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Optimizing Stress Reduction Interventions for Cardiovascular Disease Risk
The National Heart, Lung, and Blood Institute (NHLBI) convened a Workshop on September 27-28, 2010 in Bethesda, Maryland to provide recommendations to the NHLBI to inform decisions on research priorities and directions in the field of stress reduction interventions for cardiovascular disease risk. The participants included national experts in clinical trials methodology, basic and translational science as well as in cardiac rehabilitation, electrophysiology and cardiac arrhythmias, cardiovascular epidemiology, clinical cardiology, medical psychology, and behavioral medicine. These experts were asked to:
The workshop focused on bringing key decision leaders together to consider the state of the science concerning the role of psychosocial stress reduction on cardiovascular disease risk, and providing recommendations regarding conceptualization, measurement, and design strategies for conducting rigorous research in this area. Detailed discussion included animal models of stress; experimental studies in humans of the mechanisms through which stress influences cardiovascular function; epidemiological evidence of associations between stress and cardiovascular risk; and key randomized controlled trials of stress reduction for decreasing cardiovascular morbidity and relevant clinical endpoints. A substantial discussion ensued of design considerations for an adequately-powered study of stress management interventions for cardiovascular disease (CVD) endpoints.
Significant evidence has accumulated that psychosocial stress contributes to the etiology and pathogenesis of coronary artery disease. In addition to direct influences through the nervous, endocrine, and immune systems, stress reduces the adoption and maintenance of a healthy lifestyle and adherence to medical care (1). Epidemiological evidence is compelling; several large and international studies have shown that individuals reporting high levels of psychosocial stress have significantly elevated risk of cardiovascular diseases. Most notably, the INTERHEART study demonstrated that among more than 30,000 individuals, those who reported elevated stress had odds ratios for myocardial infarction of 2.5 (2). High work demands and daily stress have also been associated with coronary heart disease (CHD) morbidity and mortality, with carotid artery intima-media thickness progression, and with recurrent events. The most recent addition to this literature was the finding in the prospective Women’s Health Study that women with high job-related stress were at nearly twice the risk of myocardial infarction of those with lower job-related stress, and were 43 percent more likely to undergo heart surgery. These findings are similar to several earlier reports of job strain predicting recurrent MI in both men and women (3), as well as with studies in humans and non-human primate investigations that identified a number of specific biologic and behavioral pathways through which stress promotes the progression of cardiovascular disease.
Despite these compelling findings, few randomized controlled trials have been conducted to evaluate the potential of stress management interventions to reduce cardiovascular events. Those data that are available have reported reductions in CVD risk factors, rehospitalization and cardiac events (4). However, small sample sizes and variation in the patient population, eligibility criteria and components of the interventions prevent a definitive causal conclusion regarding the role of stress management in the prevention or treatment of cardiovascular disease.
Each Workshop participant led an empirically-focused overview and discussion regarding the evidence in specific areas of the literature, each related to psychosocial stress, cardiovascular disease risk, prevention, and clinical endpoints. The studies covered the range of knowledge from epidemiological investigations, to animal models of stress and CVD, to mechanistic studies identifying the biologically relevant changes that occur during psychosocial stress and stress reduction. The most important findings include:
The participants recommended that research continue and expand on all aspects of the relationships between stress and cardiovascular outcomes. Because of the dearth of knowledge regarding the potential of stress management to improve clinical outcomes, the most urgent need is for additional clinical research in cardiovascular patients. Most importantly, the Working Group recommended that the NHLBI launch a multi-site clinical trial, preferably in a setting of cardiac rehabilitation, to evaluate whether including a stress management intervention improves clinical outcomes. Interdisciplinary collaboration would be key for success in this trial. The use of technologies that can capture essential components of the measures of interest should be exploited. The primary endpoint of this study initially should be a composite of MAJOR ADVERSE CARDIAC EVENTS (MACE), including unstable angina, re-infarction, hospitalization, and cardiovascular death.
Catherine M. Stoney, PhD
Peter Kaufmann, PhD
James Blumenthal, PhD
Last Updated: January 2011