Gender differences in the prognostic role of uric acid and confounding factors

Abstract

I read the article by Kawabe et al. [[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; https://doi.org/10.1016/j.jjcc.2015.05.009Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar] with great interest, recently published online in your journal. In their study, the authors 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). Gender differences in the prognostic role of UA in patients with ACS is not clear. Because of some flaws in the methodology, I have some serious reservations about the findings of this article. Optimal medical therapy is the key point to reduce MACE in patients with ACS. In the Kawabe et al. study, the authors reported the incidence of treatment with statins, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and beta-blockers for both men and women. These drugs are essential to reduce mortality. However, some well known medications may reduce MACE in patients with ACS, in addition to these drugs. Hence, medical therapy may still have an effect on the results of the present study. First, in the present study of Kawabe et al., the incidence of beta-blocker treatment was lower than recommended. Calcium-channel blockers may have similar benefit to beta-blockers in ACS patients, in particular in the absence of beta-blocker treatment [[2]Hamm C.W. Bassand J.P. Agewall S. Bax J. Boersma E. Bueno H. Caso P. Dudek D. Gielen S. Huber K. Ohman M. Petrie M.C. Sonntag F. Uva M.S. Storey R.F. et al.ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).Eur Heart J. 2011; 32: 2999-3054Crossref PubMed Scopus (3043) Google Scholar]. Second, it is known that intensive lipid-lowering statin treatment provides greater protection against death or MACE than does a standard regimen after ACS [[3]Cannon C.P. Braunwald E. McCabe C.H. Rader D.J. Rouleau J.L. Belder R. Joyal S.V. Hill K.A. Pfeffer M.A. Skene A.M. Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators Intensive versus moderate lipid lowering with statins after acute coronary syndromes.N Engl J Med. 2004; 350: 1495-1504Crossref PubMed Scopus (4312) Google Scholar]. Therefore, lower incidence of treatment with calcium-channel blockers and intensive statin regimen may be a reason for higher MACE in women with higher UA levels. Finally, time to revascularization is a predictor of MACE in ACS. Delay in reperfusion can cause worse outcomes [[4]De Luca G. Suryapranata H. Ottervanger J.P. Antman E.M. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts.Circulation. 2004; 109: 1223-1225Crossref PubMed Scopus (1178) Google Scholar] and early invasive strategy may be beneficial in some ACS patients [[2]Hamm C.W. Bassand J.P. Agewall S. Bax J. Boersma E. Bueno H. Caso P. Dudek D. Gielen S. Huber K. Ohman M. Petrie M.C. Sonntag F. Uva M.S. Storey R.F. et al.ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).Eur Heart J. 2011; 32: 2999-3054Crossref PubMed Scopus (3043) Google Scholar]. Hence, delay in revascularization in women with higher UA levels may be another reason for higher MACE. In conclusion, UA may indicate adverse events in ACS patients. However, the findings of the present study of Kawabe et al. may not be due to gender differences. To define the effect of gender differences in the role of UA on the prognosis of patients with ACS, all these confounding factors should be considered. I have no commercial, financial, and other relationships in any way related to the subject of this article all that might create any potential conflict of interest.