Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective stud

cat. 45 Pianta di Corfù Fortezza Vecchia e città, XVI sec., Museo Correr

Background: Premature cardiovascular disease (CVD) is treated in the same way as CVD of advanced age. However, in patients with premature CVD and a family history of CVD, different -possibly genetic-mechanisms may underlie this disease, which current medical treatment is not targeted to. This suggests that subjects with a genetic predisposition to CVD are more likely to have recurrent cardiovascular events. Methods: We retrospectively investigated 291 patients with premature CVD and assessed the amount of recurrent events according to family history in a follow-up period of 31 years. Premature CVD was defined as an event <51 years for men or <56 for women. We used a Cox proportional hazards model to estimate the relationship between a positive family history and recurrence of cardiovascular events. Results: Patients with recurrent events had more often a positive family history (60.0% vs. 47.1%; p <0.05), were more often smokers (85.2% vs. 70.7%; p <0.05), had more often hypertension (36.3% vs. 23.6%; p <0.05) and had a longer follow-up period (10.0 years vs. 5.4 years; p <0.001) than patients without recurrent events. After adjusting for these differences and modelling time to events, a positive family history was independently associated with recurrent events (Hazard ratio 1.31 (95% confidence intervals (CI) 1.01-1.72; p <0.05)). Conclusions: Patients with a genetic predisposition for CVD are at risk for recurrent events, after adjusting for risk factors and other confounders. This might imply that in subjects with a genetic predisposition for CVD different pathophysiological mechanisms are active, leading to recurrent events. (C) 2010 Elsevier Ireland Ltd. All rights reserve

18F-FDG/PET-CT imaging findings after sternotomy

Background: The clinical diagnosis of deep sternal wound infection (DSWI) is supported by imaging findings including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). To avoid misinterpretation due to normal post-surgery inflammation we assessed normal imaging findings in non-infected patients after sternotomy. Methods: This is a prospective cohort study including non-infectious patients with sternotomy. All patients underwent 18F-FDG-PET/CT at either 5 weeks (group 1), 12 weeks (group 2) or 52 weeks (group 3) post-surgery. 18F-FDG uptake was scored visually in five categories and assessed quantitatively. Results: A total of 44 patients were included. Sternal mean SUVmax was 7.34 (± 1.86), 5.22 (± 2.55) and 3.20 (± 1.80) in group 1, 2 and 3, respectively (p < 0.01). Sternal mean SUVmean was 3.84 (± 1.00), 2.69 (± 1.32) and 1.71 (± 0.98) in group 1, 2 and 3 (p < 0.01). All patients in group 1 had elevated uptake whereas group 2 and 3 showed 2/15 (13%) and 11/20 (55%) patients respectively with no elevated uptake. Group 3 still showed an elevated uptake pattern in in 9/20 (45%) and in 3/9 (33%) with a high-grade diffuse uptake pattern. Conclusion: This study shows significant lower sternal 18F-FDG at 55 weeks compared to 5 weeks post-sternotomy however elevated uptake patterns may persist

Normal imaging findings after ascending aorta prosthesis implantation on 18F-Fluorodeoxyglucose Positron Emission Tomography with computed tomography

Background: To diagnose abnormal 18F-Fluorodeoxyglucose (18F-FDG) uptake in suspected endocarditis after aortic root and/or ascending aorta prosthesis (ARAP) implantation, it is important to first establish the normal periprosthetic uptake on positron emission tomography with computed tomography (PET/CT). Methods: Patients with uncomplicated ARAP implantation were prospectively included and underwent 18F-FDG-PET/CT at either 12 (± 2) weeks (group 1) or 52 (± 8) weeks (group 2) after procedure. Uptake on three different locations of the prosthesis (“cranial anastomosis (CA),” “prosthetic heart valve (PHV),” “ascending aorta prosthesis (AAP)”) was scored visually (none/low/intermediate/high) and quantitatively (maximum standardized uptake value (SUVmax) and target-to-background ratio (SUVratio). Results: In total, 20 patients (group 1: n = 10, group 2: n = 10) (mean age 64±7 years, 70% male) were included. Both groups had similar visual uptake intensity for all measured areas (CA: mostly low-intermediate (16/20 (80%)), p = .17; PHV: low-intermediate (16/20 (80%)), p = .88; AAP: low-intermediate (19/20 (95%)), p = .48). SUVmax for CA was 5.6 [4.1-6.1] and 3.8 [3.1-5.9] (median [IQR], p = .19), and around PHV 5.0 [4.1-5.7] and 6.3 [4.6-7.1] (p = .11) for groups 1 and 2, respectively. SUVratio for CA was 2.8 [2.3-3.2] and 2.0 [1.7-2.6] (median [IQR], p = .07) and around PHV 2.5 [2.4-2.8] and 2.9 [2.3-3.5] (median [IQR], p = .26) for groups 1 and 2, respectively. Conclusion: No significant differences were observed between PET/CT findings at 3 months and 1 year after ARAP implantation, warranting caution in interpretation of PET/CT in the first year after implantation

Arterial stiffness is increased in families with premature coronary artery disease

Objective A positive family history of premature coronary artery disease (CAD) is a risk factor for cardiovascular disease (CVD), independent of traditional risk factors. Therefore, currently used risk algorithms poorly predict risk in these individuals. Novel methods are thus needed to assess cardiovascular risk. Pulse-wave velocity (PWV) might be such a method, but it is unknown whether PWV is increased in first-degree relatives of patients with premature CAD. Design Observational case-control study. Setting Academic hospital. Patients Patients with premature CAD and a positive family history of premature CVD (n = 50), their first-degree relatives without CVD (n = 50) and unrelated controls (n = 50). Interventions None. Main Outcome Measures PWV was measured with using an Arteriograph system. Differences in PWV were assessed by a generalised linear model and multinomial logistic regression. Results Patients with premature CAD had a higher PWV compared with first-degree relatives and controls (9.69+/-2.90 m/s vs 8.15+/-61.96 m/s and 7.38+/-61.08 m/s; p <0.05 patients vs all groups). Linear regression showed all groups related to PWV, with patients having the highest PWV and controls the lowest (p <0.0001). Furthermore, PWV was associated with first-degree relatives (OR 1.32, 95% CI 1.02 to 1.72; p <0.05) and premature CAD (OR 1.72, 95% CI 1.32 to 2.24; p <0.05) compared with controls. These findings were independent of blood pressure and other traditional risk factors. Conclusions Patients with premature CAD and their first-degree relatives had higher PWV compared with controls, independent of other risk factors. This holds promise for the future, in which arterial stiffness might play a role in risk prediction within families with premature CA

Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease

There is discussion about incorporating a family history (FamHis) of premature coronary artery disease (CAD) in risk score algorithms. However, FamHis provides information on individual risk. Coronary artery calcification score (CACS) is a metric of atherosclerosis that may determine the individual risk within families at high risk of premature CAD. In asymptomatic individuals (n = 704), we assessed the association between FamHis of CAD and elevated CACS. To assess the predictive value of CACS in individuals with a FamHis of CAD, we performed a post-hoc analysis on the St. Francis Heart Study (n = 834). We assessed, in a case control design, the risk of future CAD in individuals with a FamHis of CAD and either CACS >80th percentile or no CACS at all. Individuals with a FamHis for CAD had an increased risk for elevated CACS (adjusted odds ratio (OR) 2.23 (95% CI 1.48-3.36); p 80(th) percentile, a FamHis of CAD doubled the CAD event rate (positive FamHis 12.5% vs. negative FamHis 6.8%; adjusted HR 2.08 (95% CI 1.09-3.87; p < 0.05). CAC scoring leads to risk discrimination among those with a positive FamHis for premature CAD. These results support testing CAC score in asymptomatic individuals with a positive FamHis to identify a high risk populatio