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DOI 10.4070 / kcj.2010.40.10.491

Print ISSN 1738-5520 / On-line ISSN 1738-5555 Copyright © 2010 The Korean Society of Cardiology

Open Access

High Lipoprotein(a) Levels are Associated With Long-Term Adverse Outcomes in Acute Myocardial Infarction Patients in High Killip Classes
Jae Yeong Cho, MD, Myung Ho Jeong, MD, Youngkeun Ahn, MD, Young Joon Hong, MD, Hyung Wook Park, MD, Nam Sik Yoon, MD, Hyun Ju Yoon, MD, Kye Hun Kim, MD, Ju Han Kim, MD, Jeong Gwan Cho, MD, Jong Chun Park, MD and Jung Chaee Kang, MD
Heart Research Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, Gwangju, Korea

Background and Objectives: An elevated concentration of lipoprotein(a) {Lp(a)} is associated with an increased preva-

lence and increased severity of coronary artery disease. However, the relationship between Lp(a) levels and outcomes after acute myocardial infarction (AMI) is unclear. Subjects and Methods: Between October 2005 and June 2007, we measured serum Lp(a) levels in 832 consecutive AMI patients (age, 62.8±12.4 years, 600 men) on admission. They were divided into tertiles according to their serum Lp(a) levels {Tertile 1 (n=276), Lp(a)<13.8 mg/dL; Tertile 2 (n=279), Lp(a)=13.8-30.6 mg/dL; Tertile 3 (n=277), Lp(a)>30.6 mg/dL}. Results: There were no differences in baseline clinical characteristics among Tertiles 1, 2, and 3, except for proportions of Killip class III-IV patients (5.8% vs. 10.0% vs. 18.8%, respectively, p<0.001). There were significant differences in left ventricular ejection fractions (57.3±11.4% vs. 55.9±12.3% vs. 53.1±13.1%, p<0.001). Among the laboratory findings, there were significant differences in total cholesterol (173.3±37.2 vs. 183.5±38.9 vs. 185.3±43.8 mg/dL, p=0.001), low density lipoprotein-cholesterol (111.3±34.3 vs. 122.9±34.7 vs. 123.3±39.4 mg/dL, p<0.001), apolipoprotein B (92.8±25.4 vs. 100.8±26.0 vs. 101.9±28.8 mg/dL, p<0.001), and amino-terminal pro-brain natriuretic peptide levels (1805.2± 4343.3 vs. 2607.9±5216.3 vs. 3981.5±7689.7 pg/mL, p<0.001). After adjusting for multiple variables in the high Killip class (III-IV) subgroup, the risk estimate for major adverse cardiovascular events (MACE) at 1-year follow-up was significantly higher in Tertile 3 than in Tertiles 1 or 2 (hazard ratio 6.723, 95% confidence interval 1.037-43.593, p=0.046). Conclusion: In patients in high Killip classes, high serum levels of Lp(a) were significantly associated with long-term adverse outcomes after AMI. (Korean
Circ J 2010;40:491-498) KEY WORDS: Myocardial infarction; Lipoproteins; Prognosis.

Lipoprotein(a) {Lp(a)} consists of a low-density lipoprotein
Received: February 13, 2010 Revision Received: April 20, 2010 Accepted: April 21, 2010 Correspondence: Myung Ho Jeong, MD, Heart Research Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, 8 Hak-dong, Dong-gu, Gwangju 501-751, Korea Tel: 82-62-220-6243, Fax: 82-62-228-7174 E-mail:
cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

particle covalently bound to a specific glycoprotein, apolipoprotein(a), by apolipoprotein B-100.1) Since apolipoprotein(a) and plasminogen mutually compete for plasminogen receptors on endothelial cells,2) high concentrations of circulating Lp(a) may inhibit thrombolysis and fibrin clearance.3) Moreover, the binding of native Lp(a) to fibrin is significantly enhanced in the presence of homocysteine, glutathione, and cysteine.4) A number of prospective and retrospective studies have demonstrated that increased levels of Lp(a) are associated with atherosclerosis, ischemic heart disease, and stroke.5)6) In numerous trials, patients with high Lp(a) levels had markedly increased risk of coronary heart disease.7-9) However, the relationship between Lp(a) levels and outcomes after acute myo-


left ventricular ejection fraction.6 mg/dL. Germany). These variables were selected on the basis of previous studies and multivariable linear regression analyses. patients were classified into tertiles as follows: Tertile 1 (n=276).0 Lp(a) (mg/dL) Fig. USA). multivessel disease. over one year. smoking.0 200. We also evaluated the following as coronary risk factors: hypertension (systolic blood pressure >140 mmHg. we measured serum Lp(a) levels in 832 consecutive patients with AMI (62. Fullerton. Tertile 2 (n=279). Coronary angiography Conventional coronary angiography was performed using a digital flat-panel fluoroscopy system (Phillips) via femoral or radial approaches. Schering. Repeat percutaneous coronary interventions included target-lesion revascularization (TLR). Killip class. Miami. STsegment elevation myocardial infarction (STEMI) was diagnosed in patients with 30 minutes of continuous chest pain. 1). CA. IL. Lp(a)<13. categorical variables were compared using the χ2 test.8-30. or receiving antihypertensive drugs). and non-TVR. apolipoprotein B.492 Lipoprotein(a) in Acute Myocardial Infarction cardial infarction (AMI) is unclear. Subjects and Methods Between October 2005 and June 2007.0 100. target-vessel revascularization (TVR). were measured by standard enzymatic methods. Based on their serum Lp(a) levels. nonfatal myocardial infarction. fasting triglyceride level ≥150 mg/dL. C-reactive protein (CRP) was analyzed by a highly-sensitive turbidimetric test using sheep antibodies against human CRP. and coronary artery bypass grafting. Mannheim. At least four orthogonal views were obtained.. triglyceride. This test has been validated against the Dade-Behring method. FL. Arrows mark the tertile boundaries. diabetes mellitus (fasting glucose level ≥126 mg/dL or random blood glucose level ≥200 mg/dL). Coulter Inc. USA). low-density lipoprotein cholesterol. Lp(a)≥30. highsensitivity C-reactive protein (hsCRP). Non-STEMI (NSTEMI) was diagnosed by chest pain and a positive cardiac biochemical marker without new ST-segment elevation. troponin I levels were measured using paramagnetic particles and a chemiluminescent immunoenzyme assay (Beckman. current smoking habit. total cholesterol. and Tertile 3 (n= 277).0 50.. Serum amino-terminal pro-brain natriuretic peptide was measured using an electrochemiluminescence sandwich immunoassay and an Elecsys 2010 analyzer (Roche Diagnostics.8 mg/dL. sex. . and serum was removed and stored at -70°C until the assays could be performed. 600 men) upon admission to the Heart Center of Chonnam National University Hospital. Statistical analysis Continuous variables with normal distributions were presented as means±standard deviation and were compared by 1-way analysis of variance. Gwangju. Laboratory testing Peripheral blood samples were obtained by direct venipuncture. and Lp(a) were measured using a Behring Nephelometer II (Dade Behring Inc. and a family history of coronary artery disease. We determined that the proportional hazard assumption was satisfied by examining plots of the log-negative-log of the withingroup survivorship functions versus log-time. Deerfield.4 years. Berlin. Lp(a): lipoprotein (a). apolipoprotein B. and number of stents. repeat percutaneous coronary intervention.8± 12. applying nonionic contrast material (Ultravist 370.0 150. 1. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing MACE-free survival rates between Lp(a) tertiles. Germany).6 mg/dL (Fig. Serum levels of total cholesterol. noncardiac death.. USA). total cholesterol. To test for differences between Lp(a) tertiles. Inc. a new 2 mm ST-segment elevation on at least two contiguous electrocardiographic leads. The levels of serum Lp(a). Total cholesterol. Korea. and low. Lp(a) was measured by an immunonephelometric assay using a latex Lp(a) reagent composed of polystyrene particles coated with a rabbit antihuman Lp(a) γ-globulin fraction. high density lipoprotein-cholesterol. The purpose of this study was to assess the relationship between high serum Lp(a) levels and major adverse cardiac events after AMI. or receiving hyperlipidemia medication). including cardiac death. Absolute CK-MB levels were determined by radioimmunoassay (Dade Behring. Distribution of serum concentrations of Lp(a) at baseline. Apolipoprotein A1. Study outcomes The primary outcome for this analysis was a composite of major adverse cardiovascular events (MACE). Lp(a)=13. and remnant lipoprotein cholesterol were determined on admission. and a creatine kinase-MB (CKMB) level greater than three times the upper limit of normal. hyperlipidemia (total cholesterol level ≥240 mg/dL.and high density lipoprotein-cholesterol. The blood samples were centrifuged. triglyceride. amino-terminal probrain natriuretic peptide. We used models that adjusted for age. Cardiacspecific 200 Numbers of patients 150 100 50 0 Arrows indicate Lower & upper boundary of mid-tertile of Lp(a) 0. diastolic blood pressure >90 mmHg.

4±8.099 0.3±34.7 0005.5±3.001 0.00 092.6±7.0 0001.5 0046.001 0.7) 024.8±26.1 0005.0) 245 (90.50 132.7±1761.4±25.8 0171.2±11.1) 007 (2.6±28.001 <0. et al.640 0.775 0.26 0002.2±1.9±34.25 0002.248 <0.6 062.5±17.3) 015 (5.8)0 122 (44.7)0 172 (61.8 0058.4 0126.5±38.5±1.304 0.9 0122.096 0.519 0.123 0.7 0100.3±77.8) 133 (48.8 0092.40 086.2 0046.937 0.109 <0.1 0001. n (%) Aspirin.Jae Yeong Cho.9 0109.0) 016 (5.16 was subtracted from apolipoprotein B Tertile 2 (n=279) 13.4±17.4) 239 (89. toTable 1.3±37.0 083.6 0170.339 0.333 0.3±25.8±25.054 0. Lp(a): lipoprotein(a) Table 2.9 077.5)0 188 (68. Comparisons of laboratory findings between Lp(a) tertiles Lp(a) (mg/dL) Glucose (mg/dL) Creatinine (mg/dL) Creatine Kinase (IU/L) Creatine Kinase-MB (IU/L) Troponin-I (ng/mL) Troponin-T (ng/mL) Total cholesterol (mg/dL) Triglycerides (mg/dL) High density lipoprotein-cholesterol (mg/dL) Low density lipoprotein-cholesterol (mg/dL) Apolipoprotein A1 (mg/dL) Apolipoprotein B (mg/dL) Lp(a) (mg/dL) Apolipoprotein B/A1 ratio High-sensitivity C-reactive protein (mg/dL) Amino-terminal pro-brain natriuretic peptide (pg/mL) Left ventricular ejection fractions (%) Lp(a): lipoprotein(a) Tertile 1 (n=276) <13.1 1573.3 0057.2) 010 (3.4 0010.1±2.2±3.1) 208 (76. Baseline clinical characteristics of patients by Lp(a) tertiles tal Lp(a) mass was multiplied by 0.80 134.4 Tertile 2 (n=279) 13.5 3981.3±29.847 0.1) 219 (80.3±3.9±28.367 0.001 0.1) 006 (2.3±43.001 0.694 <0.2±12.058 0.9 0101. n (%) Diabetes mellitus.6 197 (70.8 0111.001 <0.136 0.9 0046.0 0021.7 0128.10 086.891 0.8 061.7 0057. Similarly.9 076.11)12) Thus.059 0.1 p 0.40 133.7 0051.951 0.7 0096.001 <0.6) Tertile 3 (n=277) ≥30.6)0 167 (60.3 Tertile 3 (n=277) ≥30.6±6. n (%) Clopidogrel.1±1.7±77.2 0122.0) 024.544 0.1 000.80 093.1 052 (18.8 0005.2±7.8±109.707 0.0) 122 (43.9±58.1±7. n (%) Family history.6) 014 (5.6±1756.0±16.9 0111.5±11.9±29.2±1845.6±6.0 194 (70.3±73.7 074.2±12.930 <0.1) 218 (80.268 Abdominal circumference (cm) Hip circumference (cm) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Heart rate (/minute) Killip class ≥III.3 0130.5±160.4 0065.0 1805.1±7.4±114. n (%) Hypertension.6) 024.1±1.5) p 0.7 028 (10. n (%) Body mass index (kg/m ) 2 Tertile 1 (n=276) <13.7±12.27 0002.8 016 (5.1 083.81±0.811 0.3.2) 255 (94.6±8.9) 201 (75.6 0123. total Lp(a) mass multiplied by 0.1±18.60 093.8 0185. n (%) Continuous variables are expressed as means±standard deviation.001 .0±3.8±89.9) 072 (26. n (%) Smoking.9±5216. n (%) Hyperlipidemia.4±17.5±7690.6 0179.3±11.4±63.2)0 261 (96.8±112.0 1563.6 0173.8-30. and this value was subtracted from total cholesterol and low density lipoprotein-cholesterol values in all individuals. and apolipoprotein B levels were adjusted for Lp(a) contribution.4) 080 (29.0)0 259 (97.9 0183.9 084.9±12.3±4.5±30.7±78.5 0095.4)0 266 (98.0 0053.90 087.5) 077 (28.6±19.3 0055. 493 low density lipoprotein-cholesterol.0±27. n (%) Beta-blockers.5±4.0 1506.056 0.4 0093.8±6. n (%) Statins.0 2607.6 064.2±4343.74±0.1±12.83±0.1 000.3±39.1 0001.10) according to compositional data in which cholesterol accounts for ≒30% and apolipoprotein B for ≒16% of total Lp(a) mass.8) 218 (80.5 209 (75.1±13.5 000.7±64.8) 210 (78.4) Lp(a) (mg/dL) Age (years) Male.8-30.

n (%) Lesion type.6±5.6±0.8)0 111 (40.2) 036 (13.2)0 110 (39.8) 1. USA) for Windows (Microsoft Corp. the amino-terminal pro-brain natriuretic peptide level was significantly higher in Tertile 3 (1805. 10. 123.2) 064 (25. 62.44 24.3 vs. p=0.1 3. p=0.6 004 (1. respectively.8-30. Although the hsCRP was also increased in Tertile 3.05 was deemed significant.4) 102 (36. 183. as was low density lipoprotein-cholesterol (111.9 vs. The mean concentration of apolipoprotein B was highest in Tertile 3 (p<0.3) 091 (32.3±34.4) 048 (21. respectively. Lp(a): lipoprotein(a).1) 073 (28. Body mass indices.3) 1.001).3) 071 (25. Washington. The left ventricular ejection fraction was signifiTertile 2 (n=279) 13.6) 055 (15. 18.8% (Tertile 3).8)0 060 (23. respectively.1) 149 (54. n (%) Left main Left anterior descending artery Left circumflex artery Right coronary artery Diseased vessel number. n (%) 1 2 3 Multi-vessel disease. However.0 (SPSS Inc. and hip circumferences.30 Tertile 3 (n=277) ≥30. A p less than 0.5±38.017 0.6 years.0% (Tertile 2) vs.6) 157 (56.4) 077 (27. Chicago. 2.1) 126 (46.5±0.5) 1.001).7) 046 (16.80 Laboratory findings Laboratory findings are summarized in Table 2. Both serum glucose and creatinine levels were highest in Tertile 3.2) 008 (3.0 vs.3) 109 (43.25±0.7±5.2 vs.494 Lipoprotein(a) in Acute Myocardial Infarction values. heart rates.0) 092 (33. 61. 185.1) 015 (5.8) 0.0) 119 (47.932 0.1) 078 (28.4) 0. Redmond.001). p<0.6 006 (2. 2. Among Tertiles 1.011 0.3±37.* n (%) B1 B2 C TIMI flow.3) 040 (14.0) 064 (23.1±12.757 *Lesion type according to American College of Cardiology/American Heart Association.8 005 (1. TIMI: thrombolysis in myocardial infarction .8% (Tertile 1) vs. and 3. 2607.40 0.5) 047 (20.7 vs. the increase was not statistically significant.194 Table 3. There was a trend toward a decrease in mean apolipoprotein A1 levels as Lp(a) levels increased.059) and there was a trend for females to have increased Lp(a) levels.8 3.8 mg/dL. There were also no differences seen in blood pressures.438 0..0)0 064 (25. respectively.001). and therefore the apolipoprotein B/apolipoprotein A1 ratio tended to increase as Lp(a) levels increased (p<0. abdominal circumferences.9 3.6) 098 (35.3±43. n (%) 0 1 2 3 Percutaneous coronary intervention Bare metal stent.2) 036 (13.23±0.4)0 118 (42. total cholesterol was highest in Tertile 3 (173.39 24.8±1.8) 010 (4.0) 097 (35.077 134 (52. Among Tertiles 1.5±7690. n (%) Number of deployed stents Stent diameter (mm) Stent length (mm) p 0.7) 066 (26.5) 096 (34.0) 078 (28. 122.3) 061 (21.4 mg/dL. There were no significant differences seen in cardiac enzyme levels. there was a higher incidence of Killip classes III and IV as Lp(a) levels increased {5.9) 094 (34.2)0 061 (24. Tertile 1 (n=276) <13.3±39.0) 100 (36.458 0.9±5216.7±12.9) 081 (29. and 3.3 vs. p<0. 3981. Comparisons of coronary angiographc findings betweeg Lp(a) tertiles Lp(a) (mg/dL) Culprit lesion. were almost the same between tertiles.1) 042 (17.9) 035 (12. The mean age was higher in Tertile 3 than in Tertiles 1 and 2 (64.3 vs..5±5. version 15.907 112 (43.2±4343. USA).9) 071 (23.0 pg/mL. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software.38 24.2±12. Results Baseline characteristics Baseline characteristics are summarized in Table 1. IL. but the increases were not statistically significant.001} (Table 1).001). and past medical histories.9±34.5 vs. p<0.6) 087 (31.20±0.

009 0. but one-month and six-month outcomes were different.0) 0 (0.0)0 3 (1.5)0 1 (0. Coronary angiography findings Coronary angiography findings are summarized in Table 3.002) and six-month follow-ups (13.Jae Yeong Cho.7) 0 (0.4 vs.563 0. 19.9) n=279 15 (5.4)0 4 (1.2) 13 (5.8) 23 (8.236 0.742 0. p=0.271 0. In-hospital mortalities were not significantly different among tertiles.922 0. 46.8) 15 (5.0) 44 (18.4)0 3 (1.529 0.0)0 2 (0.6 8 (2. the Cox proportional hazards model was applied with adjustment of multiple variables.540. p=0. 495 cantly decreased in Tertile 3 (57. p=0.7) 2 (0. The lack of significance was also seen with adjustments ac- Lp(a) (mg/dL) In-hospital mortality One month after discharge Cardiac death Non-cardiac death Non-fatal myocardial infarction Target lesion revascularization Target vessel revascularization Non-target vessel revascularization Coronary artery bypass graft Composite MACE Six-month outcomes Cardiac death Non-cardiac death Non-fatal myocardial infarction Target lesion revascularization Target vessel revascularization Non-target vessel revascularization Coronary artery bypass graft Composite MACE One-year outcomes Cardiac death Non-cardiac death Non-fatal myocardial infarction Target lesion revascularization Target vessel revascularization Non-target vessel revascularization Coronary artery bypass graft Composite MACE Lp(a) Tertile 1 (n=276) <13. among Tertiles 1.4) 29 (10.8) 51 (19. 1.3) 0 (0.9 vs.2) 7 (2. the increased risk for MACE was not significant. However.4)0 1 (0.2) n=277 16 (5.8) 7 (2.5) n=268 20 (7. p=0.084 Lp(a): lipoprotein(a). and stent diameters and lengths. 8.018 0.5) 1 (0.612 0.4) 2 (0.2)0 9 (3. respectively.2) 2 (0. Thrombolysis in Myocardial Infarction flow grades. Higher levels of baseline Lp(a) were associated with increased risk for MACE until levels were adjusted according to hsCRP values (HR 1.6)0 0 (0.2% vs.3% vs.4)0 n=276 10 (3.8 04 (1.3 vs.098 0.4)0 2 (0.1± 13.6 6 (2.4) 59 (22.1.462 0.0%.0) 11 (4.1) p 0.4) 14 (5. American College of Cardiology/American Heart Association lesion types.4) 0 (0.065 0.018).8) 2 (0.8) 16 (6. 1.2) 10 (4. multivessel disease was most common (36.000 0.8) 1 (0. et al.002 0.1) 14 (5.9% vs.3)0 n=244 14 (5. The percent of patients with composite MACE was highest in Tertile 3 at both one-month (4.0)0 n=271 12 (4. 2. MACE: major adverse cardiac event .156 1.7) 14 (5.8±1.8) 3 (1.3±11.5%.2)0 n=265 20 (7.917 0.2)0 2 (0. But when adjusted for Killip class.5)0 7 (2.4% vs.6±0. 95% CI 1.011).045 0.2% vs.6)0 2 (0.8 vs.0) Lp(a) Tertile 2 (n=279) 13.009).9) Lp(a) Tertile 3 (n=277) >30. 22. 55.1) 3 (1.0% vs. p<0.8) 2 (0.8)0 3 (1.2)0 1 (0.2)0 2 (0.8) 13 (5.643 0.161 0. 34.001).2) 60 (23.2) 16 (6.0) 2 (0.5±0.089 0. To analyze the association between serum Lp(a) levels and clinical outcomes. 53. respectively.666. Clinical outcomes Comparisons of clinical outcomes between groups are sumTable 4.8) 6 (2. There were no significant differences in occurrences of culprit lesions.7)0 3 (1. Comparisons of clinical outcomes betweeg Lp(a) tertiles marized in Table 4.311 0.0) 0 (0. 10. but by one-year follow-up there were no significant differences between numbers of patients with composite MACE among the tertiles (Table 5).4) 2 (0.174 0.9±12.0) 36 (13.1) 2 (0. and 3.4) 0 (0.017).8)0 3 (1.147 0.0) 1 (0.0) 4 (1.3) 0 (0. and the number of deployed stents was highest in Tertile 3 (1.2) n=251 21 (8.6) 3 (1.092-2.6)0 1 (0.0) n=267 22 (8.3%.7) 66 (25. p=0.8-30.475 0.4) 3 (1.0) 0 (0.1%.

526 0.666 0.046 MACE-free survival (%) 80 60 40 20 0 Tertile 1 Tertile 2 Tertile 3 0 100 200 300 400 Time to MACE (days) Fig. In the present study.046) compared to the referent Tertile (Table 6) (Fig.000 1.262 95% CI p Model 5† (fully adjusted) Risk estimate 1.813 0.170 0.678-2.181 1.540 0. high-sensitivity C-reactive protein. hsCRP: high sensitivity C-reactive protein Table 6.006).000 1. and number of stents. Lp(a): lipoprotein(a) 100 Discussion p=0.593 0. 2). After completely adjusting for the risk for MACE. the risk in Tertile 3 was 6. 95% CI 1.271.021 1.042 95% CI p Model 2 (Model 1+TC+LDL-C+ApoB) Risk estimate 1.348 0.897-2.908-2.684 0.065 0. but we do not know the severities of the conditions of the patients in their study.037-43.875 1.921-2. Thus. The reason why Lp(a) was only associated with MACE in patients in high Killip classes remains unclear.496 Lipoprotein(a) in Acute Myocardial Infarction Table 5. p=0. one of the confounding variables. After multifactorial adjustment using the Cox proportional hazards model. smoking. 2. Fully-adjusted time-to-clinical outcomes by baseline Lp(a) tertiles. The results of this study indicate that high serum levels of Lp(a) are significantly associated with long-term adverse outcomes in AMI patients. multivessel disease.234 95% CI 0.099 0.156 1.720 0.549 0. log N-terminal pro-B type natriuretic peptide.458 6. Lp(a): lipoprotein (a).112 0. amino-terminal pro-brain natriuretic peptide.401 1.593. number of stents.823-2.893 0. It has been reported that the biologi- .997. There were more patients in a high Killip class in the highest Lp(a)-level tertile. low density lipoprotein-cholesterol.137 0. patients with higher Lp(a) levels also had more serious initial presentations. total cholesterol.877-2.120 0. Therefore. apolipoprotein B.092-2.504 Risk estimate 1. ApoB: apolipoprotein B. Hazard ratios have been adjusted for age. LDL-C: low density lipoprotein-cholesterol.186-11.015-2.512 1. preprocedural Lp(a) levels could provide data for risk stratification in patients with AMI.062 1.054 0.000 1.378 1. Killip class. TC: total cholesterol.157 0.442 1. MACE: major adverse cardiovascular events. 8) have observed stepwise increases in risk for myocardial infarction with increasing levels of Lp(a) in the general population. we analyzed risk estimates according to Killip class.355 1.297 1. and smoking. left ventricular ejection fraction. it seems unlikely that the differences in left ventricular ejection fraction among the Lp(a) tertiles were actually of clinical significance. The other three variables did not show significant risk estimates for MACE.501 Risk estimate 1. Kamstrup et al. smoking.723 (95% CI 1.992-2. and multivessel disease. low density lipoprotein-cholesterol. sex. sex.018 0. One potential mechanism may be oxidative stress on Lp(a) in acute heart failure caused by AMI. apolipoprotein B.046 0. number of stents.911-2. especially in those in a high Killip class. total cholesterol.045 p 95% CI p Model 4 (Model 3+Killip class ≥3) *Model 1 adjusted for age.557 95% CI p I-II Tertile 2 Tertile 3 Tertile 1 III-IV Tertile 2 Tertile 3 *Model 1 includes age.220-3. Risk estimates for a major adverse cardiac event according to Lp(a) tertile and Killip class Killip class Lp(a) subgroup Tertile 1 Model 1* Risk estimate 1. left ventricular ejection fraction.423-2. gender.640 0.043 0.060 0. †Model 5 includes age.008-2.000 0.290-2. cording to amino-terminal pro-brain natriuretic peptide.229 Model 3 (Model 2+hsCRP) 95% CI p 0. whereas high Killip classes were seen to be an independent risk factor for MACE (HR 1.037-43.000 1. p=0. gender. left ventricular ejection fraction.000 1. high-sensitivity C-reactive protein.357 1. Risk estimates for a major adverse cardiac event according to Lp(a) tertile Lp(a) subgroup Tertile 1 Tertile 2 Tertile 3 Lp(a) subgroup Tertile 1 Tertile 2 Tertile 3 Model 1* Risk estimate 1.723 0.368 1.125 0. Lp(a): lipoprotein(a). Left ventricular ejection fraction also decreased linearly with increasing serum Lp(a) levels.120 0.886-2.000 1. and smoking. multivessel disease.000 1.

Some studies have demonstrated association of high serum Lp(a) levels with restenosis after percutaneous coronary angioplasty. this was a retrospective study. but no significant differences were found in the one-year outcomes.26) We suggest that these Lp(a) effects could explain the trend toward a high non-TVR rate in patients with high Lp(a) levels. there are some results that need to be clarified. Some reports have indicated that niacin. decreased oxygen delivery to the ischemic myocardium should be considered. Korean Circ J 1993. and 70%. respectively. Lp(a) is not easily modified by statin therapy. the study population comprised mainly men. First. the results of this study should be verified by prospective investigations. With respect to revascularization in newly developed lesions. and it has been recently determined that far fewer Asian women take HRT compared with women in Western countries. so that it contributes to the development of atherosclerosis and atherothrombosis. Republic of Korea. These effects include stimulation of atherosclerosis. In conclusion. Lipoprotein(a). Second. Patients in high Killip classes with pulmonary edema or in cardiogenic shock have increased wedge pressure. the incidence of non-TVR was too small to analyze by the Cox proportional hazards model.23:631-3. and we need to use assay systems that are insensitive to apo(a) isoforms. The TLR rates were very similar among the tertiles. Lp(a) tends to increase in AMI or in surgery as an acute phase reactant. showed that most adverse cardiac events occurred within the first six-months.13) Therefore.3) These two effects could aggravate myocardial ischemia and might result in worse outcomes. which results in the suppression of instent restenosis in patients with high serum Lp(a) levels. which can affect serum Lp(a) levels.Jae Yeong Cho. Since apolipoprotein(a) and plasminogen compete for plasminogen receptors on endothelial cells. The present study was limited in several respects. However. & Family Affairs. it is difficult to determine a causal relationship for Lp(a). An analysis of the nationwide Korea Acute Myocardial Infarction Registry.20)21) However. HRT should be considered in future studies.30) Nevertheless. one. These deaths were caused by bleeding. the number of patients in this group was too small to interpret the results accurately. Welfare. Additional prospective studies may determine causal relationships and treatments.17-19) No patients in this study took any of these medications. Second. Lp(a).22)23) Hoffmann et al. Third. Ministry for Health. Second. Although not completely understandable. Standardization of serum Lp(a) measurement should be undertaken. and mitogenic stimulation of human vascular smooth muscle cells. which enrolled 13. reduce Lp(a) levels about 20%.14) Although there are contradictory findings about the effect of statins on Lp(a) serum concentrations. Lp(a) promotes growth of vascular smooth muscles cells and inhibits plasminogen activity.28) Even after standardization.15) it is uncertain whether statin use prevents the coronary heart disease associated with Lp(a). there was a problem with laboratory standardization.133 patients with AMI. there might be some variations in Lp(a) measurements. How- ever.16) Nearly 80% of patients in our study were administered statins. First. an antisense oligonucleotide directed at human apoB-100. Acknowledgments This study was supported by grants from the Korea Healthcare Technology R&D project (A084869). because it was a single-center study.16) Fourth. it has been suggested that the metallic scaffolding in stents strongly inhibits recoil. and mipomersen.26) studied patients with high Lp(a) levels undergoing POBA as well as PCI and found that there was less difference of TLR rate in the PCI group. Last. 40%. Asia. elevated levels of serum Lp(a) are significantly associated with one-year adverse outcomes in AMI patients in high Killip classes.25) However. was not considered in this study. However. International reference material for Lp(a) laboratory standardization only became available in 2000.13) in the future it may be determined to be a very important risk factor. and since the numbers of patients taking statins were almost equally distributed among the tertiles. statin therapy probably did not influence our results. it has also been reported that serum Lp(a) levels do not influence restenosis after elective coronary stenting. REFERENCES 1) Lee CK.29) There was difficulty timing the measurements and assessments of Lp(a) levels. . there were significant differences between the tertiles in the number of noncardiac deaths at the six-month follow-up. Morita et al. and the Cardiovascular Research Foundation.27) The less frequent occurrence of adverse cardiac events between the six-month to one-year followups may have influenced our results. Basically. and therefore subject to the limitations inherent in this type of clinical investigation. Regarding clinical outcomes in this study. 497 cal effects of oxidized Lp(a) are more potent than those of native Lp(a). we suggest that high serum Lp(a) is predictive of more adverse outcomes in patients in higher Killip classes than in lower Killip classes. et al. Our results are consistent with this data. and aggravation of underlying diseases. inhibition of vessel dilatation. which has been attributed to Lp(a) in vitro. hormone replacement therapy (HRT) in female patients. medical therapy seems unlikely to be a confounder in this study. Therefore. 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