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16: Markers of atherosclerosis and of inflammation for prediction of coronary heart disease in older adults
Journal of Clinical Lipidology, Vol 2, No 5S, October 2008
gene expression patterns in the vascular wall. Results: PTX3 expression increases in the vascular wall of ApoE KO mice from 3 months of age up to 18 months. At 8 weeks of age double knock out animals were fed an atherogenic diet for 16 weeks. Aortic lesions were significantly increased in double KO and mice heterozygous for PTX3 (41% and 25% respectively, p<0.05 for both) compared to Apo E KO mice. Mice lacking PTX3 showed a more pronounced inflammatory profile in vascular wall as detected by cDNA microarray and Q-PCR analysis. The increased expression of alpha actin in the lesion was not associated with an increased plaque stability as detected by collagen content analysis. Conclusion: Our data suggest that PTX3 has an atheroprotective role in mice which, in light of the cardioprotective effects recently reported, suggest a cardiovascular protective function of the long pentraxin 3 through the modulation of the immunoinflammatory balance in the cardiovascular system.
correlated to HDL-C (r=0.488, p<0.001) and apoA-I (r=0.646, p<0.001). After correction for a regression model including age, gender, race, blood pressure and BMI, cholesterol efflux capacity remained positively associated with HDL-C levels (p<0.001). When the regression model included also apoA-I levels, HDL-C was no longer statistically significant while apoA-I was significantly associated with cholesterol efflux (p<0.001). However, apoA-I could explain only about 7% of the variability in efflux capacity suggesting that it is, at best, a weak surrogate for efflux capacity.Conclusion: Cholesterol efflux capacity of serum is better correlated with apoA-I than with HDL-C levels. These data are consistent with the concept that HDL-C levels may not fully reflect HDL functionality, that apoA-I levels may be more predictive, and that parameters that directly assess HDL functionality may prove more useful in predicting cardiovascular risk. Funding: NIH-NHLBI
Funding: none 16 15 CHOLESTEROL EFFLUX CAPACITY OF SERUM IS BETTER CORRELATED WITH CONCENTRATIONS OF APOA-I THAN HDL-C M. Cuchel1, M. de la Llera-Moya2, J.A. Phillips3, M.L. Wolfe1, G.H. Rothblat2, D.J. Rader1. 1 University of Pennsylvania School of Medicine, Philadlephia, PA, USA, 2Children's Hospital of Philadelphia, Philadelphia, PA, USA, 3Rutgers University, New Brunswick, NJ, USA Objective: HDL-C levels are inversely correlated to CHD. However, recent studies raise the possibility that HDL functionality may be more important in assessing atheroprotection than HDLC levels. We determined cholesterol efflux capacity of serum as a measure of HDL functionality and tested its association with HDLC and other lipid and lipoprotein parameters. Methods: Cholesterol efflux capacity was measured in healthy adults (n=265) using a validated in vitro system: the serum HDL fraction from each subject was incubated with c-AMP treated J774 cells to upregulate ABCA1, at a concentration equivalent to 2% serum. Results: Cholesterol efflux capacity was positively
MARKERS OF ATHEROSCLEROSIS AND OF INFLAMMATION FOR PREDICTION OF CORONARY HEART DISEASE IN OLDER ADULTS N. Rodondi1, P. Marques-Vidal1, J. Butler2, J. Cornuz1, K. Sutton-Tyrrell3, S. Satterfield4, T. Harris5, D. Bauer6, E. Vittinghoff6, A. Newman3. 1 University of Lausanne, Lausanne, Switzerland, 2 Emory University, Atlanta, GA, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA, 4 University of Tennessee, Memphis, TN, USA, 5 National Institute on Aging, Bethesda, MD, USA, 6University of California, San Francisco, CA, USA Objective: To compare the predictive value of markers of atherosclerosis and of inflammation for coronary heart disease (CHD), as data on head-tohead comparisons of these markers are limited. Methods In 2202 adults, aged 70-79, without cardiovascular disease, we compared two measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and three inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]) to predict CHD. CHD events included nonfatal myocardial infarction or coronary death
S7
Multiple Risk Factors in Cardiovascular Disease—Abstracts
(hard events), and hard events plus hospitalization for angina or coronary-revascularizations (total CHD events). Results: Over 6 years, 297 participants had CHD events (136 hard events). IL6 and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest vs. the lowest quartile for IL-6 of 2.03 (95%CI: 1.55-2.85, p for trend<0.001) and of 1.78 (95%CI: 1.29-2.46) for AAI ³0.9 vs. AAI 1.01-1.30. CRP, TNF-a and aPWV had weaker associations with CHD. Results were similar for hard CHD events. C-index for hard/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL6+AAI. In models including IL-6, AAI or both, 8.0 to 12.1% of participants were correctly reclassified. Conclusions: Among older adults, IL-6 and AAI are independently associated with CHD, and modestly improve risk prediction beyond traditional risk factors.
of the thickest plaques present in each of both carotid and femoral bifurcations) Plasma Fb, sCD40L and hsCRP levels were determined.High Fb was associated with presence (p=0.001) and number of plaques (p=0.006), plaque echogenicity (fibrotic plaques) (p<0.001) but not TPT (p=0.14). sCD40L was also associated with number of plaques (p=0.001) and plaque echogenicity (p=0.014) but not with plaque presence (p=0.23). It was, however, associated with TPT (p=0.019). hsCRP levels were not associated with plaque presence, number, echogenicity (MPT) or thickness (TPT). hsCRP levels were not associated with subclinical atherosclerosis as assessed by ultrasound. In contrast, increased Fb and sCD40L levels were associated not only with the presence of plaques but also with plaque echogenicity. Our data suggest that both Fb and sCD40L play a major part in subclinical atherosclerosis formation as shown by presence of plaques and more specifically echolucent, vulnerable plaques.
Funding: National Institute on Aging, NIH
Funding: none
17 FIBRINOGEN, CD40L, CRP AND SUBCLINICAL ATHEROSCLEROSIS A. Panayiotou1, M. Griffin2, T. Tyllis3, D. Bond2, N. Georiou3, A. Nicolaides1,2,3. 1University of Cyprus, Department of Biological Sciences, Nicosia, Cyprus, 2Vascular Screening and Diagnostic Center, London, United Kingdom, 3Vascular Screening and Diagnostic Center, Nicosia, Cyprus Fibrinogen (Fb), soluble CD40L (sCD40L) and high-sensitivity CRP (hsCRP) are inflammatory markers, elevated in the presence of atherosclerotic disease. The aim of the study was to determine whether this is also true for subclinical atherosclerosis. Both common carotid and femoral bifurcations were scanned with ultrasound in 767 volunteers over 40. Three ultrasonic features were considered: (a) number of vessels with plaque; (b) plaque echodensity, as indicated by mean plaque type (MPT) using the Widder classification with type 1 being the most echogenic (stable) and type 5 the most echolucent (unstable) and (c) total plaque thickness (TPT- sum
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18 HIGH LEVELS OF PLASMA FIBRINOGEN AT ADMISSION AND DURING HOSPITALIZATION ARE PREDICTIVE OF TARGET VESSEL REVASCULARIZATION FOLLOWING PRIMARY PTCA A. Lupi, S. Ferraro, L. Rossi, M. Santagostino, M. Sansa, R. Rosso, A.S. Bongo. Azienda Ospedaliera Universitaria Maggiore della Carità, Novara, Italy Plasma fibrinogen is a known coronary risk factor in patients (pts) with stable coronary disease, but little is known about the information from fibrinogen in pts with acute myocardial infarction (STEMI) treated by primary PTCA. To this end in 129 consecutive STEMI pts who underwent primary PTCA (106 M, 60.9±12.2 years), plasma samples were obtained at admission, at 12, 24, 48 and 72h following primary PTCA. Fibrinogen plasma citrated levels were evaluated by Clauss method (DADE-Behring). For each pts major adverse coronary events (MACE: myocardial infarction+death+need for urgent revascularization) and target vessel revascularization (TVR) were assessed over a 6 month follow up. 152 coronary lesions (1.2 lesion/pts) were treated, with 175 stents
gene expression patterns in the vascular wall. Results: PTX3 expression increases in the vascular wall of ApoE KO mice from 3 months of age up to 18 months. At 8 weeks of age double knock out animals were fed an atherogenic diet for 16 weeks. Aortic lesions were significantly increased in double KO and mice heterozygous for PTX3 (41% and 25% respectively, p<0.05 for both) compared to Apo E KO mice. Mice lacking PTX3 showed a more pronounced inflammatory profile in vascular wall as detected by cDNA microarray and Q-PCR analysis. The increased expression of alpha actin in the lesion was not associated with an increased plaque stability as detected by collagen content analysis. Conclusion: Our data suggest that PTX3 has an atheroprotective role in mice which, in light of the cardioprotective effects recently reported, suggest a cardiovascular protective function of the long pentraxin 3 through the modulation of the immunoinflammatory balance in the cardiovascular system.
correlated to HDL-C (r=0.488, p<0.001) and apoA-I (r=0.646, p<0.001). After correction for a regression model including age, gender, race, blood pressure and BMI, cholesterol efflux capacity remained positively associated with HDL-C levels (p<0.001). When the regression model included also apoA-I levels, HDL-C was no longer statistically significant while apoA-I was significantly associated with cholesterol efflux (p<0.001). However, apoA-I could explain only about 7% of the variability in efflux capacity suggesting that it is, at best, a weak surrogate for efflux capacity.Conclusion: Cholesterol efflux capacity of serum is better correlated with apoA-I than with HDL-C levels. These data are consistent with the concept that HDL-C levels may not fully reflect HDL functionality, that apoA-I levels may be more predictive, and that parameters that directly assess HDL functionality may prove more useful in predicting cardiovascular risk. Funding: NIH-NHLBI
Funding: none 16 15 CHOLESTEROL EFFLUX CAPACITY OF SERUM IS BETTER CORRELATED WITH CONCENTRATIONS OF APOA-I THAN HDL-C M. Cuchel1, M. de la Llera-Moya2, J.A. Phillips3, M.L. Wolfe1, G.H. Rothblat2, D.J. Rader1. 1 University of Pennsylvania School of Medicine, Philadlephia, PA, USA, 2Children's Hospital of Philadelphia, Philadelphia, PA, USA, 3Rutgers University, New Brunswick, NJ, USA Objective: HDL-C levels are inversely correlated to CHD. However, recent studies raise the possibility that HDL functionality may be more important in assessing atheroprotection than HDLC levels. We determined cholesterol efflux capacity of serum as a measure of HDL functionality and tested its association with HDLC and other lipid and lipoprotein parameters. Methods: Cholesterol efflux capacity was measured in healthy adults (n=265) using a validated in vitro system: the serum HDL fraction from each subject was incubated with c-AMP treated J774 cells to upregulate ABCA1, at a concentration equivalent to 2% serum. Results: Cholesterol efflux capacity was positively
MARKERS OF ATHEROSCLEROSIS AND OF INFLAMMATION FOR PREDICTION OF CORONARY HEART DISEASE IN OLDER ADULTS N. Rodondi1, P. Marques-Vidal1, J. Butler2, J. Cornuz1, K. Sutton-Tyrrell3, S. Satterfield4, T. Harris5, D. Bauer6, E. Vittinghoff6, A. Newman3. 1 University of Lausanne, Lausanne, Switzerland, 2 Emory University, Atlanta, GA, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA, 4 University of Tennessee, Memphis, TN, USA, 5 National Institute on Aging, Bethesda, MD, USA, 6University of California, San Francisco, CA, USA Objective: To compare the predictive value of markers of atherosclerosis and of inflammation for coronary heart disease (CHD), as data on head-tohead comparisons of these markers are limited. Methods In 2202 adults, aged 70-79, without cardiovascular disease, we compared two measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and three inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]) to predict CHD. CHD events included nonfatal myocardial infarction or coronary death
S7
Multiple Risk Factors in Cardiovascular Disease—Abstracts
(hard events), and hard events plus hospitalization for angina or coronary-revascularizations (total CHD events). Results: Over 6 years, 297 participants had CHD events (136 hard events). IL6 and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest vs. the lowest quartile for IL-6 of 2.03 (95%CI: 1.55-2.85, p for trend<0.001) and of 1.78 (95%CI: 1.29-2.46) for AAI ³0.9 vs. AAI 1.01-1.30. CRP, TNF-a and aPWV had weaker associations with CHD. Results were similar for hard CHD events. C-index for hard/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL6+AAI. In models including IL-6, AAI or both, 8.0 to 12.1% of participants were correctly reclassified. Conclusions: Among older adults, IL-6 and AAI are independently associated with CHD, and modestly improve risk prediction beyond traditional risk factors.
of the thickest plaques present in each of both carotid and femoral bifurcations) Plasma Fb, sCD40L and hsCRP levels were determined.High Fb was associated with presence (p=0.001) and number of plaques (p=0.006), plaque echogenicity (fibrotic plaques) (p<0.001) but not TPT (p=0.14). sCD40L was also associated with number of plaques (p=0.001) and plaque echogenicity (p=0.014) but not with plaque presence (p=0.23). It was, however, associated with TPT (p=0.019). hsCRP levels were not associated with plaque presence, number, echogenicity (MPT) or thickness (TPT). hsCRP levels were not associated with subclinical atherosclerosis as assessed by ultrasound. In contrast, increased Fb and sCD40L levels were associated not only with the presence of plaques but also with plaque echogenicity. Our data suggest that both Fb and sCD40L play a major part in subclinical atherosclerosis formation as shown by presence of plaques and more specifically echolucent, vulnerable plaques.
Funding: National Institute on Aging, NIH
Funding: none
17 FIBRINOGEN, CD40L, CRP AND SUBCLINICAL ATHEROSCLEROSIS A. Panayiotou1, M. Griffin2, T. Tyllis3, D. Bond2, N. Georiou3, A. Nicolaides1,2,3. 1University of Cyprus, Department of Biological Sciences, Nicosia, Cyprus, 2Vascular Screening and Diagnostic Center, London, United Kingdom, 3Vascular Screening and Diagnostic Center, Nicosia, Cyprus Fibrinogen (Fb), soluble CD40L (sCD40L) and high-sensitivity CRP (hsCRP) are inflammatory markers, elevated in the presence of atherosclerotic disease. The aim of the study was to determine whether this is also true for subclinical atherosclerosis. Both common carotid and femoral bifurcations were scanned with ultrasound in 767 volunteers over 40. Three ultrasonic features were considered: (a) number of vessels with plaque; (b) plaque echodensity, as indicated by mean plaque type (MPT) using the Widder classification with type 1 being the most echogenic (stable) and type 5 the most echolucent (unstable) and (c) total plaque thickness (TPT- sum
S8
18 HIGH LEVELS OF PLASMA FIBRINOGEN AT ADMISSION AND DURING HOSPITALIZATION ARE PREDICTIVE OF TARGET VESSEL REVASCULARIZATION FOLLOWING PRIMARY PTCA A. Lupi, S. Ferraro, L. Rossi, M. Santagostino, M. Sansa, R. Rosso, A.S. Bongo. Azienda Ospedaliera Universitaria Maggiore della Carità, Novara, Italy Plasma fibrinogen is a known coronary risk factor in patients (pts) with stable coronary disease, but little is known about the information from fibrinogen in pts with acute myocardial infarction (STEMI) treated by primary PTCA. To this end in 129 consecutive STEMI pts who underwent primary PTCA (106 M, 60.9±12.2 years), plasma samples were obtained at admission, at 12, 24, 48 and 72h following primary PTCA. Fibrinogen plasma citrated levels were evaluated by Clauss method (DADE-Behring). For each pts major adverse coronary events (MACE: myocardial infarction+death+need for urgent revascularization) and target vessel revascularization (TVR) were assessed over a 6 month follow up. 152 coronary lesions (1.2 lesion/pts) were treated, with 175 stents