The association of posttraumatic stress disorder and metabolic syndrome: a study of increased health risk in veterans

Several lines of research suggest that stress and post-stress adaptational responses are related to long-term health outcomes. Studies of survivors of disasters, veterans and prisoners of war, and others exposed to severe trauma, suggest higher rates of physical morbidity and mortality and increased healthcare utilization related to lifetime prevalence of trauma [1–7]. There is accumulating evidence from epidemiological studies that chronic posttraumatic stress disorder (PTSD) may moderate the link between trauma and secondary negative health outcomes such as cardiovascular, metabolic and autoimmune conditions [4–9]. Furthermore, Chrousos and colleagues have linked maladaptive neuro-endocrine-immune responses to psychiatric, endocrine and/or autoimmune disease or vulnerability to such diseases [10, 11]. Evidence for neuro-endocrine-immune abnormalities associated with PTSD, also provides a biological rationale for downstream health effects observed in the epidemiological studies [12–16].

Metabolic syndrome or syndrome × is composed of a cluster of clinical signs including dyslipidemia, hyperglycemia (insulin resistance), central obesity and hypertension [17]. Recent research on the impact of stress on health has focused on metabolic syndrome as a possible consequence of pathophysiological adaptations to chronic stress [18]. Brunner and colleagues studied metabolic syndrome status in the Whitehall II cohort and found markers associated with increased stress-related neuroendocrine and autonomic activation such as lowered heart rate variability, increased cortisol output and higher levels of IL-6, C-reactive protein and blood viscosity among cases with metabolic syndrome as compared with those who did not meet diagnostic criteria [19]. Additional analyses of prospective data from the Whitehall cohort also suggest a dose-response relationship between stress and the presence of metabolic syndrome such that participants with chronic exposure to work stress were found to be more than twice as likely to have the syndrome after controlling for age, sex and health behaviors [20]. In a recent study of 2189 Gulf War I veterans, those with chronic multisymptom illness, as defined by presence of fatigue, musculoskeletal pain, mood or cognitive abnormalities for at least 6 months, had significantly higher prevalence of metabolic syndrome [21].

While there is a lack of consensus in specific clinical definitions of metabolic syndrome, prospective studies have shown it to be an important predictor of physical morbidity and mortality [22–25]. For example, in a comparison of four definitions based on guidelines from the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP), metabolic syndrome was found to predict incidence and prevalence of diabetes mellitus in a prospective study [24]. Similarly, in a sample of 5128 men, metabolic syndrome was found to be a significant predictor of the development of cardiovascular disease (CVD) and diabetes mellitus [25].

In this study, we examined physical measures and laboratory values in a sample of veterans, to examine the association between PTSD severity and the presence of metabolic syndrome. We hypothesized that greater severity of PTSD would be associated with a higher likelihood of metabolic syndrome.

In a sample of 253 male and female veterans, greater severity of PTSD was associated with higher likelihood of metabolic syndrome after controlling for relevant demographic, behavioral and psychiatric factors. This finding aligns with and extends existing research examining metabolic syndrome in populations vulnerable to PTSD. Violanti and colleagues found metabolic syndrome to be three times more likely in police officers with severe PTSD symptoms as compared with police officers in the lowest PTSD severity category [33], while others have found that that 31–35% of male war veteran samples with combat PTSD evidenced concomitant metabolic syndrome [34, 35]. Of note, the current study utilized the largest sample size to date and the most diverse in terms of gender, given the small but extant presence of women.

The importance of the association between PTSD and metabolic syndrome becomes apparent when one considers the fact that metabolic syndrome has been shown to predict CVD-related morbidity and mortality [23, 25]. Our findings suggest that metabolic syndrome provides a useful framework for assessing and describing the physiologic burden of PTSD and can be used prospectively to evaluate the increased health risk associated with combat exposure and PTSD.

The prevalence of metabolic syndrome in our sample (40%) and specifically among those with PTSD (43%) were slightly higher than rates observed among adults in the general population as reported in the National Health and Nutrition Examination Survey (NHANES) which ranged from 20% to 31% [36–38]. Loucks and colleagues reported mean values from men and women ages 25 years and over on individual metabolic syndrome components also collected in our sample (HDL, serum triglycerides, SBP, DBP, and fasting glucose) [36]. Compared with the women and men surveyed in NHANES, our sample of veterans tended to have higher mean triglycerides (189.5 mg dl^-1 versus 132.3 and 164.0 mg dl^-1 for women and men, respectively), higher SBP (130.8 mm/Hg versus 122.1 and 123.1 mm/Hg), higher DBP (81.7 mm/Hg versus 71.2 and 74.4 mm/Hg), higher fasting glucose (106.4 mg dl^-1 versus 98.8 and 103.4 mg dl^-1), and lower HDL (42.7 mg dl^-1 versus 55.8 and 45.3 mg dl^-1). While our sample appeared to be 'less healthy' based on the pattern of mean values, our participants also tended to be older (mean age of 51.5 years as compared with mean ages of 47.2 and 44.7 years for women and men, respectively, in NHANES).

In spite of the growing attention on the importance and surveillance of metabolic syndrome, it should be noted that there is still considerable controversy regarding its definition and utility. Recent reviews pose questions regarding the need for a consensus in the definition of metabolic syndrome, lack of certainty about the underlying pathophysiological process, whether the syndrome itself conveys more information about health risk than the sum of its individual components, and how different combinations of risk factors should guide clinical management [39–41]. In addition to research examining long-term health risk from PTSD, prospective studies are similarly needed to continue to address these remaining questions about metabolic syndrome.

A closely related concept, allostatic load, represents the cumulative biological burden of exposure to repeated cycles of adaptation to stress [42]. It incorporates the notion of stress, as well as the contribution of genetic, developmental, and lifestyle factors that might underpin the physiologic response to daily life events and traumatic stressors [42–45]. The selected factors that contribute to metabolic syndrome in this study closely approximate the secondary mediators of allostatic load, with the exception of serum triglycerides [46, 47]. Our cross-sectional findings show a relationship between PTSD and metabolic syndrome suggesting that perhaps metabolic syndrome in itself is a useful clinical tool in quantifying the cardiovascular and metabolic impact of PTSD. In comparing those with and without PTSD on individual measures of metabolic syndrome components, we only found significant group differences for DBP, suggesting the utility of considering these measures collectively as the presence or absence of metabolic syndrome. It should be noted, however, that these multiple comparisons were not adjusted according to the Bonferroni principle, thereby potentially inflating Type I error in our analysis. Several studies appear to support the dysregulating effect of PTSD on a number of physiologic systems [12–16, 33–35, 48]. Given this association, future prospective studies examining physical morbidity and mortality related to PTSD should also assess metabolic syndrome to determine whether the pattern of dysregulation represented by metabolic syndrome mediates long-term health risk in PTSD.

Interestingly, we did not find MDD to be a significant and unique predictor of risk for metabolic syndrome, in spite of preliminary findings suggesting increased HPA activity with depression [49–55]. These previous studies, however, focused on depression and did not assess or control for PTSD. Our findings may provide preliminary evidence for a higher relative contribution of PTSD to metabolic syndrome after controlling for MDD.

One limitation of the current study is the under-representation of women and minority groups. While female gender was found to be associated with decreased risk of metabolic syndrome, in spite of the small number of women in the study (7.9%), race did not appear to have unique effects on metabolic syndrome. A more diverse sample may yield important information on whether the relationship between PTSD and metabolic syndrome is robust across different racial/ethnic groups.

Finally, given the cross-sectional design of our study, we cannot fully establish a causal relationship between PTSD and metabolic syndrome. Prospective studies are clearly needed in this area to fully examine the long-term health risk related to PTSD.

This study extends the current knowledge of PTSD and diminished health status by examining metabolic syndrome while controlling for relevant health and psychiatric variables. After controlling for MDD, and alcohol, nicotine and substance abuse or dependence, we found a robust and significant association between PTSD severity and health risk as measured by metabolic syndrome. Further exploration, using prospective studies with assessment of CVD- and metabolic-related conditions, are indicated to determine whether metabolic syndrome can sufficiently account for the higher morbidity and mortality observed among those exposed to trauma or with PTSD.