BackgroundAlthough 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.PurposeThe 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.MethodsNew 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).ResultsNew 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.ConclusionsPassive 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.

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.

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.

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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; nϭ79) and pravastatin (40 mg/d; nϭ82) 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 76Ϯ23 mg/dL after 12 months (Ϫ48.5%); LDL cholesterol was 110Ϯ30 mg/dL in the pravastatin group (Ϫ27.2%; PϽ0.001). Atorvastatin induced progressive CIMT regression over 12 months (change in CIMT, Ϫ0.034Ϯ0.021 mm), whereas CIMT was stable in the pravastatin group (change of 0.025Ϯ 0.017 mm; Pϭ0.03). Conclusions-Marked LDL reduction (Ͻ100 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. (Circulation.