Distress related to myocardial infarction and cardiovascular outcome: a retrospective observational study

Myocardial infarction (MI) is an unexpected life-threatening event which is perceived as stressful by many patients who may expect death or serious disability [1, 2]. For instance, after symptom onset three out of four patients with an acute coronary syndrome (ACS) indicated to have experienced moderate or high levels of MI-related distress, including being frightened and thinking they might be dying when symptoms came on [3]. In another study, fear of dying and perceived severity of MI (e.g. fright of recurrent chest pain) together accounted for more than half of the variance in distress perceived during MI [4]. Fear of dying and distress were also highly associated with intensity of chest pain at the time of MI [3]. Given that chest pain experience is greatly modulated by affective states [5], chest pain intensity was discussed as an equivalent of emotional distress perceived at the time of MI [3].

Distress during ACS profoundly impacts psychological adjustment in the wake of the cardiac event, particularly bringing on symptoms of anxiety, depression, and posttraumatic stress disorder. For instance, patients who were more distressed and frightened during ACS showed higher levels of anxiety and depressive symptoms, one week and three months, respectively, after the cardiac event [3]. Fright and the intensity of acute pain during ACS were both associated with posttraumatic stress symptoms three months later [6, 7]. We found that retrospectively assessed levels of MI-related fear of dying, helplessness, or pain were associated with posttraumatic stress symptoms after a median of 40 days following MI [8].

The aforementioned studies suggest that distress conceptualized as MI-related fear of dying, helplessness or pain might be an important clinical entity, since it is associated with negative affective risk factors for cardiovascular morbidity and mortality, including depression, anxiety, and posttraumatic stress disorder [9‐11]. Virtually all descriptions of negative affect distinguish among anxiety and related constructs (e.g. fear) and depression and related constructs (e.g. helplessness) [12]. Therefore, MI-related fear of dying and helplessness could be understood as part of the negative affective spectrum being associated with poor cardiovascular prognosis in the aftermath of MI. Moreover, increasing attempts have been made to dismantle negative affective constructs in order to identify for instance the "cardiotoxic" components of depression in patients with coronary heart disease [13]. In other words, MI-related fear of dying and helplessness may seem to tap into specific qualities of negative affect, thereby having the potential to emerge as risk factors of poor cardiovascular prognosis and as specific targets for behavioral interventions in their own right. Several processes might help to explain the putative relation between MI-related distress and subsequent CVD-related events. As has been shown for other types of negative affect, these might relate to poor life style choices, low adherence with cardiac therapy, and distinct pathophysiologic processes directly harming the cardiovascular system [14].

As a first step of testing the value of MI-related distress for post-MI prognosis, we investigated the hypothesis that greater fear of dying, helplessness, or pain intensity (i.e., perceived distress during acute MI) would be associated with increased risk of future hospital readmissions due to non-fatal cardiovascular events and related interventions. We further hypothesized that MI-related distress would be associated with poor cardiovascular outcome independent of other important prognostic factors.

We investigated the association between retrospectively rated MI-related fear of dying, helplessness, or pain intensity and non-fatal CVD outcome. These measures showed acceptable reliability for a construct of "MI-related distress" and they are also shown to be clinically important because of their predictive value for poor psychological adjustment during recovery from MI [3, 6‐8]. We found that MI-related distress was associated with an increased risk of hospital readmissions due to cardiovascular events and related interventions during a mean follow-up of almost three years. This association was independent of potentially important prognostic factors, namely age, coronary heart disease severity, hypertension and smoking: of these, hypertension alone emerged as a significant predictor of event risk. The relations between MI-related distress measures and CVD event risk seems relevant, as a change of 2 points (or between 30% and 36%) in pain intensity on numeric rating scales ranging from 0 to 10 is considered to be clinically meaningful [16]. In our patients a 33% increase in distress severity would mean an increase in distress scores from 6 to 8 corresponding to a 1.2- to 1.4-fold increased risk of CVD-related hospital readmissions.

Our study is on the one hand to be understood as a first attempt of tracking down the prognosis of post-MI patients who perceive their MI as stressful. On the other, it suggests that MI-related distress does not only predict psychological adjustment post-MI, as was previously shown [3, 6‐8], but also CVD outcome. In other words, the focus of our study was to investigate the possibly direct association between distress and poor CVD outcome in post-MI patients by taking demographic factors, CHD severity, and major CVD risk factors into account. However, because psychological adjustment post-MI was variously predicted by distress measures, including fear of dying, helplessness, or pain intensity [6‐9], the extent to which distress is associated with poor CVD prognosis independent from its psychological sequel remains unresolved.

Patients reporting greater levels of all distress measures received more frequently antidepressant medication during follow-up. However, we do not know the type of antidepressants our patients received. For instance, particularly selective serotonin reuptake inhibitors seem to improve CVD outcome [22]. Further elucidation of the likely complex psychological pathways leading from MI-related distress to poor CVD prognosis is warranted, because these might provide cues for tailored behavioral interventions. For instance, patients might profit from reassurance and provided safety during MI [3] and later on from more trauma-focused cognitive behavioral therapy [23]. Our observation that distress measures correlated inversely with age might indicate that younger patients are in particular need of psychological support during MI.

In addition to psychological maladjustment, other explanations for the association between greater MI-related distress and an increased future risk of CVD events might relate to an unhealthy life style, poor compliance with cardiac therapy, and psychophysiologic alterations [14]. In our study, smokers showed greater helplessness than non-smokers. In another study, good medical recovery from MI was associated with positive life orientation, which in turn correlated inversely with helplessness [24]. Psychological stress is also associated with an unhealthy diet, physical inactivity, and sleep disturbances, all of which may impact cardiovascular health [14], but were not available in our study. Particularly distress and fear during ACS were shown to be lower in regular exercisers than in patients who exercised less frequently [3]. Depression and PTSD compromise prescribed intake of cardiac medication [25, 26], thereby suggesting another pathway leading from distress via psychological maladjustment and poor adherence to increased CVD risk. Future studies may also want to investigate the physiologic correlates of distress during MI to investigate their trajectories and predictive value for CVD-related events. For instance, there is some evidence that elevated heart rate and lowered cortisol in the immediate aftermath of a psychological trauma predict the development of posttraumatic stress symptoms [27, 28]. However, it is unknown how this might affect cardiovascular biology in the longer run.

We observed different results when entering all distress measures simultaneously into the survival analysis, namely that distress was no longer associated with outcomes. Because the inter-correlation among the three distress measures was substantial, one statistical explanation could be that their separate effects partialled out each other. Another explanation could be that none of the distress measure components was associated with outcomes above and beyond one another suggesting that they might be equally important in predicting cardiac outcome individually. In other words, as the three distress measures might substitute for each other, it might seem unnecessary to measure all of them in solitude. However, future studies may want to test how distress measures as proposed here and possibly others might best be integrated into a unifying measure of distress to reliably predict cardiac prognosis after MI.

We mention several limitations of our study. Although comparable with our studies in this field, the response rate of 44.8% of the originally approached 951 patients was rather low, and, as previously reported, women responded less than men [9]. This might limit the generalizibility of our results to the general post-MI population and particularly women patients. We assessed MI-related distress retrospectively bearing the risk of biased reporting because of concomitant negative affect. We did not assess negative affect like depression and anxiety to control our results for this possibility. However, another study found only borderline significance between a negative affect scale and distress (including fear of dying) during ACS [3]. Patients varied considerably in time since index MI which might have variably affected distress measurements; for instance, fear of dying seemed to be greater with more time elapsed since the index MI. We excluded patients who had reported unexplained chest pain since index MI but we did not have data available on symptoms such as thoracic pain the patients and their physicians might have attributed to the heart. Such symptom attributions might potentially affect retrospective reports of MI-related distress. There might be events, which have happened during the time since index MI which may contribute to the retrospective evaluation of distress (e.g., familial difficulties, death or other illnesses in the family, economical problems) for which we could not control our analysis. The number of outcome events limited the adjustment of hazard models for additional potentially important confounding variables like sex and diabetes.

The findings from this study suggest that retrospectively assessed MI-related distress in the form of fear of dying, helplessness, or pain intensity is associated with an increased risk of future non-fatal cardiovascular events and related interventions. Numeric rating scales to assess symptom severity (incl. pain) are widely used in clinical settings. Particularly, the numeric rating scales applied in this study to measure distress are easy administrable even in a busy clinical setting and thus of potential clinical applicability in screening post-MI patients at risk of poor cardiovascular outcome. The association between MI-related distress and poor cardiac outcome was independent of other important prognostic factors. The downstream psychopathology and behavior as well as the underlying physiology of this association remain to be elucidated.