| Author | Roland von Känel. |
| Title | Psychological Distress and Cardiovascular Risk: What Are the Links? |
| Full source | J Am Coll Cardiol 2008;52:2163-5 |
| Text |
Abundant literature has been accumulated on the relationship between psychological stress and cardiovascular disease (CVD) (1). The first scientific quote about the brain affecting the heart and emotion-triggered cardiovascular changes leading to heart disease dates back 4 centuries. In 1628, the English physician William Harvey noted that “every affection of the mind that is attended either with pain or pleasure, hope or fear, is the cause of an agitation whose influence extends to the heart” (2). Nowadays affections of the mind refer to the numerous environmental challenges setting the stage for the development of biological alterations, which several decades down the line will manifest as overt cardiovascular events. Chronic psychosocial stressors as diverse as job strain, marital conflict, family caregiving, and low socioeconomic status have been previously shown to be predictive of CVD independent of classic cardiovascular risk factors (3–6). Conceptually, life circumstances attain the status of psychological stressors if a person perceives an amount of threat and challenge that he or she judges to overwhelm current coping resources (7). Depending on the quantity and quality of stress appraisal, accompanying neurobiological and neuroendocrine activation patterns shape the stress response to elicit a wide range of initially adaptive physiological, behavioral, and emotional changes in an attempt to maintain homeostasis (8). The stress response becomes maladaptive in individuals under chronic stress exposure and fosters low-grade systemic inflammation and coagulation activity, poor lifestyle habits, and elevated levels of negative affect (9–12). This explains why negative emotions like depression, anxiety, and hopelessness considered together as psychological distress have emerged as risk factors of CVD in their own right (13). Behavioral cardiology has come a long way in identifying the biobehavioral pathways leading from chronic psychological stressors and perceived psychological distress, respectively, to hard CVD end points (13). However, because behavioral and pathophysiological stress responses to some extent intertwine, it remains a challenge to disentangle their relative contribution to CVD. For instance, a highly stressed individual is more likely to smoke than a person who copes relatively better with stress. Smoking kindles inflammation, which in turn accelerates atherosclerosis progression. Additionally, chronic stress elicits inflammation by altering autonomic nervous system function (14). How much of the variance in the stress-related CVD risk is attributable to smoking-triggered inflammation, and how much is accounted for by a direct autonomic effect on inflammation? These questions are of clinical and public health importance alike because they may prompt tailored behavioral interventions directed at smoking cessation in the first scenario (13) and toward restoring vagal function by relaxation techniques in the second instance (14). In this issue of the Journal, Hamer et al. (15) address some of these topics by prospectively studying 6,576 healthy middle-age community-dwelling men and women from the Scottish Health Survey. The investigators found that psychological distress rated by the 12-item version of the General Health Questionnaire predicted an increased risk of incident fatal and nonfatal CVD events combined after a mean follow-up of 7 years. The likelihood of experiencing a cardiovascular event during follow-up was 54% increased in individuals with psychological distress relative to those without, whereby a gradual relationship between psychological distress severity and CVD risk also was observed. Most important, the investigators found behavioral factors to account for 65% of the relationship between psychological distress and CVD risk and pathophysiological factors to explain an additional 19% after controlling for behavior. In other words, their model left but 16% of the variance in factors linking psychological distress with CVD unexplained. Smoking, decreased physical activity, and hypertension accounted for the majority of the variance, whereas alcohol consumption and increased C-reactive protein explained comparably lower proportions. Interestingly enough, psychological distress also predicted all-cause mortality, with behavioral and pathophysiological factors explaining a substantial proportion of the variance. This supports the long-stated notion that psychological distress might indeed impact the risk of developing various diseases by adversely affecting health behavior and physiology (16). The large sample permitted collection of a reasonably high number of CVD events and definition of a level of psychological distress that seemed clinically meaningful because less than one-sixth of subjects were defined to be psychologically distressed at enrollment. The results of this intriguing investigation need to be discussed within the limitations of the study design. Psychological distress as well as behavioral and pathophysiological factors were all assessed at study entry. Therefore, a bidirectional relationship cannot be discounted. Only repeated measurements of data points during follow-up might have allowed identifying more causally associated relationships in their trajectories. The comparably small number of 63 fatal CVD events prevented an analysis of nonfatal and fatal cardiovascular events as separate outcomes. Different types of CVD (i.e., coronary heart disease, heart failure, cerebrovascular disease) also had to be combined in 1 outcome variable to gain enough statistical power. An even larger population would be necessary to differentiate among the relative contributions of psychological distress to the risk of fatal CVD events, nonfatal CVD events, and the individual entities of CVD. This may seem too cost intensive; however, we must acknowledge that behavioral factors and pathophysiology play partially different pathogenetic roles in chronic heart failure and stroke as an example. Although its score correlates reasonably well with scores of more specific instruments to rate depression and anxiety, the 12-item General Health Questionnaire comprises items related to depression, anxiety, and poor sleep that in their own right have been shown to predict CVD risk in apparently healthy populations (17–19). Poor sleep quality and associated obstructive sleep apnea are prevalent in the community and are variably associated with hypertension, inflammation, and psychological distress, particularly depressed mood (19–22). Additional adjustment for sleep quality and disorders might have accounted for some of the residual nonexplained variance of the distress–CVD relationship. Separate questionnaires to rate depression, anxiety, and sleep quality might have revealed whether these dimensions are equally important predictors of CVD risk in relation to the mediating behavioral and pathophysiological risk factors. There is a vast literature on biological alterations in depression in addition to low-grade inflammation, including autonomic imbalance, endothelial dysfunction, and platelet hyperactivity (23). An interesting hypothesis to test is whether in depression, relative to general psychological distress, pathophysiology contributes a comparably greater proportion to CVD risk. Biomarker status is ideally assessed at several points in time because a single blood draw to determine C-reactive protein as in the study by Hamer et al. (15) reflects only an erratic estimate of inflammatory status. Cardiovascular diseases are projected to be the leading cause of death in the year 2020 worldwide (24), with a considerable amount of this risk being attributable to psychological stress (25). Psychosocial intervention studies aiming at the modification of psychological distress to reduce mortality in patients with CVD are cumbersome to perform and show mixed results (26,27). Whether preventive reduction of psychological distress in a healthy community will ultimately reduce CVD mortality is unknown. In spite of these uncertainties, the results from the study by Hamer et al. (15) encourage clinicians to consider behavioral interventions to target intermediate pathways linking psychological distress with CVD manifestation (13,14). With regard to the investigators' findings, clinicians might pragmatically be recommended to exercise a multimodal therapeutic approach to the psychologically distressed individual at risk for CVD. Specifically, behavioral interventions targeting smoking cessation and increasing physical exercise, as well as blood pressure-lowering and inflammation-lowering relaxation techniques, are best delivered in combination with psychotherapeutic and psychopharmacologic means aimed at directly alleviating psychological distress. To conclude, randomized clinical trials testing the hypothesis that such multimodal treatment programs will not only show benefit with regard to the quality of life but also decrease stress-related CVD morbidity and mortality are sorely needed. References |