No, ha sido desde el primer día que empecé a ir con esta gente, ya vuelvo a que ha sido una evolución, y yo creo que todos estos rollos de pelear, gente agresiva, supongo

Negative emotional disorders have been associated with worse prognosis in CVD patients. Depression is prevalent and persistent in CHD patients and a comprehensive review has shown that 19.8% of acute MI survivors meet the criteria for major depression, while approximately 30% have mild-to-moderate depressive symptoms (Thombs et al., 2006). A number of meta-analyses have provided evidence for the link between depressive symptoms and worse prognosis in CVD patients. Van Melle and colleagues included 22 papers examining associations between depressives symptoms in acute MI patients and long-term cardiovascular prognosis in a meta-analysis (n=6,367) (Van Melle et al., 2004). The results indicated that MI patients with depression had more than a 2.5-fold increase in cardiac mortality, and an almost two-2.5-fold risk for new cardiovascular events. Interestingly, neither follow-up duration nor method of measuring depression significantly affected the association between depression and mortality. A meta-analysis of 29 papers published in the same year also reported a two-fold increase of mortality in depressed patients in the two years after initial assessment (Barth, Schumacher, &

Herrmann-Lingen, 2004). This association weakened after two years, but remained significant long-term.

44 In a 2006 meta-analysis of 34 prognostic studies, the pooled relative risk of all-cause or CHD mortality associated with depression was 1.80 (Nicholson et al., 2006).

Interestingly, left ventricular function was only adjusted for in a small number of studies and inclusion of this covariate attenuated the relative risk by 48%. Although depression plays a role in CVD prognosis, this led the authors to suggest that depression was not yet an established independent risk factor for poor CHD prognosis as many studies failed to adjust for relevant risk factors. Meijer and colleagues identified 29 studies for inclusion in a meta-analysis examining the relationship between depression following the occurrence of an MI and cardiac prognosis (n=16,889) (Meijer et al., 2011). Similar to both meta-analyses carried out in 2004, the authors reported a 2.7-fold increased risk of cardiac mortality and a 1.6-fold increased risk of cardiac events in patients with post-MI depression. However, the strength of the association between depression and cardiac events decreased as follow-up duration increased – a finding also reported in Barth et al.’s (2004) meta-analysis. A recent meta-analysis sought to ascertain whether the cognitive/affective or somatic/affective symptoms of depression were more relevant for cardiovascular prognosis (de Miranda Azevedo, Roest, Hoen, & de Jonge, 2014).

Thirteen prospective studies of 11,128 participants were included in the meta-analysis. In the fully adjusted analysis, somatic/affective depression symptoms, but not cognitive/affective symptoms, were associated with poor prognosis in CVD patients (hazard ratio = 1.19).

There is evidence that anxiety is also associated with poorer prognosis in CVD patients.

A 2010 meta-analysis of 12 studies comprising 5,750 MI patients reported associations between anxiety and cardiac mortality as well as new cardiac events independent of clinical variables, including depression (Roest, Martens, Denollet, & de Jonge, 2010).

Roest and colleagues followed up this meta-analysis with a study examining associations

45 between generalised anxiety disorder (GAD) and adverse cardiac outcomes in MI patients with a 7-10 year follow-up period (Roest, Zuidersma, & de Jonge, 2012). Results from simple age and sex adjusted models showed that GAD was associated with an almost twofold risk of adverse events. Adjustment for various other clinical factors, including depression, did not affect the magnitude of the association greatly. However, the authors did not adjust for any social or behavioural factors.

A systematic review of studies examining the role of worry and GAD in cardiovascular health found that three studies had reported associations between GAD and poorer prognosis in CHD patients, even after adjusting for depression (Tully, Cosh, & Baune, 2013). However, a year later Tully and colleagues carried out a meta-analysis on five studies examining the role of GAD in CHD patients and reported no significant associations (Tully, Cosh, & Baumeister, 2014). The latest meta-analysis in the area of anxiety and CVD prognosis included 44 articles examining prospective associations between anxiety and mortality in CHD patients (n=30,527) (Celano et al., 2015). After adjusting for a number of covariates, anxiety was not associated with mortality or poorer outcomes in CHD patients. The authors performed sensitivity analyses and found that when they separated the samples into post-ACS patients and stable CHD patients, the risk of poorer outcomes in anxious stable CHD patients was significantly elevated after adjusting for a number of relevant covariates. There were no significant increases in outcome risk in anxious post-ACS patients.

In summary, the evidence suggests that negative emotional disorders play a role in prognosis in those already with CVD. Three meta-analyses to date have reported 2 to 2.5-fold increases in risk of future cardiac events and mortality in CHD patients with depression (Barth et al., 2004; Meijer et al., 2011; Van Melle et al., 2004). However, the largest meta-analysis carried out so far (Nicholson et al., 2006) found that many studies

46 failed to adjust for relevant risk factors such as smoking and BMI, leading to inflated associations between depression and prognosis in CVD patients. More than 50% of patients suffering from depression or anxiety will also suffer from a comorbid depressive or anxiety disorder (Hirschfeld, 2001). Therefore, failure to adjust for symptoms of anxiety in many of these studies could also lead to inflated risk estimates. Adjusting for symptoms of depression seems to be more commonplace in prognostic studies measuring anxiety in CHD patients. This may be why the results of meta-analyses in this field are a little more mixed. Another reason for the mixed results seen in the prognostic meta-analyses related to anxiety may be failure to define samples correctly, i.e. separate stable CHD patients from post-ACS patients who are likely more symptomatic (Celano et al., 2015). Nevertheless, the literature suggests that both depression and anxiety play a significant role in CVD prognosis, but more work is needed with both well-adjusted statistical models and well-defined patient samples.