model with biological sex as the dependent variable and gender-derived components as covariate. A gender index was then calculated through the construction of a propensity score, which was derived from coefficient estimates in the final logistic regression model. The propensity score for each person was defined as the conditional probability of being a female vs a male based on gender-related variables. This score ranges from 0 to 1, with higher scores relating to characteristics traditionally ascribed to women.
      Multivariable linear regression was applied to assess the association between gender score, biological sex, and cardiovascular health measured by CANHEART/ATHEART indices (including smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension) in both populations. The models were adjusted for age. The same approach was used for testing the association with overt heart disease. Multivariable logistic regression was used to assess the relationships between sex, gender, and overt heart disease. These models were adjusted for age and CANHEART/ATHEART indices. A 2-way sex–gender score interaction was assessed in all models.
      Data analysis was performed with the use of R software (version 1.2.5042). P values of ≤ 0.05 were considered to be statistically significant.

      Results

      The CCHS 2014 included 63,522 respondents 55.3% were female (n = 35,114; 42.3% < 50 years old) and the AT-HIS 2014 included 15,771 respondents, 55.7% of whom were female (n = 8786; 53.86% < 50 years old). About 45% of the Canadians and 53% of the Austrians had normal body mass index (BMI < 25 kg/m2). Rate of diabetes was double in Canadians, whereas rate of smoking was double in Austrian population (Supplemental Tables S3-S6).
      Among all gender-related variables, household size, perceived life stress, education level, sense of belonging to community, marital status, and household income were selected from the first 6 components of the CCHS based on their factor loadings. In the AT-HIS, frequency of negative emotions, education level, marital status, and household income were gender-related variables selected from retained components. The first 6 components accounted for 84% of total variance in the CCHS, and a combination of the first 3 components in the AT-HIS constituted 61% of total variance in the dataset. A gender score was calculated for all participants using propensity scores with biological sex as dependent variable (Table 2). While greater household size, perceived life stress, higher education, sense of belonging to community, being divorced or widowed, and lower household income were associated with female sex in the Canadian population, lower education, greater frequency of having negative emotion, being divorced or widowed, and having a lower household income were associated with being female in the Austrian population. Higher scores represent characteristics traditionally ascribed to women in these countries. The mean gender scores in Canadian and Austrian populations were 0.55 ± 0.09 (median 0.53, interquartile range [IQR] 0.49-0.60), and 0.55 ± 0.12 (median 0.54, IQR 0.46-0.64), respectively.
      Table 2Multivariate logistic model for assessing association of gender variables with biological sex as dependent variable
      CCHSAT-HIS
      Gender variableOR (95% CI)Gender variableOR (95% CI)
      Household sizeFrequency of negative emotions
      (Reference: 1 person)(Reference: 1 = never)
      2 persons1.22 (1.15-1.30)2 = not often1.62 (1.49-1.75)
      3 persons1.25 (1.17-1.34)3 = intermittently2.57 (2.33-2.83)
      4 persons1.37 (1.28-1.47)4 = often2.71 (2.33-3.15)
      ≥ 5 persons1.36 (1.25-1.47)5 = always2.03 (1.41-2.93)
      Perceived life stress: stress during the dayEducation
      (Reference: 1 = not at all)(Reference: < secondary)
      2 = not very1.37 (1.29-1.44)Secondary0.57 (0.51-0.62)
      3 = a bit1.57 (1.49-1.66)Postsecondary0.65 (0.58-0.69)
      4 = quite a bit1.76 (1.66-1.88)> Postsecondary0.51 (0.45-0.59)
      5 = extremely1.81 (1.62-2.03)Marital status
      Education(Reference: single)
      (Reference: < secondary)Divorced/widowed2.14 (1.92-2.38)
      Secondary1.23 (1.17-1.30)Common-in-law/married1.18 (1.1-1.27)
      Postsecondary1.12 (1.03-1.22)Household income
      > Postsecondary1.20 (1.15-1.26)(Reference: high)
      Sense of belonging to communityMedium1.20 (1.1-1.31)
      (Reference:1 = very weak)Low1.24 (1.15-1.34)
      2 = somewhat weak1.03(0.96-1.11)
      3 = somewhat strong1.16 (1.08-1.24)
      4 = very strong1.19 (1.10-1.28)
      Marital status
      (Reference: single)
      Divorced/widowed2.62 (2.47-2.77)
      Common-in-law/married1.16 (1.11-1.22)
      Household income
      (Reference: high)
      Medium1.37 (1.32-1.43)
      Low1.81 (1.69-1.94)
      Gender index was calculated through the construction of a propensity score, which was derived from coefficient estimates in the final logistic regression model with biological sex as dependent variable and gender-related variables as covariates. The propensity score for each person was defined as the conditional probability of being a female vs a male based on gender-related variables. This score ranges from 0 to 1, with higher scores relating to characteristics traditionally ascribed to women.
      AT-HIS, Austria Health Interview Survey; CCHS, Canadian Community Health Survey; CI, confidence interval; OR, odds ratio.
      Figure 1 represents the distribution of gender score in males and females. The blue color demonstrates gender score in females, the red color males, and the purple color shows the overlap of the score in males and females. Higher gender score shows more feminine characteristics. The distribution of the gender score in men and women did not entirely overlap with biological sex in both populations, which shows their partially independent effect (Fig. 1, I).
      Figure 1
      Figure 1Density plots: y-axis: probability density of gender; x-axis: gender score. Higher gender score demonstrates more feminine characteristics. (I) Gender score distribution in male and females in (A) Canadian and (B) Austrian populations. Red: gender score in males; blue: gender score in females; purple: overlapping of gender score in both groups. The distribution of the gender score in men and women did not entirely overlap with biological sex in both populations, which shows their partially independent effect. (II) Gender score distribution in CANHEART/ATHHEART index < 3 and ≥ 3 in (A) Canadian and (B) Austrian populations. Dark green: gender score in CANHEART/ATHHEART index < 3 (ie, worse cardiovascular health); yellow: gender score in CANHEART/ATHHEART score ≥ 3 (ie, better cardiovascular health); light green: overlapping of gender score in both groups. Higher gender score, ie, more feminine characteristics, demonstrates worst cardiovascular health in both populations. AT-HIS, Austria Health Interview Survey; CANHEART, Cardiovascular Health in Ambulatory Care Research Team; CCHS, Canadian Community Health Survey.
      The mean cardiovascular health scores were 3.88 ± 1.3 (median 4, IQR 3-5) in the Canadian population, and 3.78 ± 1.23 (median 4, IQR 3-5) in the Austrian population. The cardiovascular health scores were significantly higher in females in both populations (Austria: male 3.4 vs female 4.02; Canada: male 3.74 vs female 3.99; P < 0.001).
      While a higher gender score (β = −1.33; 95% confidence interval [CI] −1.44 to −1.22; P < 0.001) was associated with worse cardiovascular health, female sex (β = 0.35; 95% CI 0.32 to 0.37; P < 0.001) was associated with better cardiovascular health in the Canadian population when adjusted for age (Table 3; Fig. 1, II). A similar trend was observed in the Austrian cohort, where higher gender score (β = −1.08; 95% CI −1.26 to −0.89; P < 0.001) was associated with worse cardiovascular health, whereas female sex (β = 0.60; 95% CI 0.55 to 0.64: P < 0.001) was associated with better cardiovascular health when adjusting for age (Table 3; Fig. 1, II).
      Table 3Association of cardiovascular health with biological sex and gender in Canadian and Austrians populations
      Cardiovascular health in Canadians (CANHEART score)Cardiovascular health in Austrians (ATHEART score)
      Unstandardised coefficient (β)95% CIP valueUnstandardised coefficient (β)95% CIP value
      Gender score−1.33−1.44 to −1.22< 0.001−1.08−1.26 to −0.89< 0.001
      Sex (female)0.350.33 to 0.37< 0.0010.60.55 to 0.64< 0.001
      Age group, y
       < 20 (reference)
       20-29−0.49−0.53 to −0.44< 0.001−0.5−0.62 to −0.37< 0.001
       30-39−0.65−0.70 to −0.61< 0.001−0.83−0.95 to −0.71< 0.001
       40-49−0.88−0.92 to −0.83< 0.001−0.86−0.97 to −0.74< 0.001
       50-59−1.14−1.18 to −1.10< 0.001−1.1−1.22 to−0.99< 0.001
       60-69−1.23−1.27 to −1.19< 0.001−1.2−1.34 to −1.10< 0.001
       ≥ 70−1.24−1.29 to −1.20< 0.001−1.19−1.31 to −1.07< 0.001
      CANHEART, Cardiovascular Health in Ambulatory Care Research Team; CI, confidence interval.
      The prevalence of heart disease was 8.7% (n = 2,453) and 2.14% (n = 150) in males and 6.3% (n = 2,212) and 1.59% (n = 140) in females in the Canadian and Austrian populations, respectively. Higher gender scores were associated with a higher risk of heart disease when compared to female sex in both populations (Table 4). This association was stronger in the Austrian population (Austria: odds ratio 22.14, 95% CI 7.28-68.17; Canada: odds ratio 3.87, 95% CI 2.71-5.52).
      Table 4Associations between sex, gender, and heart disease in Canadian and Austrian populations
      CanadiansAustrians
      Predictor of heart diseaseOR95% CIP valueOR95% CIP value
      CANHEART score (Canadians)/ATHEART score (Austrians)0.730.71 to 0.75< 0.0010.770.69 to 0.86< 0.001
      Gender score3.872.71 to 5.52< 0.00122.147.28 to 68.17< 0.001
      Sex (female)0.580.54 to 0.62< 0.0010.610.46 to 0.820.002
      Age group, y
       < 20 (reference)
       20-290.950.62 to 1.480.960.940.2 to 4.420.70
       30-390.700.45 to 1.10.120.320.07 to 1.670.08
       40-491.821.26 to 2.680.0010.530.16 to 2.380.21
       50-594.623.34 to 6.60< 0.0012.140.77 to 8.910.34
       60-698.786.38 to 12.47< 0.0013.951.44 to 16.360.04
       ≥ 7019.4514.16 to 27.59< 0.0017.282.32 to 26.000.001
      CANHEART, Cardiovascular Health in Ambulatory Care Research Team; CI, confidence interval; OR, odds ratio.
      There was no significant interaction between sex and gender score in predicting cardiovascular health (CANHEART/ATHEART indices) of the Austrian and Canadian populations (P = 0.5 and P = 0.09, respectively). However, in the Canadian population there was a statistically significant interaction between sex and gender for predicting the occurrence of overt heart disease (P = 0.04).

      Discussion

      The results of this study conducted in population-based samples of Canadians and Austrians demonstrate that sociocultural gender, referring to personality traits and social characteristics typically ascribed to women, is associated with poorer cardiovascular health and a higher prevalence of heart disease regardless of sex. In contrast, females exhibited better cardiovascular health and a lower prevalence of heart disease than males in both populations independently from baseline cardiovascular risk factors.
      In this study, we created a composite gender index in Canadian and Austrian populations. Previous literature
      • Pelletier R
      • Khan NA
      • Cox J
      • et al.
      Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
      • Pelletier R
      • Ditto B
      • Pilote L
      A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
      • Lippa R
      • Connelly S
      Gender diagnosticity: a new bayesian approach to gender-related individual differences.
      ,
      • Koch CG
      • Mangano CM
      • Schwann N
      • Vaccarino V
      Is it gender, methodology, or something else?.
      • Whittaker KS
      • Krantz DS
      • Rutledge T
      • et al.
      Combining psychosocial data to improve prediction of cardiovascular disease risk factors and events: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.
      • Glynn RJ
      • Schneeweiss S
      • Stürmer T
      Indications for propensity scores and review of their use in pharmacoepidemiology.
      has highlighted the need for building a composite measure to assess the impact of psychosocial variables owing to the inherent statistical difficulties associated with addressing the large amount of variables. The present study shows that a gender score can be created with different gender-related factors depending on the study population. Although there are a number of overlapping variables such as education, marital status, and household income, factors such as perceived life stress and household size were specific to the Canadian population, and frequency of negative emotions was reported only for the Austrian database. Importantly, despite the different components that contribute to the construction of the gender score, the results of the PCA revealed a very similar distribution of the gender score in both countries.
      In both populations, females experienced better cardiovascular health, and had a lower prevalence of CVD. This finding is similar to the result of the study by Maclagan et al.
      • Maclagan LC
      • Park J
      • Sanmartin C
      • et al.
      The CANHEART health index: a tool for monitoring the cardiovascular health of the Canadian population.
      that also reported better cardiovascular health in females than males and further reported that males had poorer healthy behaviours compared with females except for physical activity. Some studies have suggested that caregiver status and family commitments are barriers to physical activity in females, which may explain the observed discrepancy in this variable.
      • Pilote L
      • Dasgupta K
      • Guru V
      • et al.
      A comprehensive view of sex-specific issues related to cardiovascular disease.
      ,
      • King AC
      • Castro C
      • Wilcox S
      • et al.
      Personal and environmental factors associated with physical inactivity among different racial-ethnic groups of U.S. middle-aged and older-aged women.
      In contrast, people with characteristics ascribed to women (higher gender scores) experienced worse cardiovascular health and higher risk of heart disease in both populations. The magnitude of this risk was greater in the Austrian population compared with Canada.
      The Gender Inequality Index (GII), a measure of institutionalised gender, was generated by the United Nations and measures gender inequality in 3 areas: reproductive health, empowerment, and economic status.

      United Nations Development Programme. Gender Inequality Index (GII). Available at:http://hdr.undp.org/en/content/gender-inequality-index-gii. Accessed March 24, 2021.

      The GII is standardised such that 0 indicates perfect gender equality and 1 indicates perfect inequality (in favour of males). Canada (0.083) and Austria (0.073) have similar low GIIs. Therefore the difference in the impact of gender could be attributed to differences in sociocultural characteristics, health care system, or institutionalised structures (education, income) of both populations (Supplemental Table S6). For example, cultural differences in social support or mother-role expectations could lead to the slight difference between Canada and Austria.
      • Tandon A
      • Murray CJ
      • Lauer JA
      • Evans DB
      Measuring overall health system performance for 191 countries. Global Programme on Evidence for Health Policy discussion paper no. 30.
      Our findings are consistent with the findings reported by Pelletier et al,
      • Pelletier R
      • Khan NA
      • Cox J
      • et al.
      Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
      ,
      • Pelletier R
      • Ditto B
      • Pilote L
      A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
      where a higher risk of adverse cardiovascular outcomes after a premature acute coronary syndrome was evident in patients with personality traits and social roles traditionally ascribed to women, independently from biological sex. Cardiovascular health is determined by various factors, most of which are interacting with living conditions and environment of the individual. Our study explored the impact of classical risk factors such as hypertension, dyslipidemia, diabetes, smoking, and overweight/obesity, in addition to psychosocial factors such as depression, anxiety, chronic life stress, lack of social support, and socioeconomic factors such as low educational level and low income, on CVD.
      • Greenland P
      • Knoll MD
      • Stamler J
      • et al.
      Major risk factors as antecedents of fatal and nonfatal coronary heart disease events.
      • Khot UN
      • Khot MB
      • Bajzer CT
      • et al.
      Prevalence of conventional risk factors in patients with coronary heart disease.
      • Rozanski A
      • Blumenthal JA
      • Kaplan J
      Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.
      • Dorner T
      • Kiefer I
      • Kunze M
      • Rieder A
      [Gender aspects of socioeconomic and psychosocial risk factors of cardiovascular diseases].
      • Kaplan GA
      • Keil JE
      Socioeconomic factors and cardiovascular disease: a review of the literature.
      • Diez Roux AV
      • Merkin SS
      • Arnett D
      • et al.
      Neighborhood of residence and incidence of coronary heart disease.
      Currently, one can find studies investigating the effect of some components of our gender index on cardiovascular health. The relationship between a multigenerational household and the risk of suffering a coronary artery incident has also been reported in a study by Ikeda et al.
      • Ikeda A
      • Iso H
      • Kawachi I
      • et al.
      Living arrangement and coronary heart disease: the JPHC study.
      In that study, living with a spouse and children/parents compared with a spouse alone increased the risk of developing coronary artery disease by 2-fold. Being divorced or separated was an additional factor that was considered in the gender score. While studies have demonstrated a better prognosis after myocardial infarction in married males, middle-aged married females demonstrated a higher fatality risk than unmarried females.
      • Kilpi F
      • Konttinen H
      • Silventoinen K
      • Martikainen P
      Living arrangements as determinants of myocardial infarction incidence and survival: a prospective register study of over 300,000 Finnish men and women.
      Evidence for the role of psychosocial distress and social/environmental adversity on cardiovascular outcomes have been discussed in a variety of disciplines.
      • Chida Y
      • Steptoe A
      Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence.
      ,
      • Greaney JL
      • Surachman A
      • Saunders EF
      • Alexander LM
      • Almeida DM
      Greater daily psychosocial stress exposure is associated with increased norepinephrine-induced vasoconstriction in young adults.
      The present study reveals the importance of psychosocial and gender-related factors in cardiovascular health. Further prospective studies are warranted to assess the multidimensionality of such factors and their impact on CVD outcome. Such investigation would facilitate the development of gender-based promotion strategies with the goal of endorsing healthy behaviours to further improve the cardiovascular health within the population.
      • Bartz D
      • Chitnis T
      • Kaiser UB
      • et al.
      Clinical advances in sex-and gender-informed medicine to improve the health of all: a review.
      ,
      • Chida Y
      • Steptoe A
      Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence.
      ,
      • White-Williams C
      • Rossi LP
      • Bittner VA
      • et al.
      Addressing social determinants of health in the care of patients with heart failure: a scientific statement from the American Heart Association.
      ,
      • Maclagan LC
      • Park J
      • Sanmartin C
      • et al.
      The CANHEART health index: a tool for monitoring the cardiovascular health of the Canadian population.
      There are number of limitations with this study. The first limitation is the difference in definition of heart disease in the 2 countries. The CCHS reported heart disease as chronic heart disease diagnosed by a health care professional, whereas the AT-HIS definition was history of coronary heart disease or angina pectoris within the past 12 months. That could be the reason why we see differences in the magnitude of higher cardiovascular risk in people with characteristics ascribed to women between the 2 countries. In addition, owing to the harmonisation of both databases, some granularity of information was lost. For example, we had to use household income instead of personal income, because the AT-HIS reported only household income.

      Conclusion

      The results of the present study demonstrate that individuals with characteristics typically ascribed to women have poorer cardiovascular health and higher risk of heart disease, independently from biological sex and difference in baseline cardiovascular risk factors in both Canadian and Austrian populations. This is while female biological sex exhibited better cardiovascular health and a lower prevalence of heart disease than males in both populations. The study represents a practical approach to assess the complexity of the role of sociocultural gender (ie, role, identity, relation, institutionalised gender) in a country-specific manner. Current investigations revealed that the magnitude of gender impact varied by country, being greater in the Austrian than the Canadian population. This study highlights the need for the consideration and implementation of country specific gender-related factors to improve cardiovascular health.

      Funding Sources

      The GOING-FWD Consortium is funded by the GENDER-NET Plus European Research Area Network (ERA-NET) Initiative (project reference number GNP-78 ), the Canadian Institutes of Health Research ( GNP-161904 ), “La Caixa” Foundation (ID 100010434 with code LCF/PR/DE18/52010001), the Swedish Research Council ( 2018-00932 ), and THE Austrian Science Fund ( FWF I 4209 ). V.R. was funded by the Scientific Independence of Young Researcher Program of the Italian Ministry of University, Education, and Research ( RBSI14HNVT ).

      Disclosures

      The authors have no conflicts of interest to disclose.

      Appendix. Supplementary materials

      References

        • Virani Salim S
        • Alonso A
        • Benjamin Emelia J
        • et al.
        Heart disease and stroke statistics—2020 update: a report from the American Heart Association.
        Circulation. 2020; 141: e139-e596
        • Norris CM
        • Yip CYY
        • Nerenberg KA
        • et al.
        State of the science in women's cardiovascular disease: a Canadian perspective on the influence of sex and gender.
        J Am Heart Assoc. 2020; 9e015634
        • Regitz-Zagrosek V
        • Oertelt-Prigione S
        • Prescott E
        • et al.
        Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes.
        Eur Heart J. 2016; 37: 24-34
        • Bartz D
        • Chitnis T
        • Kaiser UB
        • et al.
        Clinical advances in sex-and gender-informed medicine to improve the health of all: a review.
        JAMA Intern Med. 2020; 180: 574-583
        • Pelletier R
        • Khan NA
        • Cox J
        • et al.
        Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
        J Am Coll Cardiol. 2016; 67: 127-135
        • Pelletier R
        • Ditto B
        • Pilote L
        A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
        Psychosom Med. 2015; 77: 517-526
        • Lippa R
        • Connelly S
        Gender diagnosticity: a new bayesian approach to gender-related individual differences.
        J Pers Soc Psychol. 1990; 59: 1051
        • Johnson JL
        • Greaves L
        • Repta R
        Better science with sex and gender: a primer for health research.
        Women's Health Research Network, Vancouver2007
        • Carothers BJ
        • Reis HT
        Men and women are from Earth: examining the latent structure of gender.
        J Pers Soc Psychol. 2013; 104: 385
        • Unger RK
        Toward a redefinition of sex and gender.
        American Psychologist. 1979; 34: 1085
      1. Canadian Institutes of Health Research. Online training modules: integrating sex & gender in health research. Available at: https://cihr-irsc.gc.ca/e/49347.html. Accessed March 24, 2021.

        • Phillips SP
        Defining and measuring gender: a social determinant of health whose time has come.
        Int J Equity Health. 2005; 4: 11
        • World Health Organisation. A conceptual framework for action on the social determinants on health
        (July 13, 2010. Available at:) (Accessed March 24, 2021)
        • Huxley VH
        Sex and the cardiovascular system: the intriguing tale of how women and men regulate cardiovascular function differently.
        Adv Physiol Educ. 2007; 31: 17-22
        • Huxley RR
        • Woodward M
        Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies.
        Lancet. 2011; 378: 1297-1305
        • Peters SA
        • Huxley RR
        • Woodward M
        Smoking as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes.
        Stroke. 2013; 44: 2821-2828
        • Spence JD
        • Pilote L
        Importance of sex and gender in atherosclerosis and cardiovascular disease.
        Atherosclerosis. 2015; 241: 208-210
        • Izadnegahdar M
        • Singer J
        • Lee MK
        • et al.
        Do younger women fare worse? Sex differences in acute myocardial infarction hospitalization and early mortality rates over ten years.
        J Womens Health (Larchmt). 2014; 23: 10-17
        • Sozzi FB
        • Danzi GB
        • Foco L
        • et al.
        Myocardial infarction in the young: a sex-based comparison.
        Coron Artery Dis. 2007; 18: 429-431
        • Kawase K
        • Kwong A
        • Yorozuya K
        • et al.
        The attitude and perceptions of work-life balance: a comparison among women surgeons in Japan, USA, and Hong Kong China.
        World J Surg. 2013; 37: 2-11
        • Winham SJ
        • de Andrade M
        • Miller VM
        Genetics of cardiovascular disease: importance of sex and ethnicity.
        Atherosclerosis. 2015; 241: 219-228
        • Forouzanfar MH
        • Afshin A
        • Alexander LT
        • et al.
        Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.
        Lancet. 2016; 388: 1659-1724
        • Lee SK
        • Khambhati J
        • Varghese T
        • et al.
        Comprehensive primary prevention of cardiovascular disease in women.
        Clin Cardiolo. 2017; 40: 832-838
        • Shiroma EJ
        • Lee IM
        Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity.
        Circulation. 2010; 122: 743-752
        • Lacasse A
        • Pagé MG
        • Choinière M
        • et al.
        Conducting gender-based analysis of existing databases when self-reported gender data are unavailable: the GENDER Index in a working population.
        Can J Public Health. 2020; 111: 155-168
        • Norris CM
        • Murray JW
        • Triplett LS
        • Hegadoren KM
        Gender roles in persistent sex differences in health-related quality-of-life outcomes of patients with coronary artery disease.
        Gender Med. 2010; 7: 330-339
        • Chida Y
        • Steptoe A
        Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence.
        Hypertension. 2010; 55: 1026-1032
        • Peterson PN
        JAHA Spotlight on Psychosocial Factors and Cardiovascular Disease.
        J Am Heart Assoc. 2020; 9e017112
        • White-Williams C
        • Rossi LP
        • Bittner VA
        • et al.
        Addressing social determinants of health in the care of patients with heart failure: a scientific statement from the American Heart Association.
        Circulation. 2020; 141: e841-e863
        • Fortier I
        • Raina P
        • van den Heuvel ER
        • et al.
        Maelstrom Research guidelines for rigorous retrospective data harmonization.
        Int J Epidemiol. 2017; 46: 103-105
        • Maclagan LC
        • Park J
        • Sanmartin C
        • et al.
        The CANHEART health index: a tool for monitoring the cardiovascular health of the Canadian population.
        CMAJ. 2014; 186: 180-187
        • Koch CG
        • Mangano CM
        • Schwann N
        • Vaccarino V
        Is it gender, methodology, or something else?.
        J Thorac Cardiovasc Surg. 2003; 4: 932-935
        • Whittaker KS
        • Krantz DS
        • Rutledge T
        • et al.
        Combining psychosocial data to improve prediction of cardiovascular disease risk factors and events: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.
        Psychosom Med. 2012; 74: 263
        • Glynn RJ
        • Schneeweiss S
        • Stürmer T
        Indications for propensity scores and review of their use in pharmacoepidemiology.
        Basic Clin Pharmacol Toxicol. 2006; 98: 253-259
        • Pilote L
        • Dasgupta K
        • Guru V
        • et al.
        A comprehensive view of sex-specific issues related to cardiovascular disease.
        CMAJ. 2007; 176: S1-44
        • King AC
        • Castro C
        • Wilcox S
        • et al.
        Personal and environmental factors associated with physical inactivity among different racial-ethnic groups of U.S. middle-aged and older-aged women.
        Health Psychol. 2000; 19: 354-364
      2. United Nations Development Programme. Gender Inequality Index (GII). Available at:http://hdr.undp.org/en/content/gender-inequality-index-gii. Accessed March 24, 2021.

        • Tandon A
        • Murray CJ
        • Lauer JA
        • Evans DB
        Measuring overall health system performance for 191 countries. Global Programme on Evidence for Health Policy discussion paper no. 30.
        World Health Organisation, January 2000
        • Greenland P
        • Knoll MD
        • Stamler J
        • et al.
        Major risk factors as antecedents of fatal and nonfatal coronary heart disease events.
        JAMA. 2003; 290: 891-897
        • Khot UN
        • Khot MB
        • Bajzer CT
        • et al.
        Prevalence of conventional risk factors in patients with coronary heart disease.
        JAMA. 2003; 290: 898-904
        • Rozanski A
        • Blumenthal JA
        • Kaplan J
        Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.
        Circulation. 1999; 99: 2192-2217
        • Dorner T
        • Kiefer I
        • Kunze M
        • Rieder A
        [Gender aspects of socioeconomic and psychosocial risk factors of cardiovascular diseases].
        Wien Med Wochenschr. 2004; 154 ([in German]): 426-432
        • Kaplan GA
        • Keil JE
        Socioeconomic factors and cardiovascular disease: a review of the literature.
        Circulation. 1993; 88: 1973-1998
        • Diez Roux AV
        • Merkin SS
        • Arnett D
        • et al.
        Neighborhood of residence and incidence of coronary heart disease.
        N Engl J Med. 2001; 345: 99-106
        • Ikeda A
        • Iso H
        • Kawachi I
        • et al.
        Living arrangement and coronary heart disease: the JPHC study.
        Heart. 2009; 95: 577-583
        • Kilpi F
        • Konttinen H
        • Silventoinen K
        • Martikainen P
        Living arrangements as determinants of myocardial infarction incidence and survival: a prospective register study of over 300,000 Finnish men and women.
        Soc Sci Med. 2015; 133: 93-100
        • Greaney JL
        • Surachman A
        • Saunders EF
        • Alexander LM
        • Almeida DM
        Greater daily psychosocial stress exposure is associated with increased norepinephrine-induced vasoconstriction in young adults.
        J Am Heart Assoc. 2020; 9e015697