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The role of montelukast in cardiovascular events
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Abstracts / Atherosclerosis 263 (2017) e111ee282
PO123. IMPACT OF PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR ON BIOLOGICAL RISK FACTORS OF CAROTID ATHEROSCLEROTIC PLAQUE INSTABILITY Pauline Mury1, Antoine Millon2, 3, Mathilde Mura1, Virginie Nicaise4, Vincent Pialoux1, 5. 1 University Claude Bernard Lyon 1, Inter-university Laboratory of Human Movement Science, EA 7424, Lyon, France; 2 University Claude Bernard Lyon 1, CarMeN Laboratory INSERM, 1060, Lyon, France; 3 University Hospital Edouard Herriot of Lyon, Department of Vascular Surgery, Lyon, France; 4 University Claude Bernard Lyon 1, Laboratory of Vulnerabilities and Innovation in Sports, EA 7428, Lyon, France; 5 Institut Universitaire de France, Paris, France Aim: Carotid atherosclerosis plaque instability is increased by intraplaque hemorrhage (IPH) and neovascularization. Oxidative stress is known to promote these two risk factors and induce a vicious circle with IPH and neovascularization. Moreover, it was shown that regular physical activity can reduce oxidative stress by increasing antioxidant defenses whereas sedentary behavior can increase oxidative stress independently to physical activity. The aim of this study was therefore to evaluate the effects of both physical activity and sedentary behavior on the carotid plaque histological characteristics and oxidative stress in patients at high-risk of stroke. Methods: Plasma and carotid plaques were collected in ninety patients, respectively before and after carotid endarterectomy. IPH, neovascularization and inflammation of plaques were assessed by histological analyses and oxidative stress was measured in both plaque and plasma. Physical activity and sedentary behavior were determined by questionnaires and patients were divided in quartiles according to physical activity or sedentary behavior. Results: Plasma oxidative stress was significantly higher in the most sedentary patients (vs. the least sedentary) while it was higher in the least active patients (vs. the most active). Moreover, the prevalence of IPH was significantly higher in the least active patients whereas the prevalence of inflammatory plaques was significantly higher in the most sedentary patients. Conclusions: Our results suggest that physical activity and sedentary behavior have independent effects on the histological features of carotid plaque instability. Furthermore, the higher oxidative stress and inflammation in the most sedentary patients confirm the detrimental effects of sedentary behavior on cardiovascular morbidity as previously observed.
PO124. LDL APHERESIS e LONG-TERM FOLLOW-UP IN A CZECH CENTRE Milan Blaha1, Miriam Lanska1, Vladimir Blaha2, Lubos Sobotka2, Pavel Zak1. 1 Charles University, Medical Faculty, 4th Dpt of Medicine, Hradec Kralove, Czech Republic; 2 Charles University, Medical Faculty, 3th Dpt of Medicine, Hradec Kralove, Czech Republic Aim: The therapy of severe familial hypercholesterolaemia (FH) using LDL Apheresis is concentrated in two centres in the Czech Republic, the absolute majority being treated in our centre. Methods: Fourteen patients, (8 males, 6 females) with severe FH, age 44±17 years (28-70), treated by lipoprotein apheresis 11.3+5.3 years, were studied. Five patients had simultaneously elevated serum lipoprotein (a). Two methods of lipidapheresis were applied: immunoadsorption and rheohaemapheresis (our modification of double plasma filtration). Results: 1787 procedures were evaluated (immuno-adsorption 1314 times, rheohaemapheresis 473 times). Average cholesterol and LDL-cholesterol values before procedures were 6.60 and 4.63 mmol/l in immunoadsorption and 5.71 and 3.50 in rheohaemapharesis; values after the procedure were 1.98 and 0.80 (69% and 81% drop) and 1.84 and 0.70 mmol/l, resp. (59.30% and 70.20% drop). Adverse reactions occurred in 4.9% (not clinically severe). Discussion: The results of our group show that lipidapheresis is an effective method in the treatment of patients with severe FH. Recently, the Czech Society of Atherosclerosis established a multidisciplinary working group for providing lipidapheresis in the Czech Republic. The main purpose of this group is to promote accessibility of lipidapheresis for Czech
patients. The group also defined the selection criteria for lipidapheresis. Broader use of this therapy is curtailed mainly by the economic situation. Conclusions: In our cohort, a statistically significant reduction of required parameters was observed, although the target LDL-cholesterol levels were not achieved. Acknowledgements: This work was supported by the project: MH CZ DRO (UHHK, 00179906) 8134, 8177.
PO125. THE ROLE OF MONTELUKAST IN CARDIOVASCULAR EVENTS rie Capra2, Visar Malaj3, Angelo Sala2, Gianenrico Malvina Hoxha1, Vale Rovati2. 1 Catholic University Our Lady of Good Counsel, Department of Chemical, Toxicological & Pharmacological Evaluation of Drugs, Tirana, degli studi di Milano, Department of Pharmacological Albania; 2 Universita and Biomolecular Sciences, Milan, Italy; 3 University of Tirana, Department of Economics, Faculty of Economics, Tirana, Albania Aim: Cysteinyl-Leukotrienes (cysteinyl-LTs) are arachidonic acid metabolites that are involved in different inflammatory conditions, including CV disorders. CysLT receptor antagonists (LTRAs) are commonly used in diverse inflammatory pulmonary pathologies such as asthma, chronic obstructive pulmonary disease (COPD), or allergic rhinitis. Data have shown, however, that LTRA can prevent atherosclerosis progression, and can play a protective role after cerebral ischemia. Montelukast is a potent CysLT1 antagonist approved in patients with asthma and allergic rhinitis. The aim of our study was to evaluate the possible role of montelukast in the prevention of myocardial infarction (MI) and ischemic stroke (IS) in asthmatic patients. Methods: We performed a retrospective study of eight hundred asthmatic patients exposed or not to montelukast. The drug use, age, and other population data were analysed. The study was designed to determine whether or not there was a correlation (Fisher’s exact test) between montelukast use and the primary or secondary prevention of a major CV event. Results: 1.25% of our study group suffered ischemic stroke, while 3.62% suffered MI. The IS event rate was 9 fold higher (p<0.05) for the study group not exposed to montelukast with respect to the exposed patients, whereas the MI event rate was more than 6 fold higher (p<0.05) in patients not exposed to montelukast with respect to the exposed ones. Conclusions: This study suggests that by targeting the AA metabolites, particularly cysteinyl-LTs, we can contribute in the prevention of cardiovascular events in patients with different pathologies.
PO126. THE IMPACT OF INTER-ARM BLOOD PRESSURE DIFFERENCES TO CORONARY INTERVENTION IN PATIENTS WITH CORONARY ARTERY DISEASES Se-Jun Park1, Jung-Woo Son2, Sang-Min Park1, Hyun-Hee Choi1, KyungSoon Hong1. 1 Chun-Cheon Sacred Heart Hospital, Hallym University, ChunCheon, South Korea; 2 Wonju Christian Hospital, Yonsei University, Wonju, South Korea Aim: The present study investigated the effect of IABPD in clinical outcomes of percutaneous coronary intervention (PCI) in patients with coronary artery diseases. Methods: We retrospectively reviewed data of blood pressures measured simultaneously in both arms in 231 patients (155 males and 76 females) who underwent PCI. IABPD was defined as the difference of blood pressures in both arms,while a modified parameter defined as IABPD divided by the mean blood pressure (mIAPBD) was also investigated to adjust the effect of baseline blood pressureThe primary outcome was the presence of major adverse cardiac events (MACEs), composed of all-cause death, myocardial infarction, stroke, and target vessel revascularization. Results: The mean age of included patients was 67.1 ± 10.9 years, with the mean follow-up period of 42.2 ± 21.9 months. MACEs occurred in 46 patients (19.9%), who revealed higher IABPDs than those without MACEs (systolic IABPD: 7.6 ± 9.0 mmHg vs 4.6 ± 5.7 mmHg, p ¼ 0.033). The Kaplan-Meier survival analysis revealed a greater incidence of MACEs in
Abstracts / Atherosclerosis 263 (2017) e111ee282
PO123. IMPACT OF PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR ON BIOLOGICAL RISK FACTORS OF CAROTID ATHEROSCLEROTIC PLAQUE INSTABILITY Pauline Mury1, Antoine Millon2, 3, Mathilde Mura1, Virginie Nicaise4, Vincent Pialoux1, 5. 1 University Claude Bernard Lyon 1, Inter-university Laboratory of Human Movement Science, EA 7424, Lyon, France; 2 University Claude Bernard Lyon 1, CarMeN Laboratory INSERM, 1060, Lyon, France; 3 University Hospital Edouard Herriot of Lyon, Department of Vascular Surgery, Lyon, France; 4 University Claude Bernard Lyon 1, Laboratory of Vulnerabilities and Innovation in Sports, EA 7428, Lyon, France; 5 Institut Universitaire de France, Paris, France Aim: Carotid atherosclerosis plaque instability is increased by intraplaque hemorrhage (IPH) and neovascularization. Oxidative stress is known to promote these two risk factors and induce a vicious circle with IPH and neovascularization. Moreover, it was shown that regular physical activity can reduce oxidative stress by increasing antioxidant defenses whereas sedentary behavior can increase oxidative stress independently to physical activity. The aim of this study was therefore to evaluate the effects of both physical activity and sedentary behavior on the carotid plaque histological characteristics and oxidative stress in patients at high-risk of stroke. Methods: Plasma and carotid plaques were collected in ninety patients, respectively before and after carotid endarterectomy. IPH, neovascularization and inflammation of plaques were assessed by histological analyses and oxidative stress was measured in both plaque and plasma. Physical activity and sedentary behavior were determined by questionnaires and patients were divided in quartiles according to physical activity or sedentary behavior. Results: Plasma oxidative stress was significantly higher in the most sedentary patients (vs. the least sedentary) while it was higher in the least active patients (vs. the most active). Moreover, the prevalence of IPH was significantly higher in the least active patients whereas the prevalence of inflammatory plaques was significantly higher in the most sedentary patients. Conclusions: Our results suggest that physical activity and sedentary behavior have independent effects on the histological features of carotid plaque instability. Furthermore, the higher oxidative stress and inflammation in the most sedentary patients confirm the detrimental effects of sedentary behavior on cardiovascular morbidity as previously observed.
PO124. LDL APHERESIS e LONG-TERM FOLLOW-UP IN A CZECH CENTRE Milan Blaha1, Miriam Lanska1, Vladimir Blaha2, Lubos Sobotka2, Pavel Zak1. 1 Charles University, Medical Faculty, 4th Dpt of Medicine, Hradec Kralove, Czech Republic; 2 Charles University, Medical Faculty, 3th Dpt of Medicine, Hradec Kralove, Czech Republic Aim: The therapy of severe familial hypercholesterolaemia (FH) using LDL Apheresis is concentrated in two centres in the Czech Republic, the absolute majority being treated in our centre. Methods: Fourteen patients, (8 males, 6 females) with severe FH, age 44±17 years (28-70), treated by lipoprotein apheresis 11.3+5.3 years, were studied. Five patients had simultaneously elevated serum lipoprotein (a). Two methods of lipidapheresis were applied: immunoadsorption and rheohaemapheresis (our modification of double plasma filtration). Results: 1787 procedures were evaluated (immuno-adsorption 1314 times, rheohaemapheresis 473 times). Average cholesterol and LDL-cholesterol values before procedures were 6.60 and 4.63 mmol/l in immunoadsorption and 5.71 and 3.50 in rheohaemapharesis; values after the procedure were 1.98 and 0.80 (69% and 81% drop) and 1.84 and 0.70 mmol/l, resp. (59.30% and 70.20% drop). Adverse reactions occurred in 4.9% (not clinically severe). Discussion: The results of our group show that lipidapheresis is an effective method in the treatment of patients with severe FH. Recently, the Czech Society of Atherosclerosis established a multidisciplinary working group for providing lipidapheresis in the Czech Republic. The main purpose of this group is to promote accessibility of lipidapheresis for Czech
patients. The group also defined the selection criteria for lipidapheresis. Broader use of this therapy is curtailed mainly by the economic situation. Conclusions: In our cohort, a statistically significant reduction of required parameters was observed, although the target LDL-cholesterol levels were not achieved. Acknowledgements: This work was supported by the project: MH CZ DRO (UHHK, 00179906) 8134, 8177.
PO125. THE ROLE OF MONTELUKAST IN CARDIOVASCULAR EVENTS rie Capra2, Visar Malaj3, Angelo Sala2, Gianenrico Malvina Hoxha1, Vale Rovati2. 1 Catholic University Our Lady of Good Counsel, Department of Chemical, Toxicological & Pharmacological Evaluation of Drugs, Tirana, degli studi di Milano, Department of Pharmacological Albania; 2 Universita and Biomolecular Sciences, Milan, Italy; 3 University of Tirana, Department of Economics, Faculty of Economics, Tirana, Albania Aim: Cysteinyl-Leukotrienes (cysteinyl-LTs) are arachidonic acid metabolites that are involved in different inflammatory conditions, including CV disorders. CysLT receptor antagonists (LTRAs) are commonly used in diverse inflammatory pulmonary pathologies such as asthma, chronic obstructive pulmonary disease (COPD), or allergic rhinitis. Data have shown, however, that LTRA can prevent atherosclerosis progression, and can play a protective role after cerebral ischemia. Montelukast is a potent CysLT1 antagonist approved in patients with asthma and allergic rhinitis. The aim of our study was to evaluate the possible role of montelukast in the prevention of myocardial infarction (MI) and ischemic stroke (IS) in asthmatic patients. Methods: We performed a retrospective study of eight hundred asthmatic patients exposed or not to montelukast. The drug use, age, and other population data were analysed. The study was designed to determine whether or not there was a correlation (Fisher’s exact test) between montelukast use and the primary or secondary prevention of a major CV event. Results: 1.25% of our study group suffered ischemic stroke, while 3.62% suffered MI. The IS event rate was 9 fold higher (p<0.05) for the study group not exposed to montelukast with respect to the exposed patients, whereas the MI event rate was more than 6 fold higher (p<0.05) in patients not exposed to montelukast with respect to the exposed ones. Conclusions: This study suggests that by targeting the AA metabolites, particularly cysteinyl-LTs, we can contribute in the prevention of cardiovascular events in patients with different pathologies.
PO126. THE IMPACT OF INTER-ARM BLOOD PRESSURE DIFFERENCES TO CORONARY INTERVENTION IN PATIENTS WITH CORONARY ARTERY DISEASES Se-Jun Park1, Jung-Woo Son2, Sang-Min Park1, Hyun-Hee Choi1, KyungSoon Hong1. 1 Chun-Cheon Sacred Heart Hospital, Hallym University, ChunCheon, South Korea; 2 Wonju Christian Hospital, Yonsei University, Wonju, South Korea Aim: The present study investigated the effect of IABPD in clinical outcomes of percutaneous coronary intervention (PCI) in patients with coronary artery diseases. Methods: We retrospectively reviewed data of blood pressures measured simultaneously in both arms in 231 patients (155 males and 76 females) who underwent PCI. IABPD was defined as the difference of blood pressures in both arms,while a modified parameter defined as IABPD divided by the mean blood pressure (mIAPBD) was also investigated to adjust the effect of baseline blood pressureThe primary outcome was the presence of major adverse cardiac events (MACEs), composed of all-cause death, myocardial infarction, stroke, and target vessel revascularization. Results: The mean age of included patients was 67.1 ± 10.9 years, with the mean follow-up period of 42.2 ± 21.9 months. MACEs occurred in 46 patients (19.9%), who revealed higher IABPDs than those without MACEs (systolic IABPD: 7.6 ± 9.0 mmHg vs 4.6 ± 5.7 mmHg, p ¼ 0.033). The Kaplan-Meier survival analysis revealed a greater incidence of MACEs in