mL)

2 downloads 0 Views 54KB Size Report
CsA (10 ng/mL), RAP (1 ng/mL) and ... with MPA or RAP significantly decreased IL-8 release medi- ... healthy men (40) and women (50), free of vascular disease.
S243

Abstracts

followed by Ficoll Paque gradient centrifugation and hypotonic lysis of residual erythrocytes. CsA (10 ng/mL), RAP (1 ng/mL) and TAC (1 ng/mL) were dissolved in DMSO and MPA (20 ng/mL) in methanol. Neutrophils (5x106 cells/ml) were suspended in RPMI ⫹ 5% fetal bovine serum and stimulated with different pro-inflammatory mediators such as Nformyl-methionine-leucine-phenylalanine (fMLP) (10-7 M) lipopolysaccharide (LPS) (1 ␮g/mL) and tumor necrosis factor-alpha (TNF-␣) (10 ng/mL) at 37°C for 30 min. CsA, RAP, TAC or MPA were added alone or in combination, and the neutrophils were incubated at 37°C either for 2h or 24h. The release of interleukin-8 (IL-8) (pro-inflammatory mediator) and VEGF (pro-angiogenic mediator) was measured by ELISA. RESULTS: Neutrophils treatment with most immunosuppressive agents alone did not affect the basal release of IL-8 after a 24h incubation period. However, MPA reduced basal IL-8 release (⫺80%). We observed that CsA or TAC combined with MPA or RAP significantly decreased IL-8 release mediated by fMLP (⫺68%), LPS (⫺59%) and TNF-␣ (⫺37%). MPA and RAP alone, reduced the basal release of VEGF (⫺60%) and its release mediated by fMLP (⫺30%), LPS (⫺60%) and TNF-␣ (⫺45%) after a 2h incubation period. The combination of MPA or RAP with CsA or TAC significantly decreased by 50% the release of VEGF in both basal and pro-inflammatory conditions. CONCLUSION: Our results indicate that calcineurin inhibitors combined with MPA reduce the release of pro-inflammatory and pro-angiogenic mediators by the neutrophils. These results may suggest a potential beneficial role of a combination of immunosuppressive agents in patients suffering from CAV. Thus, our data support the pursuit of our investigations in cardiac transplant patients, having or not developed CAV at different time points post-CTX.

population was 11.7% (n⫽350). Age was similar between those with and without IFG (56.8⫾8.4y vs. 56.2⫾8.4y, P⬎0.05). Subjects with IFG had a higher body mass index (BMI) (30.4⫾6.5 vs 27.4⫾4.9 kg/m2, p⬍0.00001), greater waist circumference (101.6⫾15.4 cm vs 93.9⫾13.1 cm, p⬍0.00001) and were more likely to have the metabolic syndrome (61.7 vs 24.7%, p⬍0.00001), to have hypertension (41.7 vs 28.8%, p⬍0.00001), and to be of male gender (13.5 vs 9.0%, p⬍0.01). IFG was more prevalent in South Asians, compared to white Caucasians (17.7 vs. 11.2%, p⬍0.01) or Chinese Canadians (8.3% p⬍0.01). HDL and triglycerides were also discriminators of IFG prevalence. However, age, total cholesterol and low-density lipoprotein (LDL) levels did not differ significantly between IFG and non-IFG subjects in multivariate analysis. Levels of hsCRP were significantly higher in IFG subjects (4.2 vs 2.8 mg/L, p⬍0.00001). Subjects with IFG exhibited higher rates of urinary microalbuminuria compared to individuals without IFG, despite similar renal function as assessed by eGFR (76.1⫾15.1 vs 77.6⫾16.1 ml/min/1.73m2, p⬎0.05). The mean total cardiovascular Framingham Risk Score (FRS) was higher for subjects with IFG compared to those without IFG (18.8% vs 14.1%, p⬍0.00001). Furthermore, 75% of IFG subjects were at moderate to high risk by FRS, compared to 54% of non-IFG subjects. CONCLUSION: We provide a descriptive analysis of a large cohort of Canadian adults who have IFG. Our analysis identifies that IFG is common in otherwise healthy, non-diabetic Canadians without vascular disease. Importantly, despite similar age and LDL-cholesterol, IFG patients were at significantly higher global cardiovascular risk.

387 INTER-ARM BLOOD PRESSURE DIFFERENCE IS NOT ASSOCIATED WITH HIGH ANKLE-BRACHIAL INDEX M Sebastianski, MS McMurtry, RT Tsuyuki

386 PREVALENCE OF IMPAIRED FASTING GLUCOSE IN HEALTHY MIDDLE-AGED ADULTS: INSIGHTS FROM THE PRIMARY CARE AUDIT OF GLOBAL RISK MANAGEMENT (PARADIGM) STUDY M Gupta, M Kajil, M Tsigoulis, S Verma Brampton, Ontario

Impaired fasting glucose (IFG) is associated with an increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality. We assessed the prevalence of IFG and associated clinical characteristics in healthy, middle-aged Canadians in the PARADIGM study. METHODS: The PARADIGM study enrolled 3015 otherwise healthy men (ⱖ40) and women (ⱖ50), free of vascular disease or diabetes, in an observational registry aimed at risk stratification using conventional and novel techniques. The present analysis reports on those subjects who were found to have IFG, defined as fasting blood glucose level 6.1-6.9 mmol/l, within this cohort. RESULTS: The overall prevalence of IFG in the PARADIGM BACKGROUND:

Edmonton, Alberta BACKGROUND: Differences in inter-arm blood pressure are associated with ankle-brachial index (ABI) scores of less than 0.90 and are thought to confer additive vascular disease risk. Whether inter-arm blood pressure differences are also associated with vascular calcification artifact (ABI ⬎ 1.30), and if they influence prognosis, is unknown. METHODS: We analyzed data from a prospective cohort of 592 consecutive patients with suspected coronary artery disease referred for coronary angiography. Manual non-simultaneous measurement of systolic blood pressure was performed on the brachial, posterior tibial and dorsalis pedis arteries bilaterally using a Doppler ultrasound. Inter-arm differences greater than 10mmHg were confirmed with repeat measurement. ABI was determined by dividing the highest ankle pressure of each leg by the highest brachial pressure. Logistic regression was used to calculate odds ratios for inter-arm blood pressure difference across strata of ABI, and Cox regression was used to evaluate impact of inter-arm blood pressure differences on a composite