© 2014, Wiley Periodicals, Inc. DOI: 10.1111/joic.12137
ACUTE CORONARY SYNDROME Prospective Study of Effects of Endogenous Estrogens on Myocardial No‐Reflow Risk in Postmenopausal Women with Acute Myocardial Infarction MEI DONG, M.D., P H .D., 1 NAN MU, M.D., P H .D., 2 FAXIN REN, M.D., P H .D., 1 XIAOJIAN SUN, M.D., P H .D., 1 FENGLI LI, M.M., 1 CHUANHUAN ZHANG, M.M., 1 and JUN YANG, M.D., P H .D. 1 From the 1Department of Cardiology, Yuhuangding Hospital, Yantai City, Shang Dong Province, P.R. China; and 2Department of Gynecology, Yuhuangding Hospital, Yantai City, Shang Dong Province, P.R China
The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no‐reflow in postmenopausal women with ST‐elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal‐ reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C‐reaction protein (Hs‐CRP) were significantly higher in the no‐reflow group (P < 0.05). In univariable logistic regression models, lesion length, reference luminal diameter, thrombus score 4, and the levels of estrone, estradiol, and SHBG were all found to be positively associated with the risk of no‐reflow (P < 0.05). After adjusting for these factors, thrombus score 4 (OR ¼ 4.994, CI 1.987–10.518; P ¼ 0.035), SHBG (OR ¼ 0.800, CI 0.341–0.983; P ¼ 0.047), and estradiol levels (OR 4.091, CI 1.105–8.582; P ¼ 0.046) continued to demonstrate strong positive associations with the risk of no‐reflow. Our data showed that high circulating levels of endogenous estrogens have a positive and statistically significant relationship with no‐reflow in postmenopausal women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no‐reflow. However, our results need to be confirmed in a larger population. (J Interven Cardiol 2014;27:437–443)
Introduction Sex hormones have emerged as prominent players in cardiovascular diseases (CVDs). It is widely appreciated that estrogen has favorable effects on the cardiovascular system.1 However, clinical studies reveal an apparently poorer prognosis in females with myocardial infarction.2,3 In addition, studies on hormone replacement therapy (HRT) similarly question the cardioprotective role of estrogen.4,5 These apparently inconsistent reports suggested that the Mei Dong and Nan Mu contributed equally to this study. Grant sponsor: Scientific and Technologic Development Programme of Yantai; Grant number: 2013WS221. Address for reprints: Jun Yang, Department of Cardiology, Yantai Yuhuangding Hospital, 22 Yuhuangding Dong Road, Zhifui District, Yantai City, Shan Dong Province, P.R. China. Fax: 86‐ 0535‐6240341; e‐mail: [email protected]
Vol. 27, No. 5, 2014
association between endogenous estrogen and CVD risk had not yet been clearly established. Myocardial no‐reflow is defined as inadequate myocardial perfusion of a given coronary segment without angiographic evidence of mechanical vessel obstruction.6 We proved that endogenous estrogen was an independent risk factor of ST‐elevation myocardial infarction (STEMI) in postmenopausal women.7 We now examine the effects of endogenous estrogen on no‐reflow in postmenopausal women with STEMI. Furthermore, we investigated possible mechanisms involved in the estrogenic effects.
Subjects and Methods Patients. We consecutively recruited 100 eligible acute myocardial infarction (AMI) patients, who
Journal of Interventional Cardiology
437
DONG, ET AL.
successfully received primary percutaneous coronary intervention (PCI) in the Yantai Yuhuangding Hospital in the period between July 2012 and July 2013. The study protocol was approved by the ethic committee of the hospital. Written informed consent was obtained from all patients. STEMI was diagnosed according to the European Society of Cardiology definition.8 The patients included in our study were diagnosed AMI without history of prior CVD or heart failure. Stent implantation was successfully performed in all patients. No significant side‐branch occlusion occurred during the procedure. For all participants, exclusion criteria included factors that could affect endogenous sex hormones levels. Participants were excluded if they had endocrine‐related diseases, used hormone medications, or took any medications known to affect endogenous sex hormone levels. Primary PCI. For each patient, 300 mg of aspirin and 300 mg loading dose of clopidogrel were administered orally in the emergency room before PCI. The patients were transferred to the cardiac catheterization laboratory and primary PCI was then performed. PCI procedures were performed through a femoral approach with a 6 French guiding catheter. Intravenous unfractionated heparin (5,000 IU) was administered before PCI. IIb/IIIa inhibitors were used at the operator discretion. Selective coronary angiography was performed after the intracoronary administration of nitroglycerin and at least 5 standardized views of the left coronary artery and 3 views of the right coronary artery were obtained. After conventional wire crossing, use of Diver CE (Innovative Technologies, Brescia, Italy) was left at the operator’s discretion, then direct stenting implantation was performed whenever possible, preceded by balloon predilatation if necessary. Evaluation Coronary Blood Flow. Coronary angiography was evaluated by quantitative coronary angiography analysis.9 For objective evaluation of coronary blood flow, TIMI flow grades were assessed as previously described;10 corrected thrombolysis in myocardial infarction frame count (cTFC) method developed by Gibson et al.11 was adopted. Myocardial blush grade (MBG) was done according to van’t Hof et al.12 criteria. Because TIMI flow grades identify primarily epicardial blood flow, we used MBG to assess microvascular perfusion. In this study, we defined angiographic coronary slow flow/microvascular dysfunction as a coronary TIMI flow grade 2 after vessel reopening or TIMI flow 3 with a final MBG 2.13
438
Angiographic assessment was always performed by 2 independent angiographers who were unaware of sex hormone results, and final agreement was 90%, with discordances being resolved by consensus. Laboratory Assays. Nonfasting peripheral venous blood samples were obtained from all of the study subjects on admission. Serum estradiol (Siemens Medical Solutions Diagnostics, Malvern, PA, USA) and sex hormone binding globulin (SHBG) (Siemens Healthcare Diagnostics, Inc., Gwynedd, UK) concentrations were measured using the chemoluminescence method, while the radioimmunoassay method was used to determine estrone (Diagnostic Systems Laboratories, Inc., Webster, TX, USA) concentrations. Each target was measured within the same batch on the same day. The intra‐ and inter‐batch coefficients of variation (CV) were 4.6% and 9.0% for estrone (at 1.2 pg/mL), 9.3% and 6.4% for estradiol (at 7.0 pg/mL), and 6.0% and 7.9% for SHBG (at 0.2 nmol/L). Hypersensitive C‐reaction protein (Hs‐CRP) level was measured using an immunonephelometric high‐sensitivity method (DADE Behring, Milan, Italy). Statistical Analysis. Data were analyzed using the SAS version 9.13 (SAS Institute, Inc., Cary, NC, USA). Serum sex hormones and SHBG levels were natural logarithm transformed to normalize their distributions. Significance of differences in continuous variables was assessed using the Student’s t‐test while McNemar’s test was used to analyze the categorical variables. Univariable and multivariable logistic regression models were then used to assess the correlation between estrogens and no‐reflow after adjusting for confounding factors. Variables were considered confounding if they were found to be significant. A probability value of 0.05 or less was considered significant.
Results Clinical Characteristics of Patients. Of the 100 patients who underwent primary PCI, 23 (23%) developed no‐reflow after the procedure. Table 1 shows a comparison of the baseline characteristics of the patients. No difference was found between the normal‐reflow group and the no‐reflow group with regard to age, frequencies of major coronary risk factors (e.g., BMI, smoking, hypertension, diabetes mellitus, and blood lipid), CK‐MB peak level, Troponin‐I, and medications. However, the levels
Journal of Interventional Cardiology
Vol. 27, No. 5, 2014
PROSPECTIVE STUDY OF EFFECTS OF ENDOGENOUS ESTROGENS Table 1. General Characteristics and Demographic Data of Patients
Age, year BMI, kg/m2 WHR Smoking, n (%) Hypertension, n (%) DM, n (%) Heart rate (bpm) SBP (mmHg) SBP < 100 mmHg on admission, n (%) DBP (mmHg) CK‐MB peak (ng/mL) Troponin‐I (ng/mL) Fasting blood glucose (mmol/L) Uric acid (mmol/L) Total cholesterol (mmol/L) HDL cholesterol (mmol/L) LDL cholesterol (mmol/L) Triglycerides (mmol/L) Estrone (pg/mL) Estradiol (pg/mL) SHBG (nmol/L) Hs‐CRP (mg/L) Aspirin therapy, n (%) Clopidogrel therapy, n (%) Statin therapy, n (%) ACE‐inhibitor therapy, n (%) Calcium antagonists, n (%) b‐blocker therapy, n (%) Nitrates therapy, n (%)
Normal‐reflow (n ¼ 77)
No‐reflow (n ¼ 23)
P‐value
62.9 9.4 23.7 4.1 0.81 21 (27.3) 33 (42.9) 30 (39.0) 71.8 9.6 141.1 13.7 15 (19.5) 81.6 7.3 231.9 71.5 22.3 5.7 7.3 2.3 268.5 55.4 5.45 0.98 1.26 0.19 3.08 0.62 1.44 0.68 40.86 11.29 21.26 9.77 47.28 5.24 55.29 10.52 56 (72.7) 64 (83.1) 47 (61.0) 50 (64.9) 62 (80.5) 53 (68.8) 71 (92.2)
64.2 14.7 24.9 6.0 0.79 4 (17.4) 10 (43.5) 11 (47.8) 73.2 12.1 129.4 22.2 6 (26.1) 82.3 10.9 232.9 99.9 25.6 9.9 8.6 4.7 271.6 71.7 5.52 1.56 1.07 0.37 3.18 0.91 1.54 0.81 52.11 17.55 32.78 12.39 39.72 9.88 71.22 16.84 14 (60.9) 16 (69.6) 9 (39.1) 15 (65.2) 17 (73.9) 15 (65.2) 20 (87.0)
0.175 0.420 0.084 0.369 0.958 0.448 0.567 0.379 0.495 0.460 0.712 0.077 0.245 0.199 0.818 0.365 0.283 0.421 0.045 0.027 0.039 0.040 0.276 0.154 0.063 0.980 0.495 0.744 0.204
BMI, body mass index; WHR, waist‐hip ratio; DM, diabetes mellitus; SBP, systolic blood pressure; DBP, diastolic blood pressure; CK, creatine kinase; HDL, high‐density lipoprotein; LDH, low‐density lipoprotein; hs‐CRP, high‐sensitivity C‐reactive protein; SHBG, sex hormone‐binding globulin; ACEI, angiotensin converting enzyme inhibitors. Statistically significant.
of estrone, estradiol, SHBG, and Hs‐CRP were significantly higher in the no‐reflow group compared with the normal‐reflow group (P < 0.05 for all). Angiographic and Procedural Characteristics. No differences were noted between normal‐reflow group and no‐reflow group in terms of using IIb/IIIa inhibitors (24.0% vs. 23.8%, P > 0.05). Angiographic and procedural data are listed in Table 2. A final TIMI flow 3 was achieved in 84 patients (84%), whereas a final MBG‐3 was observed in 77 patients (77%). There were no significant differences between normal‐ reflow and no‐reflow groups with respect to number of diseased vessels culprit vessel and target lesion location. However, compared with normal‐reflow group, no‐reflow group had more lesion with thrombus score 4 (P ¼ 0.026), longer reference luminal diameter (RLD) (P ¼ 0.038), and longer lesion length (P ¼ 0.023).
Vol. 27, No. 5, 2014
Independent Predictors of No‐Reflow. A univariate logistic analysis included all the P < 0.05 variables evaluated at baseline: diabetes mellitus, lesion length, RLD, thrombus score 4, the levels of estrone, estradiol, SHBG, and Hs‐CRP, final TIMI flow 3, TIMI frame count, MBG3, time to balloon, and lesion length >20 mm. It suggested that Hs‐CRP, lesion length, RLD, thrombus score 4, and the levels of estrone, estradiol, and SHBG were risk factors in this model. Further multiple logistic regression analysis was used to estimate the final predictors of no‐reflow. Thrombus score 4 (OR ¼ 4.994, CI 1.987–10.518; P ¼ 0.035), SHBG (OR ¼ 0.800, CI 0.341–0.983; P ¼ 0.047), and estradiol levels (OR 4.091, CI 1.105–8.582; P ¼ 0.046) remained unchanged after this analysis (Table 3). Follow‐Up. All patients were followed up 30 days after PCI. No sudden cardiac death occurred in either
Journal of Interventional Cardiology
439
DONG, ET AL. Table 2. Angiographic and Procedural Findings
Time to balloon (h) Number of diseased vessels Culprit vessel, n (%) LAD LCX RCA Initial TIMI 0 flow, n (%) Target lesion location, n (%) Proximal Mid Distal Lesion length (mm) Lesion length >20 mm RLDr (mm) Thrombus score 4, n (%) Rentrop collaterals grading 0, n (%) Collateral circulation 0–1 Diver use, n (%) IABP use Direct stenting, n (%) Number of stents Final TIMI flow 3, n (%) TIMI frame count, frames Final myocardial blush grade 3, n (%)
Normal‐reflow (n ¼ 77)
No‐reflow (n ¼ 23)
P‐value
5.26 1.33 2.14 0.56
6.671 2.05 2.20 1.07
0.066 0.693 0.888
28 (36.4) 17 (22.1) 32 (41.6) 77 (100)
9 (39.1) 4 (17.4) 10 (43.5) 23 (100)
29 (37.7) 26 (33.8) 22 (28.6) 25.4 10.9 38 (49.4) 3.81 0.35 48 (62.3) 77 (100)
10 (43.5) 8 (34.8) 5 (21.7) 35.8 18.2 16 (69.6) 4.37 0.89 20 (87.0) 23 (100)
0.023 0.088 0.038 0.026 1
77 (100) 15 (19.5) 77 (100) 1.35 0.36 77 (100) 24.18 3.51 77 (100)
23 (100) 6 (26.1) 23 (100) 1.81 0.76 7 (30.4) 45.29 9.03 0 (0)
1 0.495 1 0.067
ACUTE CORONARY SYNDROME Prospective Study of Effects of Endogenous Estrogens on Myocardial No‐Reflow Risk in Postmenopausal Women with Acute Myocardial Infarction MEI DONG, M.D., P H .D., 1 NAN MU, M.D., P H .D., 2 FAXIN REN, M.D., P H .D., 1 XIAOJIAN SUN, M.D., P H .D., 1 FENGLI LI, M.M., 1 CHUANHUAN ZHANG, M.M., 1 and JUN YANG, M.D., P H .D. 1 From the 1Department of Cardiology, Yuhuangding Hospital, Yantai City, Shang Dong Province, P.R. China; and 2Department of Gynecology, Yuhuangding Hospital, Yantai City, Shang Dong Province, P.R China
The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no‐reflow in postmenopausal women with ST‐elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal‐ reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C‐reaction protein (Hs‐CRP) were significantly higher in the no‐reflow group (P < 0.05). In univariable logistic regression models, lesion length, reference luminal diameter, thrombus score 4, and the levels of estrone, estradiol, and SHBG were all found to be positively associated with the risk of no‐reflow (P < 0.05). After adjusting for these factors, thrombus score 4 (OR ¼ 4.994, CI 1.987–10.518; P ¼ 0.035), SHBG (OR ¼ 0.800, CI 0.341–0.983; P ¼ 0.047), and estradiol levels (OR 4.091, CI 1.105–8.582; P ¼ 0.046) continued to demonstrate strong positive associations with the risk of no‐reflow. Our data showed that high circulating levels of endogenous estrogens have a positive and statistically significant relationship with no‐reflow in postmenopausal women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no‐reflow. However, our results need to be confirmed in a larger population. (J Interven Cardiol 2014;27:437–443)
Introduction Sex hormones have emerged as prominent players in cardiovascular diseases (CVDs). It is widely appreciated that estrogen has favorable effects on the cardiovascular system.1 However, clinical studies reveal an apparently poorer prognosis in females with myocardial infarction.2,3 In addition, studies on hormone replacement therapy (HRT) similarly question the cardioprotective role of estrogen.4,5 These apparently inconsistent reports suggested that the Mei Dong and Nan Mu contributed equally to this study. Grant sponsor: Scientific and Technologic Development Programme of Yantai; Grant number: 2013WS221. Address for reprints: Jun Yang, Department of Cardiology, Yantai Yuhuangding Hospital, 22 Yuhuangding Dong Road, Zhifui District, Yantai City, Shan Dong Province, P.R. China. Fax: 86‐ 0535‐6240341; e‐mail: [email protected]
Vol. 27, No. 5, 2014
association between endogenous estrogen and CVD risk had not yet been clearly established. Myocardial no‐reflow is defined as inadequate myocardial perfusion of a given coronary segment without angiographic evidence of mechanical vessel obstruction.6 We proved that endogenous estrogen was an independent risk factor of ST‐elevation myocardial infarction (STEMI) in postmenopausal women.7 We now examine the effects of endogenous estrogen on no‐reflow in postmenopausal women with STEMI. Furthermore, we investigated possible mechanisms involved in the estrogenic effects.
Subjects and Methods Patients. We consecutively recruited 100 eligible acute myocardial infarction (AMI) patients, who
Journal of Interventional Cardiology
437
DONG, ET AL.
successfully received primary percutaneous coronary intervention (PCI) in the Yantai Yuhuangding Hospital in the period between July 2012 and July 2013. The study protocol was approved by the ethic committee of the hospital. Written informed consent was obtained from all patients. STEMI was diagnosed according to the European Society of Cardiology definition.8 The patients included in our study were diagnosed AMI without history of prior CVD or heart failure. Stent implantation was successfully performed in all patients. No significant side‐branch occlusion occurred during the procedure. For all participants, exclusion criteria included factors that could affect endogenous sex hormones levels. Participants were excluded if they had endocrine‐related diseases, used hormone medications, or took any medications known to affect endogenous sex hormone levels. Primary PCI. For each patient, 300 mg of aspirin and 300 mg loading dose of clopidogrel were administered orally in the emergency room before PCI. The patients were transferred to the cardiac catheterization laboratory and primary PCI was then performed. PCI procedures were performed through a femoral approach with a 6 French guiding catheter. Intravenous unfractionated heparin (5,000 IU) was administered before PCI. IIb/IIIa inhibitors were used at the operator discretion. Selective coronary angiography was performed after the intracoronary administration of nitroglycerin and at least 5 standardized views of the left coronary artery and 3 views of the right coronary artery were obtained. After conventional wire crossing, use of Diver CE (Innovative Technologies, Brescia, Italy) was left at the operator’s discretion, then direct stenting implantation was performed whenever possible, preceded by balloon predilatation if necessary. Evaluation Coronary Blood Flow. Coronary angiography was evaluated by quantitative coronary angiography analysis.9 For objective evaluation of coronary blood flow, TIMI flow grades were assessed as previously described;10 corrected thrombolysis in myocardial infarction frame count (cTFC) method developed by Gibson et al.11 was adopted. Myocardial blush grade (MBG) was done according to van’t Hof et al.12 criteria. Because TIMI flow grades identify primarily epicardial blood flow, we used MBG to assess microvascular perfusion. In this study, we defined angiographic coronary slow flow/microvascular dysfunction as a coronary TIMI flow grade 2 after vessel reopening or TIMI flow 3 with a final MBG 2.13
438
Angiographic assessment was always performed by 2 independent angiographers who were unaware of sex hormone results, and final agreement was 90%, with discordances being resolved by consensus. Laboratory Assays. Nonfasting peripheral venous blood samples were obtained from all of the study subjects on admission. Serum estradiol (Siemens Medical Solutions Diagnostics, Malvern, PA, USA) and sex hormone binding globulin (SHBG) (Siemens Healthcare Diagnostics, Inc., Gwynedd, UK) concentrations were measured using the chemoluminescence method, while the radioimmunoassay method was used to determine estrone (Diagnostic Systems Laboratories, Inc., Webster, TX, USA) concentrations. Each target was measured within the same batch on the same day. The intra‐ and inter‐batch coefficients of variation (CV) were 4.6% and 9.0% for estrone (at 1.2 pg/mL), 9.3% and 6.4% for estradiol (at 7.0 pg/mL), and 6.0% and 7.9% for SHBG (at 0.2 nmol/L). Hypersensitive C‐reaction protein (Hs‐CRP) level was measured using an immunonephelometric high‐sensitivity method (DADE Behring, Milan, Italy). Statistical Analysis. Data were analyzed using the SAS version 9.13 (SAS Institute, Inc., Cary, NC, USA). Serum sex hormones and SHBG levels were natural logarithm transformed to normalize their distributions. Significance of differences in continuous variables was assessed using the Student’s t‐test while McNemar’s test was used to analyze the categorical variables. Univariable and multivariable logistic regression models were then used to assess the correlation between estrogens and no‐reflow after adjusting for confounding factors. Variables were considered confounding if they were found to be significant. A probability value of 0.05 or less was considered significant.
Results Clinical Characteristics of Patients. Of the 100 patients who underwent primary PCI, 23 (23%) developed no‐reflow after the procedure. Table 1 shows a comparison of the baseline characteristics of the patients. No difference was found between the normal‐reflow group and the no‐reflow group with regard to age, frequencies of major coronary risk factors (e.g., BMI, smoking, hypertension, diabetes mellitus, and blood lipid), CK‐MB peak level, Troponin‐I, and medications. However, the levels
Journal of Interventional Cardiology
Vol. 27, No. 5, 2014
PROSPECTIVE STUDY OF EFFECTS OF ENDOGENOUS ESTROGENS Table 1. General Characteristics and Demographic Data of Patients
Age, year BMI, kg/m2 WHR Smoking, n (%) Hypertension, n (%) DM, n (%) Heart rate (bpm) SBP (mmHg) SBP < 100 mmHg on admission, n (%) DBP (mmHg) CK‐MB peak (ng/mL) Troponin‐I (ng/mL) Fasting blood glucose (mmol/L) Uric acid (mmol/L) Total cholesterol (mmol/L) HDL cholesterol (mmol/L) LDL cholesterol (mmol/L) Triglycerides (mmol/L) Estrone (pg/mL) Estradiol (pg/mL) SHBG (nmol/L) Hs‐CRP (mg/L) Aspirin therapy, n (%) Clopidogrel therapy, n (%) Statin therapy, n (%) ACE‐inhibitor therapy, n (%) Calcium antagonists, n (%) b‐blocker therapy, n (%) Nitrates therapy, n (%)
Normal‐reflow (n ¼ 77)
No‐reflow (n ¼ 23)
P‐value
62.9 9.4 23.7 4.1 0.81 21 (27.3) 33 (42.9) 30 (39.0) 71.8 9.6 141.1 13.7 15 (19.5) 81.6 7.3 231.9 71.5 22.3 5.7 7.3 2.3 268.5 55.4 5.45 0.98 1.26 0.19 3.08 0.62 1.44 0.68 40.86 11.29 21.26 9.77 47.28 5.24 55.29 10.52 56 (72.7) 64 (83.1) 47 (61.0) 50 (64.9) 62 (80.5) 53 (68.8) 71 (92.2)
64.2 14.7 24.9 6.0 0.79 4 (17.4) 10 (43.5) 11 (47.8) 73.2 12.1 129.4 22.2 6 (26.1) 82.3 10.9 232.9 99.9 25.6 9.9 8.6 4.7 271.6 71.7 5.52 1.56 1.07 0.37 3.18 0.91 1.54 0.81 52.11 17.55 32.78 12.39 39.72 9.88 71.22 16.84 14 (60.9) 16 (69.6) 9 (39.1) 15 (65.2) 17 (73.9) 15 (65.2) 20 (87.0)
0.175 0.420 0.084 0.369 0.958 0.448 0.567 0.379 0.495 0.460 0.712 0.077 0.245 0.199 0.818 0.365 0.283 0.421 0.045 0.027 0.039 0.040 0.276 0.154 0.063 0.980 0.495 0.744 0.204
BMI, body mass index; WHR, waist‐hip ratio; DM, diabetes mellitus; SBP, systolic blood pressure; DBP, diastolic blood pressure; CK, creatine kinase; HDL, high‐density lipoprotein; LDH, low‐density lipoprotein; hs‐CRP, high‐sensitivity C‐reactive protein; SHBG, sex hormone‐binding globulin; ACEI, angiotensin converting enzyme inhibitors. Statistically significant.
of estrone, estradiol, SHBG, and Hs‐CRP were significantly higher in the no‐reflow group compared with the normal‐reflow group (P < 0.05 for all). Angiographic and Procedural Characteristics. No differences were noted between normal‐reflow group and no‐reflow group in terms of using IIb/IIIa inhibitors (24.0% vs. 23.8%, P > 0.05). Angiographic and procedural data are listed in Table 2. A final TIMI flow 3 was achieved in 84 patients (84%), whereas a final MBG‐3 was observed in 77 patients (77%). There were no significant differences between normal‐ reflow and no‐reflow groups with respect to number of diseased vessels culprit vessel and target lesion location. However, compared with normal‐reflow group, no‐reflow group had more lesion with thrombus score 4 (P ¼ 0.026), longer reference luminal diameter (RLD) (P ¼ 0.038), and longer lesion length (P ¼ 0.023).
Vol. 27, No. 5, 2014
Independent Predictors of No‐Reflow. A univariate logistic analysis included all the P < 0.05 variables evaluated at baseline: diabetes mellitus, lesion length, RLD, thrombus score 4, the levels of estrone, estradiol, SHBG, and Hs‐CRP, final TIMI flow 3, TIMI frame count, MBG3, time to balloon, and lesion length >20 mm. It suggested that Hs‐CRP, lesion length, RLD, thrombus score 4, and the levels of estrone, estradiol, and SHBG were risk factors in this model. Further multiple logistic regression analysis was used to estimate the final predictors of no‐reflow. Thrombus score 4 (OR ¼ 4.994, CI 1.987–10.518; P ¼ 0.035), SHBG (OR ¼ 0.800, CI 0.341–0.983; P ¼ 0.047), and estradiol levels (OR 4.091, CI 1.105–8.582; P ¼ 0.046) remained unchanged after this analysis (Table 3). Follow‐Up. All patients were followed up 30 days after PCI. No sudden cardiac death occurred in either
Journal of Interventional Cardiology
439
DONG, ET AL. Table 2. Angiographic and Procedural Findings
Time to balloon (h) Number of diseased vessels Culprit vessel, n (%) LAD LCX RCA Initial TIMI 0 flow, n (%) Target lesion location, n (%) Proximal Mid Distal Lesion length (mm) Lesion length >20 mm RLDr (mm) Thrombus score 4, n (%) Rentrop collaterals grading 0, n (%) Collateral circulation 0–1 Diver use, n (%) IABP use Direct stenting, n (%) Number of stents Final TIMI flow 3, n (%) TIMI frame count, frames Final myocardial blush grade 3, n (%)
Normal‐reflow (n ¼ 77)
No‐reflow (n ¼ 23)
P‐value
5.26 1.33 2.14 0.56
6.671 2.05 2.20 1.07
0.066 0.693 0.888
28 (36.4) 17 (22.1) 32 (41.6) 77 (100)
9 (39.1) 4 (17.4) 10 (43.5) 23 (100)
29 (37.7) 26 (33.8) 22 (28.6) 25.4 10.9 38 (49.4) 3.81 0.35 48 (62.3) 77 (100)
10 (43.5) 8 (34.8) 5 (21.7) 35.8 18.2 16 (69.6) 4.37 0.89 20 (87.0) 23 (100)
0.023 0.088 0.038 0.026 1
77 (100) 15 (19.5) 77 (100) 1.35 0.36 77 (100) 24.18 3.51 77 (100)
23 (100) 6 (26.1) 23 (100) 1.81 0.76 7 (30.4) 45.29 9.03 0 (0)
1 0.495 1 0.067
