Prognostic Value of Uric Acid in Patients With ST-Elevated Myocardial Infarction Undergoing Primary Coronary Intervention

Mehmet G. Kaya, MDa,*, Huseyin Uyarel, MDb, Mahmut Akpek, MDa, Nihat Kalay, MDa, Mehmet Ergelen, MDb, Erkan Ayhan, MDc, Turgay Isik, MDc, Gokhan Cicek, MDc, Deniz Elcik, MDa, mer Sahin, MDa, Said M. Cosgun, MDa, Abdurrahman Oguzhan, MDa, Mehmet Eren, MDc, and C. Michael Gibson, MS, MDd
Elevated uric acid (UA) levels have been associated with cardiovascular disease in epidemiologic studies. The relation between UA levels and long-term outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention is not known. Data from 2,249 consecutive patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were evaluated. Patients were divided into 2 groups with high or low UA using upper limits of normal of 6 mg/dl for women and 7 mg/dl for men. There were 1,643 patients in the low-UA group (mean age 55.9 11.6 years, 85% men) and 606 patients in the high-UA group (mean age 60.5 12.6 years, 76% men). Serum UA levels were 8.0 1.5 mg/dl in the high-UA group and 5.2 1.0 mg/dl in the low-UA group (p <0.001). The in-hospital mortality rate was signicantly higher in patients with high UA levels (9% vs 2%, p <0.001), as was the rate of adverse outcomes in patients with high UA. The mean follow-up time was 24.3 months. Cardiovascular mortality, reinfarction, target vessel revascularization, heart failure, and major adverse cardiac events were all signicantly higher in the high-UA group. In a multivariate analyses, high plasma UA levels were an independent predictor of major adverse cardiac events in the hospital (odds ratio 2.03, 95% condence interval 1.25 to 3.75, p 0.006) and during long-term follow-up (odds ratio 1.64, 95% condence interval 1.05 to 2.56, p 0.03). In conclusion, high UA levels on admission are independently associated with in-hospital and long-term adverse outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention. 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:486 491) Uric acid (UA) is the nal oxidation product of purine metabolism in the circulation. UA is an independent risk factor for the development of coronary heart disease.15 Serum UA levels have been correlated with all major forms of death from cardiovascular disease, including acute, subacute, and chronic forms of coronary artery disease, heart failure, and stroke.6 Although there is an association between UA and cardiovascular disease, the underlying pathophysiology remains poorly understood. Although the association of elevated UA levels with early adverse outcomes in acute myocardial infarction has been documented, the relation between UA levels and longterm outcomes in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has not been evaluated. It was hypothesized that elevated UA levels would be associated with in-hospital and long-term adverse outcomes after primary PCI for STEMI. Methods A total of 2,568 consecutive STEMI patients who underwent primary PCI from October 2003 to January 2009 were included in this study. Three hundred nineteen patients were excluded because of a lack of compliance with the dened inclusion criteria: PCI was not performed (n 91), UA values were missing or unavailable (n 142), or no follow-up was documented after primary PCI (n 86). After these exclusions were accounted for, the nal study population consisted of 2,249 patients. Patients were divided into normal and elevated groups on the basis of upper limits of normal for UA of 6 mg/dl in women and 7 mg/dl in men. Cardiovascular risk factors were ascertained on the basis of review of medical records. Angina-to-reperfusion time and door-to-balloon time were also documented during each patients hospital stay. Electrocardiography was performed and complete blood counts and other serum values were determined on admission before catheterization procedures. Glomerular ltration rates were estimated using the simplied Modication of Diet in Renal Disease (MDRD) equation.7 Transthoracic echocardiography was performed using
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Department of Cardiology, Erciyes University School of Medicine; Department of Cardiology, Balkesir University School of Medicine, Kayseri; cSiyami Ersek Cardiovascular and Thoracic Surgery Center, Istanbul, Turkey; and dDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Manuscript received August 3, 2011; revised manuscript received and accepted September 29, 2011. *Corresponding author: Tel: 90-505-3784696; fax: 90-352-4377634. E-mail address: drmgkaya@yahoo.com (M.G. Kaya).
b

0002-9149/12/$ see front matter 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2011.09.042

Coronary Artery Disease/Uric Acid, Long-Term Follow-up in STEMI Table 1 Baseline characteristics of study patients Variable Age (years) Men Anterior myocardial infarction Hypertension Hypercholesterolemia Diabetes mellitus Current smoker Previous coronary bypass Previous PCI Previous myocardial infarction Admission cardiogenic shock Killip class 1 Reperfusion time (hours) Door-to-balloon time (minutes) Low UA Level (n 1,643) 55.9 11.6 1,393 (85%) 754 (46%) 585 (36%) 539 (33%) 370 (23%) 960 (58%) 43 (3%) 134 (8%) 163 (10%) 74 (5%) 64 (4%) 3.2 2.3 34 23 High UA Level (n 606) 60.5 12.6 460 (76%) 327 (54%) 308 (51%) 200 (33%) 172 (28%) 306 (51%) 15 (3%) 54 (9%) 72 (12%) 36 (6%) 63 (10%) 3.4 2.5 30 21 p Value 0.001 0.001 0.001 0.001 0.587 0.002 0.001 0.065 0.655 0.196 0.009 0.001 0.07 0.56 Table 3 Angiographic and procedural characteristics of patients Variable Culprit lesion Left main Left anterior descending Circumex Right Bypass graft Intermediate Number of narrowed coronary vessels 1 2 3 Preprocedural TIMI grade 0/1 2 3 Postprocedural TIMI grade 0/1 2 3 Stenting Stent use Length (mm) Diameter (mm) Type Bare metal Paclitaxel eluting Sirolimus eluting Proximal location of the lesion Left ventricular ejection fraction (%) Low UA Level (n 1,643) 2 (0.1%) 759 (46%) 226 (14%) 644 (39%) 10 (1%) 2 (0.1%) High UA Level (n 606) 1 (0.2%) 328 (54%) 60 (10%) 215 (36%) 2 (0.3%) 0

487

p Value 0.016

0.135 693 (42%) 515 (31%) 433 (26%) 1,429 (87%) 136 (8%) 78 (5%) 140 (9%) 84 (5%) 1,419 (86%) 1,331 (81%) 18.9 6.5 3.1 0.4 1,304 (98%) 13 (1%) 14 (1%) 761 (46%) 47.8 10.3 226 (37%) 209 (35%) 171 (28%) 0.045 541 (89%) 35 (6%) 30 (5%) 0.004 8 (1%) 39 (6%) 487 (80%) 502 (83%) 20.0 7.0 3.1 0.4 487 (97%) 7 (1%) 8 (2%) 294 (49%) 45.4 11.2 0.154 0.006 0.570 0.358

Data are expressed as mean SD for normally distributed data and as number (percentage) for categorical variables. Table 2 Laboratory ndings of patients Variable Creatinine concentration at admission (mg/dl) Admission glomerular ltration rate (ml/min/ 1.73 m2) Hemoglobin (g/dl) Peak creatine kinase-MB (U/L) Total cholesterol (mg/dl) Low-density lipoprotein (mg/dl) High-density lipoprotein (mg/dl) Triglycerides (mg/dl) Admission blood glucose concentration (mg/dl) UA (mg/dl) Mean platelet volume () Low UA Level (n 1,643) 0.94 91.9 0.35 22.6 High UA Level (n 606) 1.2 74.8 0.54 23.3 p Value 0.001 0.001

0.006 0.001

13.7 210.2 186.1 117.9 40.4 140.9 156 5.2 8.4

1.7 170.2 43.8 36.8 11.1 34.2 74.8 1.0 1.0

13.5 249.9 191.2 119.2 40.6 152.3 158 8.0 8.6

1.9 207.6 41 34.5 12.4 41.6 74.7 1.5 1.0

0.03 0.001 0.026 0.499 0.737 0.035 0.574 0.001 0.001

Data are expressed as mean SD for normally distributed data and as number (percentage) for categorical variables.

Data are expressed as mean

SD for normally distributed data.

a System V machine (GE Vingmed Ultrasound AS, Horten, Norway) with a 2.5-MHz phased-array transducer. Recordings were taken with patients positioned in the left lateral decubitus position. The left ventricular ejection fraction was measured using modied Simpsons rule.8 All patients received chewable aspirin 300 mg (unless contraindicated) and a 300-mg loading dose of clopidogrel before they underwent coronary angiography. The infarctrelated artery was then graded according to the Thrombolysis In Myocardial Infarction (TIMI) classication.9 Heparin (10,000 U) was administered once the coronary anatomy had been ascertained. Primary PCI was performed only in

the infarct artery. Successful primary PCI was dened as a residual stenosis 50% and TIMI grade 3 ow after the procedure. Follow-up data were obtained from hospital records or by interviewing (in person or by telephone) patients, family members, or primary care physicians. Cardiogenic shock was dened as marked and persistent ( 30 minutes) hypotension with systolic arterial pressure 80 mm Hg and signs of hypoperfusion due to left ventricular dysfunction, right ventricular infarction, or mechanical complications. Patients were also evaluated according to Killip clinical examination classication.10 Advanced heart failure was dened as New York Heart Association functional classication III. Multivessel disease was dened as stenosis 50% in 1 of the major coronary arteries. Acute stent thrombosis was dened as an abrupt onset of cardiac symptoms (i.e., acute coronary syndromes), elevations in biomarker levels, or electrocardiographic evidence of myocardial injury after stent deployment in the rst 24 hours and angiographic evidence of a ow-limiting thrombus near a previously placed stent. Cardiovascular mortality was dened as unexplained sudden death, death due to acute myocardial infarction, heart failure, and/or arrhythmia. Reinfarction was dened as serum

488 Table 4 In-hospital cardiac events and complications Variable In-hospital mortality Reinfarction Target vessel revascularization Acute stent thrombosis MACEs Stroke Serious ventricular arrhythmia Cardiopulmonary resuscitation Advanced heart failure Intra-aortic balloon pump Renal failure requiring dialysis New atrial brillation Complete atrioventricular block requiring transient pacemaker Major bleeding requiring blood transfusion Time of hospital stay (days)

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Low UA Level High UA Level p (n 1,643) (n 606) Value 39 (2%) 35 (2%) 71 (4%) 15 (1%) 121 (7%) 8 (1%) 61 (4%) 42 (3%) 93 (6%) 41 (3%) 1 (0.1%) 21 (1%) 52 (3%) 52 (9%) 25 (4%) 37 (6%) 9 (2%) 99 (16%) 7 (1%) 47 (8%) 38 (6%) 76 (13%) 39 (6%) 12 (2%) 11 (2%) 23 (4%) 0.001 0.009 0.004 0.241 0.001 0.004 0.001 0.001 0.001 0.001 0.001 0.017 0.02 Figure 1. Kaplan-Meier curve for long-term survival according to UA groups in the entire cohort of patients. Table 5 Long-term cardiac events Variable Cardiovascular mortality Reinfarction Target vessel revascularization Advanced heart failure MACEs Low UA Level (n 1,643) 73 (4%) 151 (9%) 286 (17%) 91 (6%) 424 (26%) High UA Level (n 606) 63 (10%) 81 (13%) 185 (31%) 72 (12%) 251 (41%) p Value 0.001 0.004 0.001 0.001 0.001

63 (4%) 6.9 4.4

33 (6%) 8.0 5.3

0.021 0.001

Data are expressed as mean SD for normally distributed data and as number (percentage) for categorical variables.

creatine kinase-MB enzyme levels twice the upper limit of normal and new ST-segment elevations. Major adverse cardiac events (MACEs) were dened as cardiovascular mortality, reinfarction, repeat target vessel revascularization (percutaneous or surgical), or acute stent thrombosis. Quantitative variables are expressed as mean SD and qualitative variables as percentages. Comparison of the parametric values between the 2 groups (high and low blood levels of UA) was performed using 2-tailed Students t tests. Categorical variables were compared using likelihood ratio chi-square tests. Backward elimination multivariate logistic regression analysis including variables with p values 0.10 was performed to identify independent risk factors of MACEs during in-hospital and long-term follow-up. The cumulative survival curve for long-term cardiovascular mortality was constructed using the Kaplan-Meier method, with differences assessed with log-rank tests. A p value 0.05 was considered statistically signicant. All statistical studies were carried out using SPSS version 15.0 (SPSS, Inc., Chicago, Illinois). Results There were 1,643 patients in the normal-UA group (mean age 55.9 11.6 years, and 85% men) and 606 patients (mean age 60.5 12.6 years, 76% men) in the elevated-UA group. Baseline characteristics are listed in Table 1. Patients with elevated UA tended to be older and more commonly had histories of hypertension and diabetes and had elevated Killip classes. Smoking was more prevalent in patients with normal levels of UA (Table 1). Serum UA levels were 5.2 1.0 mg/dl in the normal-UA group and 8.0 1.5 in the high-UA group (p 0.001). Baseline serum creatinine was higher and glomerular ltration rates were lower in the elevated-UA group (p 0.001 for each; Table 2).

The mean left ventricular ejection fraction on admission was lower in the high-UA group (p 0.001). There was no statistically signicant difference in the number of diseased vessels across groups. The culprit lesion was more often observed in the left anterior coronary descending artery in patients with elevated UA (Table 3). TIMI grade 3 ow was less frequently restored after primary PCI in patients with elevated UA. The percentage of stents deployed and stent diameters were similar between the groups (p 0.154 and p 0.570, respectively), but in the high-UA group, implanted stent length was signicantly longer than in the low-UA group (p 0.006). With respect to stent type, there was no statistically signicant difference between groups (p 0.358). The in-hospital mortality rate was signicantly higher in patients with elevated UA than in those with low UA (9% vs 2%, p 0.001), MACEs were more frequent (16% vs 7%, p 0.001), and the length of hospital stay was signicantly longer (8.0 vs 6.9 days, p 0.001) (Table 4). The mean follow-up time was 24.3 months. The KaplanMeier survival plot for cardiovascular death is presented in Figure 1. Cardiovascular mortality (p 0.001), reinfarction (p 0.004), target vessel revascularization (p 0.001), severe heart failure (p 0.001), and MACEs (p 0.001) were all higher in the elevated-UA group (Table 5). Certain variables that are associated with in-hospital and long-term MACEs differed between the UA groups. The

Coronary Artery Disease/Uric Acid, Long-Term Follow-up in STEMI Table 6 Multivariate predictors of in-hospital major adverse cardiac events Variable Age Diabetes mellitus Killip class 1 TIMI ow grade 3 High UA Adjusted Odds Ratio* 1.15 3.44 7.19 3.12 2.03 95% Condence Interval 1.011.35 1.525.65 1.9526.5 1.874.70 1.253.75 p Value 0.001 0.001 0.001 0.003 0.006

489

* Adjusted for male gender, hypertension, smoking, previous bypass history, glomerular ltration rate 60 ml/min/1.73 m2, time to reperfusion, mean platelet volume, stent length, left ventricular ejection fraction, creatine kinase-MB, admission anemia, and anterior myocardial infarction. Table 7 Multivariate predictors of long-term follow-up major adverse cardiac events Variable Age Diabetes mellitus Killip class 1 Admission anemia High UA Adjusted Odds Ratio* 1.03 2.56 3.91 1.74 1.64 95% Condence Interval 1.011.05 1.524.25 2.257.15 1.252.96 1.052.56 p Value 0.014 0.001 0.001 0.024 0.03

* Adjusted for male gender, hypertension, smoking, previous bypass history, glomerular ltration rate 60 ml/min/1.73 m2, TIMI ow grade 3, time to reperfusion, mean platelet volume, stent length, left ventricular ejection fraction, creatine kinase-MB, and anterior myocardial infarction.

variables for which the unadjusted p values were 0.10 on univariate analysis were identied as potential risk markers for MACEs and were included in the full model. Elevated UA levels were an independent predictor of in-hospital MACEs (odds ratio 2.03, 95% condence interval 1.25 to 3.75, p 0.006) and long-term MACEs (odds ratio 1.64, 95% condence interval 1.05 to 2.56, p 0.03) (Tables 6 and 7). Age, Killip class 1, and diabetes mellitus were also independent predictors of MACEs during the in-hospital and long-term follow-up periods. Discussion The association and putative role of UA in the long-term outcomes of patients with STEMI has not previously been fully explored. Previous studies have focused on the association of elevated UA levels with short-term STEMI outcomes. Kojima et al11 reported that mortality in patients whose serum UA levels were in the highest quartile was approximately 3.7 times higher than in those whose UA levels were in the lowest quartile. Lazzeri et al6,12 published conicting results regarding the independent association of elevated UA levels with early mortality in primary PCI patients. In addition, we recently published a report on the relation of UA with impaired coronary ow and in-hospital MACEs in 289 patients.13 We evaluated 3 markers (mean platelet volume, high-sensitivity C-reactive protein, and UA) together in patients with STEMI. There were 3 major ndings of our recent study. There was a signicant relation between serum UA levels and myocardial perfusion grade after primary PCI. Baseline serum UA, mean platelet vol-

ume, and high-sensitivity C-reactive protein were specic and sensitive predictors of poor coronary blood ow after primary PCI for STEMI. Additionally, these parameters are correlated with each other.13 However our recent study was a single-center study and had a relatively small population. However, the present multicenter large study of 2,249 patients demonstrates that elevated UA levels on admission are independently associated with impaired coronary ow after primary PCI and both short-term and long-term outcomes in patients who undergo primary PCI for the management of STEMI. Epidemiologic studies have established a relation between UA and cardiovascular disease, and hyperuricemia is sometimes cited as a risk factor for cardiovascular disease.13 Elevated levels of UA are associated not only with the presence of cardiovascular disease but also with elevated mortality and other adverse outcomes associated with cardiovascular disease.13 Recently, multiple biomarkers have been associated with mortality or adverse outcomes in patients with STEMI.14 18 Damman et al14 reported that glucose, N-terminal proBtype natriuretic peptide, and glomerular ltration rate were among the strongest predicting biomarkers of mortality in patients with STEMI and that the incorporation of these 3 predictive biomarkers in a multimarker risk score yields important prognostic information. Schoos et al15 demonstrated that preprocedural high-sensitivity C-reactive protein is a predictor of the composite end point of death and nonfatal recurrent myocardial infarction after primary PCI. In another study, Huczek et al16 reported that admission mean platelet volume was associated with impaired reperfusion (odds ratio 4.7, 95% condence interval 2.3 to 9.9, p 0.0001) and 6-month mortality (odds ratio 3.2, 95% condence interval 1.1 to 9.3, p 0.0084) in primary PCI patients. The present study suggests that the admission serum UA level is likewise an additional biomarker associated with in-hospital adverse outcomes as well as long-term outcomes. Also, high levels of UA are associated with poorer long-term survival in patients with STEMI. The underlying pathophysiologic mechanism of coronary artery disease is the atherosclerotic process.19 Significant correlations have been reported between serum UA levels and surrogate markers of atherosclerosis such as inammation,20 oxidative stress,21 and endothelial dysfunction.22,23 It may therefore be via these underlying mechanisms that elevated serum UA is associated with an increased risk for atherosclerosis. UA is an end product of xanthine oxidase enzyme activity during purine catabolism.24 Thus, the UA level is in part related to the activity of the enzyme xanthine oxidase and may be associated with the level of oxidative stress. During the production of UA and the corresponding activity of xanthine oxidase enzyme, oxygen free radicals are generated.25 The subsequent generation of oxygen free radicals is 1 of the underlying causes of impaired coronary ow after primary PCI.26 Furthermore, synthesis and secretion of vasodilators and vasoconstrictors regulate blood ow through the coronary arteries by adjusting the diameter of the vessel wall according to the blood ow demands of the cardiovascular system and the needs of the rest of the body.27 In particular, endothelial-derived nitric oxide, a potent vasodi-

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The American Journal of Cardiology (www.ajconline.org) cardial Infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical ndings through hospital discharge. Circulation 1987;76:142154. Killip T, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967;20:457 464. Kojima S, Sakamoto T, Ishihara M, Kimura K, Miyazaki S, Yamagishi M, Tei C, Hiraoka H, Sonoda M, Tsuchihashi K, Shimoyama N, Honda T, Ogata Y, Matsui K, Ogawa H; Japanese Acute Coronary Syndrome Study (JACSS) Investigators. Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study). Am J Cardiol 2005; 96:489 495. Lazzeri C, Valente S, Chiostri M, Picariello C, Gensini GF. Uric acid in the early risk stratication of ST-elevation myocardial infarction. Intern Emerg Med. In press. Akpek M, Kaya MG, Uyarel H, Yarlioglues M, Kalay N, Gunebakmaz O, Dogdu O, Ardic I, Elcik D, Sahin O, Oguzhan O, Ergin A, Gibson CM. The association of serum uric acid levels on coronary ow in patients with STEMI undergoing primary PCI. Atherosclerosis 2011; 219:334 341. Damman P, Beijk MA, Kuijt WJ, Verouden NJ, van Geloven N, Henriques JP, Baan J, Vis MM, Meuwissen M, van Straalen JP, Fischer J, Koch KT, Piek JJ, Tijssen JG, de Winter RJ. Multiple biomarkers at admission signicantly improve the prediction of mortality in patients undergoing primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction. J Am Coll Cardiol 2011;57:29 36. Schoos MM, Kelbk H, Kofoed KF, Kber L, Klvgaard L, Helqvist S, Engstrm T, Saunamki K, Jrgensen E, Holmvang L, Clemmensen P. Usefulness of preprocedure high-sensitivity C-reactive protein to predict death, recurrent myocardial infarction, and stent thrombosis according to stent type in patients with ST-segment elevation myocardial infarction randomized to bare metal or drug-eluting stenting during primary percutaneous coronary intervention. Am J Cardiol 2011; 107:15971603. Huczek Z, Kochman J, Filipiak KJ, Horszczaruk GJ, Grabowski M, Piatkowski R, Wilczynska J, Zielinski A, Meier B, Opolski G. Mean platelet volume on admission predicts impaired reperfusion and longterm mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. J Am Coll Cardiol 2005;46:284 290. Kaya MG, Ozdogru I, Kalay N, Dogan A, Inanc T, Gul I, Gunebakmaz O, Oguzhan A. Plasma B-type natriuretic peptide in diagnosing inferior myocardial infarction with right ventricular involvement. Coron Artery Dis 2008;19:609 613. Uyarel H, Ergelen M, Cicek G, Kaya MG, Ayhan E, Turkkan C, Yildirim E, Kirbas V, Onturk ET, Erer HB, Yesilcimen K, Gibson CM. Red cell distribution width as a novel prognostic marker in patients undergoing primary angioplasty for acute myocardial infarction. Coron Artery Dis 2011;22:138 144. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Juhani Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W Jr, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From vulnerable plaque to vulnerable patient: a call for new denitions and risk assessment strategies: part I. Circulation 2003;108:1664 1672. Ruggiero C, Cherubini A, Ble A, Bos AJ, Maggio M, Dixit VD, Lauretani F, Bandinelli S, Senin U, Ferrucci L. Uric acid and inammatory markers. Eur Heart J 2006;27:1174 1181. Many A, Hubel CA, Roberts JM. Hyperuricemia and xanthine oxidase in preeclampsia, revisited. Am J Obstet Gynecol 1996;174:288 291.

lator, plays an important role in the regulation of coronary blood ow.28 Hyperuricemia has been associated with decreased production of nitric oxide in the vascular endothelial cells.29 Therefore, elevated levels of UA not only contribute to oxygen free radical generation but also decrease the amount of nitric oxide in circulation, which in turn inhibits vasodilatation. Rapid restoration of normal ow in the infarct-related artery and myocardial perfusion is associated with improved ventricular performance and lower mortality in patients with acute myocardial infarction.13,30 It is notable that TIMI grade 3 ow was less frequently restored in patients with elevated levels of UA in the present study. This study carries the well-known limitations of the retrospective design. The associations of high-sensitivity C-reactive protein, B-type natriuretic peptide, and other proinammatory cytokines and markers of oxidative stress were not evaluated as part of a multivariable model. In the light of present study, we suggest that UA level, a cheaply and easily measurable biomarker, can be used in risk stratication, and patients with STEMI with high UA levels should be monitored closely for adverse outcomes. High UA levels may also carry further therapeutic implications during the in-hospital and follow-up periods. In the future, although the clinical signicance in how patients are treated after developing STEMI is not known, the association of UA levels and primary PCI outcome is still relevant, and further studies are needed to determine if treatment of hyperuricemia prevents noreow and adverse outcomes in patients with STEMI and increased UA levels.
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