12 Heart failure: new mechanisms – new therapies / The smoking room ison with CG (36.5 nmol/mg-protein). There was a significant positive correla- tion between levels of galectin-3 and ox-LDL in all groups of patients: r1=0.8, p1=0.00001; r2=0.75, p2=0.00003; r3=0.71, p3=0.00002. We found a significant decrease in the plasma level of SH-groups in patients in comparison with CG (p<0.01). We also identified a negative correlation between galectin-3 and SH- groups in patients with CHF: r1= -0.81, p1=0.00001; r2= -0.66, p2=0.00002; r3= -0.72, p3=0.00002). The level of hsCRP in groups of patients was 1.8; 3.3 and 6.5 mg/l accordingly, it was significantly higher than in CG (0,65mg/l). We also demonstrated a significant positive correlation between galectin-3 and hsCRP in groups: r1 = 0.573, p1 = 0.00085; r2 = 0.784, p2 = 0.00001; r3 = 0.687, p3 = 0.00007. Conclusions: Galectin-3 correlates with the severity of chronic heart failure. The plasma level of galectin-3 in patients with CHF is closely connected with markers for oxidative stress and inflammation, which confirms its participation in these pathogenic processes. 68 | BEDSIDE MiR-21 and miR-133 levels in peripheral blood mononuclear cells associate with left ventricular diastolic dysfunction in patients with diastolic heart failure M. Marketou, J. Kontaraki, E. Zacharis, F. Parthenakis, S. Margkoudakis, J. Logakis, P. Vardas. Heraklion University Hospital, Heraklion, Greece Purpose: MicroRNAs (miRs) are essential regulators of gene expression impli- cated in cardiovascular function and disease. MiR-21 and miR-133 have been shown to play a role in heart hypertrophy and fibrosis. They have also been shown to regulate proliferation and phenotypic switch of vascular smooth muscle cells. However, there are limited data regarding their role in Left Ventricular (LV) dias- tolic dysfunction. The aim of this study is to investigate miR-21 and miR-133 levels in peripheral blood mononuclear cells in patients with LV diastolic dysfunction. Methods: We included 29 patients with symptoms and signs of heart failure who had LVEF >50% and evidence of LV diastolic dysfunction (19 males, aged 54±10 years. Blood samples were also obtained from 29 healthy volunteers for compar- ison (17 males, aged 52±8 years). All subjects underwent a complete echocar- diographic study. Peripheral Blood Mononuclear Cells (PBMCs) were isolated and microRNA levels were determined by quantitative real time reverse transcription PCR. Results: MiR-21 levels were found to be higher (3.2±0.45 versus 2.05±0.31, p < 0.05), while miR-133 levels were found to be lower (10.16±4.81 versus 37.03±8.18, p<0.05) in patients with LV diastolic dysfunction compared to healthy controls. MiR-21 levels showed strong negative correlations with E/e’ (r=-0.41, p<0.001) while miR-133 levels showed strong positive correlations with E/e’ (r=0.42, p<0.001). Conclusions: Patients with LV diastolic dysfunction were shown to have a strong relationship with miR-21 and miR-133 levels in peripheral blood mononuclear cells. Our findings contribute to the understanding of pathogenesis of diastolic heart failure and might offer a future therapeutic target THE SMOKING ROOM 97 | BEDSIDE Smoking and risk of vascular and non-vascular mortality in old age: 15-year follow-up of 7000 men in the Whitehall resurvey J. Emberson 1 , N. Bhala 2 , M. Shipley 3 , A. Fletcher 4 , R. Clarke 1 . 1 University of Oxford, Oxford, United Kingdom; 2 University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom; 3 University College London, London, United Kingdom; 4 London School of Hygiene and Tropical Medicine, London, United Kingdom Objective: To assess the relevance of tobacco smoking to cause-specific mortal- ity in older men. Methods: In a prospective study of surviving participants of the Whitehall study of male civil servants initially recruited in 1967-1970, 7044 were resurveyed in 1997-8 (mean age 77 years; range 66-97), of which 7024 reported information on smoking habits and had follow-up information on cause-specific mortality up to the end of 2012. Hazard ratios (HR) in relation to smoking habits in old age were estimated using Cox proportional hazards models after adjustment for age, last known employment grade and previous diagnoses of vascular disease or cancer. Results: At resurvey in 1997-98, 13% of men were current smokers (median cigarette consumption 9 per day), 58% were former-smokers (median time since quitting 25 years) and 23% were never-smokers. The remaining 5% reported be- ing a never-smoker in the resurvey, but not in the initial survey in 1967-70, and were handled as a separate category. During a median follow-up of 15 years, there were 4965 deaths (74/1000/year), of which 2063 were from cardiovascular disease [CVD] (31/1000/yr), 1167 from cancer (17/1000/yr]), 802 from respiratory (12/1000/yr) and 933 (14/1000/yr) from other causes. Compared with never smok- ers, average mortality rates among former smokers were 15% higher (HR 1.15, 1.07-1.23), due chiefly to increased risks of death from cancer (1.24, 1.07-1.44) and respiratory disease (1.58, 1.29-1.93). The excess risk associated with be- ing a former smoker varied depending on years since quitting; among men who had quit within the preceding 25 years (median 14 years), mortality rates were 28% higher than those observed among never smokers (HR 1.28, 1.18-1.39), whereas among men who quit 25 or more years earlier (median 35 years ear- lier), no significant excess risk was observed when compared with never smokers (HR 1.05, 0.97-1.13). Compared with older men who had never regularly smoked, older men who remained current smokers in their seventies had 50% higher total mortality rates (HR 1.50, 95% CI 1.36-1.64), due to increased mortality from CVD (1.34, 1.16-1.55), cancer (1.74, 1.44-2.11), and respiratory disease (2.39, 1.87- 3.04). Among men who survived to age 70, the probability of survival to age 85 was 65% for never smokers compared with 48% for current smokers, with current smokers losing, on average, 3 to 4 years of life expectancy. Conclusions: Among men who survive into their seventies, continuing to smoke is associated with persistent excess vascular and non-vascular mortality which translate into important differences in remaining lifespan. 98 | BEDSIDE Smoking influence on mortality: the 40 years’ follow up results of the Serbian cohorts of the seven countries studies B. Parapid 1 , N. Milic 2 , B. Obrenovic-Kircanski 1 , V. Vukcevic 1 , O.M.S. Nedeljkovic- Arsenovic 1 , D. Simic 1 , I. Nedeljkovic 1 , B. Beleslin 1 , M.C. Ostojic 3 . 1 Clinical Center of Serbia, Division of Cardiology, Belgrade, Serbia; 2 University of Belgrade, School of Medicine, Institute for Medical Statistics and Health Research, Belgrade, Serbia; 3 Serbian Academy of Sciences and Arts, Belgrade, Serbia Purpose: The Seven Countries Study remains one of the landmark epidemio- logical studies. It encompassed over 12.000 men on 3 continents in a total of 12 cohorts in 7 countries with a follow up going beyond 5 decades and with a response rate nearing 95% worldwide. Its highly detailed design and systematic follow up, enables us nowadays to assess different aspects of the presence and impact of various risk factors on a myriad of outcomes. In this particular case, we sought to determine influence of smoking on overall and coronary artery disease mortality. Methods: All enrolled in the 3 Serbian cohorts of the Seven Countries’ Study (Velika Krsna farmers, Zrenjanin factory workers and Belgrade University profes- sors), were men aged 40-59 years at entry (1962-1964) who were subsequently followed every 5 years. Smoking status was defined as "never", "former" and "cur- rent". Results: Of 1552 men, aged 48.53 years, 1331 deaths of known cause (85.8%) were available for further analysis, while smoking status data was available for all. Looking at overall mortality, 525 participants were non-smokers, out of which 78% were deceased at the closure of the 40 years’ follow up, with 31 years’ median survival; of the 222 former smokers at entry, 87% died, with 27 years’ median survival, while of the 805 participants who were smokers at entry and then quit, 91% died, with 23.5 years’ median survival (logrank=85.453, p<0.001). Smoking resulted in a 1.76 times increased risk for overall mortality (95% CI 1.56-1.99), while the risk for former smokers were reduced to a 1.43 times (95% CI 1.20- 1.69). When CAD mortality has been additionally looked into relative risk resulted in a 1.43 times for smokers (95% CI 1.15-1.79) and a 1.38 times for former smok- ers (95% CI 1.02-1.87). Conclusion: In the Serbian cohorts of the Seven Countries Study, as a result of the 40 years follow up, we have shown that smokers, had a shorter life expectancy for both overall and coronary artery disease mortality. Overall survival was shorter for 7.5 years for smokers, while for those who quit smoking survival was shorter for 4 years. 99 | BEDSIDE Cigarette smoking induces vascular damage of both conduit arteries and small vessels and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation T. Sugiura 1 , Y. Dohi 1 , S. Yamashita 1 , S. Tanaka 1 , N. Ohte 1 , Y. Hirowatari 2 , S. Ito 1 , S. Fujii 3 . 1 Nagoya City University, Graduate School of Medical Sciences, Dpt of Cardio-Renal Medicine & Hypert., Nagoya, Japan; 2 Tosoh corp., Ayase, Japan; 3 Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan Purpose: Cigarette smoking is one of the major risk factors of cardiovascular dis- eases and induces deleterious vascular damages. Whereas serotonin released to plasma upon platelet activation modulates vascular tonus and thrombus for- mation. The purpose of this study was to examine the plasma levels of serotonin in habitual cigarette smokers and the kinetics of plasma serotonin after smoking cessation, and their association with endothelial function. Methods: In study 1, clinical profiles including endothelial function were com- pared between apparently healthy male smokers (n=27, 40±8 years) and age- adjusted non-smokers (n=21, 40±7 years). In study 2, smokers were instructed to stop smoking and clinical profiles and laboratory findings including serum level of cotinine, principal metabolite of nicotine, were investigated before and after 8 weeks of smoking cessation. Strict precautions were taken to obtain platelet poor plasma (PPP). Serotonin levels in PPP were measured by HPLC. Endothe- lial function was assessed by 2 distinct techniques, namely flow-mediated dilation (FMD) using ultrasound system for conduit arteries and peripheral arterial tonom- etry(PAT) using End-PAT 2000 for peripheral small vessels. Results: In Study 1, levels of PPP serotonin and serotonin corrected by platelets Downloaded from https://academic.oup.com/eurheartj/article-abstract/34/suppl_1/98/2859573 by guest on 29 May 2020