1278 | Miscellaneous Is There a Relationship Between Acute Coronary Syndrome and Prostate Specific Antigen Level? Tahir Durmaz,1 Hüseyin Ayhan,1 Telat Keleş,1 Emine Bilen,2 Murat Akçay,1 Nihal Akar Bayram,2 Engin Boz- kurt1 Purpose: Interestingly, prostate-specific antigen (PSA), which is used to monitor prostate disor- ders, has been suggested to be beneficial in estimating prognosis associated with coronary artery disease (CAD). The aim of the present study was to investigate the relationship of serum levels of PSA and free PSA (fPSA) with prognosis of acute coronary syndromes (ACS), extent of CAD and major adverse cardiac events in patients with acute coronary syndromes. Materials and Methods: Sixty-seven male patients who were diagnosed with acute coronary syn- dromes were included. All patients were assessed according to the Thrombolysis in Myocardial Infarction (TIMI) classification [ST elevation myocardial infarction (STEMI) and non-ST elevation (NSTE)-ACS groups, separately], the Global Registry of Acute Cardiac Events (GRACE) (differ- ence between PSA and fPSA) risk score and the Killip classification. All patients underwent angi- ography. The degree of stenosis was scored using the Gensini score to assess the extent of CAD. Results: Serum PSA, fPSA, fPSA/PSA levels, and alpha 1-antichymotrypsin-PSA (ACT-PSA) (difference between PSA and fPSA) results were found to be moderately correlated with the TIMI and GRACE risk scores, which are predictors of short- and mid-term prognosis. While there was no correlation between the Gensini score and PSA and ACT-PSA, the Gensini score was moder- ately correlated with fPSA and fPSA/PSA. There were no significant differences between patients with major adverse cardiovascular events (MACEs) and those without MACEs at the 6-month follow-up in terms of PSA, fPSA, fPSA/PSA, and ACT-PSA results. Conclusion: There may be a relationship between serum PSA and fPSA levels and prognosis of ACS and extent of CAD. It should be kept in mind that additional biomarkers could be used together with current scoring systems in risk classification in cases for which clinical decision- making is challenging. Moreover, PSA and fPSA results should be approached with caution in patients to be screened for prostate cancer as their serum levels may be influenced from several factors (ACS, infection, etc.). Keywords: acute coronary syndrome; predictive value of tests; male; prostate-specific antigen; blood. Corresponding Author: Hüseyin Ayhan, MD Department of Cardiology, Fac- ulty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey. Tel: +90 312 2912525 Fax: +90 312 2912745 E-mail: huseyinayhan44@ yahoo.com Received September 2012 Accepted March 2013 1 Department of Cardiology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey. 2 Department of Cardiology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey. MISCELLANEOUS 1279Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L Acute Coronary Syndrome and Serum PSA Level | Durmaz et al INTRODUCTION Ischemic heart disease is the leading cause of mortality and morbidity in adults worldwide. Although coronary atherosclerosis mostly results in chronic coronary artery disease (CAD), obstructive lesions in the coronary vessels, plaque erosion and rupture, and atherosclerotic plaques may also lead to acute myocardial ischemia. Rapidly progressing ischemic lesions threatening myocardial tissue are currently defined as acute coronary syndrome (ACS). ACS is main- ly classified in the following three groups: 1) ST elevation myocardial infarction (STEMI), troponin-positive, 2) non- ST elevation myocardial infarction (NSTEMI), troponin- positive, 3) unstable angina pectoris (UAP), non-ST eleva- tion, troponin-negative; the latter two being also named as NSTE-ACS. Every year, more than one million people suffer from acute myocardial infarction (MI) in the USA. Registry data consistently show that NSTE-ACS is more frequent than STE-ACS. The annual incidence is 3 per 1000 inhabitants, but varies between countries.(1) Although there has been a reduction in mortality due to the increase in the number of coronary intensive care units and advances in fibrinolytic and catheter-based reperfusion treatments, overall mortality rate associated with acute MI including deaths before admission to hospital is greater than 30%.(2) Although several markers have been identified in order to predict mortality, determine prognosis, and demonstrate the extent of CAD in ACS, novel markers are still being investi- gated. Recent case reports have suggested that there might be an association between prostate-specific antigen (PSA) and CAD and that this marker may be helpful in predicting prog- nosis. Being responsible for the liquefaction of semen, PSA is a 33000 Da single chain glycoprotein comprised of 237 amino acids and 4 carbohydrate side chains. The gene encod- ing the PSA molecule is located on the 19th chromosome. Based on gene location, and amino acid composition and function, PSA is identified as a member of the human kal- likrein (hK3) family of the serine proteases.(3) Inactive form of PSA, pro-PSA, is rapidly converted to active PSA by hK2; hK2 also activates single-chain urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1). PSA induces apoptosis and inhibits negative growth factor and angiogenesis. PSA increases the release of insulin like growth factor-1 (IGF-1), which has been shown to increase all-cause mortality and risk of development of heart failure, by binding to insulin-like growth factor binding protein-3. It has been determined that PSA exhibits antiangiogenic ac- tivity through inhibition of endothelial cell proliferation in- duced by fibroblast growth factor–2 and vascular endothelial growth factor.(4) It has also been shown that PSA levels are reduced by statin treatment and PSA production is regulated by angiotensin receptor blockers through a peroxisome pro- liferator-activated receptor gamma like effect.(5) PSA levels have been demonstrated to be increased in cases of cardio- genic shock due to prolonged cardiopulmonary resuscita- tion, cardiac surgery, on-pump bypass, and acute MI.(6,7) In a controlled study, serum PSA and fPSA levels was found to be higher in patients after elective stent implantation com- pared to those who were not treated with stent implantation, whereas no significant difference was found between these groups in terms of fPSA/PSA ratio.(8) In a study comparing NSTE-ACS and control groups, no significant difference was found between these two groups in terms of PSA level. PSA was determined to be correlated with high-sensitivity C-reactive protein (hsCRP) and increased in heart failure in 14 days of follow-up. Although there have been no large ran- domized studies, it has been observed in several case reports that coronary lesions is more common, extensive and severe and that major adverse cardiac events (MACEs) is more fre- quent within the initial 8 days after acute MI in cases with elevated PSA. These reports have suggested that large rand- omized studies were needed to confirm this association.(9-11) The aim of the present study is to investigate the relationship of serum PSA, fPSA, complex PSA (ACT-PSA; difference between PSA and fPSA) levels and fPSA/PSA ratio with prognosis of ACS, extent of CAD, development of arrhyth- mias, troponin and hsCRP levels, and MACEs (death, MI, reinfarction, re-revascularization, hospitalization, stroke). MATERIALS AND METHODS Sixty-seven male patients who were hospitalized in the Coro- nary Intensive Care Unit with the diagnosis of ACS between November 2009 and April 2010 were included in this pro- spective study. Patients with a history of Lower Urinary Tract Symptoms (LUTS), prostate cancer and benign prostatic hy- 1280 | Table 1. Baseline clinical, laboratory, and procedural characteristics of the patients. Characteristics Study Patients (n=67) Age (years) 58.4 ± 11.4 BMI (kg/m2) 27.34 ± 2.7 Time before hospital admission (hours) 6.4 ± 5.1 DM (%) 16.4 HT (%) 41.8 Smoking (%) 67.2 Family history (%) 9 Functional capacity (NYHA class) (%) I 68.6 II 23.9 III 7.5 IV 0 STEMI (%) 47.7 NSTEMI (%) 46.3 UAP (%) 6 LVEF (%) 47.8 ± 11.2 Heart rate (beats/min) 77.9 ± 18 Systolic BP (mmHg) 129.25 ± 22.6 Diastolic BP (mmHg) 77.08 ± 12.4 Total cholesterol (mg/dL) 190.08 ± 35.94 Triglyceride (mg/dL) 179.08 ± 122.45 LDL (mg/dL) 117.9 ± 36.01 HDL (mg/dL) 36.18 ± 9.33 Peak troponin I (ng/mL) 2.16 ± 27.9 Peak CK-MB (ng/mL) 71.59 ± 100.9 hsCRP (mg/L) 6.6 ± 7.1 TIMI Risk Score 3.3 ± 1.9 GRACE Risk Score (inhospital) 119 ± 26.2 GRACE Risk Score (6 months) 100 ± 29.1 Gensini score 61.2 ± 46.4 PSA (0-4 ng/mL) 1.1 ± 0.9 fPSA (0-3.7 ng/mL) 0.49 ± 0.55 PSA- fPSA 0.61±0.65 fPSA/PSA ratio 0.46 ± 0.23 Percutaneous coronary intervention (%) 67.16 Fibrinolytic treatment (%) 17.9 Infarction releated artery (%) LAD 37.3 RCA 38.8 LCx 23.9 key: BMI, body mass index; DM, diabetes mellitus, HT, hypertension, NYHA, New York Heart Association; STEMI, ST elevation myocardial infarction; NSTEMI, Non-ST elevation myocardial infarction; UAP, unstable angina pektoris; LVEF, left ventricular ejection fraction; BP, blood pressure; LDL, low- density lipoprotein; HDL, high-density lipoprotein; CK, creatinine kinase; hsCRP, high sensitivity C-reactive protein; TIMI, Thrombolysis in Myocardial Infarction; PSA, prostate-specific antigen; fPSA, free prostate-specific antigen; LAD, left anterior descending artery; RCA, right coronary artery, LCx, circumflex coronary artery. Miscellaneous 1281Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L perplasia (BPH), those who underwent urinary catheteriza- tion, those with a recent history of prostate biopsy, prostatitis or urinary tract infection, those who had a survival expectan- cy of less than one year due to non-cardiac pathologies, and those who did not provide informed consent were excluded. These were 30 patients. Routine follow-up and treatment were performed on study patients in accordance with the recommendations in the cur- rent guidelines. Blood samples were obtained from all pa- tients diagnosed with acute coronary syndromes on admis- sion for routine laboratory investigations, creatinine kinase (CK)-MB, troponin I, and hsCRP levels in addition to serum PSA and fPSA levels. fPSA/PSA ratio and ACT-PSA levels were calculated. Information regarding risk factors including age, gender, type II diabetes mellitus, hypertension, hyper- lipidemia, and smoking were recorded. All patients were as- sessed according to the Thrombolysis in Myocardial Infarc- tion (TIMI) classification (STEMI and NSTE-ACS groups, separately), the Global Registry of Acute Cardiac Events (GRACE) risk score (during inpatient period and 6 months after discharge), and the Killip classification. Left ventricu- lar ejection fraction (LVEF) was measured by transthoracic echocardiography (Vivid 3 pro, GE Vingmed, Milwaukee, WI, USA) using the modified biplane Simpson’s method. ST-segment resolution (STR) was assessed by electrocar- diography that was performed 60 min after the procedure; a STR of > 70% was defined as successful reperfusion. All patients underwent angiography. Coronary angiographies were performed by experienced cardiologists via femoral ar- terial route using standard techniques. Lesions were assessed from at least two angles and at end-diastolic phase. Accord- ing to the recommendations of current guidelines, primary percutaneous coronary intervention (PCI), early invasive intervention, medical treatment, and bypass treatments were performed. Following the procedure, coronary angiographies of all patients were evaluated in order to assess the extent of CAD, and stenosis was scored using the Gensini score. (12) The degree of angiographic stenosis was scored between 1 and 32, this score was then multiplied by a factor defined for each main coronary artery and each segment, and finally summed up. MACEs (death, MI, re-revascularization, stroke) during inpatient period, one month and 6 months after dis- charge were recorded for all patients. Informed consent was obtained from all patients at the time of admission, and the study was approved by the Hospital Local Ethics Committee. Measurement of Prostate-Specific Antigen Blood samples for PSA and fPSA measurements were ob- tained from the antecubital veins of all patients in a single puncture before the procedure. Samples were immediately frozen in citrate tubes at -20°C, and measurements were performed by electrochemiluminescence immunoassay (ECLIA) method using Cobas 6000 device (Roche Diagnos- tic). fPSA/PSA ratio and ACT-PSA were calculated for all samples. Statistical Analysis The statistical package for the social science (SPSS Inc, Chicago, Illinois, USA) version 14.0. Numerical variables were expressed as mean ± standard deviation (SD), whereas categorical variables were expressed as percentage. Groups were compared using the Student’s t test for normally distrib- Table 2. PSA, fPSA, fPSA/PSA and PSA- fPSA results and their correlation with the TIMI and GRACE risk scores. TIMI risk score GRACE Score inhospital period GRACE score at 6-month follow-up r p r P r p PSA 0.30 .01 0.08 .50 0.17 .15 fPSA 0.41 .001 0.23 .05 0.31 .01 fPSA/PSA -0.25 .04 -0.23 .05 -0.26 .03 PSA-fPSA 0.08 .48 0.09 .46 0.04 .74 Key: TIMI, Thrombolysis in Myocardial Infarction; GRACE, Global Registry of Acute Cardiac Events; PSA, prostate-specific antigen; fPSA, free prostate- specific antigen. Acute Coronary Syndrome and Serum PSA Level | Durmaz et al 1282 | uted variables and using the Mann-Whitney U test for non- normally distributed variables. The Pearson correlation test was used for normally distributed variables, and the Spear- man correlation test was used for non-normally distributed variables. A P value of < .05 was considered statistically sig- nificant. RESULTS Sixty-seven male patients with ACS were included in the present study. Their mean age was 58.4 ± 11.4 years (range, 29-86 years). Thirty-two patients had STEMI, 31 patients had NSTEMI, and four patients had UAP. Fibrinolytic treatment was administered in 18% of STEMI patients, and successful reperfusion was observed in half of these cases. Coronary an- giography was performed in all patients, and revascularization through PCI was performed in 67% of the patients. Coronary arteries were noted to be normal in two patients. General fea- tures of the study patients are presented in (Table 1). No significant difference was found between STEMI and NSTE-ACS groups in terms of PSA and fPSA levels, fPSA/ PSA ratio and ACT-PSA (P = .58). Correlation analysis of PSA, fPSA, fPSA/PSA, and ACT-PSA with other labora- tory and clinical variables revealed no significant correlation with LVEF, Killip class, peak CK-MB, peak troponin I, and hsCRP levels. However, moderate correlation was noted with the TIMI and GRACE risk scores, which are predictors of short- and mid-term prognosis (Table 2). Correlation analysis between the Gensini score, which is an indicator of the extent of CAD, and PSA, fPSA, fPSA/PSA, and ACT-PSA revealed no significant correlation with PSA and ACT-PSA, whereas a moderate correlation was noted with fPSA and fPSA/PSA ratio (Table 3). Multivariate regression analysis between the Gensini score, which is an indicator of the extent of CAD, and PSA, fPSA, fPSA/PSA, and ACT-PSA revealed significant correlation with fPSA, fPSA/PSA (Table 4). During inpatient follow-up, atrial fibrillation was noted in 3%, atrioventricular complete block was noted in 1.5%, ven- tricular tachycardia in 4.5%, and MACEs (death in 2 patients, re-revascularization in 1 patient) was noted in 4.5% of the patients. At the 1-month follow-up, MI was noted in 4 (6%) patients and death was noted in 3 (4.5%) patients, which did not reach statistical significance. MACEs were noted in 23.5% of the patients at the 6-month follow-up. There were no sig- nificant differences between patients with MACEs and those without MACEs at the 6-month follow-up in terms of PSA, fPSA, fPSA/PSA, and ACT-PSA results (P = .60). DISCUSSION The relationship of serum PSA, fPSA, fPSA/PSA levels and ACT-PSA on admission and prognosis of ACS, extent of CAD, and other biomarkers in patients diagnosed with ACS was investigated in the present study. A significant moderate correlation was found with the TIMI and GRACE risk scores and the Gensini score was not found to be correlated with PSA and ACT-PSA; however, it was found to be significantly moderately correlated with fPSA and fPSA/PSA. Gensini score was found to be correlated with fPSA and fPSA/PSA by multivariate regression analysis. No significant difference was found between STEMI and NSTE-ACS groups in terms of PSA and fPSA levels, fPSA/PSA ratio and ACT-PSA. Table 3. Correlation of PSA, fPSA, fPSA/PSA, and PSA-fPSA results with Gensini score. Gensini score Variables r p PSA 0.10 .42 fPSA 0.35 .003 fPSA/PSA -0.42 .001 PSA-fPSA -0.18 .13 Key: PSA, prostate-specific antigen; fPSA, free prostate-specific antigen. Table 4. Multivariate regression analysis for GENSINI score; including age, PSA, ACT-PSA, fPSA, fPSA/PSA.* Gensini Score Variables Coefficient β p Age 0.051 > .05 PSA 0.082 > .05 ACT-PSA 0.056 > .05 fPSA 0.418 < .001 PSA/fPSA 0.483 < .001 * A P value < .05 was considered to be significant. F ratio = 41.2, r 2 = 0.776. Key: PSA, prostate-specific antigen; fPSA, free prostate-specific anti- gen; ACT-PSA, alpha 1-antichymotrypsin-PSA. Miscellaneous 1283Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L There were no significant differences between patients with MACEs and those without MACEs at the 6-month follow-up in terms of PSA, fPSA, fPSA/PSA, and ACT-PSA results. Atherosclerosis and acute MI as its complication are still the leading cause of mortality and morbidity worldwide. Simi- lar to atherosclerosis, prevalence of prostate cancer increases with age, and it is one of the most common cancers in males. Biochemical markers indicating myocardial damage in acute coronary syndromes patients play a vital role both in estab- lishing diagnosis and in making treatment decisions. Cardiac troponins that are markers for myocardial necrosis are found to be elevated only in 1/3 of acute coronary syndromes pa- tients and are associated with increased short-term mortal- ity and nonfatal MI risk in these patients.(13) Although this risk is significantly lower in troponin-negative patients as compared to troponin-positive ones, a relatively high num- ber of troponin-negative acute coronary syndromes makes risk assessment and treatment selection rather challenging. Thus, simultaneous measurement of several biomarkers de- fining different stages of acute coronary syndromes patho- physiology may enable a better risk assessment in patients with negative myocardial necrosis markers.(14) A sensitive and specific biomarker, which can indicate plaque instabil- ity and can be measured in systemic circulation independ- ent from myocardial necrosis, can provide improvement in diagnosis and treatment decision-making. In this context, several novel biomarkers such as hsCRP, fibrinogen, PAI-1, pregnancy-associated plasma protein A (PAPP-A), and my- eloperoxidase have been introduced, and some have indeed been implemented into clinical practice, whereas others re- main at an experimental level.(15-17) Detection of unstable or potentially unstable coronary lesions, in which particularly early interventional and medical treatments provide consid- erable benefit, is an important clinical goal. It is clear that in- flammatory markers have a significant role in the detection of these unstable lesions. It has been increasingly emphasized in recent years that inflammation, which is one of the most significant steps in the pathogenesis of atherosclerosis, has an important role in clinical diagnosis and treatment. The role of PSA also appears in this context. It has been suggested that PSA may assist in the diagnosis and treatment of acute coro- nary syndromes as acute phase reactants, which are markers of inflammation. PSA is secreted into the lumen of the prostatic duct by exo- cytosis and transferred into the seminal fluid. The concen- tration of PSA is 0.5-2.0 g/L in semen.(18) Its concentration in the semen is approximately a million times of its concen- tration in the serum (0.1-4 ng/mL). PSA in serum is found predominantly in three distinct molecular forms: 1) free PSA (fPSA, molecular weight of 30 kDa), 2) alpha-2 macroglob- Figure 1. Correlation between Gensini score and free prostate- specific antigen (fPSA) (r = 0.35, P = .003). Figure 2. Correlation between Gensini score and fPSA/PSA ratio (r = -0.42, P = .001). PSA, prostate-specific antigen, fPSA, free prostate-specific antigen. Acute Coronary Syndrome and Serum PSA Level | Durmaz et al 1284 | ulin-bound PSA (A2M-PSA; molecular weight of 780 kDa) and 3) alpha 1-antichymotrypsin-PSA (ACT-PSA); molec- ular weight of 90 kDa). Malignant tissues such as adrenal neoplasms (neuroblastoma), renal cell carcinoma, and breast cancer can also synthesize PSA in low concentrations.(19,20) The mean half-life of total PSA (free + bound forms) is 2.6 days.(21) As fPSA has a relatively lower molecular weight, it can be eliminated through renal clearance. Having a half-life of 1.5 hours, fPSA constitutes 5% of serum PSA, and fPSA/ PSA ratio reduces in patients with prostate cancer. Measure- ment of fPSA is used to increase sensitivity during screening for cancer in patients with normal total PSA levels and to increase specificity and reduce the number of unnecessary prostate biopsies in patients with high total PSA levels (> 4-10 ng/mL). Prostate manipulations (firm rectal examina- tion), prostate biopsy, and urethral instrumentations lead to increase in fPSA component of total PSA. Therefore, any kind of manipulations should be avoided 48-72 hours be- fore fPSA measurement. Impairment of normal structure of prostate, which enables the diffusion of PSA into the pros- tate tissue, leads to the elevation of serum PSA levels. Major causes of elevated PSA include BPH, prostate cancer, pros- tate inflammation or infection, and trauma to the prostatic or perineal region. Serum PSA level increases with age and accompanying increase in prostate volume. This is due to PSA-producing BPH tissue.(22) Significant portion of serum PSA is found as a complex with ACT. In patients with pros- tate cancer, ACT-PSA or complex PSA levels increases more than that in patients with BPH. ACT-PSA is directly associ- ated with total PSA and calculated by subtracting fPSA from total PSA.(22-24) Although it was shown in a study that PSA is correlated with hsCRP during a 14-day of follow-up and increased in heart failure,(25) in the present study, PSA, fPSA, ACT-PSA levels, and fPSA/PSA ratio was not found to be correlated with LVEF, Killip class, peak CK-MB, peak troponin I, and hsCRP levels. However, a significant moderate correlation was found with the TIMI and GRACE risk scores, which are predictors of short- and mid-term prognosis. In certain case reports, coronary lesions were reported to be more severe and extensive in cases with elevated PSA.(11,26) In the pre- sent study, the Gensini score, which is calculated from coro- nary angiography findings and is an indicator of the extent of CAD, was not found to be correlated with PSA and ACT- PSA; however, it was found to be significantly moderately correlated with fPSA and fPSA/PSA. Also Gensini score was found to be correlated with fPSA and fPSA/PSA by multivar- iate regression analysis with there was no difference in age. Due to low number of arrhythmias and MACEs occuring during hospitalization and one month after discharge, statisti- cal analysis could not be performed. Furthermore, there were no significant differences between patients with MACEs and those without MACEs at the 6-month follow-up in terms of PSA, fPSA, fPSA/PSA, and ACT-PSA results. Recent studies have suggested that there might be a relation- ship between cardiovascular disorders and PSA levels.(27) PSA levels have been demonstrated to be increased in cases of cardiogenic shock due to prolonged cardiopulmonary resus- citation, cardiac surgery, on-pump bypass, and acute MI.(7,27- 30) Although the precise mechanism of increase in PSA levels in such conditions is unclear, it has been suggested that it might be caused by pelvic ischemia due to aortic clamp or cardiogenic shock. Therefore, PSA results should be inter- preted with caution when screening for prostate cancer in pa- tients who have sustained such events within previous weeks. Moreover, to our knowledge, there have been no previous randomized studies investigating the relationship between PSA and prognosis and the extent of CAD following acute coronary syndromes. Recently, several case reports suggest- ed that coronary lesions was more common and extensive, presenting with more severe clinical manifestations and that number of MACEs within the 8 days following acute MI was higher in cases with elevated PSA.(10,26) However, it was also reported in these case reports that PSA level was low on the 1st and 3rd days, while it was high on the 2nd day. In the pre- sent study, we measured the PSA levels of the patients on ad- mission. Monitorization of PSA levels with 12-hour intervals may be more valuable in detecting the significance of PSA in acute coronary syndromes. In another case report, a low PSA level was emphasized in a case of coronary spasm without a significant coronary stenosis.(28) In a controlled study, PSA and fPSA levels was found to be higher in patients following elective stent implantation compared to those who were not treated with stent implantation, while no significant differ- Miscellaneous 1285Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L ence was reported between these groups in terms of fPSA/ PSA ratio.(8) In another controlled study comparing NSTE- ACS and control groups, no significant difference was found between PSA levels of these two groups.(31) Supporting some of the previous studies, we also found a significant moderate correlation of PSA and fPSA with acute coronary syndromes. Large, randomized controlled studies are needed to confirm this relationship. CONCLUSION In conclusion, PSA, fPSA and fPSA/PSA were found to be correlated with the TIMI and GRACE risk scores, which are prognosis markers in acute coronary syndromes, and the Gensini scores, which are markers for the extent of CAD, in the present study. Moreover, PSA and fPSA results should be approached with caution in patients to be screened for prostate cancer as their serum levels may be influenced from various other cardiovascular disorders commonly seen in the elderly population. CONFLICT OF INTEREST None declared. 1. Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the man- agement of acute coronary syndromes in patients presenting with- out persistent ST-segment elevation. Eur Heart J. 2011;32:2999- 3054. 2. Griffin P TE, editor. Manual of Cardiovascular Medicine. Third ed: Philadelphia Pa: Lippincott Williams & Wilkins; 2009. p. 563-70. 3. Armitage TG, Cooper EH, Newling DW, Robinson MR, Appleyard I. The value of the measurement of serum prostate specific antigen in patients with benign prostatic hyperplasia and untreated prostate cancer. Br J Urol. 1988;62:584-9. 4. Cohen P, Graves HC, Peehl DM, Kamarei M, Giudice LC, Rosenfeld RG. Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma. J Clin Endo- crinol Metab. 1992;75:1046-53. 5. Crook M, Preston K, Lancaster I. Serum prostatic specific-anti- gen concentrations in acute myocardial infarction. Clin Chem. 1997;43:1670. 6. Rittenhouse HG, Finlay JA, Mikolajczyk SD, Partin AW. Human Kal- likrein 2 (hK2) and prostate-specific antigen (PSA): two closely re- lated, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci. 1998;35:275-368. 7. Hagood PG, Parra RO, Rauscher JA. Nontraumatic elevation of pros- tate specific antigen following cardiac surgery and extracorporeal cardiopulmonary bypass. J Urol. 199;152:2043-5. 8. 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