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.

Fatigued on Venus, sleepy on Mars-gender and racial differences in symptoms of sleep apnea.

OBJECTIVE: Clinical guidelines for the care of obstructive sleep apnea (OSA) recommend evaluation of daytime sleepiness but do not specify evaluation of fatigue. We studied how subjects with and without OSA experience fatigue and sleepiness, examining the role of gender and race. DESIGN, SETTING, PATIENTS: Consecutive subjects entering our heart health registry completed validated questionnaires including Berlin Questionnaire for OSA, Fatigue Scale, and Epworth Sleepiness Scale. Data analysis was performed only with Whites and Blacks as there were too few subjects of other races for comparison. RESULTS: Of 384 consecutive subjects, including 218 women (57 %), there were 230 Whites (60 %) and 154 Blacks (40 %), with average age of 55.9 ± 12.8 years. Berlin Questionnaires identified 221 subjects (58 %) as having high likelihood for OSA. Fatigue was much more common in women (75 %) than in men (46 %) with OSA (p < 0.001), while frequency of fatigue was similar in women (30 %) and men (29 %) without OSA (p = 0.86). In multivariate analysis, men with OSA were sleepier than women; Black men with OSA had higher Epworth scores (mean ± SD, 12.8 ± 5.2) compared to White men (10.6 ± 5.3), White women (10.0 ± 4.5), and Black women (10.5 ± 5.2), p = 0.05. These gender differences were not related to the effects of age, body mass index, perceived stress, sleep duration, or thyroid function. CONCLUSIONS: Women report fatigue more commonly with OSA than men. Men experience sleepiness more commonly with OSA than women. The findings suggest that evaluation of sleep disorders must include an assessment of fatigue in addition to sleepiness to capture the experience of women.

A systematic approach incorporating family history improves identification of cardiovascular disease risk.

BACKGROUND: Although family history (FH) is an independent predictor of cardiovascular disease (CVD) risk, traditional risk scores do not incorporate FH. Nurse practitioners routinely solicit FH but have no mechanism to incorporate the information into risk estimation. Underestimation of risk leaves clinicians misinformed and patients vulnerable to the CVD epidemic. OBJECTIVE: We examined a systematic approach incorporating FH in CVD risk assessment, validating risk reclassification using carotid intima-media thickness (CIMT), a surrogate measure of atherosclerosis. METHODS: Of 413 consecutive patients prospectively enrolled in the Integrative Cardiac Health Project Registry, a subgroup of 239 was low or intermediate risk by the Framingham Risk Score. A systematic approach for the assessment of FH was applied to this subgroup of the registry. A positive FH for premature CVD, defined as a first-degree relative having a CVD event before the age of 55 years in men and 65 years in women, conferred reclassification to high risk. Reclassification was validated with CIMT results. RESULTS: Chart audits revealed adherence to the systematic approach for FH assessment in 100% of cases. This systematic approach identified 115 of 239 (48%) patients as high risk because of positive FH. Of the reclassified patients, 75% had evidence of subclinical atherosclerosis by CIMT versus 55% in the patients not reclassified, P < 0.001. Logistic regression identified positive FH for premature CVD (odds ratio, 2.6; P = 0.001) among all variables, as the most significant predictor of abnormal CIMT, thus increasing risk for CVD. CONCLUSIONS: The Integrative Cardiac Health Project systematic approach incorporating FH into risk stratification enhances CVD risk assessment by identifying previously unrecognized high-risk patients, reduces variability in practice, and appropriately targets more stringent therapeutic goals for prevention.

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.

Improving assessment of cardiovascular disease risk by using family history: an integrative literature review.

BACKGROUND: Cardiovascular disease (CVD) is the number one killer in the United States. Although the causes of CVD are multifactorial, including genetic and environmental influences, it is largely a preventable disease. The cornerstone of CVD prevention is accuracy in risk prediction to identify patients who will benefit from interventions aimed at reducing risk. Nurse practitioners commonly perform CVD risk assessments and are well positioned to impact preventive therapy. Cardiovascular disease risk scoring systems currently in use substantially underestimate risk in large part because these do not include family history of premature CVD as a high-risk factor. PURPOSE: We sought to examine the state of evidence for the use of family history as a predictor in CVD risk stratification. CONCLUSIONS: A comprehensive literature search using the Medical Subject Headings terms of family history of CVD, family history of premature CVD, risk assessment, and risk estimation displayed 416 articles; a review of the titles and subsequent evaluation of the articles eliminated 392 references, leaving 24 for review. By incorporating family history in risk assessment, categorization of CVD risk improves substantially. The evidence demonstrates that family history is an independent contributor to risk appraisal and unequivocally supports its incorporation to improve accuracy in global CVD risk estimation. CLINICAL IMPLICATIONS: Underestimation of CVD risk leaves patients and providers misinformed, promoting the ongoing epidemic of chronic disease. Translating this evidence into practice by establishing a clinical algorithm that incorporates family history into risk prediction will standardize CVD risk assessment, improve the identification of high-risk patients, and provide the indicated aggressive care to prevent CVD.

Perceived stress correlates with disturbed sleep: a link connecting stress and cardiovascular disease.

The association between stress and cardiovascular disease (CVD) risk is becoming established. A mechanistic link clarifying the intermediate steps between the experience of stress and the development of CVD would support this association. We sought to examine the role of perceived stress as a factor associated with disturbed sleep with the goal of providing an explanation for the stress-CVD connection. We performed a cross-sectional analysis of data recorded by subjects at entry to our CVD prevention program. Data collection included questionnaire surveys, anthropometrics, and a CVD-relevant laboratory panel. Of 350 consecutively enrolled subjects (mean age 54.4 ± 12.4 [SD] years, 138 men, 39%), 165 (47%) scored above the mean for stress measures. These high-stress subjects displayed an increased cardiovascular risk profile including elevated body mass index (mean ± SD 31.1 ± 5.9 vs. 29.0 ± 5.9, r(s) = 0.175), increased waist circumference (102 ± 17 cm vs. 98 ± 14, r(s) = 0.135), and elevated high-sensitivity serum C-reactive protein (0.384 mg/dl vs. 0.356, r(s) = 0.109). High-stress subjects also demonstrated greater daytime sleepiness (Epworth Sleepiness Scale: 10.4 ± 5.0 vs. 7.8 ± 4.8, r(s) < 0.316), greater fatigue (fatigue scale: 5.4 ± 2.2 vs. 3.4 ± 2.4, r(s) = 0.484), poorer sleep quality (Pittsburgh Sleep Quality Index: 8.5 ± 4.4 vs. 5.9 ± 4.0, r(s) = 0.416), and shorter sleep duration (20 min less/24 h, r(s) = negative 0.177) with a higher risk for sleep apnea (60% at high risk vs. 40%, p = 0.003) than low-stress subjects. High stress was associated with significant disturbances in sleep duration and sleep quality. Stress levels also correlated with daytime consequences of disturbed sleep. The stress-sleep connection may be an important mechanistic mediator of the association between stress and CVD.

Readiness and associated health behaviors and symptoms in recently deployed Army National Guard solders.

To examine major factors affecting readiness in the Army National Guard (ARNG), 265 soldiers of the Pennsylvania ARNG redeploying in 2010 from Iraq and Afghanistan were evaluated with validated questionnaires during their first unit formation. The questionnaires assessed demographic information, health habits, levels of perceived stress, mood, diet, sleep, and exercise habits, and included a screening question for depression. Our analysis revealed no negative effects of multiple deployments in this cohort of ARNG soldiers. There was no apparent impact on readiness attributable to soldiers' living locations; there did not appear to be an urban-rural divide. There were, however, numerous opportunities to improve health behaviors, including smoking (prevalence of 41%), poor dietary choices and sleep habits, as well as management of stress and mood disorders. A striking prevalence of sleep apnea exists in these ARNG soldiers (40%), approximately double that previously measured in the general U.S. population. Soldiers with high stress, depression, poor sleep quality, and sleep apnea are at increased long-term risk for cardiovascular complications and deserve focused interventions to encourage lifestyle behavior change.

The effect of a one-year lifestyle intervention program on carotid intima media thickness.

This study assesses the impact of a year long lifestyle intervention program on carotid intima media thickness (CIMT) in 60 subjects, at-risk for or with coronary artery disease. We calculated mean CIMT at baseline (0.731 +/- 0.151 mm) and 1 year (0.720 +/- 0.129 mm), overall CIMT change and the relationship of CIMT change to the number (0-5) of achieved Heart Health Index (HHI) measures (body mass index < 25 kg/m2, exercise > or = 150 min/wk, blood pressure < 140/90 mm Hg, LDL-Cholesterol < 100 mg/dL, fiber intake > 25 g/d). CIMT was unchanged (-0.011 +/- 0.118 mm; p = 0.48); however, there was a trend toward CIMT decrease (-0.025 +/- 0.120 mm vs. +0.033 +/- 0.102 mm; p = 0.10) between subjects with HHI Score > or = 3 (n = 45) compared to those with an HHI Score < 3 (n = 15) at 1 year. These findings suggest atherosclerosis progression can be blunted with a lifestyle intervention that fully leverages nonpharmacologic approaches to cardiovascular risk reduction.

Results of a prospective cardiovascular disease prevention program.

The Cardiovascular Health Program (CHP) Registry is a 12-month, prospective study of therapeutic lifestyle change (TLC). Adult participants received comprehensive assessment of health behaviors and cardiovascular disease (CVD) risk factors. Personalized TLC action plans addressed modifiable health behaviors for diet, exercise, stress management, and sleep. Participants attended a half-day interactive workshop and met face-to-face with certified health coaches four times over 6 months. Monthly telephonic coaching for 6 more months completed the intervention. Measured outcomes included adherence to behavioral prescriptions, anthropometrics, CVD-relevant laboratory tests, and for a subset of participants, carotid intima-media thickness (CIMT). Of 965 participants, 648 (67%) completed the program and were included in the analysis. Participants were of mean age 55.4 ± 12.5 years, 57% women, and racially diverse. Adherence to prescribed TLC was substantial: dietary behaviors at goal rose from 53% to 86%, exercise 44% to 66%, perceived stress 65% to 79%, and sleep quality 28% to 49%. For participants with abnormal anthropometrics at baseline, there were improvements in body mass index in 63%, waist circumference (men 71%, women 74%), systolic BP 69%, and diastolic BP 71%. For participants with abnormal laboratory values at baseline, there were improvements in total cholesterol in 74%, LDL-cholesterol 65%, triglycerides 86%, fasting glucose 72%, and insulin resistance 71%. Improvements were not driven by prescribed medications. CIMT improved or showed no change in 70% of those measured, associated with significant improvements in sleep quality and longer total sleep time. Longer trials incorporating controls and major adverse CVD events are warranted.

Taking aim at nurse stress: a call to action.

The study investigates stress levels and related behaviors of nurses in a military medical center during wartime. In 2007, nurses completed a questionnaire survey with objective validation of data in a subsample using actigraphy over 12 weeks. Of 270 nurses, 255 (94%) returned surveys. A total of 81% reported moderately high or high stress with sources listed as work (66%) and fatigue (39%). Many reported coming to work despite feeling ill and/or stressed (13.6 days/3 months). In contrast, morale was high or moderately high in 71%. Nurses reported an average of 5.5 hours of sleep/night, 8.8 h/wk taken for self, and 3.8 h/wk for exercise. Actigraphy data showed an average of 6.0 hours of sleep/night. These findings highlight a mismatch between stress levels and coping perceptions indicating an inability to properly care for self. To manage the effects of chronic stress, nurse leaders should implement systems targeting healthy life balance.

Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy.

BACKGROUND: Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients. RESULTS: The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications. CONCLUSION: In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

Lipoprotein(a) Elevation: A New Diagnostic Code with Relevance to Service Members and Veterans.

Newly recognized as a clinical diagnosis, Lp(a) elevation is a major contributor to cardiovascular disease risk should be considered for patients with advanced premature atherosclerosis on imaging or a family history of premature cardiovascular disease, particularly when there are few traditional risk factors.

Performance of whole-genome amplified DNA isolated from serum and plasma on high-density single nucleotide polymorphism arrays.

Defining genetic variation associated with complex human diseases requires standards based on high-quality DNA from well-characterized patients. With the development of robust technologies for whole-genome amplification, sample repositories such as serum banks now represent a potentially valuable source of DNA for both genomic studies and clinical diagnostics. We assessed the performance of whole-genome amplified DNA (wgaDNA) derived from stored serum/plasma on high-density single nucleotide polymorphism arrays. Neither storage time nor usage history affected either DNA extraction or whole-genome amplification yields; however, samples that were thawed and refrozen showed significantly lower call rates (73.9 +/- 7.8%) than samples that were never thawed (92.0 +/- 3.3%) (P < 0.001). Genotype call rates did not differ significantly (P = 0.13) between wgaDNA from never-thawed serum/plasma (92.9 +/- 2.6%) and genomic DNA (97.5 +/- 0.3%) isolated from whole blood. Approximately 400,000 genotypes were consistent between wgaDNA and genomic DNA, but the overall discordance rate of 4.4 +/- 3.8% reflected an average of 11,110 +/- 9502 genotyping errors per sample. No distinct patterns of chromosomal clustering were observed for single nucleotide polymorphisms showing discordant genotypes or homozygote conversion. Because the effects of genotyping errors on whole-genome studies are not well defined, we recommend caution when applying wgaDNA from serum/plasma to high-density single nucleotide polymorphism arrays in addition to the use of stringent quality control requirements for the resulting genotype data.

Effect of a Counseling Session Bolstered by Text Messaging on Self-Selected Health Behaviors in College Students: A Preliminary Randomized Controlled Trial.

BACKGROUND: The college experience is often the first time when young adults live independently and make their own lifestyle choices. These choices affect dietary behaviors, exercise habits, techniques to deal with stress, and decisions on sleep time, all of which direct the trajectory of future health. There is a need for effective strategies that will encourage healthy lifestyle choices in young adults attending college. OBJECTIVE: This preliminary randomized controlled trial tested the effect of coaching and text messages (short message service, SMS) on self-selected health behaviors in the domains of diet, exercise, stress, and sleep. A second analysis measured the ripple effect of the intervention on health behaviors not specifically selected as a goal by participants. METHODS: Full-time students aged 18-30 years were recruited by word of mouth and campuswide advertisements (flyers, posters, mailings, university website) at a small university in western Pennsylvania from January to May 2015. Exclusions included pregnancy, eating disorders, chronic medical diagnoses, and prescription medications other than birth control. Of 60 participants, 30 were randomized to receive a single face-to-face meeting with a health coach to review results of behavioral questionnaires and to set a health behavior goal for the 8-week study period. The face-to-face meeting was followed by SMS text messages designed to encourage achievement of the behavioral goal. A total of 30 control subjects underwent the same health and behavioral assessments at intake and program end but did not receive coaching or SMS text messages. RESULTS: The texting app showed that 87.31% (2187/2505) of messages were viewed by intervention participants. Furthermore, 28 of the 30 intervention participants and all 30 control participants provided outcome data. Among intervention participants, 22 of 30 (73%) showed improvement in health behavior goal attainment, with the whole group (n=30) showing a mean improvement of 88% (95% CI 39-136). Mean improvement in any behavioral domains was not seen in the control group. Intervention participants also increased their exercise significantly compared with controls, regardless of their self-selected goal category. The increased exercise was paralleled by significantly lower fasting glucose levels. CONCLUSIONS: The health coaching session plus tailored SMS text messages improved self-selected health behaviors with a modest ripple effect to include unselected health behaviors. TRIAL REGISTRATION: Clinicaltrials.gov NCT02476604; https://clinicaltrials.gov/ct2/show/NCT02476604 (Archived by WebCite at http://www.webcitation.org/6qAAryS5t).

The role of exercise in modulating the impact of an ultralow-fat diet on serum lipids and apolipoproteins in patients with or at risk for coronary artery disease.

BACKGROUND: Ultralow-fat diets are known to reduce high-density lipoprotein cholesterol (HDL-C) levels. In the setting of a multicomponent lifestyle intervention program, relationships between exercise variables and HDL-C levels were examined to determine whether exercise moderates this dietary effect on serum lipids and apolipoproteins. METHODS: We performed a 3-month, prospective, nonrandomized lifestyle intervention study (< or = 10% dietary fat; aerobic exercise [180 min/wk], group support, and yoga [60 min/day]) in 120 subjects with or at risk for coronary artery disease. RESULTS: After 3 months, dietary fat intake was reduced to 8.7% +/- 2.6% of total intake and the median weekly exercise time was 194 minutes. High-density lipoprotein cholesterol levels decreased by 8.3 +/- 11.3 mg/dL (P < .001), and triglyceride levels increased by 17.6 +/- 102.7 mg/dL (P = .026). A small dense low-density lipoprotein cholesterol (LDL-C) phenotype emerged indicated by a 13.8% LDL-C reduction accompanied by only a 2.3% reduction in apolipoprotein B levels (P = .064). Among subjects with exercise amounts less than those of the group median, HDL-C reductions were greater in those with more than (-13.5 +/- 16.0 mg/dL) versus less than (-2.5 +/- 7.5 mg/dL) the median reductions in fat intake (P = .026). Even among subjects who exercised > 194 min/wk, HDL-C was reduced compared with baseline (-7.4 +/- 7.9 mg/dL, P < .001). CONCLUSIONS: An ultralow-fat diet as a component of a comprehensive lifestyle intervention induces reductions in HDL-C and the emergence of a dyslipidemic lipid profile. Aerobic exercise only partially mitigates this effect.

Early Empowerment Strategies Boost Self-Efficacy to Improve Cardiovascular Health Behaviors.

BACKGROUND: Self-efficacy, defined as confidence in the ability to carry out behavior to achieve a desired goal, is considered to be a prerequisite for behavior change. Self-efficacy correlates with cardiovascular health although optimal timing to incorporate self-efficacy strategies is not well established. We sought to study the effect of an empowerment approach implemented in the introductory phase of a multicomponent lifestyle intervention on cardiovascular health outcomes. DESIGN: Prospective intervention cohort study. METHODS: Patients in the Integrative Cardiac Health Project Registry, a prospective lifestyle change program for the prevention of cardiovascular disease were analyzed for behavioral changes by survey, at baseline and one year, in the domains of nutrition, exercise, stress management and sleep. Self-efficacy questionnaires were administered at baseline and after the empowerment intervention, at 8 weeks. RESULTS: Of 119 consecutive registry completers, 60 comprised a high self-efficacy group (scoring at or above the median of 36 points) and 59 the low self-efficacy group (scoring below median).  Self-efficacy scores increased irrespective of baseline self-efficacy but the largest gains in self-efficacy occurred in patients who ranked in the lower half for self-efficacy at baseline. This lower self-efficacy group demonstrated behavioral gains that erased differences between the high and low self-efficacy groups. CONCLUSIONS: A boost to self-efficacy early in a lifestyle intervention program produces significant improvements in behavioral outcomes.  Employing empowerment in an early phase may be a critical strategy to improve self-efficacy and lower risk in individuals vulnerable to cardiovascular disease.

ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness.

BACKGROUND: Whether marked LDL reduction to levels well below 100 mg/dL would further reduce the burden of cardiovascular disease is controversial. We compared the effects of 2 statins with widely differing potencies for LDL reduction (pravastatin 40 mg/d and atorvastatin 80 mg/d) on carotid intima-media thickness (CIMT). METHODS AND RESULTS: This was a single-center, randomized, clinical trial of 161 patients (mean age, 60 years; 71.4% male; 46% with known cardiovascular disease) that met National Cholesterol Education Program (NCEP) II criteria for lipid-lowering therapy. The effects of atorvastatin (80 mg/d; n=79) and pravastatin (40 mg/d; n=82) on CIMT were compared using blinded, serial assessments of the far wall of the distal common carotid artery. Baseline CIMT and other characteristics were similar between study groups. As anticipated, atorvastatin was substantially more potent for LDL reduction after 12 months: in the atorvastatin group, LDL cholesterol was 76+/-23 mg/dL after 12 months (-48.5%); LDL cholesterol was 110+/-30 mg/dL in the pravastatin group (-27.2%; P<0.001). Atorvastatin induced progressive CIMT regression over 12 months (change in CIMT, -0.034+/-0.021 mm), whereas CIMT was stable in the pravastatin group (change of 0.025+/- 0.017 mm; P=0.03). CONCLUSIONS: Marked LDL reduction (<100 mg/dL) with a high-potency statin provides superior efficacy for atherosclerosis regression at 1 year. This early effect on CIMT, a surrogate for clinical benefit, suggests that marked LDL reduction with synthetic statins may provide enhanced reduction in clinical coronary event rates.

Smallpox vaccination and myopericarditis: a clinical review.

Smallpox is a devastating viral illness that was eradicated after an aggressive, widespread vaccination campaign. Routine U.S. childhood vaccinations ended in 1972, and routine military vaccinations ended in 1990. Recently, the threat of bioterrorist use of smallpox has revived the need for vaccination. Over 450,000 U.S. military personnel received the vaccination between December 2002 and June 2003, with rates of non-cardiac complications at or below historical levels. The rate of cardiac complications, however, has been higher than expected, with two confirmed cases and over 50 probable cases of myopericarditis after vaccination reported to the Department of Defense Smallpox Vaccination Program. The practicing physician should use the history and physical, electrocardiogram, and cardiac biomarkers in the initial evaluation of a post-vaccination patient with chest pain. Echocardiogram, cardiac catheterization, magnetic resonance imaging, nuclear imaging, and cardiac biopsy may be of use in further workup. Treatment is with non-steroidal anti-inflammatory agents, four to six weeks of limited exertion, and conventional heart failure treatment as necessary. Immune suppressant therapy with steroids may be uniquely beneficial in myopericarditis related to smallpox vaccination, compared with other types of myopericarditis. If a widespread vaccination program is undertaken in the future, many more cases of post-vaccinial myopericarditis could be seen. Practicing physicians should be aware that smallpox vaccine-associated myopericarditis is a real entity, and symptoms after vaccination should be appropriately evaluated, treated if necessary, and reported to the Vaccine Adverse Events Reporting System.

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.

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

OBJECTIVE: To examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles. METHODS: A prospective nonrandomized trial was conducted over 1 year in participants undergoing intensive lifestyle modification to reverse or stabilize progression of coronary artery disease. Cardiovascular risk factors, inflammatory biomarkers, and gene expression as a function of weight loss were assessed in 89 lifestyle participants and 71 retrospectively matched controls undergoing usual care. RESULTS: Substantial weight loss (-15.2 ± 3.8%) in lifestyle participants (n = 33) was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes (false discovery rate corrected P-value <0.05 and fold-change ≥1.4). Altered molecular pathways were related to immune function and inflammatory responses involving endothelial activation. In contrast, participants losing minimal weight (-3.1 ± 2.5%, n = 32) showed only minor changes in cardiovascular risk factors and markers of inflammation and no changes in gene expression compared to non intervention controls after 1 year. CONCLUSIONS: Weight loss (≥10%) during lifestyle modification is associated with down-regulation of genetic pathways governing interactions between circulating immune cells and the vascular endothelium and may be required to successfully reduce CVD risk.