Sex and age differences in the association of depression with obstructive coronary artery disease and adverse cardiovascular events

Abstract

Background: Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women.

Methods and results: We examined 3237 patients undergoing coronary angiography for evaluation of CAD and followed them for 2.9 years (median). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)-9, and CAD burden was dichotomized based on its presence or absence. After multivariable adjustment for CAD risk factors, depressive symptoms predicted CAD presence in women aged ≤ 55 years (odds ratio=1.07 95% confidence interval [CI] 1.02 to 1.13 per 1 point increase in PHQ-9 score), but not in men aged ≤ 55 years or women aged >55 years. Depressive symptoms also predicted increased risk of death in women aged ≤ 55 years (adjusted hazard ratio=1.07, 95% CI 1.02 to 1.14, per 1 point increase in PHQ-9 score), but not in men aged ≤ 55 years and women aged >55 years, with P=0.02 for the depression-sex interaction and P=0.02 for depression-sex-age interaction.

Conclusions: Among patients with suspected or established CAD, depressive symptoms are associated with increased risk of death, particularly in young women. This group may be especially vulnerable to the adverse cardiovascular effects of depression.

Keywords: coronary artery disease; depression; sex differences.

Figure 1.

Proportion of patients with moderate or higher severity depressive symptoms (PHQ‐9≥10) according to age and sex. PHQ‐9 indicates Patient Health Questionnaire‐9.

Figure 2.

Prevalence of coronary artery disease, as well as risk of death and major adverse cardiac events according to PHQ‐9 score in women aged ≤55 years. CAD indicates coronary artery disease; MACE, major adverse cardiovascular events; PHQ‐9, Patient Health Questionnaire‐9.

Figure 3.

Adjusted odds ratio of coronary artery disease for moderate/severe depression (PHQ‐9≥10) compared with no or mild depression (PHQ<10). Models are adjusted for age, black race, hypertension, hyperlipidemia, diabetes, heart failure, current/past smoking, body‐mass index, history of stroke, and reason for cardiac catheterization (acute myocardial infarction, symptoms, or positive stress test), Gensini score, and post‐catheterization intervention. *CAD prevalence in depressed vs non‐depressed groups. Note: Sex‐depression interaction P=0.02, 0.36, and 0.45 for ages ≤55, 56 to 65, and ≥65 years, respectively. Sex‐age‐depression interaction P=0.03. CAD indicates coronary artery disease; OR, odds ratio; PHQ‐9, Patient Health Questionnaire‐9.

Figure 4.

Adjusted hazard ratio of death or major adverse cardiac events for moderate/severe depression (PHQ‐9≥10) compared with no or mild depression (PHQ<10). Models are adjusted for age, black race, hypertension, hyperlipidemia, diabetes, heart failure, current/past smoking, body‐mass index, history of stroke, and reason for cardiac catheterization (acute myocardial infarction, symptoms, or positive stress test), Gensini score, and post‐catheterization intervention. *Event rates per 100 person‐years in depressed vs non‐depressed groups. Note: For death, sex‐depression interaction P=0.09, 0.98, and 0.93 for ages ≤55, 56 to 65, and ≥65 years, respectively. For MACE, sex‐depression interaction P=0.049, 0.90, and 0.77 for ages ≤55, 56 to 65, and ≥65 years, respectively. Sex‐age‐depression interaction P=0.24 and P=0.29 for death and MACE, respectively. CAD indicates coronary artery disease; HR, hazard ratio; MACE, major adverse cardiac events; PHQ‐9, Patient Health Questionnaire‐9.