Plasma Proteins Associated With Psychosocial Factors and Heart Disease: The Jackson Heart Study

Knowledge of proteomic mechanisms explaining the link between psychosocial stress and cardiovascular disease is limited. This study aimed to (1) identify plasma proteins associated with psychosocial factors and (2) assess associational pathways between psychosocial factors, identified proteins, and incident cardiovascular disease events in a discovery cohort, JHS (Jackson Heart Study), and 2 replication cohorts, the CHS (Cardiovascular Health Study), and the MESA (Multi-Ethnic Study of Atherosclerosis).

JHS participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were included (n=2143, mean age=55.3). Depressive symptoms and perceived stress scores were measured via the 20-item Center for Epidemiological Studies scale and an 8-item perceived stress scale adapted for the JHS, respectively. Multivariable linear regression models were used to test the association between psychosocial factors and plasma proteins, controlling for age, sex, proteomics batch, and estimated glomerular filtration rate. Bonferroni correction was used for multiple testing (P<3.782×10^-5) and meta-analyses were performed across cohorts. Mediation analyses with Cox proportional hazards models were used to evaluate potential proteomic pathways in the association between psychosocial factors and coronary heart disease, heart failure, and stroke in JHS.

Angiopoietin-2 (β=0.014, SE=0.003, P<0.001), contactin-5 (β=-0.017, SE=0.003, P<0.001), growth/differentiation factor 15 or macrophage inhibitory cytokine 1 (β=0.014, SE=0.002, P<0.001), neural cell adhesion molecule 120 (β=-0.016, SE=0.003, P<0.001), and KYNU (kynureninase; β=0.014, SE=0.003, P<0.001) were each significantly associated with depressive symptoms, with angiopoietin-2, contactin-5, macrophage inhibitory cytokine 1, and neural cell adhesion molecule 120 replicating in CHS and MESA. Leukotriene A-4 hydrolase was associated with perceived stress (β=0.0235, SE=0.005, P<0.001). Macrophage inhibitory cytokine 1 partially accounted for the association between depressive symptoms and incident coronary heart disease in JHS (23%; P<0.001).

Novel associations between psychosocial factors, plasma proteins, and cardiovascular disease were identified in JHS. Circulating proteomic profiles across 3 cardiovascular disease cohorts showed differences in protein concentrations by psychosocial measures. Future investigations should identify additional potentially targetable proteomic mechanisms by which psychosocial factors contribute to disease.