Marina Vernalis

Impact of combat deployment and posttraumatic stress disorder on newly reported coronary heart disease among US active duty and reserve forces.

Background— The recent conflicts in Iraq and Afghanistan have exposed thousands of service members to intense stress, and as a result, many have developed posttraumatic stress disorder (PTSD). The role of military deployment experiences and PTSD in coronary heart disease (CHD) is not well defined, especially in young US service members with recent combat exposure. Methods and Results— We conducted a prospective cohort study to investigate the relationships between wartime experiences, PTSD, and CHD. Current and former US military personnel from all service branches participating in the Millennium Cohort Study during 2001 to 2008 (n=60 025) were evaluated for newly self-reported CHD. Electronic medical record review for International Classification of Diseases, Ninth Revision, Clinical Modification codes for CHD was conducted among a subpopulation of active duty members (n=23 794). Logistic regression models examined the associations between combat experiences and PTSD with CHD with adjustment for established CHD risk factors. A total of 627 participants (1.0%) newly reported CHD over an average of 5.6 years of follow-up. Deployers with combat experiences had an increased odds of newly reporting CHD (odds ratio, 1.63; 95% confidence interval, 1.11–2.40) and having a diagnosis code for new-onset CHD (odds ratio, 1.93; 95% confidence interval, 1.31–2.84) compared with noncombat deployers. Screening positive for PTSD symptoms was associated with self-reported CHD before but not after adjustment for depression and anxiety and was not associated with a new diagnosis code for CHD. Conclusions— Combat deployments are associated with new-onset CHD among young US service members and veterans. Experiences of intense stress may increase the risk for CHD over a relatively short period among young adults.

Intensive Cardiovascular Risk Reduction Induces Sustainable Changes in Expression of Genes and Pathways Important to Vascular Function

Background—Healthy lifestyle changes are thought to mediate cardiovascular disease risk through pathways affecting endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. We examined the effect of a rigorous cardiovascular disease risk reduction program on peripheral blood gene expression profiles in 63 participants and 63 matched controls to characterize molecular responses and identify regulatory pathways important to cardiovascular health. Methods and Results—Dramatic changes in dietary fat intake (−61%; P<0.001 versus controls) and physical fitness (+34%; P<0.001) led to significant improvements in cardiovascular disease risk factors. Analysis of variance with false discovery rate correction for multiple testing (P<0.05) identified 26 genes after 12 weeks and 143 genes after 52 weeks that were differentially expressed from baseline in participants. Controls showed little change in cardiovascular disease risk factors or gene expression. Quantitative reverse transcription polymerase chain reaction validated differential expression for selected transcripts. Lifestyle modification effectively reduced expression of proinflammatory genes associated with neutrophil activation and molecular pathways important to vascular function, including cytokine production, carbohydrate metabolism, and steroid hormones. Prescription medications did not significantly affect changes in gene expression. Conclusions—Successful and sustained modulation of gene expression through lifestyle changes may have beneficial effects on the vascular system not apparent from traditional risk factors. Healthy lifestyles may restore homeostasis to the leukocyte transcriptome by downregulating lactoferrin and other genes important in the pathogenesis of atherosclerosis. Clinical Trial Registration—URL: www.clinicaltrials.gov. Unique identifier: NCT01805492

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

Background Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. Purpose The study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. Methods New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. Conclusions Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

Achievement of heart health characteristics through participation in an intensive lifestyle change program (Coronary Artery Disease Reversal Study).

PURPOSE Lifestyle habits and cardiovascular disease (CVD) risk factors are closely linked. Unfortunately, few individuals meet the goals for cardiovascular health that are recommended in public health initiatives. The purpose of this study was to determine the effect of an intensive lifestyle intervention program on the achievement of a group of recognized heart health characteristics as well as on the reduction of individual CVD risk factors. METHODS Of 200 military healthcare beneficiaries with coronary artery disease or CVD risk factors (mean age = 61 years) who entered a 1-year, prospective, cohort, multicomponent lifestyle intervention study (lacto-ovo vegetarian diet, exercise, stress management, group support), 186 subjects enrolled and 144 participated for 1 year. RESULTS At 3 months and 1 year compared with baseline, the proportion of subjects meeting 5 recognized heart health characteristics improved (P < .001): fiber intake >25 g/d (94% and 72% vs 35%); exercise ≥150 min/wk (79% and 58% vs 31%); low-density lipoprotein cholesterol <100 mg/dL (75% and 63% vs 46%); body mass index <25 kg/m2 (34% and 38% vs 23%); and blood pressure <140/90 mm Hg (84% and 83% vs 69%). At 1 year, more subjects (72% vs 32% at baseline), especially those with intervention adherence above (94%) versus below (58%) the study population median (P < .0005), achieved 3 or more of these characteristics. CONCLUSION An intensive lifestyle intervention promotes achievement of important heart health characteristics that, if maintained, may substantially reduce CVD events.

Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification

To examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles.

Recreational music-making alters gene expression pathways in patients with coronary heart disease

Background Psychosocial stress profoundly impacts long-term cardiovascular health through adverse effects on sympathetic nervous system activity, endothelial dysfunction, and atherosclerotic development. Recreational Music Making (RMM) is a unique stress amelioration strategy encompassing group music-based activities that has great therapeutic potential for treating patients with stress-related cardiovascular disease. Material/Methods Participants (n=34) with a history of ischemic heart disease were subjected to an acute time-limited stressor, then randomized to RMM or quiet reading for one hour. Peripheral blood gene expression using GeneChip® Human Genome U133A 2.0 arrays was assessed at baseline, following stress, and after the relaxation session. Results Full gene set enrichment analysis identified 16 molecular pathways differentially regulated (P<0.005) during stress that function in immune response, cell mobility, and transcription. During relaxation, two pathways showed a significant change in expression in the control group, while 12 pathways governing immune function and gene expression were modulated among RMM participants. Only 13% (2/16) of pathways showed differential expression during stress and relaxation. Conclusions Human stress and relaxation responses may be controlled by different molecular pathways. Relaxation through active engagement in Recreational Music Making may be more effective than quiet reading at altering gene expression and thus more clinically useful for stress amelioration.

Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles.

Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type‐2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction.

Gene expression profiling during intensive cardiovascular lifestyle modification: Relationships with vascular function and weight loss.

Heart disease and related sequelae are a leading cause of death and healthcare expenditure throughout the world. Although many patients opt for surgical interventions, lifestyle modification programs focusing on nutrition and exercise have shown substantial health benefits and are becoming increasing popular. We conducted a year-long lifestyle modification program to mediate cardiovascular risk through traditional risk factors and to investigate how molecular changes, if present, may contribute to long-term risk reduction. Here we describe the lifestyle intervention, including clinical and molecular data collected, and provide details of the experimental methods and quality control parameters for the gene expression data generated from participants and non-intervention controls. Our findings suggest successful and sustained modulation of gene expression through healthy lifestyle changes may have beneficial effects on vascular health that cannot be discerned from traditional risk factor profiles. The data are deposited in the Gene Expression Omnibus, series GSE46097 and GSE66175.