Cynical Distrust, Chronic Stress, and Other Psychological Factors Fuel Inflammation, Raise CVD Risk

January 22, 2007

Carole Bullock

January 22, 2007 (Ann Arbor, MI) - Cynical distrust, depression, and chronic stress were linked with elevated levels of inflammatory markers in a new large cross-sectional study that looked at individuals aged 45 to 84 [ 1].

The study, on psychosocial factors and inflammation in the Multi-Ethnic Study of Atherosclerosis (MESA), is reported in the January 22, 2007 issue of the Archives of Internal Medicine.

"Higher levels of cynical distrust were associated with progressively higher levels of major inflammatory markers, and similar patterns were seen for chronic stress, with no clear evidence of a threshold effect," Dr Nalini Ranjit (University of Michigan, Ann Arbor) told heart wire.

The MESA cohort included 6814 men and women who were free of clinical cardiovascular disease. The study included a racial mix of white (38.5%), black (27.8 %), Hispanic (21.9%), and Chinese (11.8%) subjects.

Researchers also assessed the impact of behavior (physical activity, smoking, alcohol use) and other health factors (diabetes, body-mass index [BMI], recent infection, use of medication) on the stress-inflammation relationship. A large part of the association was accounted for by BMI and diabetes.

Associations of psychosocial factors with inflammation were reduced by about 45% to 100% after adjustment for BMI and diabetes and about 20% to 55% taking into account behavioral factors.

"It is possible that stress is associated with obesity and diabetes, resulting in increases in inflammation; this in turn could explain the relationship of stress to atherosclerosis," Ranjit said.

"The take-home message is that problems of psychosocial stress and lifestyle risk factors--particularly obesity--should be considered together during management of CVD and other inflammation-related chronic disorders," she said.

Studies linking stress to heart disease are not new--many date back to more than a quarter of a century. "However, the mechanism is unclear; the goal of this study was to find out whether inflammation is the missing link," she told heart wire .

Researchers also noted that while most psychosocial/CVD research examines major depression, MESA included chronic stress and cynical personality.

The study is also unique because it describes a mechanism, includes a large database, and measures mediating factors in detail.

CRP, IL-6 higher in those with chronic stress, depression

In the cohort of the MESA study, three major inflammatory markers were measured: C-reactive protein, IL-6, and fibrinogen. Cynical distrust was scored on an 8-item scale of the Cook-Medley Hostility Scale, depression was assessed using the Center for Epidemiologic Studies-Depression Scale score, and chronic stress used a 0 to 4 scale based on work and relationship stress.

The strongest links to psychosocial factors were found for C-reactive protein and IL-6. For cynical distrust, there was a 7% (95% CI 3%-11%) difference in IL-6 level and a 9% (95% CI 2%-16%) difference in CRP level between people at the 80th and the 20th percentiles of the scale.

Subjects with higher levels of chronic stress tended to have elevated concentrations of IL-6 and C-reactive protein. The percentage differences comparing two or more stressful circumstances against none were 4% (95% CI 1%-8%) for IL-6 and 5% (95% CI 1%-11%) for C-reactive protein.

Those whose depression scores were >21 had 7% (95% CI 1.0%-14%) higher IL-6 than those whose scores were <21.

"We hypothesized that inflammation may be the one of the pathways linking psychological factors to CVD. And it was interesting that much of this association of was accounted for by obesity and diabetes," she said in interview with heart wire.

The researchers stopped short of concluding that stress causes heart disease.

The findings are based on a cross-sectional analysis. Determining the independent effect of the behavioral factors will require a longitudinal study, noted the investigators.

However, Ranjit said the results point to a "plausible set of pathways" for stress and other psychosocial problems to contribute to heart disease.

According to Dr Valentin Fuster (Mount Sinai Medical Center; Cardiovascular Institute Mount Sinai Heart, New York, NY), it is well known that there are common aspects to obesity, diabetes, and inflammation. But this study is the first to "put all the ingredients together" and explain the interactions with stress and other psychological risk factors.

The research was funded with grants and contracts from the National, Heart, Lung, and Blood Institute and the National Institute of Child Health and Human Development.

  1. Ranjit N, Diez-Roux AV, Shea S, et al. Psychosocial factors and inflammation in the Multi-Ethnic Study of Atherosclerosis. Arch Intern Med 2007; 167:174-181.

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