FOS expression in blood as a LDL-independent marker of statin treatment.

OBJECTIVES: The expression of FOS, a gene critical for monocyte and macrophage function, can be inhibited by statins through the disruption of a cholesterol-independent signaling pathway. In this pilot study, we hypothesized that blood FOS mRNA levels will be sensitive to statin treatment independent of LDL cholesterol levels. METHODS: Three cohorts at increased risk of or with cardiovascular disease (CVD) were studied. Blood FOS mRNA levels were measured before and after statin treatment or in patients under stable treatment. RESULTS: Statin treatment for three months significantly reduced blood FOS mRNA and LDL cholesterol levels. However, in subjects with similar LDL levels achieved by different doses of long term statin treatment, there was an inverse relationship between statin dose and FOS expression. CONCLUSIONS: FOS mRNA levels appear to be a sensitive marker of statin treatment that is dissociated from cholesterol levels.

Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease.

OBJECTIVES: The goal of this study was to characterize left ventricular diastolic function in the sickle cell disease (SCD) population and to relate echocardiographic measures of dysfunction with pulmonary hypertension and mortality. BACKGROUND: Pulmonary hypertension has been identified as a predictor of death in the adult SCD population. Although diastolic dysfunction is also observed in this population, its prevalence, association with high pulmonary artery systolic pressure, and attributable mortality remain unknown. METHODS: Diastolic function assessment using tissue Doppler imaging was performed in a group of 141 SCD patients. Conventional echocardiographic parameters of diastolic function were performed in a total of 235 SCD patients. RESULTS: Diastolic dysfunction was present in 18% of patients. A combination of diastolic dysfunction and pulmonary hypertension was present in 11% of patients, and diastolic dysfunction accounted for only 10% to 20% of the variability in tricuspid regurgitation (TR) jet velocity. Diastolic dysfunction, as reflected by a low E/A ratio, was associated with mortality with a risk ratio of 3.5 (95% confidence interval 1.5 to 8.4, p < 0.001), even after adjustment for tricuspid regurgitation (TR) jet velocity. The presence of both diastolic dysfunction and pulmonary hypertension conferred a risk ratio for death of 12.0 (95% confidence interval 3.8 to 38.1, p < 0.001). CONCLUSIONS: Diastolic dysfunction and pulmonary hypertension each contribute independently to prospective mortality in patients with SCD. Patients with both risk factors have an extremely poor prognosis. These data support the implementation of echocardiographic screening of adult patients with SCD to identify high-risk individuals for further evaluation.

Myocardial strain decreases with increasing transmurality of infarction: a Doppler echocardiographic and magnetic resonance correlation study.

BACKGROUND: Regional abnormalities in myocardial systolic function can be detected with myocardial strain measurements derived from Doppler tissue echocardiography. We studied longitudinal strain measurements in patients with evidence of myocardial infarction by cardiac magnetic resonance imaging to determine whether end-systolic strain could identify the severity of the infarction. METHODS: A total of 20 patients with chronic myocardial infarctions and 10 healthy volunteers underwent 2-dimensional echocardiography and cardiac magnetic resonance with delayed gadolinium (Gd) gadopentetate dimeglumine (DTPA) contrast hyperenhancement. Delayed Gd hyperenhancement was graded using the following scale: 0 = none, 1 = less than 25%, 2 = 26% to 50%, 3 = 51% to 75%, and 4 = greater than 75%. RESULTS: There was a progressive decrease in peak systolic strain in the infarct segments as the transmural extent of infarction increased. When compared with the peak systolic strain in remote segments without evidence of infarction (-19.7 +/- 0.9), the strain was significantly lower in segments with greater than 25% Gd hyperenhancement (grade 2, -14.8 +/- 1.1, P = .001; grade 3, -12.9 +/- 2.1, P = .001; grade 4, -9.1 +/- 2.0, P < .001). CONCLUSIONS: In patients with chronic myocardial infarctions, strain measurements with echocardiography show a graded response of decreasing regional strain in segments with increasing transmural extent of infarction defined by Gd hyperenhancement.