Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Japan

Transcription

1 Association between continuously elevated C-reactive protein and restenosis after percutaneous coronary intervention using drug-eluting stent in angina patients Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Japan Kenshiro Arao, Ryo Naito, Kenichi Sakakura, Hiroshi Wada Chikashi Suga, Hiroshi Funayama, Yoshitaka Sugawara Junya Ako, Shin-ichi Momomura

2 Background Elevated high sensitivity C-reactive protein (hscrp) level partly reflects atherosclerotic vascular inflammation. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Pearson TA, et al. Circulation 2003: 107; The novel role of C-reactive protein in cardiovascular disease: risk marker or pathogen. Wilson AM, et al. Int J Cardiol : C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. Danesh J, et al. N Engl J Med. 2004; 350: Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. Ridker PM, et al. N Engl J Med :

3 Aims To identify factors associating with hscrp levels, and to clarify the association between status of elevated hscrp level and coronary artery restenosis after percutaneous coronary intervention (PCI) using drug-eluting stent in angina patients.

4 Methods hscrp used in this study Nanopia CRP, Sekisui Medical Co, Tokyo, Japan Sample: whole blood or serum Wide measurement range: mg/l Standard range 3.0 mg/l

5 Methods Study subjects Inclusive criteria 1) stable angina patient treated with drug-eluting stent (sirolimus-, paclitaxel-, zotarolimus-, or everolimus-eluting stent) in our institution 2) patient receiving almost 10 months angiography follow-up Exclusive criteria 1) patient with AMI /recent MI /unstable AP at 1st admission 2) with other inflammatory diseases 3) treated without drug-eluting stent Of 1314 consecutive angina patients treated with drug-eluting stent, 847 patients were finally enrolled. All enrolled patients were divided into three groups according to hscrp levels (cut off value of hscrp (Nanopia ) : 1.0 mg/l) measured on the index admission and follow-up angiography admission days before catheterization; both low hscrp group ( L, n=338) transiently elevated* hscrp group ( T, n=241) both high hscrp group ( H, n=268) * Either hscrp level exceeds 1.0 mg/l

6 Methods We examined attributable factors to baseline values and the changes of hscrp. and coronary artery restenosis* and target lesion revascularization** (TLR) after PCI among three groups. * in-segment restenosis defined as the diameter of stenosis 50% ** repeated PCI or CABG

7 Results (1) L (n=338) T (n=241) H (n=268) Gender (M/F), % 79/21 76/24 76/24 n.s. Age (y) 66±7 66±10 68± Overweight*, % Dyslipidemia, % n.s. Hypertension, % n.s. Diabetes Mellitus, % n.s. Hemodialysis, % Follow-up interval (day) 315±13 318±15 341±20 n.s. PCI procedure Baseline patient characteristics Stent (SES/ PES/ ZES/ EES), % 70/ 23/ 0/ 7 72/ 16/ 1/ 11 67/ 25/ 0/ 8 n.s. Lesion (RCA/LAD/LCx/LMT), % 30/42/22/6 26/46/21/7 30/42/23/5 n.s. Stent length(mm) 28.4± ± ±17.2 n.s. Stent diameter(mm) 2.96± ± ±0.34 n.s. Proximal stent diameter 3.00± ± ±0.36 n.s. Distal stent diameter 2.91± ± ±0.36 n.s. Dilation pressure (atm) 12.8± ± ±2.6 n.s. * defined as BMI 25, n.s.: no significance SES: silorimus-, PES: paclitaxel-, ZES: zotarolimus-, EES: everolimus-eluting stent p

8 Baseline Follow-up Results (2) Patient characteristics L (n=338) T (n=241) H (n=268) p Statin, % 267 (78.9) 181 (75.1) 164 (61.1) <0.001 Pioglitazone, % 29 (8.6) 17 (7.1) 19 (7.1) n.s. BMI (kg/m 2 ) 24.0± ± ± HbA1c (%) 6.0± ± ±1.1 n.s. Cr (mg/dl) 0.80± ± ± UA (mg/dl) 5.5± ± ± T-Chol (mg/dl) 182±37 187±38 187±40 n.s. TG (mg/dl) 127±57 127±55 131±59 n.s. HDL-C (mg/dl) 50±13 46±11 47± LDL-C (mg/dl) 106±31 113±33 112± L (n=338) T (n=241) H (n=268) p Statin, % 297 (87.9) 213 (88.4) 205 (76.5) Pioglitazone, % 30 (88.8) 22 (91.3) 18 (67.1) n.s. BMI (kg/m 2 ) 23.8± ± ± HbA1c (%) 5.9± ± ±0.8 n.s. Cr (mg/dl) 0.83± ± ±0.38 < UA (mg/dl) 5.4± ± ± T-Chol (mg/dl) 163±27 162±30 172± TG (mg/dl) 120±54 128±56 133±58 n.s. HDL-C (mg/dl) 51±13 49±11 48± LDL-C (mg/dl) 88±22 88±23 96±

9 Results (3) Correlation of baseline hscrp with each parameter At baseline, LDL-C levels correlated with log 10 hscrp levels in multivariate regression analysis. univariate multivariate r p r p age BMI HbA1c Cr UA T-Chol HDL-C TG LDL-C Log 10 CRP [mg/l] Log 10 CRP = * LDL R 2 = p = LDL-C [mg/dl]

10 Results (4) Correlation of the changes of hscrp with those of each parameter The changes of LDL-C levels and HDL-C levels respectively correlated with the changes of log 10 hscrp levels in multivariate regression analysis. Log 10 CRP [mg/l] 2.5 LogCRP= * HDL, R^2 = univariate multivariate r P r p BMI HbA1c Cr UA T-Chol HDL-C < TG LDL-C HDL-C Log 10 CRP [mg/l] LogCRP= * LDL, R^2= LDL-C

11 % Lesion restenosis Results (5) In overall enrolled patients, lesion restenosis was found in 12.9% (109 of 847) and TLR in 11.0% (93 of 847). Patients in H had higher restenosis rate and TLR rate compared with other two groups TLR p = p = p = % p = L T H L T H

12 Summary 1) Baseline patient characteristics showed higher age and higher level of LDL-C, and lower rate of statin administration in continuously elevated hscrp group. 2) At baseline, LDL-C levels associate with hscrp levels. 3) The changes of LDL-C and HDL-C levels during follow-up periods respectively associate with those of hscrp levels. 4) Both restenosis rate and TLR rate after PCI in continuously elevated CRP group were higher than other two groups.

13 Study limitations Small sample size Retrospective analysis Possible patients selection bias Rate of angiographic follow-up in our institution was 65 percent. The state of continuously elevated hscrp levels was defined according to only two times measurements because some patients were followed at other institutions until follow-up angiography.

14 Conclusions Continuously elevated hscrp level might be associated with coronary restenosis and target lesion revascularization after PCI. To examine whether early and intensive lipid lowering therapy using statin in such patients is effective, further evaluation with larger number of patients is needed. Thank you.