Abstract
Objectives
The association between depression and cardiovascular disease severity in younger patients has not been assessed, and sex differences are unknown. We assessed whether major depression and depressive symptoms were associated with worse cardiovascular disease severity in patients with premature acute coronary syndrome, and we assessed sex differences in these relationships.
Methods
We enrolled 1023 patients (aged ≤55 years) hospitalized with acute coronary syndrome from 26 centers in Canada, the United States, and Switzerland, through the GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome study. Left ventricular ejection fraction, Killip class, cardiac troponin I, and Global Registry of Acute Coronary Events score data were collected through chart review.
Results
The sample comprised 248 patients with major depression and 302 women. In univariate analyses, major depression was associated with a lower likelihood of having an abnormal left ventricular ejection fraction (odds ratio, 0.70; 95% confidence interval, 0.51-0.97; P = .03) and lower troponin I levels (estimate, −4.04; 95% confidence interval, −8.01 to −0.06; P = .05). After adjustment for sociodemographic and clinical characteristics, neither major depression nor depressive symptoms were associated with disease severity indices, and there were no sex differences.
Conclusion
The increased risk of adverse events in depressed patients with premature acute coronary syndrome is not explained by disease severity.
Keywords
Clinical Significance
- •Women with premature acute coronary syndrome have reduced access to care.
- •Depression seems to delay access to care in women.
- •Given that mortality is highest in young women with acute coronary syndrome, depressed women who present with acute coronary syndrome should be targeted for prompt management.
The relationship between depression and cardiovascular disease has been demonstrated.
1
, 2
Depression is a risk factor for mortality and cardiovascular disease events both in the general population3
and in patients with cardiovascular disease.4
, 5
Patients who are depressed after myocardial infarction are at high risk for subsequent events, because depression leads to a 2-fold increased risk of fatal and nonfatal events compared with nondepressed patients.6
However, the relationship between depression and cardiovascular prognosis may be explained partly by cardiac disease severity. Results of a meta-analysis suggested that the relative risk for future coronary heart disease associated with depression was reduced by 48% when models were adjusted for left ventricular ejection fraction.4
Researchers also have observed lower left ventricular ejection fraction7
, 8
, 9
and higher Killip classes2
in patients with high levels of depressive symptoms. However, others have observed no relationship between major depression or depressive symptoms and various markers of disease severity, including cardiac troponin T,10
left ventricular ejection fraction,11
, 12
and Killip class.13
It has been suggested that disparities between studies may be explained by inadequate statistical adjustments, different measures of depression, and incomplete measures of cardiovascular disease severity.11
The incidence of acute coronary syndrome in younger adults, particularly women, is increasing.
14
In the INTERHEART study, depression also was more prevalent among younger than older participants.15
Furthermore, previous evidence indicates that depression may contribute to worse cardiovascular disease outcomes in women relative to men.1
, 16
Therefore, the relationship between depression and disease severity in younger male and female patients warrants further investigation. Accordingly, in a cohort of more than 1000 patients with premature acute coronary syndrome, we sought to examine whether major depression or depressive symptoms are associated with disease severity and to ascertain whether the association differs between men and women.Materials and Methods
Study Design
The GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome (GENESIS-PRAXY) study is a multicenter project, for which 24 centers across Canada, 1 in the United States, and 1 in Switzerland participated in the recruitment of patients (See Appendix B, online, for the list of recruiting centers and sites' principal investigator). Detailed methods of the GENESIS-PRAXY study have been described.
17
Ethics
In Quebec, a multicenter ethics review allowed for the McGill University Heath Centre to act as the central review board and coordinate ethics approval for all centers. All other centers received ethics approval from their respective hospital ethics review boards.
Study Population and Data Sources
Patients who presented with acute coronary syndrome (see “Acute Coronary Syndrome Case Definition”) to one of the participating hospitals and were aged 18 to 55 years, fluent in English or French, and able to provide informed consent were eligible for the study. Eligible patients with acute coronary syndrome were approached by the research nurse in the Coronary Care Unit or cardiology wards at the earliest possible time after admission. A total of 1156 patients were recruited, and for the present substudy, 1023 patients with complete baseline data were included.
Procedure
After the completion of the consent form, participants were asked to complete a self-administered questionnaire. Anthropometric measurements and a blood sample were then taken by a research nurse. Medical chart reviews were carried out by a research nurse to collect participants' medical history and current acute coronary syndrome characteristics, including disease severity data.
Acute Coronary Syndrome Case Definition
Eligible patients had symptoms consistent with acute coronary syndrome on hospital presentation and at least 1 of the following conditions: (1) significant electrocardiogram changes: transient ST-segment elevations of ≥1 mm, ST-segment depressions of ≥1 mm, new T-wave inversions of ≥1 mm, pseudo-normalization of previously inverted T waves, new Q waves (one third the height of the R wave or ≥0.04 seconds), new R wave > S wave in lead V1 (posterior myocardial infarction), new left bundle branch block (changes had to be seen in ≥2 contiguous leads); or (2) increase in cardiac enzymes: creatine kinase-MB >2× upper limit of the hospital's normal range or if no creatine kinase-MB available, then total creatine phosphokinase >2× upper limit of the hospital's normal range, positive troponin I, positive troponin T (Global Registry of Acute Coronary Events [GRACE] Variable Definitions, Version of March 2006).
Demographic and Medical Characteristics
Age, sex, education level, marital status, income, antidepressant use, type of acute coronary syndrome (ST-elevation myocardial infarction, non–ST-elevation myocardial infarction, unstable angina), hypertension, diabetes, dyslipidemia, smoking status, and previous myocardial infarction were determined using a combination of self-report and chart review data. Body mass index was calculated from height and weight (kilograms/meters squared).
Disease Severity Measures
Measures of acute coronary syndrome severity included type of acute coronary syndrome, left ventricular ejection fraction, Killip class, cardiac troponin I level, and GRACE score. Left ventricular ejection fraction and Killip class were determined using chart review data. Left ventricular ejection fraction >50% was considered “normal,” and values ≤50% were considered as “abnormal” left ventricular function. Cardiac troponin I was determined using a blood sample drawn by the research nurse within 24 hours of hospital admission. Collected blood samples were immediately centrifuged and stored locally at −80 °C until being transported in dry ice to the McGill University Health Centre. Cardiac troponin I levels were analyzed centrally at the core laboratory of the Royal Victoria Hospital in Montreal, using a highly sensitive enzyme-linked immunosorbent assay.
18
The GRACE scores were calculated using chart review data and the Risk Calculator for 6-Month Postdischarge Mortality After Hospitalization for Acute Coronary Syndrome.19
Assessment of Depression
Major depression before the index acute coronary syndrome was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
20
As part of the self-report questionnaire, participants had to refer to how they were feeling before their acute coronary syndrome and answer 9 questions representing DSM-IV criteria for major depression. Major depression was identified when patients answered “yes” to 5 or more of the 9 questions and where 1 of the reported symptoms was a loss of interest in daily activities or feeling blue, sad, or depressed most days of the week for 2 weeks or more in a row.20
Recall of depressive symptoms before the index acute coronary syndrome was assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).
21
The HADS is a self-report questionnaire developed to detect adverse anxiety and depressive states. Participants were asked to choose 1 response from the 4 given on a Likert-type scale for each of the 7 questions on the depression subscale. Validity studies have demonstrated sensitivity and specificity values around 80% for the depression subscale of the HADS.22
Statistical Analyses
Baseline demographic and medical characteristics of patients with and without major depression were compared using t tests and chi-square tests. In the regression analyses, major depression was a binary independent variable, whereas depressive symptoms were considered as a continuous variable. Because of the bimodal distribution of left ventricular ejection fraction and Killip class, the latter 2 variables were considered as dichotomous outcomes. Left ventricular ejection fraction values >50% were considered “normal,” and values ≤50% were considered as “abnormal” left ventricular function. Killip class II, III, and IV were grouped and compared against Killip class I. Troponin I levels and GRACE score were used as continuous outcomes. To assess the main effect of major depression, as well as its interaction with sex, on left ventricular ejection fraction, Killip class, troponin I levels, and GRACE score, a series of logistic and linear regressions were performed. For each outcome, univariate and then multivariate analyses were conducted with no interaction term first, and then with the addition of an interaction term between major depression/depressive symptoms and sex. All multivariable models were adjusted for age, sex, marital status, education level, family income, previous myocardial infarction, type of current acute coronary syndrome, diabetes, dyslipidemia, hypertension, body mass index, antidepressant use, and cigarette smoking. All covariates were selected a priori on the basis of previous literature.
8
, 10
, 11
, 23
, 24
All statistical analyses were performed using SAS version 9.2 (SAS Institute Inc, Cary, NC). Statistical tests were 2-sided; a P value ≤.05 was considered statistically significant.
Results
Baseline Characteristics
Among our sample, 302 (30%) were women and 248 participants (25%) reported symptoms consistent with major depression. As detailed in Table 1, participants with major depression were more likely to be female; to have hypertension, diabetes, dyslipidemia, and a history of myocardial infarction; to be current smokers; and to be taking antidepressants. They were less often married, had lower education levels, and had lower family incomes. They also were less often diagnosed with an ST-elevation myocardial infarction and more often with a non–ST-elevation myocardial infarction.
Table 1Patients' Characteristics According to Major Depression Status
| % (n) | Major Depression n = 248 | No Major Depression n = 753 | P Value |
|---|---|---|---|
| Sociodemographic | |||
| Female | 40 (99) | 27 (202) | <.001 |
| Age, y, mean (SD) | 48 (5.9) | 48 (5.9) | .38 |
| Married | 62 (153) | 70 (530) | .01 |
| Post-secondary education | 52 (130) | 63 (475) | .003 |
| Family income, mean, $ (SD) | 58,000 (38,000) | 76,000 (36,000) | <.001 |
| Risk factors | |||
| Hypertension | 58 (143) | 44 (334) | <.001 |
| Dyslipidemia | 63 (155) | 53 (398) | .008 |
| Diabetes | 26 (65) | 13 (101) | <.001 |
| BMI, mean (SD) (weight [kg]/height [m2]) | 30 (7.1) | 29 (8.5) | .10 |
| Smoking | 52 (129) | 38 (286) | <.001 |
| Previous myocardial infarction | 21 (53) | 14 (102) | .003 |
| Antidepressant use | 16 (40) | 6 (42) | <.001 |
| Type of index ACS | |||
| STEMI | 50 (124) | 63 (473) | <.001 |
| NSTEMI | 39 (97) | 22 (220) | .004 |
| Unstable angina | 9 (23) | 7 (50) | .17 |
ACS = acute coronary syndrome; BMI = body mass index; SD = standard deviation; STEMI = ST-elevation myocardial infarction; NSTEMI = non–ST-elevation myocardial infarction.
Major Depression and Disease Severity
Table 2 shows mean levels of markers of disease severity according to major depression status. In univariate analyses, major depression was associated with less severe cardiac disease, as assessed by left ventricular ejection fraction and troponin I levels. There was no univariate effect of major depression on Killip class and GRACE score (Table 3). However, in the adjusted models, major depression was no longer associated with left ventricular ejection fraction and troponin I levels, and there was no association with Killip class and GRACE score. Analyses including the interaction term between major depression and sex revealed no interaction effect on any of the outcomes, both in the univariate and adjusted models.
Table 2Markers of Disease Severity According to Major Depression Status
| Mean (SD) | Major Depression | No Major Depression | P Value |
|---|---|---|---|
| Left ventricular ejection fraction (%) | 52 (11.0) | 50 (10.4) | .06 |
| Killip class | II (0.7) | II (0.7) | .94 |
| Troponin I level | 13.14 (23.1) | 17.17 (24.1) | .05 |
| GRACE score | 70 (18.1) | 71 (16.8) | .46 |
GRACE = Global Registry of Acute Coronary Events; SD = standard deviation.
Table 3Associations Between Major Depression and Markers of Disease Severity
| Unadjusted | Adjusted ∗ Adjusted for age, sex, marital status, education level, family income, previous myocardial infarction, type of current acute coronary syndrome (ie, ST-elevation myocardial infarction vs non–ST-elevation myocardial infarction or unstable angina), diabetes, dyslipidemia, hypertension, body mass index, antidepressant use (prior current acute coronary syndrome), and cigarette smoking. | |||
|---|---|---|---|---|
| OR (95% CI) | P | OR (95% CI) | P | |
| LVEF | 0.70 (0.51-0.97) | .03 | 0.74 (0.50-1.11) | .14 |
| Killip class | 1.11 (0.83-1.48) | .50 | 1.23 (0.87-1.73) | .24 |
| Estimate (95% CI) | P | Estimate (95% CI) | P | |
| Troponin I | −4.04 (−8.01 to −0.06) | .05 | −0.29 (−4.70 to 4.12) | .90 |
| GRACE score | −0.92 (−3.38 to 1.54) | .46 | −0.89 (−2.97 to 1.19) | .40 |
CI = confidence interval; GRACE = Global Registry of Acute Coronary Events; LVEF = left ventricular ejection fraction; OR = odds ratio.
∗ Adjusted for age, sex, marital status, education level, family income, previous myocardial infarction, type of current acute coronary syndrome (ie, ST-elevation myocardial infarction vs non–ST-elevation myocardial infarction or unstable angina), diabetes, dyslipidemia, hypertension, body mass index, antidepressant use (prior current acute coronary syndrome), and cigarette smoking.
Depressive Symptoms (Hospital Anxiety and Depression Scale D) and Disease Severity
When the HADS-D score was entered as a continuous variable, depressive symptoms were not associated with left ventricular ejection fraction, Killip class, troponin I levels, or GRACE score in both the univariate and adjusted models (Table 4). As with major depression, there were no interaction effects between sex and depressive symptoms on left ventricular ejection fraction, Killip class, troponin I levels, or GRACE score in both the univariate and adjusted models.
Table 4Associations Between Depressive Symptoms (Hospital Anxiety and Depression Scale Score) and Markers of Disease Severity
| Unadjusted | Adjusted ∗ Adjusted for age, sex, marital status, education level, family income, previous myocardial infarction, type of current acute coronary syndrome (ie, ST-elevation myocardial infarction vs non–ST-elevation myocardial infarction or unstable angina), diabetes, dyslipidemia, hypertension, body mass index, antidepressant use (prior current acute coronary syndrome), and cigarette smoking. | |||
|---|---|---|---|---|
| OR (95% CI) | P | OR (95% CI) | P | |
| LVEF | 1.01 (0.97-1.04) | .78 | 1.00 (0.96-1.05) | .99 |
| Killip class | 1.02 (0.99-1.06) | .13 | 1.02 (0.99-1.06) | .23 |
| Estimate (95% CI) | P | Estimate (95% CI) | P | |
| Troponin I | −0.25 (−0.68 to 0.17) | .25 | 0.05 (−0.44 to 0.55) | .84 |
| GRACE score | −0.01 (−0.27 to 0.25) | .94 | −0.15 (−0.39 to 0.08) | .19 |
CI = confidence interval; GRACE = Global Registry of Acute Coronary Events; LVEF = left ventricular ejection fraction; OR = odds ratio.
∗ Adjusted for age, sex, marital status, education level, family income, previous myocardial infarction, type of current acute coronary syndrome (ie, ST-elevation myocardial infarction vs non–ST-elevation myocardial infarction or unstable angina), diabetes, dyslipidemia, hypertension, body mass index, antidepressant use (prior current acute coronary syndrome), and cigarette smoking.
Covariates and Disease Severity
Multivariate models revealed that education level was the only psychosocial factor that was independently associated with markers of disease severity. Specifically, patients who had completed post-secondary education had a 36% and 30% lower probability of having abnormal left ventricular ejection fraction (95% confidence interval [CI], 0.45-0.91; P = .001) and Killip class >I (95% CI, 0.51-0.94; P = .02), respectively. ST-elevation myocardial infarction diagnosis (as opposed to non–ST-elevation myocardial infarction and unstable angina) was associated with lower left ventricular ejection fraction (odds ratio, 3.44; 95% CI, 2.42-4.90, P < .0001), increased troponin I levels (estimate, 16.59; 95% CI, 12.75-20.42; P < .001), and higher GRACE scores (estimate, 4.95; 95% CI, 3.17-6.73; P < .001). Previous myocardial infarction also was associated with lower left ventricular ejection fraction (odds ratio, 2.28; 95% CI, 1.39-3.76; P = .001) and higher GRACE scores (estimate, 12.56; 95% CI, 10.04-15.08; P < .001), whereas smoking status was related to increased troponin I levels only (estimate, 4.39; 95% CI, 0.52-8.26; P = .03). It is noteworthy that female sex was associated independently with less severe disease, as assessed using troponin I (estimate, −5.53, 95% CI, −9.76 to −1.31; P = .01).
Discussion
Results of the present study indicated that in a sample of 1023 patients hospitalized for premature acute coronary syndrome, major depression was not associated with cardiac disease severity, as assessed by left ventricular ejection fraction, Killip class, troponin I levels, and GRACE score. Likewise, we observed no association between depressive symptoms and cardiac disease severity. Our results also indicate that the relationship between major depression/depressive symptoms and disease severity does not differ between men and women hospitalized for premature acute coronary syndrome.
In univariate analyses, major depression was associated with higher left ventricular ejection fraction and lower troponin I levels. However, the results of the multivariate analyses suggest that these relationships are not independent of demographic and clinical characteristics. For example, we observed that education level was associated with left ventricular ejection fraction and Killip class in the unadjusted and adjusted model of analyses, and education level differs as a function of major depression status. Also, ST-elevation myocardial infarction diagnoses were associated with lower left ventricular ejection fraction and higher troponin I levels in both the univariate and adjusted models, and patients with major depression were less likely to be diagnosed with ST-elevation myocardial infarction compared with non–ST-elevation myocardial infarction and unstable angina (although this is not surprising because ST-elevation myocardial infarction vs non–ST-elevation myocardial infarction and unstable angina also could be considered as a marker of disease severity).
Our results confirm those of the only 2 previous studies that have adjusted their analyses for potential demographic and clinical confounders.
10
, 11
Einvik et al10
observed that major depression tended to be associated with lower levels of cardiac troponin T in univariate analysis, but they observed no association in the multivariate model. Lett et al11
observed univariate associations between major depression and better cardiac function assessed, among other measures, by left ventricular ejection fraction. However, in models adjusted for demographic and clinical confounders, major depression was not associated with indicators of disease severity, such as left ventricular ejection fraction. Inversely, previous studies reporting associations between major depression and depressive symptoms and disease severity did not adjust their models for potential confounders and rather reported descriptive statistics only,2
, 7
, 9
with the exception of 1 study, which was adjusted for anxiety and diabetes only.8
Our results, along with the previous evidence, suggest that other reports of associations between depression and disease severity may be confounded by patients' demographic and clinical characteristics.Another finding from our study is that the analyses including major depression and depressive symptoms yielded similar results. The study by Lett et al
11
was the only other study, to our knowledge, to have compared the effect of major depression with depressive symptoms using multivariate analyses. The authors observed that neither major depression nor depressive symptoms were associated with indices of disease severity, and they concluded that this finding would need confirmation in other studies, which our results seem to do.A novel finding of our study is that education level was independently associated with left ventricular ejection fraction and Killip class over and above clinical characteristics. Patients who completed post-secondary education, an indicator of higher socioeconomic status, had a 36% and 30% lower probability of having abnormal left ventricular function and Killip classes II, III, or IV (compared with Killip class I), respectively. Univariate and multivariate relationships between education and cardiovascular disease outcomes both have been reported in the past.
24
In the Framingham Offspring Study, lower education levels also were associated independently with higher levels of inflammatory markers, suggesting a biological pathway in the relationship between education and cardiovascular disease outcomes.25
However, to our knowledge, our study is the first to report independent associations between education and markers of disease severity, which may confirm the hypothesis of biological mechanisms underlying the association between education and cardiovascular disease outcomes. We also observed that ST-elevation myocardial infarction diagnosis, as opposed to non–ST-elevation myocardial infarction and unstable angina, was associated with increased disease severity on 3 of the 4 outcomes. Previous myocardial infarction also was associated with lower left ventricular ejection fraction and higher GRACE scores, whereas smoking status was associated with increased troponin I levels. Of note, female sex was associated independently with lower levels of troponin I.Study Limitations
Our study has methodological limitations. First, our sample includes patients hospitalized for premature acute coronary syndrome. Therefore, we cannot exclude the possibility that self-report measures, such as the recall of major depression and depressive symptoms before the acute coronary syndrome, may have been confounded by the mental and physical state of patients who just underwent a life-threatening event. However, this limitation is inherent to all studies having included patients hospitalized post-myocardial infarction,
2
, 7
, 9
, 13
which makes our design comparable to those in the literature. Furthermore, one would expect that if the timing of the questionnaire administration was to have a confounding effect on the outcomes, it would have led to a greater probability of a relationship between depression and disease severity, which we did not see. Second, major depression was determined using self-report symptoms consistent with DSM-IV criteria, so our measure may not be as sensitive as a clinical interview. However, the rate of major depression observed in our sample (25%) is consistent with previous studies including patients post-myocardial infarction,26
which makes us more confident in our measure. Third, blood samples were drawn within 1 day of hospital admission, and differences between patients of up to 24 hours in the delay between admission and blood draw may have influenced results of troponin I measurements. However, results were consistent across all disease severity measures, suggesting that this did not play a large part in our results. Finally, patients who died before or early after hospital admission could not be included in the study. It is plausible that these patients had greater disease severity; therefore, a selection bias may have been introduced.Despite its limitations, this study has important strengths. This is the first study to assess the association between depression and disease severity in younger men and women with acute coronary syndrome. Our large sample size, the inclusion of both men and women, the multicenter design, the objective and multiple measures of disease severity, the statistical adjustments for demographic and clinical characteristics, and the assessment of both major depression and depressive symptoms are other notable strengths of the study.
Our results are important because they indicate that the relationship between depression and cardiac outcomes may not be explained by depression as a marker of disease severity, suggesting that other mechanisms are likely involved. For example, the prevalence of traditional cardiovascular disease risk factors was higher in our patients with major depression compared with their nondepressed counterparts. However, most of these risk factors were not associated with disease severity in our cohort. Also, multiple behavioral (eg, increased smoking
27
and alcohol consumption,28
nonadherence to treatment29
) and biological (eg, decreased heart rate variability,30
, 31
endothelial dysfunction,32
dysregulated endocrine function33
) mechanisms have been suggested as moderators of the relationship between depression and cardiovascular disease outcomes. Our results suggest that future studies should focus on these mechanisms or other new avenues when attempting to explain the relationship between depression and outcomes.Conclusions
This study found no evidence of associations between depression and disease severity in patients hospitalized for premature acute coronary syndrome. Moreover, the relationship did not differ between women and men. Therefore, it is unlikely that results of prospective studies indicating poorer outcomes in depressed patients, particularly younger women and men, are confounded by disease severity.
Appendix A. Co-Investigators for GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome
Co-Principal Investigator
- Igor Karp
- Research Center of CHUM
- 3875 St-Urbain St, 3rd floor
- Montréal, Québec
- H2W 1V1
Co-Investigators
- Simon Bacon
- Department of Exercise Science
- Concordia University
- SP165.35, 7141 Sherbrooke St West
- Montréal, Québec
- H4B 1R6
- Jafna Cox
- QEII Health Sciences Center
- NHI Site
- PO Box 9000, Room 2147
- Halifax, Nova Scotia
- B3K 6A3
- Kaberi Dasgupta
- McGill University Health Centre
- Division of Clinical Epidemiology
- V Building
- 687 Pine Ave West, Room V1.08
- Montréal, Québec
- H3A 1A1
- Stella Daskalopoulou
- McGill University Health Centre
- Division of Internal Medicine
- Montreal General Hospital
- 1650 Cedar Ave
- Montréal, Québec
- H3G 1A4
- Mark Eisenberg
- Jewish General Hospital-Sir Mortimer B. Davis
- Divisions of Cardiology and Clinical Epidemiology
- 3755 Cote Ste Catherine Rd, Room A-118
- Montréal, Québec
- H3T 1E2
- James Engert
- McGill University, Division of Cardiology
- Royal Victoria Hospital, H7.11
- 687 Pine Ave West
- Montréal, Québec
- Canada
- H3A 1A1
- William Ghali
- University of Calgary
- Department of Medicine and Community Health Sciences
- 3330 Hospital Drive NW
- Calgary, Alberta
- T2N 4N1
- Karin Humphries
- St Paul's Hospital
- CHEOS
- 1081 Burrard St, Room 620B
- Vancouver, British Columbia
- V6Z 1Y6
- Nadia Khan
- Center for Health Evaluation and Outcome Sciences
- 1081 Burrard St, Room 620-B
- Vancouver, British Columbia
- V6Z 1Y6
- Kim Lavoie
- University of Québec at Montréal
- Department of Psychology
- PO Box 8888, Succursale Centre-Ville
- Montréal, Québec
- H3C 3P8
- Colleen Norris
- 4-130F Clinical Sciences Building,
- University of Alberta
- Edmonton, Alberta
- T6G 2G3
- Doreen Rabi
- Department of Community Health Sciences,
- Faculty of Medicine,
- Heritage Medical Research Building
- 3330 Hospital Drive NW, Room G02
- Calgary, Alberta
- T2N 4N1
- Derek So
- University of Ottawa Heart Institute
- 40 Ruskin St
- Ottawa, Ontario
- K1Y 4W7
- Ken Stark
- Laboratory of Nutritional and Nutraceutical Research,
- Department of Kinesiology,
- Faculty of Applied Health Sciences,
- University of Waterloo,
- Waterloo, Ontario
- N2L 3G1
- Vicky Tagalakis
- Jewish General Hospital-Sir Mortimer B. Davis,
- Center for Clinical Epidemiology and Community Studies,
- 3755 Cote Ste Catherine Rd, Room A-131,
- Montréal, Québec
- H3T 1E2
Appendix BGENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome
| Site Name | Site Principal Investigator |
|---|---|
| St Paul's Hospital | Krishan Ramanthan |
| Surrey Memorial Hospital | Jan Kornder |
| Calgary Health Region—Foothills Medical Centre | Todd Anderson/Doreen Rabi |
| University of Alberta Hospital | Colleen Norris/Michelle Graham |
| University of Ottawa Heart Institute | Derek So |
| McMaster Hamilton Health Sciences Corp—General Campus | Madhu Natarajan |
| McMaster Hamilton Health Sciences Corp—Henderson Site | Mike Rokoss |
| Ottawa General Hospital | Michele Turek |
| St Michael's Hospital | Asim Cheema |
| London Health Sciences Centre | Shahar Lavi |
| Scarborough General Hospital | Sherryn Roth |
| Hôpital Général de Montréal | Thao Huynh |
| Hôpital Royal Victoria | Viviane Nguyen |
| Hôpital Général Juif—Sir Mortimer B. Davis | Mark Eisenberg |
| Hôpital Laval | Julie Méthot |
| Hôpital du Sacré-Coeur de Montréal | Michel Doucet |
| Cité de la Santé de Laval | Martine Montigny |
| Hôtel Dieu du centre hospitalier de l'Université de Montréal | Samer Mansour |
| Centre Hospitalier de Région L'Amiante/Thetford Mines | Claude Lauzon |
| Hôpital de Chicoutimi | Tomas Cieza |
| Centre Hospitalier Fleurimont Universitaire de Sherbrooke | Michel Nguyen |
| Queen Elizabeth II Health Science Centre | Jafna Cox |
| New Brunswick Heart Centre Research Initiative | Peter Fong |
| Basset Healthcare | Dhananjai Menzies |
| Centre Médicale Universitaire, CH Lausanne | Nicolas Rodondi |
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Footnotes
Funding: This study was funded by the Canadian Institutes of Health Research and the Heart and Stroke Foundations of Quebec, Nova Scotia, Alberta, Ontario, Yukon and British Columbia, Canada. RP is supported by a Canadian Institute of Health Research Award. KLL is funded by a Canadian Institutes of Health Research New Investigator award and a Fonds de recherche en santé Québec chercheur-boursier award. SLB is supported by a Canadian Institutes of Health Research New Investigator award and a Fonds de recherche en santé Québec chercheur-boursier award. GT is funded by a Fonds de recherche en santé Québec chercheur-boursier clinicien junior I award. NK is funded by a Michael Smith Foundation for Health Research Career Scientist award. LP is supported by a Fonds de recherche en santé Québec award and holds a James McGill Chair in medicine.
Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in writing this manuscript.
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