Depression Treatment and Health Status Outcomes in Young Patients With Acute Myocardial Infarction: Insights from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients)

Depression is common among patients with AMI and associated with adverse outcomes. Because depression disproportionately affects women, we examined sex differences in depression treatment rates in young patients with depressive symptoms following AMI admission and evaluated 1-year depressive symptom and health status outcomes by sex and depression treatment status. We evaluated these using the VIRGO, a multi-center, international, prospective cohort study that enrolled patients aged 18–55 years (66.8% women).¹ VIRGO was approved by Yale’s Institutional Review Board and all patients in the study provided informed consent. We abstracted medical records and conducted in-person interviews to record patient characteristics and used the 9-item Patient Health Questionnaire (PHQ-9)² to assess depressive symptoms during or shortly after the AMI admission and 1 and 12 months later. Depression treatment was assessed among those with baseline PHQ-9 scores ≥10. Receiving depression treatment was defined as new or continued anti-depressant medications or depression counseling at discharge or within at 1 month or discharge.

To compare outcomes as a function of depression treatment, we quantified outcomes in those with (1) no significant depressive symptoms [baseline PHQ-9 <10]; (2) treated depressive symptoms [baseline PHQ-9 ≥10 and receiving treatment]; (3) untreated transient depressive symptoms [baseline PHQ-9 ≥10 and untreated, but PHQ-9 <10 at 1 month]; (4) untreated persistent depressive symptoms [baseline PHQ-9 ≥10 and untreated, and PHQ remained ≥10 at 1 month]. The clinical logic for further categorizing untreated depressive symptoms into transient and persistent was to describe the greater benefit of treating those with sustained depressive symptoms rather than transient, self-resolving symptoms. Disease-specific and generic Health Status outcomes were quantified with the Seattle Angina Questionnaire (SAQ) and the EQ-5D visual analogue scale, respectively, up to 1 year.^3,4

Depression treatment rates were calculated and compared by sex using Chi-square tests. The independent association between sex and lack of depression treatment was evaluated among those who had PHQ-9 scores ≥10 at baseline using a hierarchical logistic regression model with a random effect for site and adjusting for age, race, marital status, education, insurance status, prior peripheral arterial disease, diabetes, prior AMI, prior PCI, prior CABG, current smoking, ST-elevation AMI, ejection fraction, heart failure, renal disease, chronic lung disease, cancer, body mass index, PHQ-9 baseline score, and somatic vs. cognitive depressive symptoms.

One-year health status change scores were compared by the 4 depression treatment groups (ANOVA and Wilcoxon tests). Hierarchical, multivariable linear regression models with a random effect for site were constructed to evaluate the association between depression treatment status following AMI and 1-year changes in depressive symptoms and health status scores. In addition to the covariates used in the depression treatment model, baseline health status scores and PHQ-9 scores were also included as appropriate. Interaction terms with sex and depression treatment status were examined but excluded from the final models as they were not significant. All analyses were performed using SAS 9.3 (SAS Institute Inc., Cary, NC).

Our analytic cohort consisted of 3,324 patients, of whom 1,031 (31%) had PHQ-9 scores ≥10; 36.6% (n=813) women and 19.7% (n=218) of men (P<0.0001). Among patients with significant depressive sympoms, 57.8% (596 out of 1031) were not treated for depression. For women, this rate was 54.2% and for men, 71.1% (P<0.0001). Within the untreated depressive symptoms group, symptoms resolved on their own by 1-month follow-up in 407 out of 596 cases (68.3%), whereas in 189 cases (31.7%) the symptoms persisted.

Among patients with a PHQ-9 score ≥10, male sex (OR=1.86, 95% CI 1.30–2.66) was independently associated with untreated depressive symptoms. Overall, the lowest levels of improvements in depressive symptoms, angina, physical limitations, and disease-specific and generic quality of life were noted among patients whose depressive symptoms persisted at 1 month and who were untreated by their providers. One-year SAQ angina, physical limitations and quality of life, and EQ-5D visual analogue scores were lowest for the group with untreated persisting depressive symptoms (P-values for unadjusted comparisons baseline, 1-year, and 1-year change scores across groups all <.001, except for SAQ Quality of Life 1-year change score [P=0.046] and EQ-5D Visual Analogue Scale 1-year change score [P=0.25] – results available upon request). In adjusted models, patients with untreated persistent depressive symptoms had significantly smaller improvements in angina-frequency, and angina-specific quality of life (Table).

Table 1. Adjusted Linear Regression Results For the Association Between Depression Treatment Groups and 1-Year Depression and Health Status Change Scores.

Three groups were compared for Model 1: (1) Treated Depressive Symptoms (reference); (2) Untreated Transient Depressive Symptoms; and (3) Untreated Persistent Depressive Symptoms. Four groups were compared for Models 2–4: patients with (1) No Significant Depressive Symptoms (reference); (2) Treated Depressive Symptoms; and (3) Untreated Transient Depressive Symptoms; and (4) Untreated Persistent Depressive Symptoms. Adjusted Standardized Betas and corresponding 95% Confidence Intervals (CI), and P-values are presented. The interaction term for sex by depression treatment status was not significant in these models and were left out of the final models.

Overview of Adjusted Linear Regression Results for the Association Between Depression Treatment Groups and 1-Year Depression and Health Status Change Scores
Models	1-Year PHQ-9 Change Scores*	1-Year SAQ Angina Frequency Change Scores	1-Year SAQ Physical Limitations Change Scores	1-Year Change SAQ Quality of Life Scores	1-Year Change EQ-5D Visual Analogue Scale Scores
Treated Depressive Symptoms	Reference	0.39 (−2.50; −3.29) P=0.79	−0.23 (−3.46; 3.00) P=0.88	−0.96 (−4.78; 2.85) P=0.62	−0.42 (−3.96; 3.11) P=0.81
Untreated Transient Depressive Symptoms	−2.33 (−3.27; −1.38) P<.0001	0.34 (−2.25; 2.94) P=0.80	2.26 (−0.62; 5.14) P=0.12	2.06 (−1.39; 5.51) P=0.24	3.99 (0.79; 7.19) P=0.0145
Untreated Persistent Depressive Symptoms	0.85 (−0.31; 2.01) P=0.15	−4.21 (−7.66; −0.77) P=0.017	−1.75 (−5.62; 2.11) P=0.37	−7.30 (−11.89; −2.71) P=0.0018	−0.56 (−4.79; 3.67) P=0.79
No Significant Depressive Symptoms		Reference	Reference	Reference	Reference

Abbreviations: PHQ-9, 9-item Patient Health Questionnaire; SAQ, Seattle Angina Questionnaire SD, Standard Deviation.

^*Model 1 was run among those who had PHQ-9 scores ≥ 10 only.

Covariates in the models included age, sex, race, marital status, education, insurance status, prior peripheral arterial disease, diabetes, prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass grafting, current smoking, ST-elevation myocardial infarction, ejection fraction, heart failure, renal disease, lung disease, cancer, body mass index, PHQ-9 baseline score, somatic vs. cognitive symptoms of depression, and baseline depressive symptoms and health status scores as appropriate.

Depression rates among young AMI survivors are highest in women, but men are significantly less likely to be treated. Among patients with persistent depressive symptoms, those who were not treated had significantly more angina and worse disease-specific quality of life. This study provides the first available evidence that being treated for depression in the context of an AMI admission is associated with better AMI recovery in both women and men. It confirms that depression remains common in AMI pateints and is frequently untreated. Improving depression recognition and treatment may offer an opportunity to improve care and outcomes in patients recovering from an AMI.