In this analysis, chronic depressive symptoms were associated with higher Framingham risk scores at 9.5-year follow-up even after controlling for known risk factors including baseline Framingham risk score. Chronic depressive symptoms increased CVD risk in both HIV-infected and uninfected women. These findings are important for a number of reasons. First, depression is a modifiable risk factor that could be targeted for intervention possibly reducing CVD risk. Second, in the HAART era, CVD death is a leading cause of mortality in HIV-infected persons (French et al., 2009
The fact that there was not a statistically significant difference in chronic depressive symptoms between the HIV-infected and uninfected women was surprising although this difference (i.e., 23% HIV-infected vs. 16% uninfected) bordered on significance and may have been an issue of statistical power. Twenty-three percent of HIV-infected participants experiencing chronic depressive symptoms is somewhat lower than prior studies, but this may be due to differences in timing in data collection relative to the HAART era (Ickovics et al., 2001
). It is also likely that women with chronic depressive symptoms were underrepresented because we excluded those who did not provide CES-D data for at least 15 of the 20 visits and, in general, individuals suffering from depression are less likely to be adherent to medical appointments and exclusion analyses indicated higher baseline CES-D scores among excluded participants (Holzemer et al., 1999
; Gonzalez et al., 2008
). Despite this possible limitation, a strength of the current study is that it is one of the first to examine the impact of depressive symptom chronicity
on a CVD risk score as opposed to cross-sectionally only (Evans et al., 1995
; Kaplan, Marks, & Mertens, 1997
; Kilbourne et al., 2002
In the current study, univariate analyses indicated that higher follow-up FRS was also associated with Black race and lower household income. These findings are consistent with prior cross-sectional studies showing CVD was associated with demographic factors in the HIV and non-HIV settings (Kaplan et al., 2007
). However, these demographic factors did not maintain significance in the multivariate model with chronic depressive symptoms. Given the higher prevalence rates of depression among lower income and Black individuals in the US (Centers for Disease Control & Prevention, 2004
), it is not surprising that the impact of these factors on FRS appeared to be attenuated by depressive symptoms.
The only consistently significant variable associated with increased FRS besides chronic depressive symptoms was a lack of significant alcohol use. It is possible that this is because participants who were HIV-uninfected were more likely to be significant drinkers than HIV-infected participants and the FRS score was somewhat, although not significantly, lower (i.e., better) among HIV-uninfected participants. However, a test of the interaction between HIV-status and alcohol use was not significant. It is also possible that our definition of significant alcohol use (i.e., >3 drinks per week) is actually protective at least when the number of drinks per week is around 3 or 4 given research indicating that moderate alcohol use can increase HDL levels (Foerster et al., 2009
). A final possibility is that some of the non-drinkers in the current study are abstaining from alcohol use due to having a history of prior abuse, so it’s possible that their increased FRS is due to prior excess drinking history.
There are a number of limitations of the current study. First, we used FRS as a raw score and not as the calculated risk in order to have a large enough distribution for analysis which yields means that extend to negative numbers. Adjusted scores of 2.4 and 0.1 translate to approximate 10 year event rates of 3% and 2% (Wilson et al., 1998
). Although this difference is small, the low FRSs are largely determined by young age and female gender. The women may well have been too young to demonstrate larger differences and these differences may increase with time. Second the CES-D is a measure of depressive symptomatology and not a diagnostic measure of major depressive disorder. It is possible that use of a clinical diagnostic tool may have somewhat altered results although this has not been the case in other studies that have used such measures (Devanand et al., 2004
; Fraguas et al., 2007
; Sesso et al., 1998
). Third, the study participants were all female as well as racially and ethnically diverse and it is possible that FRS may underestimate true CV risk in female and minority populations (Cappuccio, Oakeshott, Strazzullo, & Kerry, 2002
; Michos et al., 2006
). However, among the various CV risk prediction equations, those derived from the Framingham Heart Study are most commonly recommended for use in the United States (Wilson et al., 1998
). Fourth, women included in the study were of lower cardiovascular risk and had less prevalent depression than the large number of baseline enrollees that were not be included in the present analysis due to various reasons as outlined in the methods section. Comparison of women included in the present study to those excluded, the included women (658) were a mean of 1 year younger (35.6±7.8 years vs 36.6±8.1 years, p<0.01, had lower systolic blood pressure (115±15mmHg vs 117±16mmHg, p<0.01), higher HDL (49±13mg/dL vs 47±15mg/dL, p<0.01, and were less likely to have hypertension (14.0% vs 17.7%, p=0.03. Accordingly, their mean Framingham risk score was somewhat lower than those not included (−6.2 ± 7.0 vs−4.9 ± 7.6, p<0.01). In addition, the prevalence of depression at baseline was lower in the included group (53.2% vs.58.1%, p=0.03). Among patients not included in the study, 36.5% had died prior to the follow-up visit and hence could not be included in the present analysis, indicating the presence of possible selection bias. Fifth, survivor bias is likely present especially given the large sample size decrease after baseline among the seropositive participants. Although the mortality risk of the uninfected group may be lower than the infected group, the analysis was limited to survivors who remained active participants in the longitudinal study. Finally, because the women were relatively young and about half were African-American, the results may not generalize to other HIV-infected or at-risk populations.
Despite these limitations, the results suggest that therapeutic interventions for depression should be evaluated with respect to decreasing CV risk. In the non-HIV setting, the relationship between depression and cardiovascular disease has led to efforts to use antidepressants and cognitive behavioral therapy to improve cardiovascular prognosis (Carney, Freedland, & Veith, 2005
; ENRICHD Investigators, 2003
; ENRICHD Investigators, 2004
). To date, such studies have been disappointing as neither antidepressants nor cognitive behavioral therapy have been shown to lower CV event rates, however, there were some inherent design flaws in those early intervention trials (Carney, Freedland, & Veith, 2005
; ENRICHD Investigators, 2003
; ENRICHD Investigators, 2004
). The present study findings suggest that depressive symptoms may worsen CV outcomes by deleteriously influencing CV risk factors and imply that researchers need to think critically about how best to design and evaluate interventions to target depression among both HIV-infected and uninfected women with or at risk for CVD. Given the increasing life expectancy among HIV-infected individuals due to the advent of HAART, interventions focused on the reduction of depressive symptoms may result in benefits on FRS as these women age. Further studies are needed to confirm data from the current study and to determine the specific mediators of the relationship between chronic depressive symptoms and cardiovascular risk among HIV-infected women.