Uric acid and cardiovascular risk stratification in the acute coronary syndromes: a friend we should mind

Abstract

Uric acid (UA) is the end product of purine metabolism. Whilst being primarily known as the leading risk factor for the onset of gout [ [1] Dalbeth N. Choi H.K. Joosten L.A.B. Khanna P.P. Matsuo H. Perez-Ruiz F. Stamp L.K. Gout. Nat Rev Dis Primers. 2019; 5 Crossref PubMed Scopus (114) Google Scholar ], UA has also been acknowledged as a significant CV risk factor [ [2] Virdis A. Masi S. Casiglia E. et al. Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years. Hypertension. 2020; 75: 302-308 Crossref PubMed Scopus (62) Google Scholar ]. However, international guidelines report as pathological threshold only the saturation point of UA (6.0 mg/dL in women and ≥7.0 mg/dL in men) [ [3] Li Q. Li X. Wang J. et al. Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. BMJ Open. 2019; 9 Crossref Scopus (44) Google Scholar ], yet failing to identify a specific CV prevention cut-off [ [4] Visseren F.L.J. Mach F. Smulders Y.M. et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Europe J Prev Cardiol. 2021; Crossref Google Scholar ]. This somewhat neglects UA predictive role in CV disease [ [5] Kaufman M. Guglin M. Uric acid in heart failure: a biomarker or therapeutic target?. Heart Fail Rev. 2013; 18: 177-186 Crossref PubMed Scopus (31) Google Scholar ]. In a large (n=22,714) Italian-population based observation cohort study, we have described how UA markedly impact all-cause and CV mortality starting from lower serum levels (respectively, 4.7 and 5.6 mg/dL) [ [2] Virdis A. Masi S. Casiglia E. et al. Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years. Hypertension. 2020; 75: 302-308 Crossref PubMed Scopus (62) Google Scholar ]. Several other observations have also found that UA enhances the CV mortality and morbidity risk stratification across the totality of the cardiometabolic spectrum using the same lower cut-offs [ [6] Pugliese N.R. Mengozzi A. Virdis A. et al. The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk. Clin Res Cardiol. 2021; 110: 1073-1082 Crossref PubMed Scopus (7) Google Scholar , [7] Muiesan M.L. Salvetti M. Virdis A. et al. Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the uric acid right for heart health study. J Hypertens. 2021; 39: 62-69 Crossref PubMed Scopus (12) Google Scholar ]. However, whilst in the current literature the relationship between UA in CV disease has been explored mainly in a chronic context (i.e. diabetes, hypertension, chronic kidney disease), little evidence is available to help us in defining whether the predictive power of UA holds true also for the acute setting, such as the acute coronary syndrome (ACS) [ [8] Maloberti A. Biolcati M. Ruzzenenti G. et al. The role of uric acid in acute and chronic coronary syndromes. J Clin Med. 2021; 10 Crossref Scopus (2) Google Scholar ].