Effects of 12†weeks of atorvastatin therapy on myocardial fibrosis and circulating fibrosis biomarkers in statin-naïve patients with hypertension with atherosclerosis.

UNLABELLED: The purpose of this study was to assess the effects of 12 weeks of atorvastatin treatment on myocardial fibrosis in patients with hypertension with atherosclerosis. 15 statin-naïve participants (11 males; mean age 67±10 years) with atherosclerosis were given atorvastatin (40 mg/day) for 12 weeks and underwent echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS). Serum galectin-3 and fibrosis markers including aminoterminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-2, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also analyzed. After 12 weeks of atorvastatin (40 mg/day) treatment, serum total cholesterol and low-density lipoprotein cholesterol decreased significantly (204±31 to 140±24 mg/dL and 133±26 to 69±17 ng/mL, respectively, both p<0.001). In myocardial fibrosis analysis, CVIBS increased significantly (6.6±1.9 to 8.5±2.7 dB, p=0.024). In addition, the circulating fibrosis markers serum PIIINP and TIMP-1 decreased significantly (9.5±2.7 to 6.4±1.4 ng/mL, p=0.012 and 299±65 to 250±45 ng/mL, p=0.024, respectively). 12 weeks of medium dose atorvastatin treatment resulted in a significant reduction in myocardial fibrosis as evaluated by morphofunctional parameters and plasma markers of tissue fibrosis. TRIAL REGISTRATION NUMBER: NTC00172419; results.

QTc Heterogeneity in Rest Magnetocardiography is Sensitive to Detect Coronary Artery Disease: In Comparison with Stress Myocardial Perfusion Imaging.

BACKGROUND: Stress nuclear myocardial perfusion imaging (MPI) is an established method for diagnosis and prognosis of coronary artery disease (CAD). However, radiation exposure limits its clinical application. Magnetocardiography (MCG) has been proposed as a non-contact, rapid and non-radiation technique with high reproducibility. The aim of the study was to evaluate the diagnostic efficacy of rest MCG in CAD comparing to stress MPI. METHODS: We prospectively enrolled 55 patients with suspected CAD (64 ± 10 years) who were scheduled for coronary angiography (CA). MCG, stress (201)Tl MPI and CA were performed within 3 months. The spatial distribution maps of QTc interval (21 × 21 in resolution) were derived from a 64-channel MCG system (KRISS, Korea). T-wave propagation mapping, repolarization heterogeneity index with QTc dispersion and smoothness index of QTc (SI-QTc) were analyzed, and the diagnostic criteria for CAD were developed based on the receiver operating characteristic (ROC) curve analysis. RESULTS: Patients with significant CAD (≥ 70% luminal stenosis, n = 36) had higher QTc dispersion and SI-QTc than controls (both p < 0.05). The diagnostic sensitivity and specificity were 0.8330, 0.6842 for QTc dispersion ≥ 79 ms; 0.7778, 0.6842 for SI-QTc ≥ 9.1 ms; and 0.8611, 0.6842 for combination. There was no difference of area under ROC curve by using criteria of QTc dispersion ≥ 79 ms, SI-QTc ≥ 9.1 ms or combination (0.7588, 0.7310, 0.7727, p = NS), and non-inferior to stress MPI (p = NS). CONCLUSIONS: The QTc heterogeneity parameters of rest MCG yield a good sensitivity and acceptable specificity for detection of CAD, and may provide an alternative to stress MPI without stress and radiation. KEY WORDS: Coronary artery disease (CAD); Magnetocardiography (MCG); Myocardial perfusion imaging (MPI); Repolarization.

The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers.

PURPOSE: (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. METHODS: Forty-three statin-naïve subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent (18)F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. RESULTS: The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5±0.8 year follow-up. CONCLUSION: The medium dose of atorvastatin over a 12-week period resulted in a significant reduction of arterial inflammation as well as various circulating biomarkers.

Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1.

UNLABELLED: High tissue matrix metalloproteinase (MMP) activity has been associated with advanced atherosclerosis and plaque rupture. 18F-FDG uptake has been reported to detect inflammation. This investigation examined the vascular 18F-FDG uptake by PET/CT and its correlation with circulating MMP-1 levels. METHODS: We examined 25 consecutive patients with significant carotid stenosis and 22 healthy control subjects using 18F-FDG PET/CT. The leukocyte counts, C-reactive protein (CRP), and MMP-1 were measured. RESULTS: 18F-FDG arterial uptake, as well as calcifications, was significantly higher in extensive distributions in patients with established carotid stenosis. However, their distribution was not consistently overlapping. The values of circulating MMP-1 and leukocyte counts were significantly higher in patients with carotid stenosis (all P < 0.05). In addition, subjects with higher 18F-FDG uptake (maximum SUV > 2.0) in target lesions had higher baseline and poststenting MMP-1 levels (all P < 0.05). CONCLUSION: We provide a link between 18F-FDG uptake and circulating MMP-1. 18F-FDG PET/CT could be used as an adjunct to the clinical management of high-risk atherosclerosis and an in vivo tool to study plaque biology.

Urban air pollution increases plasma fibrinogen and plasminogen activator inhibitor-1 levels in susceptible patients.

BACKGROUND: The cardiovascular effects on fibrinolytic activity by urban air pollution are still unknown. METHODS: Paired fasting blood samples during high and low air pollution days in Taipei were taken from a panel of 49 patients with coronary heart disease or multiple risk factors to study their fibrinolytic and inflammatory response to urban air pollution. Paired t-tests and mixed-effects models were used to determine the air pollution effects. RESULTS: Patients' plasma plasminogen activator inhibitor-1 levels were significantly increased when hourly concentrations of particulate matter with diameters less than 10 microm (PM10) were greater than 100 microg/m during the period 0800 to 1800 h. CONCLUSION: Urban air pollution has an adverse effect on plasma fibrinolytic function in a susceptible population.