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MS473 PSORIATIC ARTHRITIS AND ATHEROSCLEROSIS: WHAT IS THE LINK?
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
MS471 FIBRINOGEN BETA VARIANTS CONFER PROTECTION AGAINST CORONARY ARTERY DISEASE IN A GREEK CASE−CONTROL STUDY E. Theodoraki1 , T. Nikopensius2 , J. Suhorutˇsenko2 , M. Dimitriou1 , V. Peppes3 , G. Kolovou4 , N. Zakopoulos3 , D. Richter5 , A. Metspalu2 , G. Dedoussis1 . 1 Harokopio University, Athens, Greece, 2 University of Tartu, Tartu, Estonia, 3 University of Athens Medical School, 4 Onassis Cardiac Surgery, 5 Athens Euroclinic, Athens, Greece Background and Aim: Although plasma fibrinogen levels are related to cardiovascular risk, data regarding the role of fibrinogen SNPs in coronary artery disease (CAD) etiology remain inconsistent. The aim of the present study was to investigate the effect of fibrinogen A (FGA), fibrinogen B (FGB) and fibrinogen G (FGG) gene SNPs and haplotypes on susceptibility to CAD in a Greek population. Methods: Cases (n = 305) were subjects presenting acute coronary syndrome or CAD defined as >50% stenosis in at least one of the three main coronary vessels (81.6% males) (age: 60.3±14.8 years). Controls (n = 305) were subjects with normal coronary vessels assessed by coronary angiography or with negative stress test (70.2% males) (age:63.1±11.4 years). 3 SNPs were selected for FGA, 7 SNPs for FGB and 3 SNPs for FGG genes using Carlson’s algorithm. Genotyping was performed using APEX-2 method. PLINK 1.2 software was used to perform logistic regression analysis, before and after adjustment for potential confounders. THISEAS software was used to estimate haplotype effects. Results: From all SNPs and haplotypes tested only rs1800787 and rs1800789 SNPs in FGB gene were associated with CAD, even after adjustment, in the recessive model (OR = 0.42, 95% CI: 0.19–0.90, p = 0.026 and OR = 0.44, 95% CI: 0.21–0.94, p = 0.039, respectively). Conclusions: FGA and FGG SNPs, as well as FGA, FGB, FGG and FGA-FGG haplotypes do not seem to be important contributors to CAD in our sample. On the contrary, FGB rs1800787 and rs1800789 SNPs seem to confer protection to disease onset lowering the risk by about 50% in homozygotes for the minor alleles. MS472 IMMEDIATE EFFECT OF INTENSIVE ATORVASTATIN TREATMENT ON LIPID LEVELS IN PATIENTS WITH ACUTE CORONARY SYNDROME (ACS) D. Vondrakova, P. Ostadal, A. Kruger. Na Homolce Hospital, Prague, Czech Republic Introduction: Statin therapy decreases mortality and incidence of coronary events. Recently it has been reported that spontaneous lipid levels remain clinically stable during ACS. Methods: We have analyzed group of 114 patients with ACS. Atorvastatin 80 mg was administered at admission and then once daily for the rest of hospitalization. The total cholesterol (TC), LDL-cholosterol (LDL), HDL-cholesterol (HDL), and triglycerides (TG) were measured at admission (D0), and then every other morning of hospitalization (D1, D2). Results: The mean entry values (D0) of TC, LDL, HDL and TG (mmol/L) were 5.24, 3.26, 1.07 and 1.31, respectively. The therapy with atorvastatin 80 mg resulted in a decrease of TC levels in the first morning (D1) by 6.1% and on the second morning (D2) by 13.2% (p < 0.001 for all comparisons with the entry value D0); LDL was decreased by 5.8% (D1) and 15.6% (D2) (p < 0.001 vs. D0); the HDL was decreased by 7.5% (D1) and 12.1% (D2) (p < 0.001 vs. D0). In contrast, the TG level was higher in the first morning (D1) by 20.6% and in the following morning (D2) by 25.5% (p < 0.05 vs. D0). Conclusion: We have shown that intensive statin therapy started at admission in ACS patients has a highly significant, immediate effect on all monitored lipid levels. Since TC and LDL levels were decreased as predicted, reduction in HDL and increase in TG levels suggest different acute effect of high-dose statin on lipid levels in comparison with long-term treatment of ACS patients. MS473 PSORIATIC ARTHRITIS AND ATHEROSCLEROSIS: WHAT IS THE LINK? A. Abou-Raya, S. Abou-Raya. Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt Background: Inflammation plays a role in the pathogenesis of psoriatic arthritis (PsA), a chronic inflammatory disease and also in the pathogenesis of atherosclerosis. Cardiovascular disease (CVD) is an important cause of morbidity and mortality in chronic inflammatory disorders. Objectives: To evaluate the prevalence of subclinical atherosclerosis in PsA patients and to correlate it with inflammatory markers and disease activity. Methods: The study population consisted of 56 PsA patients with no previous history or clinically overt CVD and 38 healthy age-sex and traditional cardiovascular risk factors matched controls. Laboratory measurements included: hsCRP, fibrinogen, lipid profile, IL-6 and TNF-alpha. Carotid intima media thickness (CIMT) was assessed by Doppler examination and the presence of plaques documented.
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Results: PsA had a higher prevalence of subclinical atherosclerosis. Seventeen of the 56 patients (30%) demonstrated subclinical atherosclerosis. PsA patients had a significantly higher CIMT than in controls [1.14(0.29) mm versus 0.80(0.20) mm]. Levels of IL-6 and TNF-alpha were significantly higher in patients than in controls. CIMT correlated with disease duration, disease severity, IL-6 and TNF-alpha respectively. Conclusion: PsA patients have an increased prevalence of subclinical atherosclerosis. Chronic systemic inflammation appears to be the link between PsA and atherosclerosis. PsA patients are thus at an increased risk of accelerated atherosclerosis and cardiovascular morbidity and mortality. Thus there should be regular screening for subclinical CVD. Furthermore, it is imperative to control inflammation to protect against the development of CVD in PsA patients. MS474 PERIPHERAL ARTERY DISEASE AND CARDIOVASCULAR MORBIDITY IN RHEUMATOID ARTHRITIS S. Abou-Raya, A. Abou-Raya. Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt Background: Studies of the central arteries in RA patients have shown an increase in the thickness of the intimal layer, suggesting that RA predisposes to atherosclerosis and cardiovascular disease (CVD). The extent of peripheral arterial atherosclerosis however, remains unestablished in these patients. Objectives: To determine the prevalence and extent of peripheral artery subclinical atherosclerosis in RA patients with no previous history of CVD and the association with clinical and inflammatory parameters. Methods: Sixty four consecutive RA patients with no previous history of CVD and 37 age-sex-body mass index and traditional risk factors matched controls were recruited. Both patients and volunteers were chosen to be non-smokers. Biochemical measurements included glucose levels, lipid profile, hsCRP and fibrinogen. Peripheral atherosclerosis was assessed using the ankle-brachial blood pressure index (ABPI). Results: In RA patients, one or more abnormal arteries occurred in 19 of the 64 patients (30%) versus 2 of the 37 control subjects (5%), p = 0.002. A significant correlation was observed between ABPI and disease duration, disease severity, hsCRP, and fibrinogen respectively. Conclusion: The findings demonstrate an increased prevalence of an abnormal ABPI in RA patients which is an indication of subclinical atherosclerosis and consequently increased risk of CVD. The simple, relatively cheap, non-invasive tool, namely ABPI, appears to be useful in assessing peripheral arteries and peripheral artery disease in RA patients and in identifying patients who are at an increased risk of atherosclerosis and further future CVD. It is imperative that peripheral artery disease be not overlooked in RA patients. MS475 FETUIN-A: AN ADDITIONAL MEDIATOR BETWEEN CHRONIC INFLAMMATION AND CARDIOVASCULAR DISEASE IN RHEUMATOID ARTHRITIS? S. Abou-Raya1 , A. Abou-Raya1 , M. Helmii2 . 1 Internal Medicine, Faculty of Medicine, University of Alexandria, 2 Biochemistry, Medical Research Institute, Alexandria, Egypt Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder, with increased cardiovascular (CVS) morbidity is. Furthermore, atherosclerosis like RA, is characterized by chronic inflammation and increased mineral mobilization. Fetuin-A is a circulating negative acute phase protein of the cystatin superfamily of cysteine protease inhibitors involved in vascular pathology. Objective: To evaluate the level of fetuin-A in RA patients and to assess its association with subclinical atherosclerosis and the inflammatory state in RA. Methods: 87 RA patients and 46 healthy volunteers matched for age, sex, body mass index, arterial blood pressure were studied. All subjects were without CVS symptoms or clinically overt CVS disease. Serum Fetuin-A levels were determined by ELISA. High resolution B- mode ultrasound was done to compare carotid artery intima media thickness (CIMT) between RA patients and controls. Plain X-rays of the chest were used to assess the presence of aortic calcifications. Results: In RA patients, serum fetuin-A levels were significantly lower compared to controls (287±67.1 versus 449±56.4 mg/ml, p < 0.001). Mean CIMT was significantly different in RA patients compared to controls. Vascular calcifications were detected in 14% of patients. There was a significant inverse correlation between fetuin-A levels and CIMT. Conclusions: The findings of significantly lower levels of fetuin-A and the association of fetuin-A with inflammatory markers, lipid parameters and CIMT in RA patients suggest that reduced fetuin-A levels may be indicative of a chronic inflammatory state and may be associated with increased risk of subclinical atherosclerosis and thus increased CVS risk in RA patients.
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
MS471 FIBRINOGEN BETA VARIANTS CONFER PROTECTION AGAINST CORONARY ARTERY DISEASE IN A GREEK CASE−CONTROL STUDY E. Theodoraki1 , T. Nikopensius2 , J. Suhorutˇsenko2 , M. Dimitriou1 , V. Peppes3 , G. Kolovou4 , N. Zakopoulos3 , D. Richter5 , A. Metspalu2 , G. Dedoussis1 . 1 Harokopio University, Athens, Greece, 2 University of Tartu, Tartu, Estonia, 3 University of Athens Medical School, 4 Onassis Cardiac Surgery, 5 Athens Euroclinic, Athens, Greece Background and Aim: Although plasma fibrinogen levels are related to cardiovascular risk, data regarding the role of fibrinogen SNPs in coronary artery disease (CAD) etiology remain inconsistent. The aim of the present study was to investigate the effect of fibrinogen A (FGA), fibrinogen B (FGB) and fibrinogen G (FGG) gene SNPs and haplotypes on susceptibility to CAD in a Greek population. Methods: Cases (n = 305) were subjects presenting acute coronary syndrome or CAD defined as >50% stenosis in at least one of the three main coronary vessels (81.6% males) (age: 60.3±14.8 years). Controls (n = 305) were subjects with normal coronary vessels assessed by coronary angiography or with negative stress test (70.2% males) (age:63.1±11.4 years). 3 SNPs were selected for FGA, 7 SNPs for FGB and 3 SNPs for FGG genes using Carlson’s algorithm. Genotyping was performed using APEX-2 method. PLINK 1.2 software was used to perform logistic regression analysis, before and after adjustment for potential confounders. THISEAS software was used to estimate haplotype effects. Results: From all SNPs and haplotypes tested only rs1800787 and rs1800789 SNPs in FGB gene were associated with CAD, even after adjustment, in the recessive model (OR = 0.42, 95% CI: 0.19–0.90, p = 0.026 and OR = 0.44, 95% CI: 0.21–0.94, p = 0.039, respectively). Conclusions: FGA and FGG SNPs, as well as FGA, FGB, FGG and FGA-FGG haplotypes do not seem to be important contributors to CAD in our sample. On the contrary, FGB rs1800787 and rs1800789 SNPs seem to confer protection to disease onset lowering the risk by about 50% in homozygotes for the minor alleles. MS472 IMMEDIATE EFFECT OF INTENSIVE ATORVASTATIN TREATMENT ON LIPID LEVELS IN PATIENTS WITH ACUTE CORONARY SYNDROME (ACS) D. Vondrakova, P. Ostadal, A. Kruger. Na Homolce Hospital, Prague, Czech Republic Introduction: Statin therapy decreases mortality and incidence of coronary events. Recently it has been reported that spontaneous lipid levels remain clinically stable during ACS. Methods: We have analyzed group of 114 patients with ACS. Atorvastatin 80 mg was administered at admission and then once daily for the rest of hospitalization. The total cholesterol (TC), LDL-cholosterol (LDL), HDL-cholesterol (HDL), and triglycerides (TG) were measured at admission (D0), and then every other morning of hospitalization (D1, D2). Results: The mean entry values (D0) of TC, LDL, HDL and TG (mmol/L) were 5.24, 3.26, 1.07 and 1.31, respectively. The therapy with atorvastatin 80 mg resulted in a decrease of TC levels in the first morning (D1) by 6.1% and on the second morning (D2) by 13.2% (p < 0.001 for all comparisons with the entry value D0); LDL was decreased by 5.8% (D1) and 15.6% (D2) (p < 0.001 vs. D0); the HDL was decreased by 7.5% (D1) and 12.1% (D2) (p < 0.001 vs. D0). In contrast, the TG level was higher in the first morning (D1) by 20.6% and in the following morning (D2) by 25.5% (p < 0.05 vs. D0). Conclusion: We have shown that intensive statin therapy started at admission in ACS patients has a highly significant, immediate effect on all monitored lipid levels. Since TC and LDL levels were decreased as predicted, reduction in HDL and increase in TG levels suggest different acute effect of high-dose statin on lipid levels in comparison with long-term treatment of ACS patients. MS473 PSORIATIC ARTHRITIS AND ATHEROSCLEROSIS: WHAT IS THE LINK? A. Abou-Raya, S. Abou-Raya. Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt Background: Inflammation plays a role in the pathogenesis of psoriatic arthritis (PsA), a chronic inflammatory disease and also in the pathogenesis of atherosclerosis. Cardiovascular disease (CVD) is an important cause of morbidity and mortality in chronic inflammatory disorders. Objectives: To evaluate the prevalence of subclinical atherosclerosis in PsA patients and to correlate it with inflammatory markers and disease activity. Methods: The study population consisted of 56 PsA patients with no previous history or clinically overt CVD and 38 healthy age-sex and traditional cardiovascular risk factors matched controls. Laboratory measurements included: hsCRP, fibrinogen, lipid profile, IL-6 and TNF-alpha. Carotid intima media thickness (CIMT) was assessed by Doppler examination and the presence of plaques documented.
205
Results: PsA had a higher prevalence of subclinical atherosclerosis. Seventeen of the 56 patients (30%) demonstrated subclinical atherosclerosis. PsA patients had a significantly higher CIMT than in controls [1.14(0.29) mm versus 0.80(0.20) mm]. Levels of IL-6 and TNF-alpha were significantly higher in patients than in controls. CIMT correlated with disease duration, disease severity, IL-6 and TNF-alpha respectively. Conclusion: PsA patients have an increased prevalence of subclinical atherosclerosis. Chronic systemic inflammation appears to be the link between PsA and atherosclerosis. PsA patients are thus at an increased risk of accelerated atherosclerosis and cardiovascular morbidity and mortality. Thus there should be regular screening for subclinical CVD. Furthermore, it is imperative to control inflammation to protect against the development of CVD in PsA patients. MS474 PERIPHERAL ARTERY DISEASE AND CARDIOVASCULAR MORBIDITY IN RHEUMATOID ARTHRITIS S. Abou-Raya, A. Abou-Raya. Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt Background: Studies of the central arteries in RA patients have shown an increase in the thickness of the intimal layer, suggesting that RA predisposes to atherosclerosis and cardiovascular disease (CVD). The extent of peripheral arterial atherosclerosis however, remains unestablished in these patients. Objectives: To determine the prevalence and extent of peripheral artery subclinical atherosclerosis in RA patients with no previous history of CVD and the association with clinical and inflammatory parameters. Methods: Sixty four consecutive RA patients with no previous history of CVD and 37 age-sex-body mass index and traditional risk factors matched controls were recruited. Both patients and volunteers were chosen to be non-smokers. Biochemical measurements included glucose levels, lipid profile, hsCRP and fibrinogen. Peripheral atherosclerosis was assessed using the ankle-brachial blood pressure index (ABPI). Results: In RA patients, one or more abnormal arteries occurred in 19 of the 64 patients (30%) versus 2 of the 37 control subjects (5%), p = 0.002. A significant correlation was observed between ABPI and disease duration, disease severity, hsCRP, and fibrinogen respectively. Conclusion: The findings demonstrate an increased prevalence of an abnormal ABPI in RA patients which is an indication of subclinical atherosclerosis and consequently increased risk of CVD. The simple, relatively cheap, non-invasive tool, namely ABPI, appears to be useful in assessing peripheral arteries and peripheral artery disease in RA patients and in identifying patients who are at an increased risk of atherosclerosis and further future CVD. It is imperative that peripheral artery disease be not overlooked in RA patients. MS475 FETUIN-A: AN ADDITIONAL MEDIATOR BETWEEN CHRONIC INFLAMMATION AND CARDIOVASCULAR DISEASE IN RHEUMATOID ARTHRITIS? S. Abou-Raya1 , A. Abou-Raya1 , M. Helmii2 . 1 Internal Medicine, Faculty of Medicine, University of Alexandria, 2 Biochemistry, Medical Research Institute, Alexandria, Egypt Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder, with increased cardiovascular (CVS) morbidity is. Furthermore, atherosclerosis like RA, is characterized by chronic inflammation and increased mineral mobilization. Fetuin-A is a circulating negative acute phase protein of the cystatin superfamily of cysteine protease inhibitors involved in vascular pathology. Objective: To evaluate the level of fetuin-A in RA patients and to assess its association with subclinical atherosclerosis and the inflammatory state in RA. Methods: 87 RA patients and 46 healthy volunteers matched for age, sex, body mass index, arterial blood pressure were studied. All subjects were without CVS symptoms or clinically overt CVS disease. Serum Fetuin-A levels were determined by ELISA. High resolution B- mode ultrasound was done to compare carotid artery intima media thickness (CIMT) between RA patients and controls. Plain X-rays of the chest were used to assess the presence of aortic calcifications. Results: In RA patients, serum fetuin-A levels were significantly lower compared to controls (287±67.1 versus 449±56.4 mg/ml, p < 0.001). Mean CIMT was significantly different in RA patients compared to controls. Vascular calcifications were detected in 14% of patients. There was a significant inverse correlation between fetuin-A levels and CIMT. Conclusions: The findings of significantly lower levels of fetuin-A and the association of fetuin-A with inflammatory markers, lipid parameters and CIMT in RA patients suggest that reduced fetuin-A levels may be indicative of a chronic inflammatory state and may be associated with increased risk of subclinical atherosclerosis and thus increased CVS risk in RA patients.