COMMENTARY

Negative emotions and coronary heart disease: getting to the heart of the matter

Serotonin plays a modulatory role in central control of the autonomic nervous system (ANS). The nucleus tractus solitarii (NTS) in the medulla is an area of viscerosomatic integration innervated by both central and peripheral serotonergic fibers. Influences from different origins therefore trigger the release of serotonin into the NTS and exert multiple influences on the ANS. This major influence on the ANS is also mediated by activation of several receptors in the NTS. In particular, the NTS is the central zone with the highest density of serotonin₃ (5-HT₃) receptors. In this review, we present evidence that 5-HT₃ receptors in the NTS play a key role in one of the crucial homeostatic responses to acute and chronic stress: inhibitory modulation of the parasympathetic component of the ANS. The possible functional interactions of 5-HT₃ receptors with GABA_A and NK₁ receptors in the NTS are also discussed.

Type D personality (TDP) has been proposed as a risk factor for the development of depressive symptoms after an acute coronary syndrome (ACS). However, contrasting findings emerged about its predicting power on the onset of depression, since an overlap between TDP and depressive symptoms has been proposed. The present study was aimed to verify whether TDP predicts the development of a depressive disorder in the 6 months after the discharge from hospital.

Two hundred fifty consecutive patients were recruited, at the Coronary Intensive Care Unit at the University Hospital of Parma, who were both presenting their first ACS and had no history of depression. The presence and the severity of major (MD) and minor (md) depression were evaluated with the Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Hospital Anxiety and Depression Scale (HADS) respectively. Type D Personality was assessed with the DS14, both at baseline and at 1, 2, 4 and 6 month follow ups.

Out of 250 subjects (81.2% males), MD was diagnosed in 12 patients (4.8%) and md in 18 patients (7.2%). At baseline risk factors for a post-ACS depressive disorder were HADS depression scores, whereas TDP, or its subscales, did not showed any effect.

The small amount of patients with incidence of depression, due to highly selective inclusion criteria, tempers the reliability of our results.

Our data suggests that TDP does not predict the development of depressive disorders in never-depressed patients at their first ACS, when the baseline depression severity was controlled.

Although there is evidence that anxiety and anger are associated with a higher risk of cardiovascular events, studies examining the relationship between these stressors and prognosis following myocardial infarction have been mixed.

We conducted a prospective cohort study of 1968 participants (average age 60.2 years, 30.6% women) in the Determinants of Myocardial Infarction Onset Study recruited at the time of admission for myocardial infarction between 1989 and 1996. We used the state anxiety and anger subscales of the State-Trait Personality Inventory. Participants were followed for all-cause mortality through December 31, 2007 using the National Death Index. We constructed multivariable Cox proportional hazards models adjusted for demographic, behavioral, and clinical confounders and calculated hazard ratios (HR) and 95% confidence intervals (CI) to examine the relationship between high levels of anxiety and anger and all-cause mortality.

Over 10 years of follow-up, 525 participants died. Compared with those scoring lower, an anxiety score >90^th percentile was associated with a 1.31-times (95% CI, 0.93-1.84) higher mortality rate. The association was apparent in the first 3 years (HR 1.78; 95% CI 1.08-2.93), but not thereafter. Likewise, an anger score >90^th percentile was associated with a 1.25-times (95% CI, 0.87-1.80) higher mortality rate. The association was higher in the first 3 years (HR 1.58; 95% CI, 0.91-2.74) than in subsequent years, but it was not statistically significant during either follow-up period.

In this study of myocardial infarction survivors, a high level of anxiety was associated with all-cause mortality, with the strongest association in the first 3 years of follow-up.

After an unbroken series of positive, but underpowered studies seemed to demonstrate Type D personality predicting mortality in cardiovascular disease patients, initial claims now appear at least exaggerated and probably false. Larger studies with consistently null findings are accumulating. Conceptual, methodological, and statistical issues can be raised concerning the construction of Type D personality as a categorical variable, whether Type D is sufficiently distinct from other negative affect variables, and if it could be plausibly assumed to predict mortality independent of depressive symptoms and known biomedical factors, including disease severity. The existing literature concerning negative affect and health suggests a low likelihood of discovering a new negative affect variable that independently predicts mortality better than its many rivals. The apparent decline effect in the Type D literature is discussed in terms of the need to reduce the persistence of false positive findings in the psychosomatic medicine literature, even while preserving a context allowing risk-taking and discovery. Recommendations include greater transparency concerning research design and analytic strategy; insistence on replication with larger samples before accepting “discoveries” from small samples; reduced confirmatory bias; and availability of all relevant data. Such changes would take time to implement, face practical difficulties, and run counter to established practices. An interim solution is for readers to maintain a sense of pre-discovery probabilities, to be sensitized to the pervasiveness of the decline effect, and to be skeptical of claims based on findings reaching significance in small-scale studies that have not been independently replicated.

Considering the central role of the concept of blood pressure reactivity to explanations of the influence of life stress in the pathogenesis of cardiovascular disease, it is important that the underlying psychophysiological determinants of blood pressure change are elucidated. Empirical evidence is reviewed concerning the utility of the Hemodynamic Profile–Compensation Deficit (HP–CD) Model (Gregg et al., 2002), which draws on physiological theory that explains blood pressure regulation as a dynamic compensatory relation between cardiac output and total peripheral resistance. Core constructs and quantitative features of the Model are explained, accompanied by a focussed review of the Model's application in reactivity studies of stress, lifestyle behaviours, laboratory-to-field generalisability, and personality differences. Although the available studies are relatively few in number, evidence of the Model's utility is promising. Application of the Model in further research could help to elucidate cardiovascular pathogenesis in ways not achievable through the study of blood pressure reactivity alone.

To determine the relationship between Type D personality (the tendency to experience negative emotions and to be socially inhibited) and illness beliefs in postmyocardial infarction (MI) patients.

One hundred and ninety-two MI patients participated. Patients were assessed on demographic variables and completed the Type D Scale (DS14) and Brief Illness Perceptions Questionnaire one week post-MI.

Multivariate analysis of variance revealed that Type D patients were significantly different from non-Type D patients on every illness perception dimension. Type D patients believe that their illness has significantly more serious consequences (P<.001), will last significantly longer (P<.001), will be significantly less controllable by them (P<.05) or through treatment (P<.001) compared to non-Type D patients, and experience significantly more symptoms that they attribute to their illness (P<.001). In addition, they are significantly more concerned about their illness (P<.05), experience significantly more emotions as a result (P<.001), and find their illness to be significantly less comprehensible compared to non-Type D individuals (P<.001).

Type D individuals possess a distinct profile of illness beliefs, which may help explain the adverse effect of Type D on health outcomes following MI. Future research should evaluate intervention strategies to tackle illness perceptions in these high-risk patients.