Author's reply

Abstract

We thank Dr Eyuboglu for his comments in regard to our recently published paper [[1]Kawabe M. Sato A. Hoshi T. Sakai S. Hiraya D. Watabe H. Kakefuda Y. Ishibashi M. Abe D. Takeyasu N. Aonuma K. Gender differences in the association between serum uric acid and prognosis in patients with acute coronary syndrome.J Cardiol. 2015; (pii: S0914-5087(15)00159-8)https://doi.org/10.1016/j.jjcc.2015.05.009Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. In the present study, we reported that an increased level of uric acid (UA) was associated with major cardiovascular adverse events (MACE) more strongly in women than in men with acute coronary syndrome (ACS). However, Dr Eyuboglu pointed out that the findings of our present study might not be due to gender differences because of some flaws in the methodology. First, incidence of β-blocker and intensive lipid-lowering statin treatment was lower than recommended. Second, delay in revascularization in women with higher UA levels may be another reason for higher MACE. As pointed out by Dr Eyuboglu, we recognized that the rates of use of β-blockers (40%) and statins (66%) were low compared to a USA population with ACS. Previous reports have shown that even for patients with coronary artery disease, the prescription rate of β-blockers is significantly lower in Japan (≈30%) than in the West [[2]Kohro T. Hayashi D. Yamazaki T. Nagai R. The JCAD Investigators Beta-blocker prescription among Japanese cardiologists and its effect on various outcomes.Circ J. 2010; 74: 962-969Crossref PubMed Scopus (15) Google Scholar]. It has also been reported that even for patients with myocardial ischemia, calcium antagonists are preferred over β-blockers for the treatment of angina, maybe from fear of coronary spasm, the rate of which is reported to be higher in the Japanese population than in Westerners [[3]Pristipino C. Beltrame J.F. Finocchiaro M.L. Hattori R. Fujita M. Mongiardo R. Cianflone D. Sanna T. Sasayama S. Maseri A. Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction.Circulation. 2000; 101: 1102-1108Crossref PubMed Scopus (297) Google Scholar]. However, there were no significant differences in prescription of β-blockers among the 4 quartiles in the present study. Considering the enormous evidence of the beneficial effects of β-blockers in patients with cardiovascular diseases, we think that a more thorough investigation of β-blocker usage will be needed to confirm this finding. In the present study, a higher quartile of UA was associated with decreased low-density lipoprotein cholesterol (p < 0.001), and statins were used less frequently in women with a higher quartile of UA (p = 0.015) in women. The choice of statin was decided by the individual physician according to the practice guideline (low-density lipoprotein cholesterol <100 mg/dl). After adjusting for dyslipidemia, the multivariable analysis showed that the highest quartile of UA was independently associated with MACE in the women. Because of the observational registry data, there was a lack of precise information on statin dosing and noncompliance, and safety data were insufficient during the follow-up period. Regarding the delay in revascularization, there were no significant differences in door to balloon time among the 4 quartiles in the patients with ST-elevation myocardial infarction receiving percutaneous coronary intervention (PCI) (Quartile 1: 65.2 ± 50.1 min, Quartile 2: 72.6 ± 59.2 min, Quartile 3: 67.3 ± 60.1 min, Quartile 4: 67.1 ± 68.6 min, p = 0.965). Therefore, we think that delay in revascularization in women was not a confounding factor in the present study. The present study with subjects from a multicenter registry of patients with ACS undergoing PCI demonstrated that UA has gender differences on the prognosis in patients with ACS because the association remained even after adjustment for comorbidities in women, but not in men. Meta-analysis also showed that an association between hyperuricemia and cardiovascular mortality was significant in women but not in men [[4]Kim S.Y. Guevara J.P. Kim K.M. Choi H.K. Heitjan D.F. Albert D.A. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis.Arthritis Care Res (Hoboken). 2010; 62: 170-180Crossref PubMed Scopus (506) Google Scholar]. The mechanisms that cause UA to be less related to MACE in men than women remain uncertain and providing a potential explanation for this finding would be rather speculative. Further studies will be needed to determine whether UA-lowering treatment affect the prognosis of ACS patients with an elevated UA.