Depression and cardiovascular diseases

Abstract: Background and aim The concept of depression as a risk factor for cardiovascular diseases (CVD) is now well known. However, weather the severity of depression has a dose response effect on risk of CVD is not known. Also the role of risk factors which might be shared between depression and CVD, their interaction with depression and the combined effect on risk of CVD is still not well understood. For example, high level neuroticism is a risk factor for depression but also for CVD, but the combined effect of depression and high-level neuroticism on risk of CVD is not known. Likewise having comorbid conditions is linked to both depression and CVD, but the combined effect of depression and certain non-cardiovascular morbid conditions on risk of CVD is not known. The role of certain specific genotypes like Catechol-O methyltransferase (COMT) genotype and depression on risk of CVD is also less studied. The main aim of this PhD thesis is to increase the knowledge on the association between depression and cardiovascular diseases. Methods and Results For the purpose of this thesis I used the PART study (acronym in Swedish for: Psykisk hälsa, Arbete och RelaTioner, In English: Physical Health, Work and Relations), a longitudinal study of mental health, work and relations among adults > 20 years of age residing in Stockholm County, Sweden. The study included three data collections, wave 1 (W1) in 1998–2000, wave 2 (W2) in 2001–2003 and wave 3 (W3) in 2010. In total 10,443 individuals were included. Depression was assessed using the Major Depression Inventory (MDI). Severity of depression was assessed using MDI and additionally measuring anxious distress according to DSM-5 (paper I). Neuroticism was assessed by the Swedish Scale of Personality (SSP) for paper II. COMT genotype was measured using saliva from a subsample of the participants (paper III). Non-cardiovascular morbidity was assessed by asking current status of non-cardiovascular morbid conditions (paper IV). All participants from W1 were followed for cardiovascular outcomes through the National Patient register. For study III on genotype all participants from W1 were invited to contribute saliva for DNA analysis, but only 4349 participated. Logistic regression and Cox regression was used to estimate the risk of CVD. In study I, I found that depression increased the risk of CVD at different severity levels of depression, and the highest risk was for those suffering from moderate depression. The increased risk was present for both ischemic heart disease and stroke. Also, those who suffered from depression with anxious distress were at higher risk for CVD. In study II on depression, neuroticism and CVD, I found that those who were depressed and had high level neuroticism were at increased risk of CVD than those depressed with low level of neuroticism. The interaction effect was confirmed by a synergy index > 1. In study III, the genetic study on the subsample of the PART, I found that those who were depressed and had a high activity COMT Val158Met genotype were at increased risk of CVD compared to those depressed with low activity COMT Val158Met. In Study IV, those who had depression and non-cardiovascular morbidity were at increased risk for CVD compared to those depressed with no non-cardiovascular morbidity. This risk was present also after accounting for age, gender, socioeconomic status and lifestyle factors. The interaction effect was confirmed by synergy index > 1. Conclusion This thesis has overall increased the knowledge on the association between depression and CVD. It further elaborated and created new knowledge on the effect of other factors like personality trait neuroticism, genes and non-cardiovascular morbid conditions on the association between depression and CVD. More studies are required to confirm the biological mechanism in this relation and also design interventions to timely treat depression and other related factors to counter the risk of CVD.