Research paperDepression is a risk factor for incident coronary heart disease in women: An 18-year longitudinal study
Introduction
The medical sub-speciality of psychocardiology (Halaris, 2013, Jordan et al., 2007) has emerged in recognition of the contribution of psycho-social factors including stress, lack of social support and negative emotions to deleterious cardiovascular outcomes (Frasure-Smith et al., 1995a, Frasure-Smith et al., 1995b). For those with established coronary disease, depression increases the risk of morbidity, mortality (Frasure-Smith et al., 1995a, Frasure-Smith et al., 1995b), suicide (Larsen et al., 2016), poor risk factor profiles and functional outcomes (Bhattacharyya et al., 2007). Anxiety has also been linked to smoking, hypercholesterolemia and poorer diabetes control (Moylan et al., 2013).
An expert working group was recently commissioned by the American Heart Association to review the evidence and determine whether depression should be elevated to ‘risk factor’ status for poor prognosis in acute coronary syndrome (ACS) patients (Lichtman et al., 2014). Based on data from 53 individual studies and 4 meta-analyses, the group concluded that depression was predictive of all-cause/cardiac mortality and nonfatal cardiac events in both men and women with established disease. Their primary recommendation was that depression be formally recognized as a risk factor for poor outcomes in ACS populations (Lichtman et al., 2014). The authors highlighted, however, that it remained unclear whether depression was an independent risk factor for incident coronary heart disease (CHD). While there is some evidence that depression increases CHD risk (Lett et al., 2004), it has been argued that, as yet, there is “no convincing evidence that depression is an independent causal risk factor” for CHD (Stampfer et al., 2012).
Given that women have an elevated lifetime risk for depression (and anxiety) (Australian Institute of Health and Welfare, 2010), the relationship between depression and CHD in women is of particular significance. Currently, cardiovascular disease (CVD) is the leading cause of death in women in all major, developed countries including the United States and Australia (Australian Institute of Health and Welfare, 2009). From an etiological perspective, the trajectory of CHD in women is complicated. Women have been considered somewhat protected from CHD due to the effects of estrogen and elevated high density lipoprotein (HDL) cholesterol levels until menopause, after which time their risk of CHD increases with age (Matthews et al., 1989). However, new evidence indicates that the impact of traditional cardiovascular risk factors is greater in women when compared with men (Cheng et al., 2014). Moreover, once CHD manifests, female patients, particularly those of a younger age, are susceptible to adverse CHD outcomes including mortality (Davidson, 2012). While sex-specific differences in pathophysiology are not fully understood, recent data indicate that they may relate to endothelial dysfunction and the involvement of the microvascular system whereby coronary flow reserve is lower in women due to lower resting coronary flow (Kobayashi et al., 2015). Other data have specifically highlighted that the impact of depression on CHD mortality among women with suspected or established coronary disease and that this is most pronounced for those aged 30–55 years (Shah et al., 2014).
From a behavioral perspective, women are less likely to self-identify cardiovascular risk factors (Mosca et al., 2010) or seek help for a cardiac event, holding the view they can self-medicate (Higginson, 2008). From a treatment perspective, the outcomes for women are compromised. They are less likely to be referred for disease assessments (e.g. coronary angiography) (Bougouin et al., 2015), screened for depression following ACS (Smolderen et al., 2011), attend cardiac rehabilitation (Colbert et al., 2013) or benefit from invasive cardiovascular treatment (Lagerqvist et al., 2001). Thus, better understanding how depression contributes to CHD in women is crucial for determining a need to develop sex-specific preventive and therapeutic interventions.
The aim of this study was to address the gaps in the literature as identified by the American Heart Association position statement (Lichtman et al., 2014)-with a focus on how they pertain to women- and provide key data to guide subsequent preventive interventions. Specifically, we sought to examine the role of depression as a risk factor for CHD incidence (and recurrence) in a population-based, random sample of 860 women followed for (up to) 18-years for whom gold standard psychiatric, bio-behavioral and CHD data were available.
Section snippets
Participants
Details of the Geelong Osteoporosis Study (GOS) have been published elsewhere (Pasco et al., 2012). Briefly, the GOS was initiated in 1993, comprising an age-stratified, population-based sample of women (aged 20–94 years) who were randomly selected from electoral rolls of the Barwon Statistical Division, South-Eastern Australia. As voting is compulsory in Australia for adults aged+18-years, this sampling technique provides a random sample of citizens registered with the Australian Electoral
Characteristics of sample
Key characteristics of the sample are shown in Table 1 (n=860, a sub-set of the sample at baseline, for whom complete data required for analysis were available). Groups (depressed versus not) were comparable in most demographic, clinical and behavioral variables. A higher proportion of those with depression completed secondary school. At baseline, seven participants reported a past history of coronary disease and were subsequently excluded.
Eighty-three participants (9.6%) recorded at least one
Discussion
In a population-based, random sample of women, clinically-defined depressive disorder was a robust, long-term predictor of 18-year CHD incidence. Not only was this association shown to be independent of anxiety and a range of typical and atypical risk factors, moreover, the strength of association between depression and CHD incidence was of a greater magnitude than any typical and atypical risk factor. Baseline depression did not predict recurrent CHD events. There was no significant
Author disclosures
MB, AO, FNJ have received funding from Meat and Livestock, Australia. AO has received an honorarium from Novartis Pharmaceuticals. FNJ has been a paid speaker for Sanofi-Synthelabo, Janssen Cilag and Eli Lilly. MB has been a paid consultant for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck and Pfizer and a paid speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, Sanofi Synthelabo,
Contributors
AO conceptualised the paper, collated the data and the blood samples for biomarker analyses, had input into statistical analyses and wrote the original version of the manuscript. AJF conducted the statistical analyses and co-wrote the original version of the manuscript. ALS collated the data and the blood samples for biomarker analyses. KK and AR extracted the CHD events data. MAK and JAP initiated the study and oversaw study enactment. JAP co-conceptualised the paper. FNJ and LJW conducted the
Role of the funding source
The GOS was supported by grants from the Victorian Health Promotion Foundation and the NHMRC (Projects 251638, 454356, 509103 and 628582) as well as Deakin University Central Grants Scheme. The funders had no influence on the enactment or results of the study.
Acknowledgements
AO is supported by a NHMRC ECR Fellowship (1052865). LJW is supported by a NHMRC Career Development Fellowship (1064272). MB is supported by a NHMRC Senior Principal Research Fellowship. We thank all GOS Project staff and Study participants.
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