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This review provides an up-to-date summary of the evidence from clinical and epidemiologic studies indicating that persons with post-traumatic stress disorder (PTSD) may have an increased risk of coronary heart disease and possibly thromboembolic stroke. Persons with PTSD, a common anxiety disorder in both veteran and nonveteran populations, have been reported to have an increased risk of hypertension, hyperlipidemia, obesity, and cardiovascular disease. Increased activity of the sympathoadrenal axis may contribute to cardiovascular disease through the effects of catecholamines on the heart, vasculature, and platelet function. Reported links between PTSD and hypertension and other cardiovascular risk factors may partly account for reported associations between PTSD and heart disease. The associations observed between PTSD and cardiovascular diseases have implications for cardiology practice and research.
An increasing body of evidence indicates that post-traumatic stress disorder, a common anxiety disorder in both veteran and nonveteran populations, is associated with major forms of cardiovascular disease including those attributed to atherosclerosis such as coronary heart disease and thromboembolic stroke. Persons with PTSD have also been reported to be more likely to have hypertension, hyperlipidemia, obesity, and cardiovascular disease . These findings are important to the field of cardiology since coronary heart disease may develop over time as a result of hemodynamic factors (for example, elevated blood pressure with turbulence and sheer stress within coronary arteries), hyperlipidemia, and events such as the rupture of atherosclerotic plaques and thrombus formation . This review summarizes cardiovascular alterations linked to PTSD including results from epidemiologic and clinical studies and possible biological mechanisms.
Individuals may develop PTSD after being exposed to a traumatic event such as combat experiences, a motor vehicle crash, or sexual assault . Symptoms of PTSD may include nightmares, intrusive thoughts, or other re-experiencing phenomena, the avoidance of situations that remind the person of the traumatic event, a feeling of numbness or being socially detached from family and friends, and hyper-arousal (for example, feeling angry, irritable and “on edge,” or having difficulty concentrating). Hyper-arousal or hypervigilance includes a rapid and pronounced reaction to stressors which may lead to a preoccupation with signs of threat and emotional distress. Persons with PTSD may have other challenges such as difficulties with employment, relationships, or other health conditions (for example, depression, alcohol abuse or drug dependency).
Effective psychological and medical treatments for PTSD include group or individual psychotherapy (for example, cognitive-behavioral therapy) and pharmacotherapy such as the use of selective serotonin reuptake inhibitors . Cognitive-behavioral therapy helps patients to address their traumatic memories and distorted cognitions (for example, by providing education about the nature of PTSD and stress responses and helping the individual with the integration of the traumatic events).
Cardiovascular alterations associated with autonomic arousal and cardiovascular health outcomes have long been reported to be associated with PTSD or wartime traumatic exposure [1, 5]. Persons suffering from PTSD and chronic PTSD have been shown to have increases in basal heart rate and blood pressure and increased heart rate and blood pressure in response to stimuli such as loud sounds and visual slides that remind them of the trauma [6-9]. In clinical studies involving small samples of veterans, plasma norepinephrine and 24-hour urine norepinephrine levels have been reported to be elevated among veterans with PTSD as compared to those without PTSD . The increases in plasma norepinephrine are more pronounced when PTSD patients are exposed to trauma-related stimuli such as loud tones . Stress and anxiety have been associated with increased plasma and urinary norepinephrine, epinephrine, and their metabolites, which are peripheral measures of the noradrenergic system, in healthy adults [8, 12].
The effects of traumatic exposures or chronic stress on the hypothalamic pituitary adrenal axis (HPA) and the autonomic nervous system have been examined in clinical studies and in animal models. The results of these studies indicate that PTSD can result in important neurobiologic and psychophysiologic changes . Physiological dysregulation of the HPA axis and altered autonomic function may contribute to increases in cardiovascular risk factors reported in persons with PTSD. Increased activity of the sympathoadrenal axis might contribute to cardiovascular disease through the effects of catecholamines on the heart, vasculature, and platelet function . Platelet function is altered by elevated levels of circulating catecholamines. Catecholamines act on alpha-2a receptors on platelet membranes leading to increased platelet aggregation and other changes in platelet function [8, 13]. Catecholamine-induced alterations of platelet activity have been hypothesized to be a link between chronic stress, increased sympathoadrenal activation, and cardiovascular disease [13, 14].
Studies have shown that patients with PTSD have higher heart rates at rest and reduced heart rate variability which is consistent with increased sympathetic activity [8, 15]. The finding that baseline heart rate is higher among veterans suffering from PTSD than among those without PTSD is consistent with chronic hyperstimulation of the autonomic nervous system. Alternatively, the finding could be an artifact due to the research participants being anxious about the impending psychophysiological assessment . The individuals who participated in the studies may have experienced anxiety because they were anticipating exposure to stimuli that would remind them of traumatic events . McFall et al.  examined basal heart rates, systolic and diastolic blood pressures among veterans with and without PTSD over an extended period and did not find any significant differences between the two groups. However, in a separate study by Gerardi et al.  which included 32 Vietnam veterans with combat-related PTSD and 26 Vietnam era veterans with no combat exposures, those with PTSD had significantly higher heart rate, systolic and diastolic blood pressure. Buckley and Kaloupek  completed a meta-analysis of reported studies of basal heart rate and blood pressure among persons with and without PTSD. A total of 34 studies were included with a total sample size across studies of 2,670 subjects. Their results suggested that, on average, persons with PTSD have an elevated basal heart rate as compared with persons without PTSD or those who were not exposed to trauma . The average difference in resting heart rate between persons with or without PTSD was 5 beats per minute. Their meta-analysis also suggested that PTSD is associated with blood pressure elevations .
PTSD was associated with an increased risk of hypertension in the National Comorbidity Survey and in an epidemiologic study of Vietnam veterans from Australia [19, 20]. Since elevated diastolic and systolic blood pressure are established risk factors for cardiovascular disease, the apparent link between PTSD and hypertension may partly account for reported associations between PTSD and heart disease . Cohen et al.  examined associations between PTSD and hypertension and other cardiovascular risk factors using national data from veterans of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) who sought care at VA health care facilities. The majority of the PTSD patients in their cross-sectional study had comorbid mental health diagnoses including depression (53%), other anxiety disorder (29%), substance abuse disorder (10%) and other psychiatric diagnoses (33%). Veterans with mental health diagnoses had a significantly higher frequency of hypertension and other cardiovascular disease risk factors . For example, among 65,603 male OEF/OIF veterans who had PTSD with or without other mental health diagnoses, the adjusted odds ratio for the association between PTSD and hypertension was 2.88 (95% confidence interval 2.79-2.97) after controlling for age, race (white, black, Hispanic, or other), component type, rank, branch of service, and multiple deployments . Among 6,964 female OEF/OIF veterans who had PTSD with or without other mental health diagnoses, the adjusted odds ratio for the association between PTSD and hypertension was 2.88 (95% confidence interval 2.79-2.97) after controlling for age, race/ethnicity (white, black, Hispanic, or other), component type, rank, branch of service, and multiple deployments .
There is increasing evidence from clinical studies that PTSD may have effects on lipid metabolism [21, 22]. Karlovic et al.  examined total cholesterol, LDL and HDL cholesterol, and triglycerides in Croatian war veterans with PTSD and patients with major depression. Those with PTSD had higher levels of cholesterol and LDL cholesterol, and triglycerides, on average, and lower HDL cholesterol levels as compared with the patients with major depression. In the study by Cohen et al.  of associations between PTSD and cardiovascular risk factors among OEF/OIF veterans who sought care at VA health care facilities, veterans with mental health diagnoses had a significantly higher frequency of dyslipidemia . For example, among 65,603 male OEF/OIF veterans who had PTSD with or without other mental health diagnoses, the adjusted odds ratio for the association between PTSD and dyslipidemia was 2.70 (95% confidence interval 2.63-2.78) after controlling for age, race/ethnicity (white, black, Hispanic, or other), component type, rank, branch of service, and multiple deployments . Among 6,964 female OEF/OIF veterans who had PTSD with or without other mental health diagnoses, the adjusted odds ratio for the association between PTSD and dyslipidemia was 2.68 (95% confidence interval 2.44-2.95) after controlling for age, race/ethnicity (white, black, Hispanic, or other), component type, rank, branch of service, and multiple deployments . Elevated levels of total cholesterol and triglycerides have also been observed among Brazilian police officers with PTSD .
Positive associations between PTSD and cardiovascular disease (particularly coronary heart disease) have been observed in a growing number of studies of veterans and civilians who were exposed to combat or other traumatic experiences, as summarized in Table 11. Some of these studies were retrospective, relied upon self-reported information about cardiovascular disease, or had other design limitations [2, 25-31, 35, 36]. Nevertheless, an increasing number of studies have prospectively examined PTSD as a predictor of physician-diagnosed cardiovascular disease [32-34]. Taken overall, these results from observational research provide considerable evidence that persons with PTSD have an increased risk of coronary heart disease morbidity and mortality.
There is some evidence from epidemiologic studies of an association between PTSD and cerebrovascular disease. Brass and Page  found that former World War II prisoners of war (POWs) had a statistically nonsignificant increased risk of stroke. Among the 475 former POWs, 12.7% (20 of 158) of those with PTSD had strokes, compared with 7.6% (24 of 317) without PTSD (relative risk = 1.7, 95% confidence interval 0.95 to 2.9). In a cross-sectional survey of female veteran’s who received care at the VA Puget Sound Health Care System, Dobie et al.  found an association between PTSD and self-reported history of stroke. About 5% (13 of 256) of the female veterans with PTSD reported a history of stroke as compared with 3% (28 of 905) of those without PTSD (age-adjusted odds ratio = 2.9, 95% confidence interval 1.4-6.0) . A study of trauma and PTSD among 3,171 male and female adults living in the general population of a German community found that persons with a history of trauma had a higher odds of stroke (odds ratio = 1.2, 95% confidence interval 1.0-1.5), angina pectoris, and heart failure after adjustment for demographic factors, blood pressure, smoking, body mass index, depression, and alcohol-related disorders .
This review of the published literature highlights evidence from epidemiologic and clinical studies that persons with PTSD are at increased risk of cardiovascular disease including coronary heart disease and possibly stroke. These findings have several implications for cardiologists and cardiovascular researchers. Anxiety disorders such as PTSD are common in the general population . In addition, combat veterans have an increased risk of PTSD [3, 4]. Clinicians who see patients in primary care practice or in cardiology clinics should be aware that longstanding PTSD may have deleterious effects on the cardiovascular system including increased risk of coronary heart disease and hypertension. Cardiologists routinely talk with patients about alcohol drinking and cigarette smoking, both of which may be more frequent among persons suffering from PTSD. Effective evidence-based treatments are available for persons with PTSD including those who suffer from dual diagnoses such as PTSD and alcohol dependence .
The biological mechanisms that account for the observed associations between PTSD and cardiovascular disease may relate to the effects of traumatic exposures and chronic stress on the HPA axis and the autonomic nervous system . Dysregulation of the HPA axis and chronic over-stimulation of the autonomic nervous system may contribute to the increases in blood pressure and lipid levels that have been observed in PTSD patients. Catecholamine-induced alterations of platelet activity may also contribute to the apparent link between PTSD and cardiovascular disease. Changes in immune function seen in some PTSD patients may also have a role including circulating levels of interleukin-6 (IL-6), IL-1, tumor necrosis factor, and C-reactive protein . Inflammatory mediators such as IL-6, tumor necrosis factor, and C-reactive protein have been reported to stimulate atherosclerosis . Interactions among the immune and neuroendocrine systems may partly account for associations between PTSD and chronic disease outcomes.
Previous authors have proposed general models of possible mechanisms underlying the relationship between PTSD and physical health including cardiovascular disease . The models take into account biological function (e.g., HPA axis, heightened noradrenergic function, immune function), psychological comorbidities such as depression, health risk behaviors, symptom reports and functional status, and disease morbidity and mortality. A similar model of PTSD outcomes proposed by Boscarino accounts for different pathways leading to changes in health status; the influences of heredity, shared environment, history of trauma, behavior and perceptions, biological changes, and stressful life event exposures are taken into account in the model .
In conclusion, persons with PTSD have been reported to have an increased risk of hypertension, hyperlipidemia, obesity, and cardiovascular disease. Such persons have been observed to have an increased risk of coronary heart disease and possibly thromboembolic stroke. The reported link between PTSD and hypertension and other cardiovascular risk factors may partly account for the observed associations between PTSD and heart disease.