healthrelated quality of life ( hrql ) is increasingly being used as an outcome measure for the effectiveness of medical treatment and patient recovery in acute coronary syndrome ( acs ) . whereas health outcomes in acs patients have traditionally been measured using mortality and morbidity as primary endpoints , hrql is an important outcome measure in that it measures illness perception instead of the disease itself . hrql has been recognized for defining health from the patients ' perspective , in terms of how individuals feel ( distress and wellbeing ) and how they evaluate their health and prospects for the future . acs has been associated with marked impairments in hrql and considerable loss of productive years . in addition , many studies have demonstrated sex differences in hrql among patients with coronary artery disease ( cad ) , with women generally reporting lower hrql than men . however , inconsistency exists regarding the determinants of hrql for men and women , and the observed discrepancies in hrql between sexes are poorly understood . in addition to biological sex ( ie , being male or female ) , it has been suggested that gender ( ie , sociocultural factors related to masculinity and femininity ) may influence hrql . during the past decade , there has been a substantial decrease in gender gap in north america . with more young women gaining access to education and employment , shared household and workplace responsibilities are becoming more common . at the same time , other factors , such as social support and psychological distress , could be equally important in predicting hrql postacs . however , the role that different genderrelated factors may play in hrql remains to be determined , and , to date , there are no comprehensive studies on this subject . the aim of this study was to examine trends in hrql and assess the relative contribution of sex and gender among young male and female patients with acs . the study population consisted of patients enrolled in genesispraxy ( gender and sex determinants of cardiovascular disease : from bench to beyondpremature acute coronary syndrome ) , a multicenter , prospective cohort study of young adults hospitalized with acs . briefly , eligible participants included patients aged 18 to 55 years , admitted with a diagnosis of acs to the coronary care units of participating hospitals , fluent in english and/or french , and able to provide informed consent . the study began in january 2009 and includes 24 sites across canada , one in the u.s . , and one in switzerland . all participating sites received ethics approval from their respective ethics review board , and all participants provided informed consent . study participants were approached by a trained research nurse within 48 hours of hospital admission . patients who gave their consent were asked to complete a selfadministered questionnaire at the time of enrolment . medical chart reviews were carried out by the research nurse at baseline and 12 months . hrql was measured using 2 validated instruments : the short form12 ( sf12 ) version 2.0 and the seattle angina questionnaire ( saq ) . the sf12 includes 2 subscales : the physical component summary ( pcs ) and mental component summary ( mcs ) scores , transformed to a 0 to 100 scale , with higher scores representing better health status . population with a mean score of 50 and standard deviation ( sd ) of 10 . the sf12 validity , reliability , and responsiveness have been well documented in patients with cad . the saq is a 19item diseasespecific functional status measure of cad using 5 dimensions , namely , physical limitation , angina stability , angina frequency , treatment satisfaction , and disease perception . the items are summed within each of the 5 dimensions , and the scale scores are transformed to a 0 to 100 scale . a clinically significant difference in the scores of the saq dimensions is between 5 and 8 points . our main variables of interest were sex and genderrelated variables . according to the women health research network of the canadian institutes of health research ( cihr ) , there are 4 interrelated gender aspects , which are gender roles , gender identity , gender relations , and institutionalized gender . we examined 7 genderrelated variables that incorporate these gender aspects , namely , stress level at home , stress management , femininity score , housework responsibility , primary earner status , number of hours worked per week , and social support . femininity score was measured using the femininity subscale of the bem sex role inventory ( bsri ) . housework responsibility and primary earner status were assessed using the questions ,  are you the primary person responsible for doing the housework in your home ? ( yes / no )  and  are you the primary earner in the house ? social support was measured using the enrichd social support instrument ( essi ) , a valid and reliable 7item tool among populations with cad . low social support is determined based on the score of 5 of the 7 items of the essi ( items 1 , 2 , 3 , 5 , and 6 ) . patients with a score of 3 on at least 2 items or with a total score of 18 are considered as having low social support . data were additionally collected on sociodemographic factors , including age , marital status , ethnicity , education , and various factors that have been linked to hrql . these included clinical characteristics , such as anxiety , depression , presence of vascular risk factors , a previous cardiovascular ( cv ) event ( cve ) , and type of acs ( stelevation myocardial infarction [ stemi ] , nonstemi , or unstable angina ) , as well as treatment procedures ( thrombolysis , primary percutaneous coronary intervention [ pci ] , nonprimary pci , and coronary artery bypass grafting [ cabg ] ) . anxiety and depression were measured using the hospital anxiety and depression scale ( hads ) . presence of vascular risk factors was defined as having one or more of the following : diabetes , hypertension , dyslipidemia , currently smoking , obesity , and family history of cv diseases . previous cve included previous myocardial infarction , stroke , pci , or cabg or having peripheral arterial disease . descriptive statistics were used to report baseline characteristics stratified by tertiles of pcs and mcs scores . dichotomous variables were presented in percentages , whereas continuous variables were presented as mean sd . mean hrql scores were calculated for men and women , respectively , at the 4 time points ( baseline , 1 , 6 , and 12 months ) , and the differences in scores between men and women were assessed using student t tests . we conducted trend analysis on time by using polynomial transformation to account for the different time lapse between the measured time points . chisquare test was used to compare the percentages of men versus women having angina ( score < 100 ) . multiple linear regression models were created to identify predictors of pcs , mcs , physical limitation , angina stability , treatment satisfaction , and disease perception at 12 months . we used multivariable logistic models to identify predictors of having angina at 12 months . we included sex and the 7 genderrelated variables in the multivariable models , together with demographic and clinical variables that were statistically significant at p<0.10 in the univariable analyses . we used the false discovery rate method to adjust for multiple testing . in sensitivity analysis , we excluded noncanadian sites ( u.s . and switzerland ) . we also investigated for interactions between sex and genderrelated variables when they were found to be statistically significant in the same model . when there was a significant interaction effect , posthoc analyses were conducted to compare the hrql scores of men and women for the concerned genderrelated variable . all statistical analyses were performed using the sas ( version 9.2 ) statistical software package ( sas institute inc , cary , nc ) . the study population consisted of patients enrolled in genesispraxy ( gender and sex determinants of cardiovascular disease : from bench to beyondpremature acute coronary syndrome ) , a multicenter , prospective cohort study of young adults hospitalized with acs . briefly , eligible participants included patients aged 18 to 55 years , admitted with a diagnosis of acs to the coronary care units of participating hospitals , fluent in english and/or french , and able to provide informed consent . the study began in january 2009 and includes 24 sites across canada , one in the u.s . , and one in switzerland . all participating sites received ethics approval from their respective ethics review board , and all participants provided informed consent . study participants were approached by a trained research nurse within 48 hours of hospital admission . patients who gave their consent were asked to complete a selfadministered questionnaire at the time of enrolment . medical chart reviews were carried out by the research nurse at baseline and 12 months . hrql was measured using 2 validated instruments : the short form12 ( sf12 ) version 2.0 and the seattle angina questionnaire ( saq ) . the sf12 includes 2 subscales : the physical component summary ( pcs ) and mental component summary ( mcs ) scores , transformed to a 0 to 100 scale , with higher scores representing better health status . population with a mean score of 50 and standard deviation ( sd ) of 10 . the sf12 validity , reliability , and responsiveness have been well documented in patients with cad . the saq is a 19item diseasespecific functional status measure of cad using 5 dimensions , namely , physical limitation , angina stability , angina frequency , treatment satisfaction , and disease perception . the items are summed within each of the 5 dimensions , and the scale scores are transformed to a 0 to 100 scale . a clinically significant difference in the scores of the saq dimensions is between 5 and 8 points . according to the women health research network of the canadian institutes of health research ( cihr ) , there are 4 interrelated gender aspects , which are gender roles , gender identity , gender relations , and institutionalized gender . we examined 7 genderrelated variables that incorporate these gender aspects , namely , stress level at home , stress management , femininity score , housework responsibility , primary earner status , number of hours worked per week , and social support . femininity score was measured using the femininity subscale of the bem sex role inventory ( bsri ) . housework responsibility and primary earner status were assessed using the questions ,  are you the primary person responsible for doing the housework in your home ? ( yes / no )  and  are you the primary earner in the house ? social support was measured using the enrichd social support instrument ( essi ) , a valid and reliable 7item tool among populations with cad . low social support is determined based on the score of 5 of the 7 items of the essi ( items 1 , 2 , 3 , 5 , and 6 ) . patients with a score of 3 on at least 2 items or with a total score of 18 are considered as having low social support . data were additionally collected on sociodemographic factors , including age , marital status , ethnicity , education , and various factors that have been linked to hrql . these included clinical characteristics , such as anxiety , depression , presence of vascular risk factors , a previous cardiovascular ( cv ) event ( cve ) , and type of acs ( stelevation myocardial infarction [ stemi ] , nonstemi , or unstable angina ) , as well as treatment procedures ( thrombolysis , primary percutaneous coronary intervention [ pci ] , nonprimary pci , and coronary artery bypass grafting [ cabg ] ) . anxiety and depression were measured using the hospital anxiety and depression scale ( hads ) . presence of vascular risk factors was defined as having one or more of the following : diabetes , hypertension , dyslipidemia , currently smoking , obesity , and family history of cv diseases . previous cve included previous myocardial infarction , stroke , pci , or cabg or having peripheral arterial disease . descriptive statistics were used to report baseline characteristics stratified by tertiles of pcs and mcs scores . dichotomous variables were presented in percentages , whereas continuous variables were presented as mean sd . mean hrql scores were calculated for men and women , respectively , at the 4 time points ( baseline , 1 , 6 , and 12 months ) , and the differences in scores between men and women were assessed using student t tests . we conducted trend analysis on time by using polynomial transformation to account for the different time lapse between the measured time points . chisquare test was used to compare the percentages of men versus women having angina ( score < 100 ) . multiple linear regression models were created to identify predictors of pcs , mcs , physical limitation , angina stability , treatment satisfaction , and disease perception at 12 months . we used multivariable logistic models to identify predictors of having angina at 12 months . we included sex and the 7 genderrelated variables in the multivariable models , together with demographic and clinical variables that were statistically significant at p<0.10 in the univariable analyses . we used the false discovery rate method to adjust for multiple testing . in sensitivity analysis we also investigated for interactions between sex and genderrelated variables when they were found to be statistically significant in the same model . when there was a significant interaction effect , posthoc analyses were conducted to compare the hrql scores of men and women for the concerned genderrelated variable . all statistical analyses were performed using the sas ( version 9.2 ) statistical software package ( sas institute inc , cary , nc ) . among 1410 eligible patients who were approached , participation refusal rates were 18% in men and 10% in women , for an overall participation rate of 86% or 1213 enrolled patients ( 68% men ) . those in the highest pcs and mcs tertiles had lower levels of stress at home , better stress management ability , and higher social support . those in the highest mcs tertiles were also less likely to have housework responsibilities , but were more likely to be the family 's primary earners . additionally , there were fewer patients with low education , depression , anxiety , vascular risk factors , and previous cves in the highest tertiles . except for primary pci , other revascularization treatments ( thrombolysis , nonprimary pci , and cabg ) , as well as type of acs , baseline characteristics according to tertiles of physical component summary and mental component summary scores acs indicates acute coronary syndrome ; cabg , coronary artery bypass grafting ; mcs , mental component summary ; pci , percutaneous coronary intervention ; pcs , physical component summary ; stemi , stelevation myocardial infarction . at every point in time ( baseline , 1 , 6 , and 12 months ) , the mean pcs and mcs scores of this population of young acs patients were lower than the mean score of 50 of the general population , and lower in women compared to men ( figure 1 ) . an improving trend was observed for both pcs and mcs among men ( p<0.01 and p=0.01 , respectively ) , whereas an improvement was observed only for pcs and not mcs among women ( p<0.01 and p=0.55 , respectively ) . men consistently reported higher scores than women , with the difference in scores being clinically significant ( > 3 points for sf12 and > 5 points for saq ) . the proportion of men with angina decreased consistently over time , and in the longterm , women reported more angina than men ( 48.2% versus 29.4% ; p<0.01 at 12 months ) . note : difference > 3 points and p<0.01 between men and women at all points in time . in multivariable linear and logistic regressions , genderrelated variables were more likely than sex to be significant predictors of hrql ( figure 2 ) . femininity score and social support appeared to be particularly important , being statistically significant for 4 ( pcs , physical limitation , angina frequency , and disease perception ) and 3 ( pcs , physical limitation , and disease perception ) outcomes , respectively . housework responsibility was also found to be an important determinant of pcs and physical limitation . conversely , sex was not a predictor for any of the outcomes , except physical limitation ( =5.37 [ 95% ci , 8.94 , 1.79 ] ; p=0.003 ) . after adjustment for multiple testing , statistical significance persisted for most variables . in two cases where the variable of interest was no longer statistically significant , similar trends in the results were nonetheless observed . moreover , in sensitivity analysis , which included canadian sites only , we obtained similar results . note : figure 2a through 2f indicate  coefficients ; figure 2 g indicates odds ratio ( or ) . adjustments were made for variables significant at p<0.10 in univariable analyses : ( a ) education , presence of vascular risk factors , previous cardiovascular event , depression , anxiety , nonprimary percutaneous coronary intervention , type of acute coronary syndrome , and baseline score ; ( b ) education , previous cardiovascular event , depression , anxiety , and baseline score ; ( c ) education , previous cardiovascular event , depression , anxiety , type of acute coronary syndrome , and baseline score ; ( d ) depression and baseline score ; ( e ) education , depression , anxiety , and baseline score ; ( f ) education , presence of vascular risk factors , previous cardiovascular event , depression , anxiety , and baseline score ; and ( g ) education , previous cardiovascular event , depression , anxiety , and baseline score . we tested for interactions between sex and femininity score , sex and social support , and sex and housework responsibility in predicting physical limitation . we did not find an interaction between sex and femininity score or sex and housework responsibility , but found a statistically significant interaction between sex and social support ( =0.44 [ 95% ci , 0.01 , 0.88 ] ; p=0.047 ) . in posthoc analyses , there was a clinically significant difference in the physical limitation score of high versus low social support among women ( 82 versus 66 ; difference > 5 points ) , but not among men ( figure 3 ) . at every point in time ( baseline , 1 , 6 , and 12 months ) , the mean pcs and mcs scores of this population of young acs patients were lower than the mean score of 50 of the general population , and lower in women compared to men ( figure 1 ) . an improving trend was observed for both pcs and mcs among men ( p<0.01 and p=0.01 , respectively ) , whereas an improvement was observed only for pcs and not mcs among women ( p<0.01 and p=0.55 , respectively ) . men consistently reported higher scores than women , with the difference in scores being clinically significant ( > 3 points for sf12 and > 5 points for saq ) . the proportion of men with angina decreased consistently over time , and in the longterm , women reported more angina than men ( 48.2% versus 29.4% ; p<0.01 at 12 months ) . note : difference > 3 points and p<0.01 between men and women at all points in time . in multivariable linear and logistic regressions , genderrelated variables were more likely than sex to be significant predictors of hrql ( figure 2 ) . femininity score and social support appeared to be particularly important , being statistically significant for 4 ( pcs , physical limitation , angina frequency , and disease perception ) and 3 ( pcs , physical limitation , and disease perception ) outcomes , respectively . housework responsibility was also found to be an important determinant of pcs and physical limitation . conversely , sex was not a predictor for any of the outcomes , except physical limitation ( =5.37 [ 95% ci , 8.94 , 1.79 ] ; p=0.003 ) . after adjustment for multiple testing , statistical significance persisted for most variables . in two cases where the variable of interest was no longer statistically significant , similar trends in the results were nonetheless observed . moreover , in sensitivity analysis , which included canadian sites only , we obtained similar results . note : figure 2a through 2f indicate  coefficients ; figure 2 g indicates odds ratio ( or ) . adjustments were made for variables significant at p<0.10 in univariable analyses : ( a ) education , presence of vascular risk factors , previous cardiovascular event , depression , anxiety , nonprimary percutaneous coronary intervention , type of acute coronary syndrome , and baseline score ; ( b ) education , previous cardiovascular event , depression , anxiety , and baseline score ; ( c ) education , previous cardiovascular event , depression , anxiety , type of acute coronary syndrome , and baseline score ; ( d ) depression and baseline score ; ( e ) education , depression , anxiety , and baseline score ; ( f ) education , presence of vascular risk factors , previous cardiovascular event , depression , anxiety , and baseline score ; and ( g ) education , previous cardiovascular event , depression , anxiety , and baseline score . we tested for interactions between sex and femininity score , sex and social support , and sex and housework responsibility in predicting physical limitation . we did not find an interaction between sex and femininity score or sex and housework responsibility , but found a statistically significant interaction between sex and social support ( =0.44 [ 95% ci , 0.01 , 0.88 ] ; p=0.047 ) . in posthoc analyses , there was a clinically significant difference in the physical limitation score of high versus low social support among women ( 82 versus 66 ; difference > 5 points ) , but not among men ( figure 3 ) . our study found that young male and female patients with acs had poorer hrql , compared to the general population , both in terms of physical and mental functioning . importantly , our findings demonstrated that the longterm impact of acs on hrql among young adults depends more strongly on gender than on sex . even when adjusting for clinical characteristics and treatment , several genderrelated factors were found to be significant in predicting hrql , particularly femininity score , social support , and housework responsibility . we also found that social support was more important among women than men to increase their physical limitation score . our study encompasses extensive measures of genderrelated factors among young patients with acs , which have not been examined in previous studies . although most studies have consistently shown that women generally have poorer hrql after an acs event , the reasons for this are not well understood . studies that have attempted to investigate sex differences in the predictors of hrql have mostly focused on clinical characteristics and treatment procedures . yet , these only partially explain the observed sex discrepancies in hrql , and gender has been suggested as accounting for the residual discrepancies . hence , it is possible that societal views on the acceptability of residual angina in women versus men may , in part , account for less aggressive treatments among women . in addition , studies investigating hrql postacs have typically included older adults and few have focused on younger patients with acs . some studies have investigated social support as a determinant of hrql and have found it to be particularly important for women . these studies have been mostly conducted among older populations , but younger populations are a particularly vulnerable population who may have persisting disease burden leading to a loss of many years of productivity . in the monika / kora populationbased registry , it was demonstrated that hrql is greatly impaired postacs , especially among young adults ( aged 45 to 54 years ) , compared to their same agegroup counterparts in the general population . our results , based on a younger population , are concordant with previous findings and sustain the importance of social support in longterm hrql among young women after an acs event . this may be because of the fact that women , especially younger ones , may have higher combined occupational and household responsibilities than men and thus may require more social support . it is plausible that these young women who have low social support will face greater difficulties reimmersing into their normal routine and reestablishing an adequate hrql postacs . therefore , the value of social support postacs also needs to be underlined among such young adult populations . the importance of studying genderrelated factors as separate entities from sex has been increasingly emphasized in health research . in fact , different genderrelated factors , including family and societal roles , have been suggested as being key to the psychosocial response that one may have after having a cve . it has been suggested that women may have more difficulty coping after a cardiac event than men . in our young population of patients with acs , we interestingly observed that a higher femininity score may be linked to poorer hrql . the brsi considers traits such as  sensitive to the needs of others , compassionate ,  and  loves children ,  among others , as being feminine characteristics . these can be thought of as being linked to higher household responsibilities and roles traditionally occupied by women . considering an evolving society with closing gender gaps , particularly among younger generations , further research is imperative to evaluate how these changing roles may affect cv health and hrql among young patients . furthermore , in an older population with acs , higher femininity among women may be even more impactful . additional investigations in other study groups may also better show the influence of genderrelated factors on hrql in acs . our study is unique in that it is a largescale prospective cohort study of patients with premature acs . although the results may not be as accurate as with a complete data set , we obtained very similar results to those yielded from the nonimputed models . . also , there are many possible determinants of hrql , and the use of many variables in the multivariable models may have reduced the power to detect statistical significance . however , our results were similar after adjustment for multiple testing , with nearly all of the variables retaining statistical significance . as well , it would have been interesting to address medication use , but we had insufficient data to conduct these analyses . it is also possible that among eligible participants , those enrolled were in a more favorable clinical situation . moreover , because various questions on the sf12 and saq refer to questions on health status over the past 4 weeks , there is the possibility of poor recall . female patients with premature acs report significantly poorer hrql than male patients , both in terms of physical and mental functioning . future research should aim to address genderrelated factors as a means to improve hrql among young patients recovering from acs . specific genderrelated factors , such as social support , may be amenable to interventions and could improve the hrql of patients with premature acs .
backgroundlimited data exist as to the relative contribution of sex and gender on healthrelated quality of life ( hrql ) among patients with acute coronary syndrome ( acs ) . 
 this study aims to evaluate the effect of sex and genderrelated variables on longterm hrql among young adults with acs.methods and resultsgenesispraxy ( gender and sex determinants of cardiovascular disease : from bench to beyondpremature 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 form12 and seattle angina questionnaire ( saq ) among 1213 patients . 
 median age was 49 years . 
 women reported worse hrql than men over time postacs , both in terms of physical and mental functioning . 
 genderrelated factors were more likely to be predictors of hrql than sex . 
 femininity score , social support , and housework responsibility were the most common genderrelated predictors of hrql at 12 months . 
 we observed an interaction between female sex and social support ( =0.44 [ 95% confidence interval , 0.01 , 0.88 ] ; p=0.047 ) for the physical limitation subscale of the saq.conclusionsyoung women with acs report significantly poorer hrql than young men . 
 gender appears to be more important than sex in predicting longterm hrql postacs . 
 specific genderrelated factors , such as social support , may be amenable to interventions and could improve the hrql of patients with premature acs .