Supplemental Digital Content
Table S1. Baseline Characteristics of ABCB1 C3435T Genotypes
ABCB1Variables / Total / CC / CT / TT
n=670 / n=240 / n=308 / n=122
Age, y / 58.88±11.21 / 58.38±10.97 / 59.08±11.47 / 59.33±11.09
Male, n (%) / 515(76.9) / 183(76.3) / 233(75.6) / 99(81.1)
BMI, kg/m2 / 32.26±9.95 / 33.18±9.07 / 31.38±9.67 / 32.68±11.98
LVEF / 57.4±9.0 / 57.4±8.8 / 57.0±9.0 / 58.2±9.0
WBC, ×103/mm3 / 8.7±3.5 / 8.5±3.3 / 9.0±3.7 / 8.2±3.3
Hemoglobin, g/dl / 13.6±1.6 / 13.6±1.6 / 13.6±1.7 / 13.8±1.7
hs-CRP, mg/dl / 5.8±5.1 / 6.0±5.2 / 5.9±5.2 / 5.2±4.9
Index clinical presentation, n (%)
Unstable angina / 187(27.9) / 68(28.3) / 88(28.6) / 31(25.4)
AMI / 360(53.7) / 129(53.8) / 173(56.2) / 58(47.5)
Risk factor, n (%)
DM / 208(31) / 76(31.7) / 100(32.5) / 32(26.2)
Hypertension / 413(61.6) / 148(61.7)* / 178(57.8)* / 87(71.3)*
Hypercholesterolemia / 576(86) / 207(86.3) / 273(88.6)* / 96(78.7)*
Current smoking / 290(43.3) / 105(43.8) / 132(42.9) / 53(43.4)
Alcohol drinking / 189(28.2) / 77(32.1) / 83(26.9) / 29(23.8)
CHD family history / 170(25.4) / 62(25.8) / 78(25.3) / 30(24.6)
History, n (%)
Previous MI / 97(14.5) / 34(14.2) / 38(12.3) / 25(20.5)
Previous CABG / 7(1.0) / 3(1.3) / 2(0.6) / 2(1.6)
Previous PCI / 105(15.7) / 36(15) / 50(16.2) / 19(15.6)
Infarct-related artery, n (%)
LAD / 513(76.6) / 182(75.8) / 232(75.3) / 99(81.1)
LCX / 477(71.2) / 168(70) / 220(71.4) / 89(73)
RCA / 634(94.6) / 226(94.2) / 291(94.5) / 117(95.9)
LM / 51(7.6) / 21 (8.8) / 25(8.1) / 5(4.1)
Concomitant medications, n (%)
Statin / 644(96.1) / 230(95.8) / 298(96.8) / 116(95.1)
β-blocker / 566(84.5) / 206(85.8) / 261(84.7) / 99(81.1)
ACEI / 442(66) / 174(72.5) / 192(62.3) / 76(62.3)
CCB / 168(25.1) / 63(26.3) / 75(24.4) / 30(24.6)
PPI / 335(50) / 122(50.8) / 161(52.3) / 52(42.6)
Intervention method, n (%)
Drug-eluting stent / 642(95.8) / 229(95.4) / 296(96.1) / 117(95.9)
Bare metal stent / 9(1.3) / 5(2.1) / 3(1.0) / 1(0.8)
Ballooning only / 21(3.1) / 6(2.5) / 11(3.6) / 4(3.3)
ABCB1, ATP-binding cassette, sub-family B, member 1; BMI, body mass index; LVEF, left ventricular ejection fraction; WBC, white blood cell; hs-CRP, high-sensitivity C-reactive protein; AMI, acute myocardial infarction; DM, diabetes mellitus; CHD, cardiac heart disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; LAD, left anterior descending; LCX, left circumflex; RCA, right coronary artery; LM, left main; ACEI, angiotensin antagonist inhibitor; CCB, calcium channel blocker; PPI, proton pump inhibitor.
* P < 0.05.
Table S2. Baseline Characteristics of PON1 Q192R Genotypes
PON1Variables / Total / CC / CT / TT
n=669 / n=277 / n=310 / n=82
Age, y / 58.88±11.21 / 57.98±11.09 / 59.43±11.16 / 59.89±11.80
Male, n (%) / 515(76.9) / 217(78.3) / 230(74.2) / 67(81.7)
BMI, kg/m2 / 32.25±9.95 / 32.32±10.25 / 31.98±9.27 / 33.04±11.39
LVEF, % / 57.4±9.0 / 57.3±8.9 / 57.2±9.1 / 58.5±8.8
WBC,×103/mm3 / 8.7±3.5 / 8.9±3.6 / 8.6±3.5 / 8.0±3.0
Hemoglobin, g/dl / 13.6±1.6 / 13.6±1.6 / 13.6±1.7 / 13.9±1.4
hs-CRP, mg/dl / 5.8±5.1 / 5.8±5.0 / 5.7±5.2 / 6.2±5.2
Index clinical presentation, n (%)
Unstable angina / 186(27.8) / 66(23.8) / 86(27.7) / 34(41.5)
AMI / 360(53.7) / 164(59.2) / 160(51.6) / 36(43.9)
Risk factor, n (%)
DM / 208(31) / 78(28.2) / 99(31.9) / 31(37.8)
Hypertension / 413(61.6) / 170(61.4) / 194(62.6) / 49(59.8)
Hypercholesterolemia / 576(86) / 237(85.6) / 269(86.8) / 69(84.1)
Current smoking / 290(43.3) / 131(47.3) / 126(40.6) / 33(40.2)
Alcohol drinking / 189(28.2) / 83(30) / 83(26.8) / 22(26.8)
CHD family history / 170(25.4) / 70(25.3) / 82(26.5) / 18(22)
History, n (%)
Previous MI / 96(14.3) / 38(13.7) / 438(13.9) / 15(18.3)
Previous CABG / 7(1.0) / 1(0.4) / 3(1.0) / 3(3.7)
Previous PCI / 105(15.7) / 43(15.5) / 50(16.1) / 12(14.6)
Infarct-related artery, n (%)
LAD / 513(76.6) / 213(76.9) / 230(74.2) / 70(85.4)
LCX / 477(71.2) / 198(71.5) / 213(68.7) / 66(80.5)
RCA / 634(94.6) / 260(94.2) / 294(94.8) / 79(96.3)
LM / 51(7.6) / 24 (8.7) / 21(6.8) / 6(7.3)
Concomitant medications, n (%)
Statin / 644(96.1) / 268(96.8) / 297(95.8) / 78(95.1)
β-blocker / 566(84.5) / 234(84.5) / 262(84.5) / 69(84.1)
ACEI / 442(66) / 184(66.4) / 200(64.5) / 57(69.5)
CCB / 168(25.1) / 64(23.1) / 79(25.5) / 25(30.5)
PPI / 335(50) / 142(51.3) / 152(49) / 40(48.8)
Intervention method, n (%)
Drug-eluting stent / 642(95.8) / 266(96) / 297(95.8) / 78(95.1)
Bare metal stent / 9(1.3) / 5(1.8) / 2(0.6) / 2(2.4)
Ballooning only / 21(3.1) / 8(2.9) / 10(3.2) / 3(3.7)
PON1, paraoxonase 1; BMI, body mass index; LVEF, left ventricular ejection fraction; WBC, white blood cell; hs-CRP, high-sensitivity C-reactive protein; AMI, acute myocardial infarction; DM, diabetes mellitus; CHD, cardiac heart disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; LAD, left anterior descending; LCX, left circumflex; RCA, right coronary artery; LM, left main; ACEI, angiotensin antagonist inhibitor; CCB, calcium channel blocker; PPI, proton pump inhibitor.
* P < 0.05.
Table S3. Platelet Function Measurement and the Prevalence of Clopidogrel Low Response and Cardiovascular Events According to CYP2C19Metabolizer Status (excluding the CYP2C19*17 carriers)
CYP2C19Variables / *1/*1 / *1/*2 / *1/*3 / *2/*2 / *2/*3
n=276 / n=249 / n=56 / n=60 / n=16 / p
TEG platelet mapping assay
ADP-Inhibition / 66.74±28.62 / 59.04±32.68 / 51.03±27.61 / 49.53±32.17 / 48.13±32.23 / <0.001
CLR, n (%) / 39(14.1) / 58(23.6) / 15(26.1) / 21(34.6) / 6(37.5) / 0.002
Clinical endpoints
T he CIE, n (%) / 5(1.8) / 11(4.4) / 3(5.4) / 5(8.3) / 2(12.5) / 0.021
Bleeding, n (%) / 19(6.9) / 16(6.4) / 6(10.7) / 3(5.0) / 3(18.8) / 0.478
CYP, cytochrome P450; TEG, thrombelastograph; ADP, adenosine diphosphate; CLR, clopidogrel low response; CIE, composite ischemic events.
Table S4. Predictors of Clopidogrel Low Response and the Composite Ischemic Events by Univariate and Multivariate Logistic Regression Models(excluding the CYP2C19*17 carriers)
4A. Predictors of Clopidogrel Low Response
Variables / Univariate Analysis / Multivariate AnalysisOR (95% CI) / p / OR (95% CI) / p
CYP2C19 LOF allele carriage
1- LOF allele carriage / 1.93(1.21-3.09) / 0.006 / 1.91(1.18-3.08) / 0.008
2-LOF alleles carriage / 3.32(1.79-6.17） / <0.001 / 3.18(1.68-6.02) / <0.001
Female / 1.59(1.01-2.50) / 0.046 / 1.66(0.96-2.86) / 0.068
Age / 1.01(0.99-1.03) / 0.325 / 1.01(0.99-1.03) / 0.421
Body mass index / 0.99(0.97-1.01) / 0.40 / 1.00(0.98-1.02) / 0.910
Current smoking / 1.25(0.83-1.89) / 0.293 / 0.94(0.58-1.51) / 0.787
Hypertension / 1.02(0.67-1.55) / 0.93 / 1.18(0.74-1.89) / 0.494
Hypercholesterolemia / 1.67(0.91-3.08) / 0.097 / 1.44(0.76-2.74) / 0.261
Diabetes mellitus / 0.83(0.54-1.28) / 0.406 / 0.90(0.57-1.43) / 0.654
Calcium channel blocker / 0.70(0.45-1.11) / 0.126 / 0.80(0.48-1.32) / 0.376
Proton pump inhibitor / 2.09(1.38-3.16) / 0.001 / 2.11(1.36-3.29) / 0.001
OR, odds ratio; CI, confidence interval; CYP, cytochrome P450; LOF, loss of function.
4B. Predictors of the Composite Ischemic Events
Variables / Univariate Analysis / Multivariate AnalysisOR (95% CI) / p / OR (95% CI) / p
CYP2C19 LOF allele carriage
1- LOF allele carriage / 2.61 (0.93-7.34） / 0.069 / 2.66(0.93-7.60) / 0.067
2-LOF alleles carriage / 5.50 (1.69-17.85) / 0.005 / 4.98(1.50-16.53) / 0.009
Female / 1.20(0.50-2.92) / 0.684 / 1.03(0.37-2.86) / 0.951
Age / 1.02(0.98-1.05) / 0.353 / 1.02(0.98-1.06) / 0.356
Body mass index / 1.00(0.96-1.04) / 0.802 / 1.00(0.96-1.05) / 0.921
Current smoking / 2.12(0.88-5.12) / 0.094 / 1.94(0.74-5.06) / 0.179
Hypertension / 0.86(0.38-1.95) / 0.713 / 0.86(0.35-2.14) / 0.745
Hypercholesterolemia / 2.40(0.98-5.88) / 0.056 / 2.02(0.79-5.13) / 0.141
Diabetes mellitus / 2.55(0.87-7.50) / 0.089 / 2.93(0.97-8.80) / 0.056
Calcium channel blocker / 0.91(0.38-2.22) / 0.843 / 1.18(0.44-3.13) / 0.746
Proton pump inhibitor / 2.36(1.01-5.51) / 0.047 / 2.27(0.92-5.62) / 0.075
OR, odds ratio; CI, confidence interval; CYP, cytochrome P450; LOF, loss of function.