- Email: [email protected]
Phytosterol and oxyphytosterol levels in plasma and aortic valve cusps in patients with severe aortic stenosis
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Abstracts / Atherosclerosis 235 (2014) e27–e83
Center, Kansas City, USA; e Internal Medicine, Brigham and Women's Hospital, Boston, USA; f Medizinische Klinik II, Klinikum der Universität München, München, Germany Objectives: PCSK9 plays an important role in the regulation of LDLcholesterol concentrations via its influence on catabolism of the LDL receptors. It is known that PCSK9 levels are higher in patients with familial hypercholesterolemia than in normolipidemic controls. We wanted to estimate PCSK9 levels in patients currently undergoing apheresis or eligible to be treated by LA and look into the acute effects of LA on PCSK9 concentrations. Methods: We measured total serum PCSK9 levels (using an ELISA-method) in 2 cohorts: Cohort I consisted of patients actively undergoing lipoprotein apheresis as part of their routine care (n 40; 21 males, 19 females; age 55.6 years (range 32-73 years)). Blood was drawn before and immediately after 3 apheresis sessions (paying attention to standardized conditions). The following LA methods were used: Dextran Sulfate cellulose Adsorption (DSA), Heparin Extracorporeal LDL Precipitation (HELP) system, Double filtration plasmapheresis (DFPP), Direct Adsorption of Lipoproteins (DALI), and “other” systems. Cohort II consisted of patients who were eligible for lipoprotein apheresis but not undergoing the procedure (n 10; 3 males, 7 females; age 61.1 years (range 50-78 years)). Results: Mean PCSK9 pre-apheresis levels were 253.70 ng/mL in Cohort I, were decreased by approximately 50 % by LA, but returned to the preapheresis levels on the second day after the apheresis. It appeared that when compared with the DSA method HELP showed a more pronounced decline in PCSK9 concentrations, whereas DALI was associated with a less pronounced reduction than DSA. In Cohort II mean PCSK9 levels were 287.00 ng/mL. Conclusion: LA treatment reduced PCSK9 by approximately 50%, with the extent of reduction being dependent upon the type of apheresis method used. The PCSK9 concentrations were slightly higher in subjects eligible for, but not undergoing, apheresis compared to patients that were actively undergoing apheresis. 43 - Lipid and lipoprotein metabolism: Miscellaneous EAS-0696. TREATMENT WITH MIPOMERSEN REDUCES LEVELS OF APOBCONTAINING LIPOPROTEINS BY INCREASING FRACTIONAL REMOVAL OF VLDL AND LDL-APOB WITHOUT REDUCING VLDL-APOB SECRETION G. Soffera, M. Dionizovikb, J. Jimenezc, S. Holleranc, S. Ramakrishnanc, W. Karmallyd, N. Fontanezd, D. Donovane, R. Moreyf, R. Mittlemanf, W. Ching, B. Bakerh, H. Ginsberga a
Medicine-Prev Med Nutrition, Columbia University Medical Center, New York, USA; b Medicine, Columbia University Medical Center, New York, USA; c Biostatistics, Columbia University Medical Center, New York, USA; d Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, USA; e Medicine-Endocrinology, Columbia University Medical Center, New York, USA; f Clinical Research, Genzyme Corporation, Cambridge MA, USA; g Biostatistics, Genzyme Corporation, Cambridge MA, USA; h Clinical Development, Isis Pharmaceuticals, Carlsbad CA, USA Objectives: Mipomersen (MIPO), a second generation antisense oligonucleotide, targets apoB mRNA, thereby inhibiting apolipoprotein B (apoB) synthesis. In humans, MIPO reduces plasma levels of low density lipoprotein-cholesterol (LDL-C), and plasma triglycerides (TG). We hypothesized that these changes are due to reduced assembly and secretion of very low density lipoproteins (VLDL) and lower production of LDL. Methods: Healthy volunteers (HVs) (9M, 8F), mean age 43.5 14.2 yr, completed a single-blind, fixed-sequence, phase I study. They received scplacebo injections once weekly for 3-wks followed by 200mg sc-MIPO injections once weekly for 7-9 wks. Stable isotope turnover studies were performed after each treatment. Blood samples were collected over 48-hrs to determine fractional catabolic rates (FCRs) and production rates (PRs) of apoB in VLDL, IDL, and LDL, and of TG in VLDL. Rates of de novo lipogenesis (DNL) were also measured.
Results: MIPO treatment resulted in significant reductions in plasma LDL-C (45%), TG (29%), and apoB (40%). VLDL, IDL, and LDL apoB levels fell by 29%, 25%, and 42%, respectively. These changes were associated with increases in FCRs of VLDL apoB (42%) and LDL apoB (30%), and by reductions in PRs of IDL apoB (15%) and LDL apoB (27%). The PR of VLDL apoB was unaffected. The FCR of VLDL-TG increased 46% without change in PR. DNL did not change. Conclusion: In summary, 7 wks of MIPO significantly reduced levels of all apoB-lipoproteins in HVs by increasing the FCRs of VLDL and LDL apoB. The absence of a reduction in VLDL apoB secretion is consistent with many studies in isolated hepatocytes demonstrating both intracellular degradation and secretion of newly synthesized apoB. Thus, if MIPO submaximally inhibited apoB synthesis in this study, the liver could have compensated by increasing the efficiency of VLDL assembly and secretion. The basis of increases in VLDL and LDL FCRs requires further investigation. 43 - Lipid and lipoprotein metabolism: Miscellaneous EAS-0050. PLASMA PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9) AND PLASMA LIPIDS IN A FREE LIVING POPULATION: RESULTS FROM THE PLIC STUDY G. Tibolla MD a, A. Dhyani MD a, A. Baragetti MD b, K. Garlaschelli MD b, L. Grigore MD b, G.D. Norata MD a, A.L. Catapano MD a a
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; b SISA center for the study of atherosclerosis, Bassini Hospital, Cinisello B., Italy Objectives: PCSK9 is a convertase expressed in the liver, where it mediates the degradation of hepatic Low density lipoprotein receptor (LDLR), thus inhibiting the clearance of LDL cholesterol (LDL-C). Methods: Here we determined plasma PCSK9 levels and distribution in the Italian population enrolled in the PLIC study (Progression of Lesions in the Intima of the Carotid, (n¼ 1518)). Plasma PCSK9 levels were determined by a-ELISA (Perkin Elmer). Results: Plasma PCSK9 levels are highly variable with a median value of 290.7202 ng/mL and significantly higher in women (n¼906; 297.8204 ng/mL) than in men (n¼612; 280.8198 ng/mL) and in subjects under statin treatment (n¼369) compared to untreated subjects (n¼1071) (404.7236 ng/mL vs 288177 ng/mL respectively). Correlation analysis performed excluding subjects under statins and fibrates treatment shows that PCSK9 plasma levels are positively correlated to lipid parameters such as LDL-C (r¼0.062, p¼0.042), ApoB (r¼0.138, p<0.001), total cholesterol (TC) (r¼0.130, p<0.001), HDL cholesterol (r¼0.140, p<0.001), plasma triglycerides (r¼0.111, p<0.001) and Apo-A1 (r¼0.142, p<0.001). PCSK9 levels positively correlate to the right and left maximum carotid Intima media thickness (maxcIMTdx r¼0.056, p ¼0.034 and maxcIMTsx r¼0.081, p<0.01) but not to the mean cIMT (cIMT r¼0.026, p¼0.331). Further adjustment for plasma lipids shows that association with maxcIMT is dependent on the association of PCSK9 with TC and triglycerides. Conclusion: In a free living Italian population PCSK9 plasma levels vary in a wide range, are increased by lipid lowering drugs and positively correlate to several lipid parameters such as LDL-C, triglycerides and HDL-C. Furthermore PCSK9 plasma levels are not independently associated with pre-clinical carotid atherosclerosis. 43 - Lipid and lipoprotein metabolism: Miscellaneous EAS-0611. PHYTOSTEROL AND OXYPHYTOSTEROL LEVELS IN PLASMA AND AORTIC VALVE CUSPS IN PATIENTS WITH SEVERE AORTIC STENOSIS O. Weingärtnera, H.F. Schöttb, A. Luisterc, C. Huscheb, H.J. Schäfersd, M. Böhme, U. Laufse, D. Lütjohannb a Abteilung für Kardiologie, Klinikum Oldenburg European Medical School Oldenburg-Groningen, Oldenburg, Germany; b Institut für klinische Chemie und klinische Pharmakologie, Universitätsklinikum Bonn, Bonn, Germany;
Abstracts / Atherosclerosis 235 (2014) e27–e83 c Klinik für Innere Medizin III Abteilung für Kardiologie Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg, Germany; d Klinik für Thorax-und Herz-Gefäßchirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; e Klinik für Innere Medizin III Abteilung für Kardiologie Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
Objectives: We hypothesized that in patients with severe aortic stenosis phytosterol and oxyphytosterol concentrations in serum and aortic valve cusps correlate with each other, independent of statin treatment. Methods: We included 104 consecutive patients (68/36; m/f) between 40 and 87 years (mean 69.8yrs.) who were admitted for elective aortic valve replacement due to severe aortic stenosis. Study participants were assessed for established cardiovascular risk factors and concomitant statin treatment (no statins: 36/statins: 68). Venous blood samples were drawn one day prior valve surgery and the aortic valve cusps were analyzed to determine non-cholesterols (cholestanol, lathosterol, lanosterol and desmosterol) and oxyphytosterols (7 alpha-OH, 7 beta-OH, 7 keto-campesterol, -sitosterol) by gas chromatography-flame ionization/ mass spectrometry. Results: As expected, there were significantly lower absolute and cholesterol corrected serum concentrations of cholesterol precursors (lathosterol, lanosterol and desmosterol) in statin treated patients. The concentration of the two most common plant sterols (sitosterol and campesterol) strongly correlated with each other in plasma (r¼0.911; p¼0.000) and aortic valve cusps (r¼0.945; p¼0.000) as well as between the two groups (r¼0.488; p¼0.000 campesterol; r¼0.350; p¼0.000 sitosterol). We found a significant correlation between plant sterols and their oxidized forms in aortic valve cusps (r¼0.712; p¼0.000 campesterol to sum oxycampesterol; r¼0.706; p¼0.000 sitosterol to sum oxysitosterol), but not in serum (r¼0.243; p¼0.014 campesterol to sum oxycampesterol, r¼0.317; p¼0.001 sitosterol to oxysitosterol). Furthermore, there was a significant correlation between 7a-hydroxy-, 7b-hydroxy-, and 7 keto-campesterol/sitosterol in aortic valve tissues, irrespective of statin treatment. Conclusion: In patients with severe aortic stenosis phytosterols and their respective oxidized forms correlate significantly in aortic valve tissue, but not in serum. There is no correlation of oxyphytosterols in serum with their respective concentrations in aortic valve cusps. These data suggest that sterol oxidation in cardiovascular tissue is a local process that is independent of statin treatment. 44 - Gender and cardiovascular risk EAS-0547. GENDER SIGNIFICANTLY MODULATES THE ASSOCIATION OF HBA1C WITH ANGIOGRAPHICALLY DIAGNOSED CORONARY ATHEROSCLEROSIS AMONG SUBJECTS WITHOUT PREVIOUSLY KNOWN DIABETES A. Vonbanka, P. Reina, D. Zanolinb, C.H. Saelya, A. Leihererb, H. Drexelb a Academic Teaching Hospital Feldkirch, Department of Internal Medicine & Cardiology, Feldkirch, Austria; b Academic Teaching Hospital Feldkirch, Vivit-Institute, Feldkirch, Austria
Objectives: The association of HbA1c with angiographically determined coronary atherosclerosis is unclear. In particular, it has not been investigated so far whether gender modulates the association of HbA1c with angiographically diagnosed coronary atherosclerosis. We therefore aimed at clarifying this issue. Methods: We enrolled a large consecutive series of 1449 patients, 484 women and 965 men, who did not have previously known diabetes and who underwent coronary angiography for the evaluation of stable coronary artery disease. Significant coronary atherosclerosis was diagnosed in the presence of significant coronary stenoses with lumen narrowing 50%. Results: Among women, 36.4%, 56.2%, and 7.4% and among men 44.2%, 46.6%, and 9.1% had HbA1c values of trend ¼ 0.041) and 63.2%, 65.3% and 64.8% among men (ptrend ¼ 0.589). In logistic regression models, HbA1c as
e61
a continuous variable was a strong predictor of coronary atherosclerosis among women (adjusted OR for a 1% increase in HbA1c ¼ 1.61 [95% CI 1.072.43]; p ¼ 0.024) but not among men (OR ¼ 0.92 [0.74-1.13]; p ¼ 0.416). An interaction term gender x HbA1c was significant (p ¼ 0.022), indicating that HbA1c was a significantly stronger predictor of coronary atherosclerosis among women than among men. Conclusion: We conclude that gender significantly modulates the association of HbA1c with angiographically diagnosed coronary atherosclerosis among subjects without previously known diabetes. 46 - Epidemiology of cardiovascular diseases and hypertension EAS-0834. BIOMARKER DIFFERENCE BETWEEN CONTROLLED AND UNCONTROLLED HYPERTENSION AMONG US ADULTS: NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2005-2008 J. Leea, J. Sungb, J. Leec, J. Perkinsa Research Development, RTRN DCC, Madison, USA; b Epidemiology and Biostatistics, Jackson State University, Jackson, USA; c Psychology, University of Pittsburgh, Pittsburgh, USA a
Objectives: It is common clinical problem that blood pressure remains above the goal in spite of antihypertensive treatment. Although persistently high blood pressure linked to increased cardiovascular risk, limited studies have been conducted to investigate properties of these patients. This study is to characterize the uncontrolled hypertension using national survey data. Methods: The analyses utilized the data of NHANES 2005-2008 which included a valid sample of 9,346 adults who were taking hypertensive medication. Controlled hypertension was defined as systolic blood pressure < 140 mmHg AND diastolic blood pressure < 90 mmHg among hypertensive subjects taking antihypertensive medication. Uncontrolled hypertension was defined as systolic blood pressure 140 mmHg OR diastolic blood pressure 90 mmHg among those taking antihypertensive medications. The regression model adjusting for confounders was conducted using SAS SURVEY procedures to incorporate the stratification, clustering and sample weights. Results: 29.4% (S.E.¼1.7%) of hypertensive patients had blood pressure 140/90 mmHg. A higher prevalence of uncontrolled hypertension was found among older (p¼0.0004) and African-American (p¼0.0467) patients. Gender and education had no association with uncontrolled hypertension. The multivariable models adjusting for age, gender and race revealed that a significant higher level of LDL (p¼0.0017), triglyceride (p¼0.0546), albumin to creatinine ratio (p¼0.0282), parathyroid hormone (p¼0.0380), and apolipoprotein (p¼0.0153) and a significant lower level of CRP (p¼0.0535) and folate (p¼0.0769) were found among uncontrolled hypertension group. These patterns differed between black and white. Conclusion: Our study found that about 1 in 3 hypertensive individuals were uncontrolled in spite of antihypertensive medication treatment and uncontrolled hypertension was attributed to unfavorable cardiovascularrelated biomarkers. Our findings may be a partial answer for why antihypertensive treatment is not working for certain group of patients. Further study is needed to examine the cause of uncontrolled hypertension. 51 - Novel risk factors and biomarkers EAS-0444. CIRCULATING BIOMARKERS FOR EXPRESSION OF PRO-INFLAMMATORY CYTOKINES IN CAROTID PLAQUES A. Edsfeldta, H. Grufmana, M. Nitulescua, A. Perssona, M. Nilssona, J. Nilssona, I. Goncalvesa a Experimental Cardiovascular Research Unit Department of Clinical Sciences, Lund University, Malmö, Sweden
Objectives: Inflammation leading to the degradation of the atherosclerotic plaque extracellular matrix is a key mechanism in the development of
Abstracts / Atherosclerosis 235 (2014) e27–e83
Center, Kansas City, USA; e Internal Medicine, Brigham and Women's Hospital, Boston, USA; f Medizinische Klinik II, Klinikum der Universität München, München, Germany Objectives: PCSK9 plays an important role in the regulation of LDLcholesterol concentrations via its influence on catabolism of the LDL receptors. It is known that PCSK9 levels are higher in patients with familial hypercholesterolemia than in normolipidemic controls. We wanted to estimate PCSK9 levels in patients currently undergoing apheresis or eligible to be treated by LA and look into the acute effects of LA on PCSK9 concentrations. Methods: We measured total serum PCSK9 levels (using an ELISA-method) in 2 cohorts: Cohort I consisted of patients actively undergoing lipoprotein apheresis as part of their routine care (n 40; 21 males, 19 females; age 55.6 years (range 32-73 years)). Blood was drawn before and immediately after 3 apheresis sessions (paying attention to standardized conditions). The following LA methods were used: Dextran Sulfate cellulose Adsorption (DSA), Heparin Extracorporeal LDL Precipitation (HELP) system, Double filtration plasmapheresis (DFPP), Direct Adsorption of Lipoproteins (DALI), and “other” systems. Cohort II consisted of patients who were eligible for lipoprotein apheresis but not undergoing the procedure (n 10; 3 males, 7 females; age 61.1 years (range 50-78 years)). Results: Mean PCSK9 pre-apheresis levels were 253.70 ng/mL in Cohort I, were decreased by approximately 50 % by LA, but returned to the preapheresis levels on the second day after the apheresis. It appeared that when compared with the DSA method HELP showed a more pronounced decline in PCSK9 concentrations, whereas DALI was associated with a less pronounced reduction than DSA. In Cohort II mean PCSK9 levels were 287.00 ng/mL. Conclusion: LA treatment reduced PCSK9 by approximately 50%, with the extent of reduction being dependent upon the type of apheresis method used. The PCSK9 concentrations were slightly higher in subjects eligible for, but not undergoing, apheresis compared to patients that were actively undergoing apheresis. 43 - Lipid and lipoprotein metabolism: Miscellaneous EAS-0696. TREATMENT WITH MIPOMERSEN REDUCES LEVELS OF APOBCONTAINING LIPOPROTEINS BY INCREASING FRACTIONAL REMOVAL OF VLDL AND LDL-APOB WITHOUT REDUCING VLDL-APOB SECRETION G. Soffera, M. Dionizovikb, J. Jimenezc, S. Holleranc, S. Ramakrishnanc, W. Karmallyd, N. Fontanezd, D. Donovane, R. Moreyf, R. Mittlemanf, W. Ching, B. Bakerh, H. Ginsberga a
Medicine-Prev Med Nutrition, Columbia University Medical Center, New York, USA; b Medicine, Columbia University Medical Center, New York, USA; c Biostatistics, Columbia University Medical Center, New York, USA; d Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, USA; e Medicine-Endocrinology, Columbia University Medical Center, New York, USA; f Clinical Research, Genzyme Corporation, Cambridge MA, USA; g Biostatistics, Genzyme Corporation, Cambridge MA, USA; h Clinical Development, Isis Pharmaceuticals, Carlsbad CA, USA Objectives: Mipomersen (MIPO), a second generation antisense oligonucleotide, targets apoB mRNA, thereby inhibiting apolipoprotein B (apoB) synthesis. In humans, MIPO reduces plasma levels of low density lipoprotein-cholesterol (LDL-C), and plasma triglycerides (TG). We hypothesized that these changes are due to reduced assembly and secretion of very low density lipoproteins (VLDL) and lower production of LDL. Methods: Healthy volunteers (HVs) (9M, 8F), mean age 43.5 14.2 yr, completed a single-blind, fixed-sequence, phase I study. They received scplacebo injections once weekly for 3-wks followed by 200mg sc-MIPO injections once weekly for 7-9 wks. Stable isotope turnover studies were performed after each treatment. Blood samples were collected over 48-hrs to determine fractional catabolic rates (FCRs) and production rates (PRs) of apoB in VLDL, IDL, and LDL, and of TG in VLDL. Rates of de novo lipogenesis (DNL) were also measured.
Results: MIPO treatment resulted in significant reductions in plasma LDL-C (45%), TG (29%), and apoB (40%). VLDL, IDL, and LDL apoB levels fell by 29%, 25%, and 42%, respectively. These changes were associated with increases in FCRs of VLDL apoB (42%) and LDL apoB (30%), and by reductions in PRs of IDL apoB (15%) and LDL apoB (27%). The PR of VLDL apoB was unaffected. The FCR of VLDL-TG increased 46% without change in PR. DNL did not change. Conclusion: In summary, 7 wks of MIPO significantly reduced levels of all apoB-lipoproteins in HVs by increasing the FCRs of VLDL and LDL apoB. The absence of a reduction in VLDL apoB secretion is consistent with many studies in isolated hepatocytes demonstrating both intracellular degradation and secretion of newly synthesized apoB. Thus, if MIPO submaximally inhibited apoB synthesis in this study, the liver could have compensated by increasing the efficiency of VLDL assembly and secretion. The basis of increases in VLDL and LDL FCRs requires further investigation. 43 - Lipid and lipoprotein metabolism: Miscellaneous EAS-0050. PLASMA PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9) AND PLASMA LIPIDS IN A FREE LIVING POPULATION: RESULTS FROM THE PLIC STUDY G. Tibolla MD a, A. Dhyani MD a, A. Baragetti MD b, K. Garlaschelli MD b, L. Grigore MD b, G.D. Norata MD a, A.L. Catapano MD a a
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; b SISA center for the study of atherosclerosis, Bassini Hospital, Cinisello B., Italy Objectives: PCSK9 is a convertase expressed in the liver, where it mediates the degradation of hepatic Low density lipoprotein receptor (LDLR), thus inhibiting the clearance of LDL cholesterol (LDL-C). Methods: Here we determined plasma PCSK9 levels and distribution in the Italian population enrolled in the PLIC study (Progression of Lesions in the Intima of the Carotid, (n¼ 1518)). Plasma PCSK9 levels were determined by a-ELISA (Perkin Elmer). Results: Plasma PCSK9 levels are highly variable with a median value of 290.7202 ng/mL and significantly higher in women (n¼906; 297.8204 ng/mL) than in men (n¼612; 280.8198 ng/mL) and in subjects under statin treatment (n¼369) compared to untreated subjects (n¼1071) (404.7236 ng/mL vs 288177 ng/mL respectively). Correlation analysis performed excluding subjects under statins and fibrates treatment shows that PCSK9 plasma levels are positively correlated to lipid parameters such as LDL-C (r¼0.062, p¼0.042), ApoB (r¼0.138, p<0.001), total cholesterol (TC) (r¼0.130, p<0.001), HDL cholesterol (r¼0.140, p<0.001), plasma triglycerides (r¼0.111, p<0.001) and Apo-A1 (r¼0.142, p<0.001). PCSK9 levels positively correlate to the right and left maximum carotid Intima media thickness (maxcIMTdx r¼0.056, p ¼0.034 and maxcIMTsx r¼0.081, p<0.01) but not to the mean cIMT (cIMT r¼0.026, p¼0.331). Further adjustment for plasma lipids shows that association with maxcIMT is dependent on the association of PCSK9 with TC and triglycerides. Conclusion: In a free living Italian population PCSK9 plasma levels vary in a wide range, are increased by lipid lowering drugs and positively correlate to several lipid parameters such as LDL-C, triglycerides and HDL-C. Furthermore PCSK9 plasma levels are not independently associated with pre-clinical carotid atherosclerosis. 43 - Lipid and lipoprotein metabolism: Miscellaneous EAS-0611. PHYTOSTEROL AND OXYPHYTOSTEROL LEVELS IN PLASMA AND AORTIC VALVE CUSPS IN PATIENTS WITH SEVERE AORTIC STENOSIS O. Weingärtnera, H.F. Schöttb, A. Luisterc, C. Huscheb, H.J. Schäfersd, M. Böhme, U. Laufse, D. Lütjohannb a Abteilung für Kardiologie, Klinikum Oldenburg European Medical School Oldenburg-Groningen, Oldenburg, Germany; b Institut für klinische Chemie und klinische Pharmakologie, Universitätsklinikum Bonn, Bonn, Germany;
Abstracts / Atherosclerosis 235 (2014) e27–e83 c Klinik für Innere Medizin III Abteilung für Kardiologie Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg, Germany; d Klinik für Thorax-und Herz-Gefäßchirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; e Klinik für Innere Medizin III Abteilung für Kardiologie Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
Objectives: We hypothesized that in patients with severe aortic stenosis phytosterol and oxyphytosterol concentrations in serum and aortic valve cusps correlate with each other, independent of statin treatment. Methods: We included 104 consecutive patients (68/36; m/f) between 40 and 87 years (mean 69.8yrs.) who were admitted for elective aortic valve replacement due to severe aortic stenosis. Study participants were assessed for established cardiovascular risk factors and concomitant statin treatment (no statins: 36/statins: 68). Venous blood samples were drawn one day prior valve surgery and the aortic valve cusps were analyzed to determine non-cholesterols (cholestanol, lathosterol, lanosterol and desmosterol) and oxyphytosterols (7 alpha-OH, 7 beta-OH, 7 keto-campesterol, -sitosterol) by gas chromatography-flame ionization/ mass spectrometry. Results: As expected, there were significantly lower absolute and cholesterol corrected serum concentrations of cholesterol precursors (lathosterol, lanosterol and desmosterol) in statin treated patients. The concentration of the two most common plant sterols (sitosterol and campesterol) strongly correlated with each other in plasma (r¼0.911; p¼0.000) and aortic valve cusps (r¼0.945; p¼0.000) as well as between the two groups (r¼0.488; p¼0.000 campesterol; r¼0.350; p¼0.000 sitosterol). We found a significant correlation between plant sterols and their oxidized forms in aortic valve cusps (r¼0.712; p¼0.000 campesterol to sum oxycampesterol; r¼0.706; p¼0.000 sitosterol to sum oxysitosterol), but not in serum (r¼0.243; p¼0.014 campesterol to sum oxycampesterol, r¼0.317; p¼0.001 sitosterol to oxysitosterol). Furthermore, there was a significant correlation between 7a-hydroxy-, 7b-hydroxy-, and 7 keto-campesterol/sitosterol in aortic valve tissues, irrespective of statin treatment. Conclusion: In patients with severe aortic stenosis phytosterols and their respective oxidized forms correlate significantly in aortic valve tissue, but not in serum. There is no correlation of oxyphytosterols in serum with their respective concentrations in aortic valve cusps. These data suggest that sterol oxidation in cardiovascular tissue is a local process that is independent of statin treatment. 44 - Gender and cardiovascular risk EAS-0547. GENDER SIGNIFICANTLY MODULATES THE ASSOCIATION OF HBA1C WITH ANGIOGRAPHICALLY DIAGNOSED CORONARY ATHEROSCLEROSIS AMONG SUBJECTS WITHOUT PREVIOUSLY KNOWN DIABETES A. Vonbanka, P. Reina, D. Zanolinb, C.H. Saelya, A. Leihererb, H. Drexelb a Academic Teaching Hospital Feldkirch, Department of Internal Medicine & Cardiology, Feldkirch, Austria; b Academic Teaching Hospital Feldkirch, Vivit-Institute, Feldkirch, Austria
Objectives: The association of HbA1c with angiographically determined coronary atherosclerosis is unclear. In particular, it has not been investigated so far whether gender modulates the association of HbA1c with angiographically diagnosed coronary atherosclerosis. We therefore aimed at clarifying this issue. Methods: We enrolled a large consecutive series of 1449 patients, 484 women and 965 men, who did not have previously known diabetes and who underwent coronary angiography for the evaluation of stable coronary artery disease. Significant coronary atherosclerosis was diagnosed in the presence of significant coronary stenoses with lumen narrowing 50%. Results: Among women, 36.4%, 56.2%, and 7.4% and among men 44.2%, 46.6%, and 9.1% had HbA1c values of trend ¼ 0.041) and 63.2%, 65.3% and 64.8% among men (ptrend ¼ 0.589). In logistic regression models, HbA1c as
e61
a continuous variable was a strong predictor of coronary atherosclerosis among women (adjusted OR for a 1% increase in HbA1c ¼ 1.61 [95% CI 1.072.43]; p ¼ 0.024) but not among men (OR ¼ 0.92 [0.74-1.13]; p ¼ 0.416). An interaction term gender x HbA1c was significant (p ¼ 0.022), indicating that HbA1c was a significantly stronger predictor of coronary atherosclerosis among women than among men. Conclusion: We conclude that gender significantly modulates the association of HbA1c with angiographically diagnosed coronary atherosclerosis among subjects without previously known diabetes. 46 - Epidemiology of cardiovascular diseases and hypertension EAS-0834. BIOMARKER DIFFERENCE BETWEEN CONTROLLED AND UNCONTROLLED HYPERTENSION AMONG US ADULTS: NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2005-2008 J. Leea, J. Sungb, J. Leec, J. Perkinsa Research Development, RTRN DCC, Madison, USA; b Epidemiology and Biostatistics, Jackson State University, Jackson, USA; c Psychology, University of Pittsburgh, Pittsburgh, USA a
Objectives: It is common clinical problem that blood pressure remains above the goal in spite of antihypertensive treatment. Although persistently high blood pressure linked to increased cardiovascular risk, limited studies have been conducted to investigate properties of these patients. This study is to characterize the uncontrolled hypertension using national survey data. Methods: The analyses utilized the data of NHANES 2005-2008 which included a valid sample of 9,346 adults who were taking hypertensive medication. Controlled hypertension was defined as systolic blood pressure < 140 mmHg AND diastolic blood pressure < 90 mmHg among hypertensive subjects taking antihypertensive medication. Uncontrolled hypertension was defined as systolic blood pressure 140 mmHg OR diastolic blood pressure 90 mmHg among those taking antihypertensive medications. The regression model adjusting for confounders was conducted using SAS SURVEY procedures to incorporate the stratification, clustering and sample weights. Results: 29.4% (S.E.¼1.7%) of hypertensive patients had blood pressure 140/90 mmHg. A higher prevalence of uncontrolled hypertension was found among older (p¼0.0004) and African-American (p¼0.0467) patients. Gender and education had no association with uncontrolled hypertension. The multivariable models adjusting for age, gender and race revealed that a significant higher level of LDL (p¼0.0017), triglyceride (p¼0.0546), albumin to creatinine ratio (p¼0.0282), parathyroid hormone (p¼0.0380), and apolipoprotein (p¼0.0153) and a significant lower level of CRP (p¼0.0535) and folate (p¼0.0769) were found among uncontrolled hypertension group. These patterns differed between black and white. Conclusion: Our study found that about 1 in 3 hypertensive individuals were uncontrolled in spite of antihypertensive medication treatment and uncontrolled hypertension was attributed to unfavorable cardiovascularrelated biomarkers. Our findings may be a partial answer for why antihypertensive treatment is not working for certain group of patients. Further study is needed to examine the cause of uncontrolled hypertension. 51 - Novel risk factors and biomarkers EAS-0444. CIRCULATING BIOMARKERS FOR EXPRESSION OF PRO-INFLAMMATORY CYTOKINES IN CAROTID PLAQUES A. Edsfeldta, H. Grufmana, M. Nitulescua, A. Perssona, M. Nilssona, J. Nilssona, I. Goncalvesa a Experimental Cardiovascular Research Unit Department of Clinical Sciences, Lund University, Malmö, Sweden
Objectives: Inflammation leading to the degradation of the atherosclerotic plaque extracellular matrix is a key mechanism in the development of