- Email: [email protected]
Obesity paradox in Korean patients undergoing primary percutaneous coronary intervention in ST-segment elevation myocardial infarction
Journal of Cardiology (2010) 55, 84—91
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/jjcc
Original article
Obesity paradox in Korean patients undergoing primary percutaneous coronary intervention in ST-segment elevation myocardial infarction Won Yu Kang (MD) a, Myung Ho Jeong (MD, PhD) a,∗,1, Young Keun Ahn (MD) a, Jong Hyun Kim (MD) b, Shung Chull Chae (MD) c, Young Jo Kim (MD) d, Seung Ho Hur (MD) e, In Whan Seong (MD) f, Taek Jong Hong (MD) g, Dong Hoon Choi (MD) h, Myeong Chan Cho (MD) i, Chong Jin Kim (MD) j, Ki Bae Seung (MD) k, Wook Sung Chung (MD) k, Yang Soo Jang (MD) h, Seung Woon Rha (MD) l, Jang Ho Bae (MD) m, Jeong Gwan Cho (MD) a, Seung Jung Park (MD) n , other Korea Acute Myocardial Infarction Registry Investigators a
Chonnam National University Hospital, South Korea Busan Hanseo Hospital, South Korea c Kyungpook National University Hospital, South Korea d Yeungnam University Hospital, South Korea e Keimyung University Hospital, South Korea f Chungnam National University Hospital, South Korea g Pusan National University Hospital, South Korea h Yonsei University Hospital, South Korea i Chungbuk National University Hospital, South Korea j Kyunghee University Hospital, South Korea k Catholic University Hospital, South Korea l Korea University Hospital, South Korea m Konyang University Hospital, South Korea n Asan Medical Center, South Korea b
Received 20 May 2009; received in revised form 26 August 2009; accepted 6 October 2009 Available online 25 November 2009
∗ Corresponding author at: The Heart Center of Chonnam National University Hospital, 671 Jaebongro, 8 Hakdong, Dong Ku, Gwangju 501-757, South Korea. Tel.: +82 62 220 6243; fax: +82 62 228 7174. E-mail address: [email protected] (M.H. Jeong). 1 Myung Ho Jeong, MD, PhD, FACC, FAHA, FESC, FSCAI, FAPSIC, Principal Investigator of Korea Acute Myocardial Infarction Registry (KAMIR), Professor, Director of Cardiovascular Research Institute of Chonnam National University.
0914-5087/$ — see front matter © 2009 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jjcc.2009.10.004
Obesity paradox in primary PCI
KEYWORDS Acute myocardial infarction; Coronary artery disease; Obesity; Prognosis
85 Summary The effect of body mass index (BMI) on outcomes after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is not well known. In patients registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between November 2005 and November 2007, 3824 STEMI patients who arrived at hospital within 12 h after onset of chest pain and underwent primary PCI were analyzed, and divided into four groups according to their BMI: underweight (BMI < 18.5 kg/m2 , n = 129); normal weight (18.5 ≤ BMI < 23.0 kg/m2 , n = 1253); overweight (23.0 ≤ BMI < 27.5 kg/m2 , n = 1959); and obese (BMI ≥ 27.5 kg/m2 , n = 483). In-hospital mortality, revascularization in 1 year, mortality in 1 year, and overall mortality were compared between groups. Overweight and obese group were significantly younger, had normal left ventricular ejection fraction, and were more likely to be men with a higher incidence of hypertension, diabetes, and hyperlipidemia. There were no significant differences in symptom-to-door time and door-to-balloon time between groups. Obese patients had significantly lower in-hospital and overall mortalities. Major adverse cardiac events showed a bimodal pattern. Obese STEMI patients treated with primary PCI were associated with lower mortality, which may be explained by better use of medical treatment, hemodynamic stability, and younger age. © 2009 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.
Introduction Generally, overweight and obesity are associated with an increased risk of developing cardiovascular disease [1,2]. Furthermore, obesity is associated with endothelial dysfunction, insulin resistance, and inflammation that may contribute to the increased risk for adverse cardiovascular clinical outcomes [3]. However, once coronary artery disease (CAD) developed in obese patients, poor clinical outcomes did not occur according to some reports [4—9]. Despite some data concerning the relationship between body mass index (BMI) and CAD existing, the clinical effect of BMI on outcomes after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is not well known. Furthermore, the available data are based on western populations, not on the oriental population. Thus, we intended to evaluate the clinical effect of BMI on outcomes after PCI in Korean patients with STEMI using the Korean Acute Myocardial Infarction Registry (KAMIR).
Materials and methods Study design and sample KAMIR is a Korean prospective, open, observational, multicenter on-line registry investigating the risk factors of mortality in acute myocardial infarction (AMI) and establishing the universal management for the prevention of AMI with support of the Korean Circulation Society since November 2005. A total of 41 hospitals, which were capable of primary PCI, participated. This study evaluated age, sex, body mass index, initial symptoms, vital signs, Killip class, symptoms, onset time, ambulance arrival time, first medical contact time, transfer time from first hospital to the primary PCI centers, door to needle time, doorto-balloon time, each risk factor, past regular medication, co-morbidities, electrocardiographic locations of MI, initial treatment strategy, drugs, angiographic findings, in-hospital complications, medical therapy in hospital, 1-, 6-, and 12-month follow-up major adverse cardiac events (MACEs) (cardiac death, re-infarction, re-PCI, coronary artery bypass
graft), and so on. We used KAMIR to define a cohort of patients with AMI. The study protocol was approved by the ethics committee at each participating institution. The diagnosis of AMI was based on the triad of chest pain, ECG changes, and raised serum cardiac enzyme level. During our study period of November 2005 to November 2007, 3824 STEMI patients who arrived at hospital within 12 h after onset of chest pain and underwent primary PCI were registered in KAMIR. For this analysis, patients were classified into four groups based on the suggestion by the World Health Organization for the Asian population [10]: underweight (Group I: BMI < 18.5 kg/m2 , n = 129); normal weight (Group II: 18.5 ≤ BMI < 23.0 kg/m2 , n = 1253); overweight (Group III: 23.0 ≤ BMI < 27.5 kg/m2 , n = 1959); and obese (Group IV: BMI ≥ 27.5 kg/m2 , n = 483). Patients’ characteristics consisted of medical history (diabetes mellitus, hypertension, smoking, hyperlipidemia, previous AMI, previous angina, previous coronary artery bypass graft, previous PCI, and family history); presentation characteristics (systolic blood pressure and heart rate, symptom-to-door time, door-to-balloon time, and left ventricular ejection fraction, which was obtained within 24 h after admission in most cases); the laboratory findings (glucose, creatinine, cardiac enzymes, serum cholesterol, high-sensitivity C-reactive protein, and N-terminal pro-brain natriuretic peptide); and the medical treatment; and angiographic and procedural findings. In-hospital mortality, MACEs, including in-hospital mortality, revascularization, mortality in 1, 6, 12 months, and overall mortality were compared among the four groups.
Statistical analysis Statistical analysis was performed using SPSS software, version 15.0 (SPSS-PC Inc., Chicago, IL, USA). All continuous variables are reported as mean value ± standard deviation (SD). We used Chi-square tests for linear-by-linear association, or one-way ANOVA for statistical comparisons of clinical characteristics among groups. Survival analysis after AMI was estimated using the Kaplan—Meier method with logrank tests to compare survival among groups. Univariate and multivariate analysis were done to identify the prognostic factors affecting results. We used Chi-square tests and
86
W.Y. Kang et al.
independent-samples t-tests to find the predictors for overall mortality and used logistic regression analysis to adjust confounding factors. A p-value < 0.05 was considered as significant.
Results
Laboratory findings
Baseline characteristics Baseline characteristics of the patient groups are listed in Table 1. Overweight and obese group were significantly younger (Group I: 69.7 ± 12.7 years, II: 64.7 ± 12.2 years, III: 59.4 ± 11.9 years, and IV: 56.5 ± 12.5 years, p < 0.001) and more likely to be male patients (Group I: 62.8%, II: 70.9%, III: 79.5%, and IV: 76.4%, p = 0.009) with higher incidences of hypertension (Group I: 33.3%, II: 39.9%, III: 47.2%, and IV: 54.2%, p < 0.001), diabetes (Group I: 17.3%, II: 22.5%, III: 23.5%, and IV: 28.7%, p = 0.005), smoking (Group I: 58.9%, II: 60.3%, III: 64.2%, and IV: 66.2%, p = 0.006), and hyperlipidemia (Group I: 9.8%, II: 7.0%, III: 10.4%, and IV: 12.7%, p = 0.001). There were no significant statistical differences in symptom-to-door time and doorto-balloon time (p > 0.05). Underweight patients had lower left ventricular ejection fraction (Group I: 48.3 ± 14.0%, II: 50.3 ± 11.7%, III: 51.3 ± 11.3%, and IV: 52.6 ± 11.6%, p < 0.001), lower systolic (Group I: 117.9 ± 33.6 mmHg, II: 122.6 ± 38.7 mmHg, III: 125.8 ± 30.1 mmHg, and IV:
Table 1
129.1 ± 30.8 mmHg, p < 0.001) and diastolic blood pressure (Group I: 71.7 ± 19.8 mmHg, II: 75.7 ± 31.9 mmHg, III: 78.7 ± 24.8 mmHg, and IV: 80.6 ± 18.3 mmHg, p < 0.001) and higher rate of Killip class 1 (Group I: 28.7%, II: 25.4%, III: 22.4%, and IV: 22.5%, p = 0.001) (Table 1).
Table 2 shows results of the laboratory examination. Overweight and obese patients had higher levels of total cholesterol (Group I: 163.9 ± 50.2 mg/dL, II: 175.4 ± 42.8 mg/dL, III: 185.3 ± 42.7 mg/dL, and IV: 191.7 ± 44.6 mg/dL, p < 0.001) and low-density lipoprotein cholesterol (Group I: 101.9 ± 42.5 mg/dL, II: 111.3 ± 36.6 mg/dL, III: 120.4 ± 44.7 mg/dL, and IV: 124.2 ± 53.1 mg/dL, p < 0.001). N-terminal pro-brain natriuretic peptide became significantly lower, as BMI increased (Group I: 3991.1 ± 7436.2 pg/mL, II: 1863.3 ± 4854.7 pg/mL, III: 1194.5 ± 3661.2 pg/mL, and IV: 845.9 ± 2901.5 pg/mL, p < 0.001). Also, there were no clinical differences in the levels of glucose, creatinine, and high-sensitivity C-reactive protein between groups.
Medical treatment parameters At admission, we used -blockers (Group I: 57.0%, II: 72.0%, III: 75.4%, and IV: 78.9%, p < 0.001) and statins (Group I:
Baseline clinical characteristics.
Age (years)* Female, n (%)* CPR prior on arrival, n (%) Typical pain, n (%)* SBP (mmHg)* DBP (mmHg)* SDT (min) DBT (min) LVEF (%)* Killip ≥ II, n (%)* Anterior ECG, n (%)* Inferior ECG, n (%)* AF, n (%) Risk factors, n (%) Hypertension* Diabetes mellitus* Smoking* Hyperlipidemia* Previous AMI, n (%) Previous angina, n (%) Previous CABG, n (%) Previous PCI, n (%) Family history, n (%)
Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
69.7 ± 12.7 48 (37.2) 5 (3.9) 107 (84.9) 117.9 ± 33.6 71.7 ± 19.8 195.2 ± 131.3 105.6 ± 78.7 48.3 ± 14.0 35 (28.7) 66 (54.1) 55 (45.1) 3 (2.4)
64.7 ± 12.2 365 (29.1) 42 (3.4) 1095 (88.9) 122.6 ± 38.7 75.7 ± 31.9 189.9 ± 136.4 100.4 ± 73.9 50.3 ± 11.7 307 (25.4) 641 (54.4) 550 (46.7) 55 (4.5)
59.4 ± 11.9 401 (20.5) 54 (2.8) 1786 (92.1) 125.8 ± 30.1 78.7 ± 24.8 179.3 ± 132.3 101.9 ± 78.9 51.3 ± 11.3 421 (22.4) 968 (52.0) 903 (48.5) 53 (2.8)
56.5 ± 12.5 114 (23.6) 11 (2.3) 447 (93.3) 129.1 ± 30.8 80.6 ± 18.3 183.4 ± 134.1 97.0 ± 65.1 52.6 ± 11.6 104 (22.5) 220 (47.4) 242 (52.2) 23 (4.9)
<0.001 <0.001 0.147 <0.001 <0.001 <0.001 0.115 0.578 <0.001 0.035 0.015 0.041 0.806
492 (39.9) 278 (22.5) 748 (60.3) 76 (7.0)
914 (47.2) 454 (23.5) 1250 (64.2) 179 (10.4)
257 (54.2) 135 (28.7) 317 (66.2) 52 (12.7)
<0.001 0.005 0.006 0.001
33 (2.7) 48 (3.9) 9 (0.7) 53 (4.3) 70 (6.4)
64 (3.3) 78 (4.0) 2 (0.1) 89 (4.6) 142 (8.0)
15 (3.1) 15 (3.1) 2 (0.4) 27 (5.6) 37 (8.6)
0.825 0.657 0.175 0.177 0.067
42 (33.3) 22 (17.3) 76 (58.9) 11 (9.8) 6 (4.7) 5 (3.9) 0 (0) 4 (3.1) 7 (6.1)
CPR: cardiopulmonary resuscitation; SBP: systolic blood pressure; DBP: diastolic blood pressure; SDT: symptom-to-door time; DBT: doorto-balloon time; LVEF: left ventricular ejection fraction; ECG: electrocardiogram; AF: atrial fibrillation; AMI: acute myocardial infarction; CABG: coronary arterial bypass graft; PCI: percutaneous coronary intervention. * Significance is p < 0.05.
Obesity paradox in primary PCI Table 2
87
Laboratory findings. Group I (N = 129)
Glucose (mg/dL) Creatinine (mg/dL) CK (U/L)* CK-MB (U/L)* TnI (ng/mL) TC (mg/dL)* LDL-C (mg/dL)* HDL-C (mg/dL)* hsCRP (mg/dL) NT-proBNP (pg/mL)*
164.7 1.26 2291.9 247.4 69.2 163.9 101.9 47.8 15.0 3991.1
± ± ± ± ± ± ± ± ± ±
72.4 1.48 3165.5 234.0 83.2 50.2 42.5 12.6 56.0 7436.2
Group II (N = 1253) 177.2 1.16 1871.9 191.5 70.1 175.4 111.3 46.4 15.7 1863.3
± ± ± ± ± ± ± ± ± ±
79.7 1.52 2224.2 206.5 194.9 42.8 36.6 24.6 80.4 4854.7
Group III (N = 1959) 177.0 1.13 2185.2 231.1 74.7 185.3 120.4 44.2 16.1 1194.5
± ± ± ± ± ± ± ± ± ±
78.6 0.86 2337.9 360.1 256.4 42.7 44.7 15.9 85.4 3661.2
Group IV (N = 483)
p-Value
± ± ± ± ± ± ± ± ± ±
0.380 0.566 0.003 0.003 0.513 <0.001 <0.001 0.048 0.860 <0.001
177.6 1.18 2146.4 225.6 55.5 191.7 124.2 45.3 12.1 845.9
72.7 1.50 2374.7 293.4 69.8 44.6 53.1 35.7 67.5 2901.5
CK: creatine kinase; TnI: troponin-I; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; hsCRP: high-sensitivity C-reactive protein; NT-proBNP: N-terminal pro-brain natriuretic peptide. * Significance is p < 0.05.
75.0%, II: 73.0%, III: 77.2%, and IV: 79.3%, p = 0.003) more frequently for the overweight and obese patients. Vasopressors (Group I: 34.4%, II: 20.9%, III: 17.4%, and IV: 14.0%, p < 0.001) and diuretics (Group I: 35.9%, II: 28.4%, III: 24.9%, and IV: 25.1%, p = 0.005) were prescribed more frequently in the underweight group. Except for those medications, there were no significant differences between groups in the usage of other medications (Table 3).
Coronary angiogram and PCI In underweight group, there was a higher incidence of left main complex lesion (Group I: 2.4%, II: 1.8%, III: 1.5%, and IV: 0.2%, p = 0.017) and left anterior descending coronary artery for the target vessel (Group I: 54.0%, II: 50.4%, III: 49.5%, and IV: 43.5%, p = 0.015). The higher BMI, the bigger stent (Group I: 3.11 ± 0.4 mm, II: 3.18 ± 0.4 mm, III: 3.24 ± 0.4 mm, and IV: 3.28 ± 0.5 mm, p < 0.001) was used and the lower events of complication (Group I: 26.8%, II: 18.0%, III: 16.2%, and IV: 15.3%, p = 0.007) occurred. Despite the use of drug-eluting stents in most cases, there was a trend to use bare metal stents in the underweight group (Table 4).
Table 3
Major adverse cardiac events and all-cause mortality Table 5 demonstrates in-hospital outcomes and MACEs at 1, 6, and 12 months for each of the patient groups. Obese patients had significantly lower mortalities (in-hospital mortality: 7.9% in Group I, 4.4% in II, 3.0% in III, and 1.7% in Group IV, p < 0.001; mortality at 1-year: 15.4% in Group I, 3.3% in II, 2.6% in III, and 1.1% in Group IV, p < 0.001; overall mortality: 17.3% in Group I, 6.1% in II, 4.5% in III, and 2.3% in Group IV, p < 0.001). MACEs showed a somewhat bimodal pattern (underweight: 28.2%, normal weight: 15.2%, overweight: 13.0%, and obese: 14.8%, p = 0.031).
Survival curves and multivariate analysis for overall mortality Kaplan—Meier survival curves for mortality showed significantly higher mortality in underweight patients (Fig. 1). In the multivariate regression analysis, we found that no use of statins, old age, higher Killip class, and lower left ventricu-
Prescribed medications.
Medications (%)
Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
Aspirin Clopidogrel Cilostazole Nitrate Unfractionated heparin Low molecular weight heparin -Blocker* Calcium channel blocker Angiotensin-converting enzyme inhibitor* Angiotensin receptor blocker Vasopressors* Diuretics* Statins*
99.2 99.2 39.1 69.5 60.9 37.5 57.0 9.4 71.1
99.3 98.3 37.4 65.1 58.2 33.4 72.0 7.3 70.7
99.2 98.9 35.1 69.3 60.7 31.9 75.4 9.1 72.1
98.7 98.1 33.9 68.6 62.3 36.4 78.9 10.3 76.2
0.399 0.954 0.082 0.109 0.139 0.939 <0.001 0.62 0.046
13.3 34.4 35.9 75.0
12.2 20.9 28.4 73.0
13.0 17.4 24.9 77.2
12.3 14.0 25.1 79.3
0.839 <0.001 0.005 0.003
*
Significance is p < 0.05.
88 Table 4
W.Y. Kang et al. Coronary angiogram and percutaneous intervention. Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
Lesion characteristics Left main complex (%)* Left main simple (%) Three-vessel disease (%) Two-vessel disease (%) One-vessel disease (%)
2.4 0 26.2 27.0 44.4
1.8 0.2 21.0 28.1 48.8
1.5 0.3 19.3 29.7 49.3
0.2 0.2 21.1 29.0 49.5
0.017 0.847 0.270 0.429 0.472
Target vessel Left main (%) LAD (%)* LCX (%) RCA (%)*
0.8 54.0 9.5 35.7
1.3 50.4 9.6 38.7
1.0 49.5 10.2 39.3
0.4 43.5 11.8 44.3
0.185 0.015 0.229 0.043
ACC/AHA lesion classification Type A (%) 6.8 Type B1 (%) 11.9 Type B2 (%) 24.6 Type C (%) 56.8
3.1 16.5 27.7 52.7
3.7 16.3 26.3 53.7
3.6 19.7 25.6 51.0
0.812 0.096 0.524 0.557
Pre-PCI TIMI TIMI 0 (%) TIMI I (%) TIMI II (%) TIMI III (%)
61.5 7.4 12.3 18.9
60.7 10.7 14.7 13.9
63.7 9.8 13.2 13.3
65.0 8.9 12.2 13.9
0.067 0.535 0.245 0.380
Post-PCI TIMI TIMI 0 (%) TIMI I (%) TIMI II (%) TIMI III (%)
0 1.6 3.3 95.1
0.7 0.7 4.6 94.0
0.9 1.0 4.1 93.9
0.9 0.2 6.6 92.3
0.318 0.465 0.176 0.207
Drug-eluting stent (%) Stent size (mm) Stent diameter (mm)* Stent number Success rate (%) Complication rate (%)*
94.8 25.4 ± 5.9 3.11 ± 0.4 1.44 ± 0.8 98.4 26.8
92.4 24.9 ± 6.2 3.18 ± 0.4 1.39 ± 0.7 97.4 18.0
90.1 25.1 ± 6.4 3.24 ± 0.4 1.40 ± 0.7 97.7 16.2
91.3 25.0 ± 5.8 3.28 ± 0.5 1.38 ± 0.7 98.5 15.3
0.071 0.811 <0.001 0.824 0.336 0.007
LAD: left anterior descending coronary artery; LCX: left circumflex coronary artery; RCA: right coronary artery; ACC/AHA: American College of Cardiology/American Heart Association; PCI: percutaneous coronary intervention; TIMI: thrombolysis in myocardial infarction. * Significance is p < 0.05.
lar ejection fraction were independent predictors of overall mortality (Table 6).
Discussion Our data revealed that overweight and obese patients had worse baseline characteristics, including hypertension, diabetes, smoking, and hyperlipidemia. Conversely, underweight patients had poor profiles associated with hemodynamic instability, including older age, lower blood pressure, higher Killip class, and lower left ventricular ejection fraction. Our clinical follow-up results showed that obese and overweight patients had better short- and longterm prognosis than underweight patients. Not only are overweight and obesity associated with increased risk of developing cardiovascular disease [1,2], but also obesity is associated with endothelial dysfunction, insulin resistance, and inflammation that may contribute
to an increased risk for adverse clinical outcomes [3]. So, we initially hypothesized that the obese and overweight patients who received primary PCI in STEMI would have poor prognosis compared with counterparts, despite some data supporting the obesity paradox in coronary artery disease [4—9]. What made these results? Our analysis showed that increased body mass index is associated with greater use of guideline-recommended therapies on admission. Blockers, angiotensin-converting enzyme inhibitors, and statins were prescribed more frequently for overweight and obese patients. As shown in Table 6, statins provide an independent protective effect in overall mortality. This trend was consistent with a previous report advocated by Steinberg et al. [11]. They concluded that overweight and obese patients with acute myocardial infarction or unstable angina were more likely to receive aspirin, -blockers, inhibitors of the rennin—angiotensin system, and lipid-lowering agents, and that they also were more likely to undergo cardiac
Obesity paradox in primary PCI Table 5
89
In-hospital, mid-term, and long-term outcomes.
*
CCU stay days (%) In-hospital mortality (%)*
Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
4.6 ± 5.6 7.9
3.4 ± 4.4 4.4
3.3 ± 3.9 3.0
3.1 ± 5.4 1.7
0.014 <0.001
1-Month follow-up
Group I (N = 107)
Group II (N = 1058)
Group III (N = 1657)
Group IV (N = 415)
p-Value
MACE (%) All-cause mortality (%) Cardiac death (%)* Non-cardiac death (%) Myocardial infarction Revascularization (%) CABG (%) Re-PCI (%) TLR (%) TVR (%) Non-TVR (%)*
4.0 2.0 2.0 0 1.0
2.3 1.2 1.0 0.2 0.2
1.9 1.0 0.5 0.5 0.1
3.5 0.2 0.2 0 0.2
0.844 0.085 0.022 0.781 0.418
0 1.0 1.0 0 0
0.1 0.9 0.2 0 0.6
0 0.8 0.4 0 0.4
0.2 2.7 0.2 0 2.5
0.604 0.032 0.870
6-Month follow-up
Group I (N = 86)
Group II (N = 865)
Group III (N = 1344)
Group IV (N = 341)
p-Value
MACE (%) All-cause mortality (%)* Cardiac death (%)* Non-cardiac death (%) Myocardial infarction Revascularization (%) CABG (%) Re-PCI (%) TLR (%) TVR (%) Non-TVR (%)
20.7 10.3 5.7 4.6 1.1
8.2 2.0 1.6 0.4 0.6
8.4 1.6 1.0 0.7 0.3
10.3 0.9 0.6 0.3 0.6
0.401 <0.001 0.002 0.062 0.460
0 9.2 2.3 1.1 5.7
0.2 5.5 2.1 0.5 2.8
0.1 6.4 2.4 0.8 3.1
0.3 8.5 2.4 0.9 5.0
0.844 0.237 0.745 0.523 0.354
12-Month follow-up
Group I (N = 69)
Group II (N = 648)
Group III (N = 1041)
Group IV (N = 255)
p-Value
MACE (%)* All-cause mortality (%)* Cardiac death (%)* Non-cardiac death (%)* Myocardial infarction Revascularization (%) CABG (%) Re-PCI (%) TLR (%) TVR (%) Non-TVR (%)
28.2 15.4 9.0 7.7 2.6
15.2 3.3 2.6 0.8 1.1
13.0 2.6 1.5 1.1 0.5
14.8 1.1 0.8 0.4 1.1
0.031 <0.001 <0.001 0.007 0.246
0 11.5 2.6 1.3 7.7
0.5 10.8 4.6 1.2 5.0
0.4 9.6 3.3 1.3 4.9
0.4 12.1 3.8 1.1 6.8
0.946 0.985 0.584 0.989 0.773
Overall mortality (%)*
17.3
6.1
4.5
2.3
<0.001
0.003
CCU: coronary care unit; MACE: major adverse cardiac event; CABG: coronary artery bypass graft; PCI: percutaneous coronary intervention; TLR: target lesion revascularization; TVR: target vessel revascularization. * Significance is p < 0.05.
Table 6
Multivariate analysis for overall mortality.
Use of statins Old age High Killip class High left ventricular ejection fraction High body mass index Significance is p < 0.05*.
Odds ratio
95% CI
p-Value
0.346 1.094 1.599 0.946 1.040
0.133—0.896 1.036—1.155 1.002—2.559 0.899—0.995 0.905—1.195
0.029 0.001 0.049 0.031 0.583
90
W.Y. Kang et al. consistent with previous studies. Physicians had a tendency of more aggressive use of medications for younger patients that may influence a favorable effect on outcomes [23]. Recent studies demonstrated that younger age in obesity had a major impact on protection in AMI [24,25].
Study limitations
Figure 1 Kaplan—Meier survival curves for the four groups. Survival curve analysis reveals a significantly higher mortality rate in Group I than the other groups (Group I: underweight; Group II: normal weight; Group III: overweight; Group IV: obese).
catheterization, PCI, and coronary artery bypass graft. Because obese and overweight patients have more traditional risk factors for CAD and are expected to better tolerate aggressive management, medical teams give more guideline-recommended therapies on admission [12—15]. As proven in previous studies, there is a link between invasive management of acute coronary syndrome and use of proved, evidence-based treatments [16,17]. This is why we first thought that the most important reason why overweight and obese patients with STEMI undergoing PCI had good outcomes. In addition, overweight and obese patients had higher blood pressure, lower Killip class, and higher left ventricular ejection fraction compared with underweight patients, indicating they were relatively in a more hemodynamically stable state. Our multivariate analysis showed hemodynamic instability, including lower left ventricular ejection fraction and higher Killip class are independent predictors of overall mortality. Underweight patients, in whom there was hemodynamic instability, had a trend of less frequent use of -blockers and angiotensin-converting enzyme inhibitors, and more frequent use of vasopressors and diuretics. Also, we could find the hemodynamic state in laboratory findings. Serum N-terminal pro-brain natriuretic peptide level was significantly lower in overweight and obese patients. The level of N-terminal pro-brain natriuretic peptide, an indicator of the hemodynamic severity of MI and left ventricular dysfunction, is considered one of the most powerful predictors of death in AMI [18—20]. Therefore, overweight and obese patients who were in a hemodynamically stable state compared with underweight and normal weight patients may have favorable outcomes according to the present study. In the present study, elderly patients were more frequently in the underweight and normal weight groups. Previous reports revealed that elderly patients had worse outcomes after AMI regardless of treatment [21,22]. Our multivariate analysis demonstrated that age is an independent risk factor for overall mortality. This result was
Although BMI has been considered as a marker of obesity, it is a crude indicator of body adiposity, not a direct measurement of body composition. So, it may not reflect the actual degree of body fat content. We did not define obesity by other methods such as waist circumference, waist—hip ratio, or abdominal height. Also, we did not have the data related to the change in BMI or weight during the follow-up period. Therefore, we could not determine the impact of weight reduction on outcomes after primary PCI, especially in overweight or obese patients. KAMIR is an observational registry rather than a randomized trial. Therefore, our analysis has all the limitations of retrospective analysis using prospectively collected data. Also, the follow-up duration was relatively short. Therefore we could not exclude the possibility that obesity may influence the very long-term outcomes, because obesity may have a delayed effect on the progression of coronary artery disease.
Conclusion Obesity is not an independent predictor of overall mortality in patients with STEMI undergoing primary PCI. However, obese patients are associated with lower mortality. These results can be explained by better use of guideline-recommended medical treatment, hemodynamic stability, and younger age. To identify the impact of obesity on outcomes in patients undergoing primary PCI and to elucidate the long-term effect, a well-designed prospective study may be needed.
Acknowledgment This study was performed with the support of the Korean Circulation Society (KCS) as a memorandum of the 50th Anniversary of the KCS.
Appendix A. KAMIR Investigators: Myung Ho Jeong, MD; Young Jo Kim, MD; Chong Jin Kim, MD; Myeong Chan Cho, MD; Young Keun Ahn, MD; Jong Hyun Kim, MD; Shung Chull Chae, MD; Seung Ho Hur, MD; In Whan Seong, MD; Taek Jong Hong, MD; Dong Hoon Choi, MD; Jei Keon Chae, MD; Jae Young Rhew, MD; Doo Il Kim, MD; In Ho Chae, MD; Junghan Yoon, MD; Bon Kwon Koo, MD; Byung Ok Kim, MD; Myoung Yong Lee, MD; Kee Sik Kim, MD; Jin Yong Hwang, MD; Seok Kyu Oh, MD; Nae Hee Lee, MD; Kyoung Tae Jeong, MD; Seung Jea Tahk, MD; Jang Ho Bae, MD; Seung Woon Rha, MD; Keum Soo Park, MD; Kyoo Rok Han, MD; Tae Hoon Ahn, MD; Moo Hyun Kim, MD; Joo Young Yang, MD; Chong Yun Rhim, MD; Hyeon Cheol Gwon, MD; Seong Wook Park, MD; YoungYoup Koh, MD; Seung
Obesity paradox in primary PCI Jae Joo, MD; Soo Joong Kim, MD; Dong Kyu Jin, MD; Jin Man Cho, MD; Wook Sung Chung, MD; Yang Soo Jang, MD; Jeong Gwan Cho, MD; Ki Bae Seung, MD; Seung Jung Park, MD.
References [1] Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968—77. [2] Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai Jr P, Razak F, Sharma AM, Anand SS. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case—control study. Lancet 2005;366:1640—9. [3] Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath Jr CW. Bodymass index and mortality in a prospective cohort of US adults. N Engl J Med 1999;341:1097—105. [4] Gurm HS, Whitlow PL, Kip KE, for the BARI Investigators. The impact of body mass index on short- and long-term outcomes in patients undergoing coronary revascularization. Insights from the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 2002;39:834—40. [5] Gurm HS, Brennan DM, Booth J, Tcheng JE, Lincoff AM, Topol EJ. Impact of body mass index on outcome after percutaneous coronary intervention (the obesity paradox). Am J Cardiol 2002;90:42—5. [6] Gruberg L, Weissman NJ, Waksman R, Fuchs S, Deible R, Pinnow EE, Ahmed LM, Kent KM, Pichard AD, Suddath WO, Satler LF, Lindsay Jr J. The impact of obesity on the short-term and longterm outcomes after percutaneous coronary intervention: the obesity paradox? J Am Coll Cardiol 2002;39:578—84. [7] Minutello RM, Chou ET, Hong MK, Bergman G, Parikh M, Iacovone F, Wong SC. Impact of body mass index on in-hospital outcomes following percutaneous coronary intervention (report from the New York State Angioplasty Registry). Am J Cardiol 2004;93:1229—32. [8] Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, Mookadam F, Lopez-Jimenez F. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 2006;368:666—78. [9] Buettner HJ, Mueller C, Gick M, Ferenc M, Allgeier J, Comberg T, Werner KD, Schindler C, Neumann FJ. The impact of obesity on mortality in UA/non-ST-segment elevation myocardial infarction. Eur Heart J 2007;28:1694—701. [10] WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157—63. [11] Steinberg BA, Cannon CP, Hernandez AF, Pan W, Peterson ED, Fonarow GC. Medical therapies and invasive treatments for coronary artery disease by body mass: the ‘‘obesity paradox’’ in the Get With The Guidelines database. Am J Cardiol 2007;100:133—5. [12] Franklin K, Goldberg RJ, Spencer F, Klein W, Budaj A, Brieger D, Marre M, Steg PG, Gowda N, Gore JM. Implications of diabetes in patients with acute coronary syndromes. The Global Registry of Acute Coronary Events. Arch Intern Med 2004;164:145714—63. [13] Januzzi JL, Cannon CP, DiBattiste PM, Murphy S, Weintraub W, Braunwald E. Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (the TACTICS-TIMI 18 Trial). Am J Cardiol 2002;90: 1246—9.
91 [14] Bhatt DL, Roe MT, Peterson ED, Li Y, Chen AY, Harrington RA, Greenbaum AB, Berger PB, Cannon CP, Cohen DJ, Gibson CM, Saucedo JF, Kleiman NS, Hochman JS, Boden WE, et al. Utilization of early invasive management strategies for highrisk patients with non-ST segment elevation acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. JAMA 2004;292:2096—104. [15] Bach RG, Cannon CP, Weintraub WS, DiBattiste PM, Demopoulos LA, Anderson HV, DeLucca PT, Mahoney EM, Murphy SA, Braunwald E. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med 2004;141:186—95. [16] Steg PG, Iung B, Feldman LJ, Cokkinos D, Deckers J, Fox KA, Keil U, Maggioni AP. Impact of availability and use of coronary interventions on the prescription of aspirin and lipid lowering treatment after acute coronary syndromes. Heart 2002;88:20—4. [17] Steinberg BA, Steg PG, Bhatt DL, Fonarow GC, Zeymer U, Cannon CP. Comparisons of guideline-recommended therapies in patients with documented coronary artery disease having percutaneous coronary intervention versus coronary artery bypass grafting versus medical therapy only (from the REACH International Registry). Am J Cardiol 2007;99:1212—5. [18] de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, Hall C, Cannon CP, Braunwald E. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001;345:1014—21. [19] Jernberg T, Lindahl B, Siegbahn A, Andren B, Frostfeldt G, Lagerqvist B, Stridsberg M, Venge P, Wallentin L. N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease. J Am Coll Cardiol 2003;42:1909—16. [20] Lindahl B, Lindbäck J, Jernberg T, Johnston N, Stridsberg M, Venge P, Wallentin L. Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease (FRISC)-II substudy. J Am Coll Cardiol 2005;45:533—41. [21] Prasad A, Stone GW, Zimetbaum PJ, McLaughlin M, Mehran R, Garcia E, Tcheng JE, Cox DA, Grines CL, Gersh BJ, for the CADILLAC trial. Impact of ST-segment resolution after primary angioplasty on outcomes after myocardial infarction in elderly patients: an analysis from the CADILLAC trial. Am Heart J 2004;147:669—75. [22] Tespili M, Guaglium G, Valsecchi O, Musumeci G, Vassileva A, Saino A, Scuri PM, Gavazzi A. In-hospital clinical outcomes in elderly patients with acute myocardial infarction treated with primary angioplasty. Ital Heart J 2003;4:193—8. [23] Nigam A, Wright RS, Allison TG, Williams BA, Kopecky SL, Reeder GS, Murphy JG, Jaffe AS. Excess weight at time of presentation of myocardial infarction is associated with lower initial mortality risks but higher long-term risks including recurrent re-infarction and cardiac death. Int J Cardiol 2006;110:153—9. [24] Mehta L, Devlin W, McCullough PA, O’Neill WW, Skelding KA, Stone GW, Boura JA, Grines CL. Impact of body mass index on outcomes after percutaneous coronary intervention in patients with acute myocardial infarction. Am J Cardiol 2007;99:906—10. [25] Nikolsky E, Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Negoita M, Lansky AJ, Mehran R. Impact of body mass index on outcomes after primary angioplasty in acute myocardial infarction. Am Heart J 2006;151:168—75.
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/jjcc
Original article
Obesity paradox in Korean patients undergoing primary percutaneous coronary intervention in ST-segment elevation myocardial infarction Won Yu Kang (MD) a, Myung Ho Jeong (MD, PhD) a,∗,1, Young Keun Ahn (MD) a, Jong Hyun Kim (MD) b, Shung Chull Chae (MD) c, Young Jo Kim (MD) d, Seung Ho Hur (MD) e, In Whan Seong (MD) f, Taek Jong Hong (MD) g, Dong Hoon Choi (MD) h, Myeong Chan Cho (MD) i, Chong Jin Kim (MD) j, Ki Bae Seung (MD) k, Wook Sung Chung (MD) k, Yang Soo Jang (MD) h, Seung Woon Rha (MD) l, Jang Ho Bae (MD) m, Jeong Gwan Cho (MD) a, Seung Jung Park (MD) n , other Korea Acute Myocardial Infarction Registry Investigators a
Chonnam National University Hospital, South Korea Busan Hanseo Hospital, South Korea c Kyungpook National University Hospital, South Korea d Yeungnam University Hospital, South Korea e Keimyung University Hospital, South Korea f Chungnam National University Hospital, South Korea g Pusan National University Hospital, South Korea h Yonsei University Hospital, South Korea i Chungbuk National University Hospital, South Korea j Kyunghee University Hospital, South Korea k Catholic University Hospital, South Korea l Korea University Hospital, South Korea m Konyang University Hospital, South Korea n Asan Medical Center, South Korea b
Received 20 May 2009; received in revised form 26 August 2009; accepted 6 October 2009 Available online 25 November 2009
∗ Corresponding author at: The Heart Center of Chonnam National University Hospital, 671 Jaebongro, 8 Hakdong, Dong Ku, Gwangju 501-757, South Korea. Tel.: +82 62 220 6243; fax: +82 62 228 7174. E-mail address: [email protected] (M.H. Jeong). 1 Myung Ho Jeong, MD, PhD, FACC, FAHA, FESC, FSCAI, FAPSIC, Principal Investigator of Korea Acute Myocardial Infarction Registry (KAMIR), Professor, Director of Cardiovascular Research Institute of Chonnam National University.
0914-5087/$ — see front matter © 2009 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jjcc.2009.10.004
Obesity paradox in primary PCI
KEYWORDS Acute myocardial infarction; Coronary artery disease; Obesity; Prognosis
85 Summary The effect of body mass index (BMI) on outcomes after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is not well known. In patients registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between November 2005 and November 2007, 3824 STEMI patients who arrived at hospital within 12 h after onset of chest pain and underwent primary PCI were analyzed, and divided into four groups according to their BMI: underweight (BMI < 18.5 kg/m2 , n = 129); normal weight (18.5 ≤ BMI < 23.0 kg/m2 , n = 1253); overweight (23.0 ≤ BMI < 27.5 kg/m2 , n = 1959); and obese (BMI ≥ 27.5 kg/m2 , n = 483). In-hospital mortality, revascularization in 1 year, mortality in 1 year, and overall mortality were compared between groups. Overweight and obese group were significantly younger, had normal left ventricular ejection fraction, and were more likely to be men with a higher incidence of hypertension, diabetes, and hyperlipidemia. There were no significant differences in symptom-to-door time and door-to-balloon time between groups. Obese patients had significantly lower in-hospital and overall mortalities. Major adverse cardiac events showed a bimodal pattern. Obese STEMI patients treated with primary PCI were associated with lower mortality, which may be explained by better use of medical treatment, hemodynamic stability, and younger age. © 2009 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.
Introduction Generally, overweight and obesity are associated with an increased risk of developing cardiovascular disease [1,2]. Furthermore, obesity is associated with endothelial dysfunction, insulin resistance, and inflammation that may contribute to the increased risk for adverse cardiovascular clinical outcomes [3]. However, once coronary artery disease (CAD) developed in obese patients, poor clinical outcomes did not occur according to some reports [4—9]. Despite some data concerning the relationship between body mass index (BMI) and CAD existing, the clinical effect of BMI on outcomes after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is not well known. Furthermore, the available data are based on western populations, not on the oriental population. Thus, we intended to evaluate the clinical effect of BMI on outcomes after PCI in Korean patients with STEMI using the Korean Acute Myocardial Infarction Registry (KAMIR).
Materials and methods Study design and sample KAMIR is a Korean prospective, open, observational, multicenter on-line registry investigating the risk factors of mortality in acute myocardial infarction (AMI) and establishing the universal management for the prevention of AMI with support of the Korean Circulation Society since November 2005. A total of 41 hospitals, which were capable of primary PCI, participated. This study evaluated age, sex, body mass index, initial symptoms, vital signs, Killip class, symptoms, onset time, ambulance arrival time, first medical contact time, transfer time from first hospital to the primary PCI centers, door to needle time, doorto-balloon time, each risk factor, past regular medication, co-morbidities, electrocardiographic locations of MI, initial treatment strategy, drugs, angiographic findings, in-hospital complications, medical therapy in hospital, 1-, 6-, and 12-month follow-up major adverse cardiac events (MACEs) (cardiac death, re-infarction, re-PCI, coronary artery bypass
graft), and so on. We used KAMIR to define a cohort of patients with AMI. The study protocol was approved by the ethics committee at each participating institution. The diagnosis of AMI was based on the triad of chest pain, ECG changes, and raised serum cardiac enzyme level. During our study period of November 2005 to November 2007, 3824 STEMI patients who arrived at hospital within 12 h after onset of chest pain and underwent primary PCI were registered in KAMIR. For this analysis, patients were classified into four groups based on the suggestion by the World Health Organization for the Asian population [10]: underweight (Group I: BMI < 18.5 kg/m2 , n = 129); normal weight (Group II: 18.5 ≤ BMI < 23.0 kg/m2 , n = 1253); overweight (Group III: 23.0 ≤ BMI < 27.5 kg/m2 , n = 1959); and obese (Group IV: BMI ≥ 27.5 kg/m2 , n = 483). Patients’ characteristics consisted of medical history (diabetes mellitus, hypertension, smoking, hyperlipidemia, previous AMI, previous angina, previous coronary artery bypass graft, previous PCI, and family history); presentation characteristics (systolic blood pressure and heart rate, symptom-to-door time, door-to-balloon time, and left ventricular ejection fraction, which was obtained within 24 h after admission in most cases); the laboratory findings (glucose, creatinine, cardiac enzymes, serum cholesterol, high-sensitivity C-reactive protein, and N-terminal pro-brain natriuretic peptide); and the medical treatment; and angiographic and procedural findings. In-hospital mortality, MACEs, including in-hospital mortality, revascularization, mortality in 1, 6, 12 months, and overall mortality were compared among the four groups.
Statistical analysis Statistical analysis was performed using SPSS software, version 15.0 (SPSS-PC Inc., Chicago, IL, USA). All continuous variables are reported as mean value ± standard deviation (SD). We used Chi-square tests for linear-by-linear association, or one-way ANOVA for statistical comparisons of clinical characteristics among groups. Survival analysis after AMI was estimated using the Kaplan—Meier method with logrank tests to compare survival among groups. Univariate and multivariate analysis were done to identify the prognostic factors affecting results. We used Chi-square tests and
86
W.Y. Kang et al.
independent-samples t-tests to find the predictors for overall mortality and used logistic regression analysis to adjust confounding factors. A p-value < 0.05 was considered as significant.
Results
Laboratory findings
Baseline characteristics Baseline characteristics of the patient groups are listed in Table 1. Overweight and obese group were significantly younger (Group I: 69.7 ± 12.7 years, II: 64.7 ± 12.2 years, III: 59.4 ± 11.9 years, and IV: 56.5 ± 12.5 years, p < 0.001) and more likely to be male patients (Group I: 62.8%, II: 70.9%, III: 79.5%, and IV: 76.4%, p = 0.009) with higher incidences of hypertension (Group I: 33.3%, II: 39.9%, III: 47.2%, and IV: 54.2%, p < 0.001), diabetes (Group I: 17.3%, II: 22.5%, III: 23.5%, and IV: 28.7%, p = 0.005), smoking (Group I: 58.9%, II: 60.3%, III: 64.2%, and IV: 66.2%, p = 0.006), and hyperlipidemia (Group I: 9.8%, II: 7.0%, III: 10.4%, and IV: 12.7%, p = 0.001). There were no significant statistical differences in symptom-to-door time and doorto-balloon time (p > 0.05). Underweight patients had lower left ventricular ejection fraction (Group I: 48.3 ± 14.0%, II: 50.3 ± 11.7%, III: 51.3 ± 11.3%, and IV: 52.6 ± 11.6%, p < 0.001), lower systolic (Group I: 117.9 ± 33.6 mmHg, II: 122.6 ± 38.7 mmHg, III: 125.8 ± 30.1 mmHg, and IV:
Table 1
129.1 ± 30.8 mmHg, p < 0.001) and diastolic blood pressure (Group I: 71.7 ± 19.8 mmHg, II: 75.7 ± 31.9 mmHg, III: 78.7 ± 24.8 mmHg, and IV: 80.6 ± 18.3 mmHg, p < 0.001) and higher rate of Killip class 1 (Group I: 28.7%, II: 25.4%, III: 22.4%, and IV: 22.5%, p = 0.001) (Table 1).
Table 2 shows results of the laboratory examination. Overweight and obese patients had higher levels of total cholesterol (Group I: 163.9 ± 50.2 mg/dL, II: 175.4 ± 42.8 mg/dL, III: 185.3 ± 42.7 mg/dL, and IV: 191.7 ± 44.6 mg/dL, p < 0.001) and low-density lipoprotein cholesterol (Group I: 101.9 ± 42.5 mg/dL, II: 111.3 ± 36.6 mg/dL, III: 120.4 ± 44.7 mg/dL, and IV: 124.2 ± 53.1 mg/dL, p < 0.001). N-terminal pro-brain natriuretic peptide became significantly lower, as BMI increased (Group I: 3991.1 ± 7436.2 pg/mL, II: 1863.3 ± 4854.7 pg/mL, III: 1194.5 ± 3661.2 pg/mL, and IV: 845.9 ± 2901.5 pg/mL, p < 0.001). Also, there were no clinical differences in the levels of glucose, creatinine, and high-sensitivity C-reactive protein between groups.
Medical treatment parameters At admission, we used -blockers (Group I: 57.0%, II: 72.0%, III: 75.4%, and IV: 78.9%, p < 0.001) and statins (Group I:
Baseline clinical characteristics.
Age (years)* Female, n (%)* CPR prior on arrival, n (%) Typical pain, n (%)* SBP (mmHg)* DBP (mmHg)* SDT (min) DBT (min) LVEF (%)* Killip ≥ II, n (%)* Anterior ECG, n (%)* Inferior ECG, n (%)* AF, n (%) Risk factors, n (%) Hypertension* Diabetes mellitus* Smoking* Hyperlipidemia* Previous AMI, n (%) Previous angina, n (%) Previous CABG, n (%) Previous PCI, n (%) Family history, n (%)
Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
69.7 ± 12.7 48 (37.2) 5 (3.9) 107 (84.9) 117.9 ± 33.6 71.7 ± 19.8 195.2 ± 131.3 105.6 ± 78.7 48.3 ± 14.0 35 (28.7) 66 (54.1) 55 (45.1) 3 (2.4)
64.7 ± 12.2 365 (29.1) 42 (3.4) 1095 (88.9) 122.6 ± 38.7 75.7 ± 31.9 189.9 ± 136.4 100.4 ± 73.9 50.3 ± 11.7 307 (25.4) 641 (54.4) 550 (46.7) 55 (4.5)
59.4 ± 11.9 401 (20.5) 54 (2.8) 1786 (92.1) 125.8 ± 30.1 78.7 ± 24.8 179.3 ± 132.3 101.9 ± 78.9 51.3 ± 11.3 421 (22.4) 968 (52.0) 903 (48.5) 53 (2.8)
56.5 ± 12.5 114 (23.6) 11 (2.3) 447 (93.3) 129.1 ± 30.8 80.6 ± 18.3 183.4 ± 134.1 97.0 ± 65.1 52.6 ± 11.6 104 (22.5) 220 (47.4) 242 (52.2) 23 (4.9)
<0.001 <0.001 0.147 <0.001 <0.001 <0.001 0.115 0.578 <0.001 0.035 0.015 0.041 0.806
492 (39.9) 278 (22.5) 748 (60.3) 76 (7.0)
914 (47.2) 454 (23.5) 1250 (64.2) 179 (10.4)
257 (54.2) 135 (28.7) 317 (66.2) 52 (12.7)
<0.001 0.005 0.006 0.001
33 (2.7) 48 (3.9) 9 (0.7) 53 (4.3) 70 (6.4)
64 (3.3) 78 (4.0) 2 (0.1) 89 (4.6) 142 (8.0)
15 (3.1) 15 (3.1) 2 (0.4) 27 (5.6) 37 (8.6)
0.825 0.657 0.175 0.177 0.067
42 (33.3) 22 (17.3) 76 (58.9) 11 (9.8) 6 (4.7) 5 (3.9) 0 (0) 4 (3.1) 7 (6.1)
CPR: cardiopulmonary resuscitation; SBP: systolic blood pressure; DBP: diastolic blood pressure; SDT: symptom-to-door time; DBT: doorto-balloon time; LVEF: left ventricular ejection fraction; ECG: electrocardiogram; AF: atrial fibrillation; AMI: acute myocardial infarction; CABG: coronary arterial bypass graft; PCI: percutaneous coronary intervention. * Significance is p < 0.05.
Obesity paradox in primary PCI Table 2
87
Laboratory findings. Group I (N = 129)
Glucose (mg/dL) Creatinine (mg/dL) CK (U/L)* CK-MB (U/L)* TnI (ng/mL) TC (mg/dL)* LDL-C (mg/dL)* HDL-C (mg/dL)* hsCRP (mg/dL) NT-proBNP (pg/mL)*
164.7 1.26 2291.9 247.4 69.2 163.9 101.9 47.8 15.0 3991.1
± ± ± ± ± ± ± ± ± ±
72.4 1.48 3165.5 234.0 83.2 50.2 42.5 12.6 56.0 7436.2
Group II (N = 1253) 177.2 1.16 1871.9 191.5 70.1 175.4 111.3 46.4 15.7 1863.3
± ± ± ± ± ± ± ± ± ±
79.7 1.52 2224.2 206.5 194.9 42.8 36.6 24.6 80.4 4854.7
Group III (N = 1959) 177.0 1.13 2185.2 231.1 74.7 185.3 120.4 44.2 16.1 1194.5
± ± ± ± ± ± ± ± ± ±
78.6 0.86 2337.9 360.1 256.4 42.7 44.7 15.9 85.4 3661.2
Group IV (N = 483)
p-Value
± ± ± ± ± ± ± ± ± ±
0.380 0.566 0.003 0.003 0.513 <0.001 <0.001 0.048 0.860 <0.001
177.6 1.18 2146.4 225.6 55.5 191.7 124.2 45.3 12.1 845.9
72.7 1.50 2374.7 293.4 69.8 44.6 53.1 35.7 67.5 2901.5
CK: creatine kinase; TnI: troponin-I; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; hsCRP: high-sensitivity C-reactive protein; NT-proBNP: N-terminal pro-brain natriuretic peptide. * Significance is p < 0.05.
75.0%, II: 73.0%, III: 77.2%, and IV: 79.3%, p = 0.003) more frequently for the overweight and obese patients. Vasopressors (Group I: 34.4%, II: 20.9%, III: 17.4%, and IV: 14.0%, p < 0.001) and diuretics (Group I: 35.9%, II: 28.4%, III: 24.9%, and IV: 25.1%, p = 0.005) were prescribed more frequently in the underweight group. Except for those medications, there were no significant differences between groups in the usage of other medications (Table 3).
Coronary angiogram and PCI In underweight group, there was a higher incidence of left main complex lesion (Group I: 2.4%, II: 1.8%, III: 1.5%, and IV: 0.2%, p = 0.017) and left anterior descending coronary artery for the target vessel (Group I: 54.0%, II: 50.4%, III: 49.5%, and IV: 43.5%, p = 0.015). The higher BMI, the bigger stent (Group I: 3.11 ± 0.4 mm, II: 3.18 ± 0.4 mm, III: 3.24 ± 0.4 mm, and IV: 3.28 ± 0.5 mm, p < 0.001) was used and the lower events of complication (Group I: 26.8%, II: 18.0%, III: 16.2%, and IV: 15.3%, p = 0.007) occurred. Despite the use of drug-eluting stents in most cases, there was a trend to use bare metal stents in the underweight group (Table 4).
Table 3
Major adverse cardiac events and all-cause mortality Table 5 demonstrates in-hospital outcomes and MACEs at 1, 6, and 12 months for each of the patient groups. Obese patients had significantly lower mortalities (in-hospital mortality: 7.9% in Group I, 4.4% in II, 3.0% in III, and 1.7% in Group IV, p < 0.001; mortality at 1-year: 15.4% in Group I, 3.3% in II, 2.6% in III, and 1.1% in Group IV, p < 0.001; overall mortality: 17.3% in Group I, 6.1% in II, 4.5% in III, and 2.3% in Group IV, p < 0.001). MACEs showed a somewhat bimodal pattern (underweight: 28.2%, normal weight: 15.2%, overweight: 13.0%, and obese: 14.8%, p = 0.031).
Survival curves and multivariate analysis for overall mortality Kaplan—Meier survival curves for mortality showed significantly higher mortality in underweight patients (Fig. 1). In the multivariate regression analysis, we found that no use of statins, old age, higher Killip class, and lower left ventricu-
Prescribed medications.
Medications (%)
Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
Aspirin Clopidogrel Cilostazole Nitrate Unfractionated heparin Low molecular weight heparin -Blocker* Calcium channel blocker Angiotensin-converting enzyme inhibitor* Angiotensin receptor blocker Vasopressors* Diuretics* Statins*
99.2 99.2 39.1 69.5 60.9 37.5 57.0 9.4 71.1
99.3 98.3 37.4 65.1 58.2 33.4 72.0 7.3 70.7
99.2 98.9 35.1 69.3 60.7 31.9 75.4 9.1 72.1
98.7 98.1 33.9 68.6 62.3 36.4 78.9 10.3 76.2
0.399 0.954 0.082 0.109 0.139 0.939 <0.001 0.62 0.046
13.3 34.4 35.9 75.0
12.2 20.9 28.4 73.0
13.0 17.4 24.9 77.2
12.3 14.0 25.1 79.3
0.839 <0.001 0.005 0.003
*
Significance is p < 0.05.
88 Table 4
W.Y. Kang et al. Coronary angiogram and percutaneous intervention. Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
Lesion characteristics Left main complex (%)* Left main simple (%) Three-vessel disease (%) Two-vessel disease (%) One-vessel disease (%)
2.4 0 26.2 27.0 44.4
1.8 0.2 21.0 28.1 48.8
1.5 0.3 19.3 29.7 49.3
0.2 0.2 21.1 29.0 49.5
0.017 0.847 0.270 0.429 0.472
Target vessel Left main (%) LAD (%)* LCX (%) RCA (%)*
0.8 54.0 9.5 35.7
1.3 50.4 9.6 38.7
1.0 49.5 10.2 39.3
0.4 43.5 11.8 44.3
0.185 0.015 0.229 0.043
ACC/AHA lesion classification Type A (%) 6.8 Type B1 (%) 11.9 Type B2 (%) 24.6 Type C (%) 56.8
3.1 16.5 27.7 52.7
3.7 16.3 26.3 53.7
3.6 19.7 25.6 51.0
0.812 0.096 0.524 0.557
Pre-PCI TIMI TIMI 0 (%) TIMI I (%) TIMI II (%) TIMI III (%)
61.5 7.4 12.3 18.9
60.7 10.7 14.7 13.9
63.7 9.8 13.2 13.3
65.0 8.9 12.2 13.9
0.067 0.535 0.245 0.380
Post-PCI TIMI TIMI 0 (%) TIMI I (%) TIMI II (%) TIMI III (%)
0 1.6 3.3 95.1
0.7 0.7 4.6 94.0
0.9 1.0 4.1 93.9
0.9 0.2 6.6 92.3
0.318 0.465 0.176 0.207
Drug-eluting stent (%) Stent size (mm) Stent diameter (mm)* Stent number Success rate (%) Complication rate (%)*
94.8 25.4 ± 5.9 3.11 ± 0.4 1.44 ± 0.8 98.4 26.8
92.4 24.9 ± 6.2 3.18 ± 0.4 1.39 ± 0.7 97.4 18.0
90.1 25.1 ± 6.4 3.24 ± 0.4 1.40 ± 0.7 97.7 16.2
91.3 25.0 ± 5.8 3.28 ± 0.5 1.38 ± 0.7 98.5 15.3
0.071 0.811 <0.001 0.824 0.336 0.007
LAD: left anterior descending coronary artery; LCX: left circumflex coronary artery; RCA: right coronary artery; ACC/AHA: American College of Cardiology/American Heart Association; PCI: percutaneous coronary intervention; TIMI: thrombolysis in myocardial infarction. * Significance is p < 0.05.
lar ejection fraction were independent predictors of overall mortality (Table 6).
Discussion Our data revealed that overweight and obese patients had worse baseline characteristics, including hypertension, diabetes, smoking, and hyperlipidemia. Conversely, underweight patients had poor profiles associated with hemodynamic instability, including older age, lower blood pressure, higher Killip class, and lower left ventricular ejection fraction. Our clinical follow-up results showed that obese and overweight patients had better short- and longterm prognosis than underweight patients. Not only are overweight and obesity associated with increased risk of developing cardiovascular disease [1,2], but also obesity is associated with endothelial dysfunction, insulin resistance, and inflammation that may contribute
to an increased risk for adverse clinical outcomes [3]. So, we initially hypothesized that the obese and overweight patients who received primary PCI in STEMI would have poor prognosis compared with counterparts, despite some data supporting the obesity paradox in coronary artery disease [4—9]. What made these results? Our analysis showed that increased body mass index is associated with greater use of guideline-recommended therapies on admission. Blockers, angiotensin-converting enzyme inhibitors, and statins were prescribed more frequently for overweight and obese patients. As shown in Table 6, statins provide an independent protective effect in overall mortality. This trend was consistent with a previous report advocated by Steinberg et al. [11]. They concluded that overweight and obese patients with acute myocardial infarction or unstable angina were more likely to receive aspirin, -blockers, inhibitors of the rennin—angiotensin system, and lipid-lowering agents, and that they also were more likely to undergo cardiac
Obesity paradox in primary PCI Table 5
89
In-hospital, mid-term, and long-term outcomes.
*
CCU stay days (%) In-hospital mortality (%)*
Group I (N = 129)
Group II (N = 1253)
Group III (N = 1959)
Group IV (N = 483)
p-Value
4.6 ± 5.6 7.9
3.4 ± 4.4 4.4
3.3 ± 3.9 3.0
3.1 ± 5.4 1.7
0.014 <0.001
1-Month follow-up
Group I (N = 107)
Group II (N = 1058)
Group III (N = 1657)
Group IV (N = 415)
p-Value
MACE (%) All-cause mortality (%) Cardiac death (%)* Non-cardiac death (%) Myocardial infarction Revascularization (%) CABG (%) Re-PCI (%) TLR (%) TVR (%) Non-TVR (%)*
4.0 2.0 2.0 0 1.0
2.3 1.2 1.0 0.2 0.2
1.9 1.0 0.5 0.5 0.1
3.5 0.2 0.2 0 0.2
0.844 0.085 0.022 0.781 0.418
0 1.0 1.0 0 0
0.1 0.9 0.2 0 0.6
0 0.8 0.4 0 0.4
0.2 2.7 0.2 0 2.5
0.604 0.032 0.870
6-Month follow-up
Group I (N = 86)
Group II (N = 865)
Group III (N = 1344)
Group IV (N = 341)
p-Value
MACE (%) All-cause mortality (%)* Cardiac death (%)* Non-cardiac death (%) Myocardial infarction Revascularization (%) CABG (%) Re-PCI (%) TLR (%) TVR (%) Non-TVR (%)
20.7 10.3 5.7 4.6 1.1
8.2 2.0 1.6 0.4 0.6
8.4 1.6 1.0 0.7 0.3
10.3 0.9 0.6 0.3 0.6
0.401 <0.001 0.002 0.062 0.460
0 9.2 2.3 1.1 5.7
0.2 5.5 2.1 0.5 2.8
0.1 6.4 2.4 0.8 3.1
0.3 8.5 2.4 0.9 5.0
0.844 0.237 0.745 0.523 0.354
12-Month follow-up
Group I (N = 69)
Group II (N = 648)
Group III (N = 1041)
Group IV (N = 255)
p-Value
MACE (%)* All-cause mortality (%)* Cardiac death (%)* Non-cardiac death (%)* Myocardial infarction Revascularization (%) CABG (%) Re-PCI (%) TLR (%) TVR (%) Non-TVR (%)
28.2 15.4 9.0 7.7 2.6
15.2 3.3 2.6 0.8 1.1
13.0 2.6 1.5 1.1 0.5
14.8 1.1 0.8 0.4 1.1
0.031 <0.001 <0.001 0.007 0.246
0 11.5 2.6 1.3 7.7
0.5 10.8 4.6 1.2 5.0
0.4 9.6 3.3 1.3 4.9
0.4 12.1 3.8 1.1 6.8
0.946 0.985 0.584 0.989 0.773
Overall mortality (%)*
17.3
6.1
4.5
2.3
<0.001
0.003
CCU: coronary care unit; MACE: major adverse cardiac event; CABG: coronary artery bypass graft; PCI: percutaneous coronary intervention; TLR: target lesion revascularization; TVR: target vessel revascularization. * Significance is p < 0.05.
Table 6
Multivariate analysis for overall mortality.
Use of statins Old age High Killip class High left ventricular ejection fraction High body mass index Significance is p < 0.05*.
Odds ratio
95% CI
p-Value
0.346 1.094 1.599 0.946 1.040
0.133—0.896 1.036—1.155 1.002—2.559 0.899—0.995 0.905—1.195
0.029 0.001 0.049 0.031 0.583
90
W.Y. Kang et al. consistent with previous studies. Physicians had a tendency of more aggressive use of medications for younger patients that may influence a favorable effect on outcomes [23]. Recent studies demonstrated that younger age in obesity had a major impact on protection in AMI [24,25].
Study limitations
Figure 1 Kaplan—Meier survival curves for the four groups. Survival curve analysis reveals a significantly higher mortality rate in Group I than the other groups (Group I: underweight; Group II: normal weight; Group III: overweight; Group IV: obese).
catheterization, PCI, and coronary artery bypass graft. Because obese and overweight patients have more traditional risk factors for CAD and are expected to better tolerate aggressive management, medical teams give more guideline-recommended therapies on admission [12—15]. As proven in previous studies, there is a link between invasive management of acute coronary syndrome and use of proved, evidence-based treatments [16,17]. This is why we first thought that the most important reason why overweight and obese patients with STEMI undergoing PCI had good outcomes. In addition, overweight and obese patients had higher blood pressure, lower Killip class, and higher left ventricular ejection fraction compared with underweight patients, indicating they were relatively in a more hemodynamically stable state. Our multivariate analysis showed hemodynamic instability, including lower left ventricular ejection fraction and higher Killip class are independent predictors of overall mortality. Underweight patients, in whom there was hemodynamic instability, had a trend of less frequent use of -blockers and angiotensin-converting enzyme inhibitors, and more frequent use of vasopressors and diuretics. Also, we could find the hemodynamic state in laboratory findings. Serum N-terminal pro-brain natriuretic peptide level was significantly lower in overweight and obese patients. The level of N-terminal pro-brain natriuretic peptide, an indicator of the hemodynamic severity of MI and left ventricular dysfunction, is considered one of the most powerful predictors of death in AMI [18—20]. Therefore, overweight and obese patients who were in a hemodynamically stable state compared with underweight and normal weight patients may have favorable outcomes according to the present study. In the present study, elderly patients were more frequently in the underweight and normal weight groups. Previous reports revealed that elderly patients had worse outcomes after AMI regardless of treatment [21,22]. Our multivariate analysis demonstrated that age is an independent risk factor for overall mortality. This result was
Although BMI has been considered as a marker of obesity, it is a crude indicator of body adiposity, not a direct measurement of body composition. So, it may not reflect the actual degree of body fat content. We did not define obesity by other methods such as waist circumference, waist—hip ratio, or abdominal height. Also, we did not have the data related to the change in BMI or weight during the follow-up period. Therefore, we could not determine the impact of weight reduction on outcomes after primary PCI, especially in overweight or obese patients. KAMIR is an observational registry rather than a randomized trial. Therefore, our analysis has all the limitations of retrospective analysis using prospectively collected data. Also, the follow-up duration was relatively short. Therefore we could not exclude the possibility that obesity may influence the very long-term outcomes, because obesity may have a delayed effect on the progression of coronary artery disease.
Conclusion Obesity is not an independent predictor of overall mortality in patients with STEMI undergoing primary PCI. However, obese patients are associated with lower mortality. These results can be explained by better use of guideline-recommended medical treatment, hemodynamic stability, and younger age. To identify the impact of obesity on outcomes in patients undergoing primary PCI and to elucidate the long-term effect, a well-designed prospective study may be needed.
Acknowledgment This study was performed with the support of the Korean Circulation Society (KCS) as a memorandum of the 50th Anniversary of the KCS.
Appendix A. KAMIR Investigators: Myung Ho Jeong, MD; Young Jo Kim, MD; Chong Jin Kim, MD; Myeong Chan Cho, MD; Young Keun Ahn, MD; Jong Hyun Kim, MD; Shung Chull Chae, MD; Seung Ho Hur, MD; In Whan Seong, MD; Taek Jong Hong, MD; Dong Hoon Choi, MD; Jei Keon Chae, MD; Jae Young Rhew, MD; Doo Il Kim, MD; In Ho Chae, MD; Junghan Yoon, MD; Bon Kwon Koo, MD; Byung Ok Kim, MD; Myoung Yong Lee, MD; Kee Sik Kim, MD; Jin Yong Hwang, MD; Seok Kyu Oh, MD; Nae Hee Lee, MD; Kyoung Tae Jeong, MD; Seung Jea Tahk, MD; Jang Ho Bae, MD; Seung Woon Rha, MD; Keum Soo Park, MD; Kyoo Rok Han, MD; Tae Hoon Ahn, MD; Moo Hyun Kim, MD; Joo Young Yang, MD; Chong Yun Rhim, MD; Hyeon Cheol Gwon, MD; Seong Wook Park, MD; YoungYoup Koh, MD; Seung
Obesity paradox in primary PCI Jae Joo, MD; Soo Joong Kim, MD; Dong Kyu Jin, MD; Jin Man Cho, MD; Wook Sung Chung, MD; Yang Soo Jang, MD; Jeong Gwan Cho, MD; Ki Bae Seung, MD; Seung Jung Park, MD.
References [1] Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968—77. [2] Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai Jr P, Razak F, Sharma AM, Anand SS. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case—control study. Lancet 2005;366:1640—9. [3] Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath Jr CW. Bodymass index and mortality in a prospective cohort of US adults. N Engl J Med 1999;341:1097—105. [4] Gurm HS, Whitlow PL, Kip KE, for the BARI Investigators. The impact of body mass index on short- and long-term outcomes in patients undergoing coronary revascularization. Insights from the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 2002;39:834—40. [5] Gurm HS, Brennan DM, Booth J, Tcheng JE, Lincoff AM, Topol EJ. Impact of body mass index on outcome after percutaneous coronary intervention (the obesity paradox). Am J Cardiol 2002;90:42—5. [6] Gruberg L, Weissman NJ, Waksman R, Fuchs S, Deible R, Pinnow EE, Ahmed LM, Kent KM, Pichard AD, Suddath WO, Satler LF, Lindsay Jr J. The impact of obesity on the short-term and longterm outcomes after percutaneous coronary intervention: the obesity paradox? J Am Coll Cardiol 2002;39:578—84. [7] Minutello RM, Chou ET, Hong MK, Bergman G, Parikh M, Iacovone F, Wong SC. Impact of body mass index on in-hospital outcomes following percutaneous coronary intervention (report from the New York State Angioplasty Registry). Am J Cardiol 2004;93:1229—32. [8] Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, Mookadam F, Lopez-Jimenez F. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 2006;368:666—78. [9] Buettner HJ, Mueller C, Gick M, Ferenc M, Allgeier J, Comberg T, Werner KD, Schindler C, Neumann FJ. The impact of obesity on mortality in UA/non-ST-segment elevation myocardial infarction. Eur Heart J 2007;28:1694—701. [10] WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157—63. [11] Steinberg BA, Cannon CP, Hernandez AF, Pan W, Peterson ED, Fonarow GC. Medical therapies and invasive treatments for coronary artery disease by body mass: the ‘‘obesity paradox’’ in the Get With The Guidelines database. Am J Cardiol 2007;100:133—5. [12] Franklin K, Goldberg RJ, Spencer F, Klein W, Budaj A, Brieger D, Marre M, Steg PG, Gowda N, Gore JM. Implications of diabetes in patients with acute coronary syndromes. The Global Registry of Acute Coronary Events. Arch Intern Med 2004;164:145714—63. [13] Januzzi JL, Cannon CP, DiBattiste PM, Murphy S, Weintraub W, Braunwald E. Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (the TACTICS-TIMI 18 Trial). Am J Cardiol 2002;90: 1246—9.
91 [14] Bhatt DL, Roe MT, Peterson ED, Li Y, Chen AY, Harrington RA, Greenbaum AB, Berger PB, Cannon CP, Cohen DJ, Gibson CM, Saucedo JF, Kleiman NS, Hochman JS, Boden WE, et al. Utilization of early invasive management strategies for highrisk patients with non-ST segment elevation acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. JAMA 2004;292:2096—104. [15] Bach RG, Cannon CP, Weintraub WS, DiBattiste PM, Demopoulos LA, Anderson HV, DeLucca PT, Mahoney EM, Murphy SA, Braunwald E. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med 2004;141:186—95. [16] Steg PG, Iung B, Feldman LJ, Cokkinos D, Deckers J, Fox KA, Keil U, Maggioni AP. Impact of availability and use of coronary interventions on the prescription of aspirin and lipid lowering treatment after acute coronary syndromes. Heart 2002;88:20—4. [17] Steinberg BA, Steg PG, Bhatt DL, Fonarow GC, Zeymer U, Cannon CP. Comparisons of guideline-recommended therapies in patients with documented coronary artery disease having percutaneous coronary intervention versus coronary artery bypass grafting versus medical therapy only (from the REACH International Registry). Am J Cardiol 2007;99:1212—5. [18] de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, Hall C, Cannon CP, Braunwald E. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001;345:1014—21. [19] Jernberg T, Lindahl B, Siegbahn A, Andren B, Frostfeldt G, Lagerqvist B, Stridsberg M, Venge P, Wallentin L. N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease. J Am Coll Cardiol 2003;42:1909—16. [20] Lindahl B, Lindbäck J, Jernberg T, Johnston N, Stridsberg M, Venge P, Wallentin L. Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease (FRISC)-II substudy. J Am Coll Cardiol 2005;45:533—41. [21] Prasad A, Stone GW, Zimetbaum PJ, McLaughlin M, Mehran R, Garcia E, Tcheng JE, Cox DA, Grines CL, Gersh BJ, for the CADILLAC trial. Impact of ST-segment resolution after primary angioplasty on outcomes after myocardial infarction in elderly patients: an analysis from the CADILLAC trial. Am Heart J 2004;147:669—75. [22] Tespili M, Guaglium G, Valsecchi O, Musumeci G, Vassileva A, Saino A, Scuri PM, Gavazzi A. In-hospital clinical outcomes in elderly patients with acute myocardial infarction treated with primary angioplasty. Ital Heart J 2003;4:193—8. [23] Nigam A, Wright RS, Allison TG, Williams BA, Kopecky SL, Reeder GS, Murphy JG, Jaffe AS. Excess weight at time of presentation of myocardial infarction is associated with lower initial mortality risks but higher long-term risks including recurrent re-infarction and cardiac death. Int J Cardiol 2006;110:153—9. [24] Mehta L, Devlin W, McCullough PA, O’Neill WW, Skelding KA, Stone GW, Boura JA, Grines CL. Impact of body mass index on outcomes after percutaneous coronary intervention in patients with acute myocardial infarction. Am J Cardiol 2007;99:906—10. [25] Nikolsky E, Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Negoita M, Lansky AJ, Mehran R. Impact of body mass index on outcomes after primary angioplasty in acute myocardial infarction. Am Heart J 2006;151:168—75.