This study examined the associations of depressive symptoms and hopelessness with carotid atherosclerosis in a cohort of healthy African-American and white women. As hypothesized, higher levels of hopelessness were associated with more IMT whereas depressive symptoms were not, independent of important CVD risk factors, when these constructs were considered simultaneously. Findings are consistent with previous studies reporting that hopelessness relates to CVD in men,14–16
and clinical outcomes in women with documented CAD.17
To our knowledge, this is the first study to report the association of hopelessness with subclinical CVD among healthy women.
Clinical significance of our findings is highlighted by considering the magnitude of difference in IMT observed with increasing hopelessness; each 1-point higher hopelessness score related to a .0061-mm higher mean IMT and a .0074-mm higher maximum IMT (). Thus, a 2-SD difference in hopelessness score would relate to a .0195-mm difference in mean IMT and a .0237-mm difference in maximum IMT. Moreover, women with high hopelessness scores had more than .06-mm greater levels of both mean and maximum IMT than women with lower hopelessness scores. These differences are potentially clinically significant. Average annual change in common carotid artery IMT over 10 years among black and white women in the Atherosclerosis Risk in Communities study was .008 to .009 mm20
; other studies report that IMT increases by .01–.03 mm per year.21
Such small, incremental differences in IMT are associated with increasing cardiovascular risk21
as well as incident CVD and stroke.22
Mechanisms linking hopelessness with subclinical atherosclerosis need to be elucidated. Age, BMI and resting SBP were significant covariates, yet none diminished the relation of hopelessness with IMT. Similarly, the relation of hopelessness with IMT was independent of smoking and income (nonsignificant in the multivariable models), and race (significantly related to mean IMT; marginally related to maximum IMT). Effects of hopelessness have been robust, independent of behavioral, biologic and demographic characteristics14–17
, indicating other mechanisms should be considered. Animal studies show exposure to learned helplessness and uncontrollable stressors – analogs to hopelessness in humans – triggers autonomic, inflammatory and neuroendocrine alterations23, 24
that can potentiate atherogenesis. Alterations in serotonergic function centrally and peripherally may contribute to mood alterations, including depression and hopelessness, and exacerbate CVD risk.25
Significant positive associations of whole blood serotonin (WBS) with hopelessness have been reported in a cohort of older women and men26
but WBS is unrelated to IMT in that cohort.27
Hopelessness likely operates through multiple pathways to influence atherosclerotic risk; future work should focus on several potential mediating mechanisms.
This study raises the question of how hopelessness and depressive symptoms are related. DSM-IV-TR diagnostic criteria for depression do not include hopelessness12
, but consistent evidence for a hopelessness subtype of depression exists11
and hopelessness commonly is included in depressive symptom checklists, such as the CES-D. Moreover, severe depression often is accompanied by feelings of hopelessness. In our study, the correlation between the 2-item measure of hopelessness and the 20-item CES-D is small but statistically significant (r=0.27, p<.0001); the association of the single CES-D item, “I felt hopeful about the future,” with the hopelessness scale also is small (r=−0.31, p<.0001). The correlation of the hopelessness scale with the CES-D is strikingly similar to its association with other depressive symptom checklists.28
It is clear this measure captures feelings of futility or loss of hope that do not map directly onto other depressive symptoms. Moreover, our pattern of findings suggests hopelessness confers unique risk of CVD.
African-Americans have significantly greater mean IMT than whites in our cohort; however, no significant interactions with hopelessness or depressive symptoms were observed. Other reports from SWAN Heart have observed racial differences. CES-D scores were significantly related to aortic calcification amongst African-American participants only in a multivariable model29
, but hopelessness was not included in those analyses. Aortic calcification and IMT represent structural changes to the vasculature and are considered early markers of the atherosclerotic disease process in women30
; however, these two indices are only modestly correlated in SWAN (r=.2, p<.001) and may represent differing underlying processes.31, 32
Our study has several strengths. The SWAN Heart Study focuses on community-dwelling women, thus enhancing generalizability of findings. We used state-of-the-art assessments of IMT in a well-characterized cohort of women. Finally, we controlled for important CVD risk factors to demonstrate the independent associations of hopelessness and depressive symptoms with IMT.
Limitations include the cross-sectional nature of the data. It remains to be seen whether hopelessness influences atherosclerotic progression in women. Also, SWAN women are relatively healthy and the majority came from middle or upper-middle income households; it is unknown if similar associations would be observed in women with more adverse cardiovascular profiles or who experience greater socioeconomic disadvantage, for example, or who differ in other ways from our cohort.
In conclusion, this study demonstrates that hopelessness is a strong and significant correlate of subclinical atherosclerosis in African-American and white women, independent of depressive symptoms and known CVD risk factors. Further research is needed to understand mechanisms that may mediate this association and to determine whether hopelessness predicts accelerated progression of atherosclerosis in women.