Prostate-specific antigen kallikrein is not a marker of non-ST elevation acute coronary syndrome

Abstract

We have read with great interest the letter entitled “Prostatespecific antigen (PSA) kallikrein and acute myocardial infarction (AMI): Where we are. Where are we going?”, recently published by Patane S and Marte F [1] where the authors very concisely reviewed the role of the PSA in AMI. Currently, a growing interest has been directed towards PSA and the cardiovascular system [2]. The investigation of novel circulating serum and plasma biomarkers in patients with cardiovascular disease has been accelerating at a remarkable place. For example, a Medline search that uses the terms “biomarkers” and “acute coronary syndromes” (ACS) reveals an approximate doubled in the number of published reports during the 2-year interval from 2005 to 2006 compared with the period from 2003 to 2004. Although this expanding body of research has established firm evidence for the value of biomarkers, such as for diagnosis and risk assessment among patients with suspected ACS [3], it has also deluged the clinical and research communities with candidate biomarkers, very few of which are likely to survive the test of time as useful clinical tools [3]. It is thus increasingly important for researchers, manufacturers, regulators, and clinicians to critically appraise the value of new biomarkers as they emerge as candidates for further investigation and possible clinical application. PSA is a 33Kda single chain glycoprotein that was first identified in seminal plasma [4] andwas subsequently isolated from prostate tissue [5]. It has been identified as a member of the human kallikrein family of serine proteases [2] and was initially considered only as a marker for the detection of prostate cancer [6]. Recently, attention has been focused on PSA serum levels and the PSA unspecificity to prostate, semen, and gender has been demonstrated [2]. Increased PSA serum level, are a common finding in patients with nonprostatic illnesses including AMI [7–11]. In this line, we have conducted a pilot study to determine the ability of PSA to predict ACS. In contrast to previous published studies, our data do not support PSA as a biomarker of ACS. Since April 2010 to the end of December 2010 we included one hundred and ten male patients with a first non-ST elevation ACS (STEACS). Thirty three patients were excluded from analysis for the following reasons: history of adenocarcinoma of the prostate gland, n=11 and history of prostatic hyperplasia, n=22. Hence, the data from 77 patients were analyzed. We also recruited 55 apparently healthy men as controls. The study was approved by the local research ethics committee and all subjects gave written informed consent before study entry. We obtained venous blood samples to determine PSA. The assay for total PSA is based on microparticle enzyme immunoassay technology and was performed on the Abbott IMx System (Abbott Laboratories). The analytical sensitivity of this method was calculated to 0.02 ng/mL at the 95% confidence interval. Results of normally distributed continuous variables are expressed as the mean value± SD. Continuous variables with a non-normal distribution are presented as median value (interquartile interval) and qualitative variables are presented as frequencies. Analysis of normality of the continuous variables was performed with the Kolmogorov–Smirnov test. Differences between non-STEACS and control subjects were assessed by unpaired t test for continuous variables and χ testing was used for discrete variables. We assessed differences in PSA levels between non-STEACS and controls using a binary logistic regression analysis. This analysis was performed adjusting by age, given the known correlation between PSA levels and age. Differences were considered to be significant if the null hypothesis could be rejected with N95% confidence. The SPSS 11.5 statistical software package (SPSS Inc, Chicago, Illinois, USA) was used for all calculations. Baseline characteristics of subjects enrolled in the study are shown in the Table 1. There were significant differences between groups regarding age, hypertension, hypercholesterolemia and diabetes mellitus. Glucose levels were higher in patients than in controls. PSA levels did not differ between the non-STEACS group and control group after adjusting by age (1.17 [0.56-2.93] vs 1.01 [0.43-1.64]μg/L, P=0.79) (Table 1 and Fig. 1). In our study, we found that PSAmay not be an idealmarker for ACS. Crook et al. [12] have reported that mean serum PSA concentration during AMI was significantly lower on day 2 compared to days 1 or 3, suggesting that these results could reflect several factors, such as thrombolysis treatment, reduced physical activity, or an acute-phase response. In our study, PSA concentration was analyzed in the nonSTEACS group on day 3. Previous preliminary observations have