Prevalence of Kawasaki disease in young adults with suspected myocardial ischemia.

BACKGROUND: Up to 25% of patients with untreated Kawasaki disease (KD) and 5% of those treated with intravenous immunoglobulin will develop coronary artery aneurysms. Persistent aneurysms may remain silent until later in life when myocardial ischemia can occur. We sought to determine the prevalence of coronary artery aneurysms suggesting a history of KD among young adults undergoing coronary angiography for evaluation of possible myocardial ischemia. METHODS AND RESULTS: We reviewed the medical histories and coronary angiograms of all adults <40 years of age who underwent coronary angiography for evaluation of suspected myocardial ischemia at 4 San Diego hospitals from 2005 to 2009 (n=261). History of KD-compatible illness and cardiac risk factors were obtained by medical record review. Angiograms were independently reviewed for the presence, size, and location of aneurysms and coronary artery disease by 2 cardiologists blinded to the history. Patients were evaluated for number of risk factors, angiographic appearance of their coronary arteries, and known history of KD. Of the 261 young adults who underwent angiography, 16 had coronary aneurysms. After all clinical criteria were assessed, 5.0% had aneurysms definitely (n=4) or presumed (n=9) secondary to KD as the cause of their coronary disease. CONCLUSIONS: Coronary sequelae of KD are present in 5% of young adults evaluated by angiography for myocardial ischemia. Cardiologists should be aware of this special subset of patients who may benefit from medical and invasive management strategies that differ from the strategies used to treat atherosclerotic coronary artery disease.

Aspirin for primary prevention of coronary heart disease: using the Framingham Risk Score to improve utilization in a primary care clinic.

OBJECTIVES: Coronary heart disease (CHD) is the number one cause of death in adults in the industrialized world, and several large studies show that aspirin is helpful for the primary prevention of this disease. Unfortunately, few physicians are aware of its benefit, resulting in the underutilization of aspirin for the primary prevention of CHD. The purpose of this study was to demonstrate the underuse of aspirin for the primary prevention of CHD, and to improve appropriate utilization by implementing an easy-to-use clinic tool that quickly estimates a patient's risk. PATIENTS AND METHODS: This is a retrospective cohort analysis conducted in the Internal Medicine Clinic in the Naval Medical Center in San Diego, California. Random samples of 494 patients before and 593 after intervention who were followed in the Internal Medicine Clinic were screened. Inclusion criteria were a 10-year risk of myocardial infarction or coronary death of more than 10%, or diabetes with one other cardiac risk factor. A poster was placed in each clinic examination room showing the Framingham Risk Score, the indications for aspirin use, and common contraindications to assist physicians in determining if a patient warranted aspirin for primary prevention of CHD. A physician documented regular use of aspirin, 81 to 325 mg per day. RESULTS: Age and sex demographics were similar between the two measurement groups. Diabetics comprised a significantly greater percentage of patients in the postintervention group. There was a trend toward increase in utilization of aspirin from 63.5% to 72.8% (P = 0.054) after our intervention. In subgroup analysis, significant improvement in appropriate aspirin use was found amongst males (P = 0.01) and nondiabetics (P = 0.02). CONCLUSION: Aspirin has proven beneficial in the primary prevention of CHD, but is clearly underutilized in this role. By implementing the Framingham Risk Score to streamline the decision process, appropriate utilization can be improved, and in turn, cardiac events can be reduced and patients can benefit.

Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial aims to test whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus a fibrate is more efficacious in reducing cardiovascular events than a statin plus placebo in patients with type 2 diabetes mellitus with defined glycemic control. This is a blinded component in a 5,518-patient subset of the ACCORD cohort. These participants were randomized to either be (1) treated with simvastatin (titrated to 40 mg/day if necessary to achieve a goal low-density lipoprotein [LDL] cholesterol level of <2.59 mmol/L [100 mg/dL]) plus placebo or (2) treated to the same goal LDL cholesterol level with the statin plus active fenofibrate 160 mg/day or its bioequivalent (or 54 mg/day if the estimated glomerular filtration rate ranges from 30 to <50 mL/min per 1.73 m2). Setting an upper limit of LDL cholesterol qualifying for randomization excluded patients who would not likely achieve the LDL cholesterol goal. Recruitment for ACCORD began in January 2001, and follow-up is scheduled to end in June 2009. Since recruitment began, several clinical trials and consensus statements have been published that led to changes in the details of the lipid treatment algorithm and protocol. This report describes the design of the lipid protocol and modifications to the protocol during the course of the study in response to and in anticipation of these developments. The current protocol is designed to provide an ethically justifiable test of combined statin plus fibrate treatment consistent with the highest level of safety and lipid treatment standards of care.

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.

Characteristics associated with informed consent for genetic studies in the ACCORD trial.

BACKGROUND: Prior studies found that some groups have lower genetic consent rates than others. Participant consent for genetic studies enables randomized trials to examine effects of interventions compared to control in participants with different genotypes. METHODS: Unadjusted and multivariate associations between genetic consent rates and participant, study, and consent characteristics in 9573 participants approached for genetics consent in the multicenter Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which used a layered genetics consent. RESULTS: Eighty-nine percent of eligible participants consented to genetic studies ("Any Consent") and 64.7% consented to studies of any genes by any investigator ("Full Consent"), with similar rates in randomized groups. Controlling for multiple characteristics, African-Americans had lower consent rates than others (Any Consent Odds Ratio, OR = 0.62, p = 0.0004; Full Consent OR = 0.67, p < 0.0001). Those with high school or higher education level had higher rates than less than high school graduates (Full Consent ORs 1.41-1.69, p-values < 0.0001). Consent rates were lower when genetics consent was separate from the main trial consent on the same day (Any Consent OR 0.30; Full Consent OR 0.52, p values < 0.0001) or on a subsequent day (Any Consent OR 0.70, p = 0.0022; Full Consent OR 0.76, p = 0.0002). CONCLUSION: High rates of consent for genetic studies can be obtained in complex randomized trials, with lower consent rates in African-Americans, in participants with less than high-school education, and for sharing samples with other investigators. A genetics consent separated from the main trial consent was associated with lower consent rates.

Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: the ACCORD Lipid Trial.

OBJECTIVE: To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND METHODS: The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L]) during the trial. RESULTS: Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106% higher among those randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P < 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization). CONCLUSIONS: Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.

Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial.

IMPORTANCE: Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. OBJECTIVE: To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS: A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. MAIN OUTCOME MEASURES: Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. RESULTS: Baseline mean HbA1c level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, -4.4 [95% CI, -7.8 to -1.1] cm(3); P = .01). Fibrate therapy had no effect on TBV compared with placebo. CONCLUSIONS AND RELEVANCE: In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000620.