The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes.

The inflammation underlying both atherosclerosis and acute coronary syndromes is strongly related to monocyte-related actions. However, different monocyte subsets can play differential roles in the formation and destabilization of atherosclerotic plaque as well as healing of damaged myocardial tissue. Monocytes are currently being divided into three functionally distinct subsets with different levels of CD14 (cluster of differentiation 14) and CD16 expression. Thus, there are classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. Here, we summarize the current knowledge on complex activities of different monocyte subsets in atherosclerosis and acute coronary syndromes. Moreover, we discuss which monocyte subsets can serve either as predictive biomarkers of cardiovascular risk or as potential targets used in atherosclerosis and its complications.

Anti-inflammatory effects of atorvastatin treatment in chronic obstructive pulmonary disease. A controlled pilot study.

UNLABELLED: Observational studies have suggested that statins may have beneficial effects on outcomes in chronic obstructive pulmonary disease (COPD) patients. These effects may be mediated through an anti-inflammatory effect of statins. The purpose of this pilot-study was to determine whether statins have an anti-inflammatory effect on the lungs of COPD patients. We conducted randomized, controlled, parallel group pilot-study to compare the effects of atorvastatin (n=12) or placebo (n=6) on lung inflammation in patients with mild to moderate COPD. The primary endpoint was change in CD45+ cells expression measured by immunohistochemistry and changes in expression of genes measured using microarrays in lung biopsy (TBB) samples before and after 12 weeks of treatment with atorvastatin 40 mg/day. All subjects had spirometry, lung volumes, diffusing capacity of the lungs for carbon monoxide (DLCO), St George's Respiratory Questionnaire (SGRQ), 6 minute walk distance (6 MWD), serum lipids, hs-CRP, induced sputum (IS), bronchoscopy and TBB carried out at baseline and after treatment. TBB specimens were processed for histology, immunohistochemistry and genome-wide association studies (GWAS) profiling. Seventeen subjects completed the study. There was a significant improvement in SGRQ with mean SGRQ decreased by 12 points after treatment with atorvastatin (P=0.012). Atorvastatin treatment produced a significant 34% reduction in sputum neutrophil count, and a 57% reduction in CD45+ cells in lung biopsies (expressed as integrated optical density -IOD; median IOD 62.51% before, 27.01% after atorvastatin treatment, P=0.008). In patients' lung tissue atorvastatin treatment produced downregulation of key genes involved in inflammatory processes, immune response, and leukocyte activation. These data demonstrate the pulmonary anti-inflammatory effects of atorvastatin in COPD patients with the potential for beneficial clinical effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01748279.

Usefulness of automatic measurement of contrast flow intensity: an innovative tool in contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization. A pilot study.

AIM: Contrast-enhanced ultrasound imaging of the carotid arteries (CECU) permits direct, real-time visualization of neovascularization in atherosclerotic plaques and is a confirmed predictor of unstable atheromatous lesions. The aim of the study was the assessment of a new, automatically measured index of intensity in quantitative estimation of the contrast flow through the carotid plaque (till now assessed only visually). METHODS: Forty-four patients (mean age 70.4±11.4) with ultrasound diagnosed significant stenosis of internal carotid artery (ICA), after cerebrovascular or cardiovascular events, qualified for carotid artery stenting (CAS) were examined. The carotid ultrasound examinations with contrast agent Sonovue were performed. RESULTS: Visually in 22 patients (50%) contrast flow through the atherosclerotic plaques was found. In 17 patients (38.6%) massive, calcified atherosclerotic plaques were present. Patients with preserved contrast flow through the plaque more frequently had a history of cerebral stroke (P=0.04). Massive calcifications of atherosclerotic plaques correlated with a previous MI (P=0.03) and the degree of advancement of coronary artery disease (P=0.04), but not with a previous cerebral stroke. Contrast flow through the atherosclerotic plaque positively correlated with values of the index of intensity (r=0.69, P<0.00001). In patients with preserved contrast flow the mean value of the index of intensity was 22.24±3.55 dB as compared with 12.37±7.67 dB - a value present in patients without preserved contrast flow. No significant relation for the degree of calcifications and the value of the index of intensity was found. CONCLUSION: The assessment of the index of intensity is a novel, simple and automatic method to estimate the degree of contrast flow through the carotid plaque. The values of the index of intensity correlate with the contrast flow through the atherosclerotic plaque, but not with its calcification.

Myocardial perfusion and intima-media thickness in patients with subclinical hypothyroidism.

PURPOSE: The data concerning the relation between subclinical hypothyroidism (SH) and the risk of cardiovascular disease are divergent. We aimed to assess myocardial perfusion in contrast-enhanced echocardiography and intima-media thickness (IMT) in patients with SH. MATERIAL/METHODS: Forty females with SH without symptoms of coronary artery disease and 15 healthy female volunteers were examined. Echocardiographic evaluation of the left ventricle function as well as carotid and femoral IMT complex measurements were performed at baseline. Thereafter, dobutamine stress echocardiography with myocardial perfusion assessment at rest and on the peak of stress test was performed. SonoVue® intravenous bolus as a contrast medium was used. The myocardial perfusion was assessed by quantitative method using Q-LAB Philips software (ROI modality). The perfusion index was calculated (a number of left ventricle segments with improved perfusion/a number of all segments). RESULTS: A mean IMT value in the SH group was significantly higher than in the controls (0.7 mm vs. 0.38 mm, p=0.001). Myocardial perfusion at rest and at the peak of stress test was significantly lower in the SH patients as compared to the controls (at rest 120 Db in SH vs. 181 Db in controls, p=0.039 and at the peak of stress 115 Db and 188 Db, p=0.01, respectively). The perfusion index was not significantly worse in the SH group (p=0.6). IMT values negatively correlated with the myocardial perfusion index at the peak of stress (r=-0.54, p=0.014). CONCLUSIONS: In patients with SH contrast-enhanced echocardiographic examination revealed myocardial hypoperfusion and increased IMT. Our results may suggest that the patients with SH are at risk of the development of cardiovascular disease.

Effect of on-pump versus off-pump coronary bypass surgery on cardiac function assessed by intraoperative transesophageal echocardiography.

PURPOSE: To compare cardiac function assessed by intraoperative transesophageal echocardiography in patients undergoing cardiac revascularization with or without cardiopulmonary bypass. MATERIAL AND METHODS: Forty-one patients scheduled for elective, isolated cardiac revascularization (21 on-pump and 20 off-pump) were prospectively analyzed. Patients were matched for demographic (age and gender), anthropometric (BMI), clinical (co-morbidities, EuroScore) and laboratory variables (blood counts, renal function, left ventricular function). Transesophageal echocardiography was performed after induction of anesthesia, protamine sulfate administration, and chest closure. Left ventricular wall motion score index, end-diastolic area, fractional area change, right ventricular area change and end-diastolic area were assessed. Troponin I and C-reactive protein concentrations were measured. RESULTS: Regarding echocardiographic parameters of left and right ventricular function no significant differences between on-pump and off-pump groups at any point-of-time measurements were found. Troponin I and C-reactive protein were higher in on-pump as compared to off-pump group (p=0.001 and p=0.002; p=0.003 and p=0.001, respectively). CONCLUSIONS: In elective patients scheduled for cardiac revascularization there were no difference in cardiac performance assessed by intraoperative echocardiography regardless of surgical method used.

Adiponectin--an independent marker of coronary artery disease occurrence rather than a degree of its advancement in comparison to the IMT values in peripheral arteries.

OBJECTIVE: The aim of the study was to establish whether adiponectin may act as an independent risk factor of coronary artery disease (CAD) and if adiponectin has potential relations with a new marker of cardiovascular risk -intima-media thickness (IMT). METHODS: 165 patients, who had undergone coronary angiography due to symptoms of CAD were enrolled. Selected clinical and biochemical risk factors were assessed, adiponectin concentrations and IMT were measured. RESULTS: A significantly lower adiponectin concentrations in the CAD group, as compared to the controls, were found. Adiponectin concentration did not correlate with a degree of coronary vessels changes advancement. No correlation between adiponectin concentrations and IMT values in the studied peripheral arteries were found. The value of 9.8 ug/ml has been assigned as a cut-off value. Adiponectin concentrations <9.8 µg/ml had the highest positive predictive value (PPV=95.7%) and specificity (90.9), but low sensitivity (30.8). In the multilogistic regression analysis significant variables influencing the appearance of CAD were found: HDL-C (p=0.011, OR=0.88, 95%CI 0.80-0.97), IMT in CCA (p=0.0048, OR=5.25, 95%CI 1.65-16.75), IMT in CFA (p=0.015, OR=1.65, 95%CI 1.10-2.48 ), and adiponectin concentration <9.8 µg/ml (p=0.032, OR=28.95, 95%CI 1.31-641.48). CONCLUSIONS: Adiponectin is an independent risk factor of coronary artery disease occurrence, but not its advancement. No correlation between adiponectin concentration and IMT values in peripheral arteries was shown.

Blood pressure in relation to neurogenic, inflammatory and endothelial dysfunction biomarkers in patients with treated essential arterial hypertension.

PURPOSE: Clinical relevance of relations among blood pressure (BP), inflammation, endothelial dysfunction and sympathetic activation is unknown. Study aimed, whether in patients with diagnosed and treated essential arterial hypertension (HTN) biomarkers of inflammation (hs-C-reactive protein, hs-CRP), endothelial dysfunction (endothelin-1, ET-1), and sympathetic nervous system modulation (epinephrine, E and norepinephrine, NE) could be related to BP values. MATERIAL AND METHODS: In 62 patients with diagnosed and treated HTN (mean time of disease 5±3.2 years), serum hs-CRP and ET-1 as well as plasma E and NE concentrations were measured. 24-hour ambulatory blood pressure measurement device (ABPM) was used to estimate efficacy of treatment. RESULTS: A positive correlation between epinephrine and norepinephrine concentrations was found (r=0.246, p=0.05), however such a statistically significant correlation neither to hs-CRP, nor ET-1 were found. Patients with the highest hs-CRP and NE concentrations had the highest systolic (SBP) and diastolic (DBP) blood pressure values. Similar relation was found in subgroup of patients with suboptimal blood pressure values (SPB l 130mmHg, DBP l 80mmHg). In a group of optimal treated patients, elevated levels of ET-1 and NE related to increased blood pressure values. ROC analysis identified ET-1 as statistically significant to diagnose elevated blood pressure: 0.665 (95% Confidence interval 0.512 to 0.796). CONCLUSIONS: In patients with diagnosed and treated arterial hypertension, there are relations among measurements of hs-CRP, ET-1, NE and blood pressure values in spite of treatment, which may improve understanding of mechanisms involving inflammation, endothelial dysfunction and sympathetic nerve activation and may identify patients with refractory hypertension.