Coronary artery disease (CAD) is the leading cause of death and disability for both women and men in Canada 1, and although there have been substantial medical advances that improve survival for cardiac ischemic events, gender differences in the pathophysiology, treatment, course of recovery and outcomes for patients with CAD continue to exist 123456. For example, it has been reported that women with CAD are older, have a higher burden of co-morbid illnesses 7, are more often widowed, more likely to live alone, have more depressive symptoms, have poorer psychosocial adjustment following a CAD event 389 and lower referral/participation in cardiac rehabilitation programs compared to men 10. Further, there is growing evidence that suggests CAD presents differently in women and men 11, which in turn contributes to gender differences in the delivery of care 7. The differences between men and women with CAD have great relevance particularly when addressing secondary prevention programs. If these programs are to be successful, it is not only crucial to carry out comprehensive follow-up, but to recognize that men and women may require different approaches to achieve maximal benefit from treatment for CAD.

There is a general paucity of data comparing men and women with CAD for differences with respect to health-related quality of life (HRQOL) outcomes. Although researchers have explored the association between gender, heart disease and HRQOL, the results are contradictory depending on the subset of patients studied and the definitions used for HRQOL. To our knowledge, no studies have explored the association between gender, CAD and HRQOL outcomes, using a comprehensive sample of patients with single or multi-vessel CAD and a disease specific HRQOL measure. The sex of patients with CAD has been reported to be associated with factors such as demographic, co-morbid illnesses, and clinical presentation 212131415161718192021. Women with CAD are older, have a higher burden of co-morbid illnesses 7, and have poorer psychosocial adjustment following a CAD event 389. We therefore hypothesized that following statistical adjustment women would also experience worse HRQOL outcomes compared to men. Therefore, the purpose of this study was to compare the HRQOL outcomes of men and women in Alberta with CAD at or near one-year following initial catheterization, after adjustment for known demographic, co-morbid, and disease severity predictors of outcome.

A total of 10,108 consenting patients who underwent cardiac catheterization between January 1996 and December 1998 in the province of Alberta were sent one-year follow-up surveys. Of these, 4,344 patients were eligible for this study among whom 3392 (78.1%) patients responded to the follow-up survey while 952 (21.9%) surveys remained outstanding. Among responders, 3243 surveys were returned completed and 149 surveys were returned notifying the investigators that the patient had died prior to completion of the survey.

An analysis of the differences in the baseline demographic data and clinical characteristics of responders and non-responders demonstrated a few significant differences (Table 1). Compared with responders, non-responders tended to be younger, were more likely to have diabetes mellitus (p < 0.001) and a lower ejection fraction (p = 0.001). As well, non-responders were more likely to have been treated with medical therapy during the first year following their index catheterization (35.1% versus 26.7% p < 0.001).

The mean age of the responders at the time of the index catheterization was 64.6 years and the median age was 65.7 years. Seventy-eight percent of the sample were men. Baseline demographic and clinical characteristics of the analytic cohort grouped by sex are described in Table 2. Women were significantly older (mean age: women = 66.7 years, men = 63.9 years p < 0.001), and this difference was most pronounced in the oldest age quintile (women > 72 years 35.1%, men > 72 years 21.9%). Compared to men, women were more likely to have congestive heart failure (p = 0.001), hypertension (p < 0.001) and diabetes mellitus (p < 0.001). Women were also more likely to have 2 vessel disease, although the same percentage of women and men had left main disease. Finally, women were more likely to have an ejection fraction >50%, have unstable angina as the indication for catheterization, and to be treated medically or with percutaneous coronary intervention.

It has been well recognized that important differences exist between women and men with regard to the function and progression of diseases of the cardiovascular system. 29 Further it has been suggested that for optimal treatment of CAD it is necessary to recognize gender differences and their impact on the outcomes of care 30. The results of this study indicate that women have worse HRQOL than men one year after cardiac catheterization. Similar to published reports 789, the women in our study were significantly older, and more likely to have more co-morbid illnesses compared to men. At the same time the women were more likely to be treated medically or with PCI whereas the men were more likely to be treated with CABG. Although some studies have suggested that women have less access to care or have poorer outcomes, consistent findings are still unavailable 31323334. Despite these crude differences in co-morbid illnesses, ejection fraction and treatment modality, after risk adjusting the SAQ dimensional scores for all demographic, clinical, co-morbid and treatment variables, gender remained independently associated with HRQOL outcomes with women reporting worse HRQOL outcomes compared to men.

The literature on gender differences in HRQOL for patients with CAD is sparse and somewhat contradictory. Three studies examined gender differences in HRQOL following acute myocardial infarction, and these reported no gender differences in HRQOL 133536, yet found that women reported higher levels of depression and less social support 13, were at increased risk of death and long length of stay in subsequent hospitalizations 36, and less likely to undergo rehabilitation if diagnosed as hypertensive 35. In contrast, two studies 3738 reported that women reported worse HRQOL following acute myocardial infarction compared to men as measured by elevated levels of anxiety, depression, poorer general health 37 and overall worse psychosocial profiles 38. One study investigated the HRQOL of patients with stable angina on a waiting list for coronary revascularization, and reported that women had higher frequencies of chest pain, dyspnea and more sleep disorders 39. King and colleagues 40 used the McMaster Health State Profile to examine the effect of gender on short-term recovery from cardiac surgery and found that although the women in the study were more functionally limited and reported lower life satisfaction and social support pre-operatively compared to men, there were in fact few significant differences between men and women 3 months postoperatively aside from persistently lower social support. Finally, two studies that examined the gender differences in HRQOL of patients with heart failure 4142 reported that women had worse HRQOL ratings than men particularly for physical health status and activities of daily living. Based on the conflicting nature of these studies, one might speculate that higher levels of depression 131516 and less social support 1318 in women following a cardiac event may have influenced their overall reported HRQOL.

The predictive value of psychosocial factors such as social support and depression in CAD outcomes is not well understood, regardless of gender. The influence of psychosocial factors in the course and outcomes of CAD has generated considerable interest since traditional risk factors have been unable to provide a comprehensive explanatory model, accounting for, at best, 50% of the variance in morbidity and mortality outcomes. These two variables should be included in future studies of HRQOL in patients with CAD as they may explain some of the gender differences in HRQOL in this population. Indeed, in our study, adjustment for a number of measured clinical variables did not 'explain away' sex differences in HRQOL, leaving us to speculate that variables that we did not measure – like social support and depression – may be contributing to sex differences in outcome.

A systematic review of the SAQ identified 62 studies that either referenced or used the SAQ to measure HRQOL outcomes 43. Although the SAQ was tested and determined to be a valid, reliable, responsive instrument to measure the HRQOL of patients with CAD 24, and has been used in a variety of settings with a variety of samples including men and women, the original scale was validated on a sample of older men who were inpatients or outpatients at a Veterans Medical Centre. Consequently the items that make up the dimensional scores may be gender biased. There is growing evidence to suggest that women may experience angina differently than men. Rather than a heavy localized chest pain that some refer to as the typical 'Hollywood Heart Attack', women often report more diffuse, hot, burning chest pain, jaw pain, shoulder blade pain 44 and/or nausea 4546474849. As a result, the items that make up the exertional capacity scale that address the limitations in activities of daily living due to 'chest pain, chest tightness and/or shortness of breath' 24, may actually overestimate women's exertional capacity. The results of this study indicate that women reported greater limitations in exertional capacity compared to men indicating that regardless of how angina is manifested, the items in the exertional capacity scale appear to be identifying limitations to functional status resulting from CAD.

There are limitations to this study. This study is an observational study based on a clinical registry that although quite detailed, may lack information on clinical variables that may confound the association between gender and quality of life. Consequently, the observed differences between genders in HRQOL outcomes may be due to residual confounding. Since HRQOL outcomes may be associated with a variety of demographic and clinical characteristics, we have attempted to adjust for baseline differences in our analysis. A second limitation is that HRQOL outcomes for this study were measured only at one time point, one-year post catheterization. As such we are not able to determine exactly when the HRQOL gender differences noted in this study emerge. Further research is required to analyze when HRQOL gender differences begin in the natural history of coronary artery disease, and the subsequent HRQOL "trajectories" that ensue for men and women. To that end a study is presently underway in which we collect 'baseline' HRQL data at one-week post catheterization.

Notwithstanding these limitations, this study is unique on several fronts. Of primary significance is the fact that the study covered a large geographically defined study population that yielded a high response rate to a one-year follow-up questionnaire. HRQOL questionnaires are particularly beneficial at enhancing the scope of outcome measures beyond the traditional ones of disability and/or death. By using a validated HRQOL measure (SAQ), we were able to evaluate the HRQOL outcomes of treatment for patients with CAD. More importantly, this study provides the opportunity to gain knowledge, insight, and a better understanding of the impact of CAD, and 'real world' HRQOL outcomes of a population based cohort with multi-vessel CAD.

CAD imposes a great influence on HRQOL outcomes. Women report poorer HRQOL than do men at one year following treatment for multi-vessel CAD. Gender differences were noted in all 5 dimensions measured by the SAQ including exertional capacity, anginal stability, anginal frequency, treatment satisfaction and quality of life. These findings underline the fact that conclusions based on research performed on men with CAD may not be valid for women and that more gender-related research is needed. Future studies are needed to further examine gender differences in psychosocial adjustment following treatment for CAD, as adjustment for traditional clinical variables fails to explain sex differences in quality of life outcomes.

CAD: Coronary artery disease

HRQOL: Health related quality of life

SAQ: Seattle Angina Questionnaire

APPROACH: The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease

PORs Proportional Odds Ratio

CMN conceived of the study, participated in the design, performed the statistical analysis, and drafted the manuscript. WAG participated in the design, oversaw the statistical analysis, and edited initial draft copies of the manuscript. PDG edited drafts of the manuscript, read and approved the final manuscript. MMG edited drafts of the manuscript, read and approved the final manuscript. LAJ edited drafts of the manuscript, read and approved the final manuscript. MLK is the principal investigator of the APPROACH project and read and approved the final manuscript. The APPROACH Investigators read and approved the final manuscript.