October 2011
Reviewer: Jeff C. Huffman, MD
Optimism in relation to inflammation and endothelial dysfunction in older men: the VA Normative Aging Study
Ikeda A, Schwartz J, Peters JL, et al
Psychosom Med 2011; 73(8):664-671
Background: There is increasing interest in the relationship between more positive psychological states—such as optimism—and health related outcomes, especially those related to cardiac health. There is ample evidence that optimism has been associated with improved cardiac outcomes in long-term studies, and some prior work has examined associations between optimism and objective markers of cardiac prognosis, including inflammatory and endothelial biomarkers. However, such optimism-biomarker studies have previously been cross-sectional, with no suggestion of directionality/causality of these effects (e.g., does being optimistic lower inflammation, or do lower levels of circulating inflammatory markers lead to improved vitality and greater optimism?).
Methods: This is a substudy from the large VA Normative Aging Study, a study of men who were medically healthy at initial recruitment in the 1960s and who return every three years for follow-up evaluation. This substudy from 1999-2008 (for a maximum of 4 visits) excluded patients with coronary heart disease (and elevated hsCRP, indicating infection) but included all other subjects. The Life Orientation Test (LOT) was used to measure optimism; this scale has both a total score and optimism/pessimism subscales. The scale was largely used as a continuous measure, though preliminary analyses assessed scores by quartiles. At each visit, inflammatory markers (hsCRP, IL-6, and soluble tumor necrosis factor receptor II) and endothelial markers (sICAM-1 and sVCAM-1) were drawn. To account for them in analyses, multiple relevant covariates were collected, including age, smoking status, alcohol use, BMI, physical activity, education, blood pressure, serum glucose, cholesterol, statin use, and depressive symptoms. Analysis of the connection between optimism and biomarkers used linear mixed-effects models to allow inclusion of subjects with missing data and to both examine the main effect of optimism on biomarker levels for the group and assess associations between optimism and rate of biomarker change within subjects.
Results: Overall, 340 subjects (mean age 71) were included. On unadjusted analyses, greater LOT scores (split by quartile) were associated with lower levels of all markers except hsCRP. Using continuous LOTS scores, unadjusted analyses found LOT scores to be significantly associated with sICAM-1, sVCAM-1, and IL-6 levels; on multivariate analyses that included all of the above relevant covariates, higher optimism (LOT) score was significantly associated with sICAM-1 and IL-6. There was no association between optimism and rate of change for any of the markers.
Commentary: These interesting results from this well-designed study suggest some connection between optimism and levels of inflammatory and endothelial biomarkers, even with correction for many relevant behavioral, medical, and psychosocial factors (including depression). However, the associations between optimism and inflammatory/endothelial biomarkers were not consistent across all biomarkers, and there was no link between optimism and rate of change of the markers.
Overall, this work is generally consistent with other work in the area—both in terms of finding some (but somewhat inconsistent) associations between optimism and biomarkers in cardiac patients—and suggests that there is a real signal here, especially considering how carefully controlled these analyses were in terms of medical, psychiatric, and behavioral variables. It adds to the field by assessing rate of change of biomarkers, essentially rejecting the hypothesis that optimism prospectively leads to lower inflammation/endothelial dysfunction, at least in older men without heart disease.
As an added comment, though the findings are largely supportive of prior work and the immediate clinical implications are relatively limited, this seemed to be an incredibly well-designed and well-implemented study. The authors were careful to control for many critical covariates, often using objective biological measures (e.g., glucose levels, blood pressure). They also carefully assessed for sampling bias (i.e., whether subjects without heart disease had different characteristics than the entire sample, whether subjects with more visits were healthier), included depression as a covariate (to ensure they were not seeing effects of lack of depression rather than optimism), and completed additional analyses using only the pessimism subscale (which has specifically been associated with poor outcomes). Finally, they used state of the art statistical methods, such as mixed regression models, to test their hypotheses.
Overall, there is still much to be learned about the association of positive psychological states with cardiac biomarkers and clinical cardiac outcomes, and ongoing work should continue to explore the exact psychological states, exact mechanisms, and exact biomarkers that are most relevant here, in addition to finding ways to impact these states in cardiac patients.