Gouty Offense in Patients With Obstructive Coronary Artery Disease Despite State‐of‐the‐Art Therapy

G out is a painful condition of the joints and affects up to 2% of the world’s population, mainly in industrialized and emerging countries. It is caused by hyperuricemia and triggered by the incorporation of crystallized salts of uric acid (urates) in the joints. However, hyperuricemia is also associated with hypertension, type 2 diabetes mellitus, obesity, chronic kidney disease, and cardiovascular disease (CVD). While earlier studies explained the strong associations between CVD and prevalent hyperuricemia with comorbid conditions such as metabolic syndrome, renal dysfunction, and hypertension, large epidemiological studies have now demonstrated that gout is an independent risk factor for CVD. Nevertheless, in this issue of the Journal of the American Heart Association (JAHA), Pagidipati et al revisited this paradigm since treatment regimens of CVDs have improved lately and individuals included in earlier investigations were not separated by the type of coronary artery disease (CAD) present or the studies were mainly conducted in men. The authors surveyed the long-term association between gout and CVD in a contemporary population of men and women with known CAD from the Duke Databank for Cardiovascular Diseases. The 17201 patients who were included in this study underwent cardiac catheterization at Duke University Medical Center between 1998 and 2013 and were found to have obstructive CAD. Furthermore, 1406 of these individuals had a baseline history of gout (8.2%), while 15 795 did not. Notably, from these patients with a history of gout at time of catheterization a majority (66.9%) already received at least 1 gout medication at baseline. Gout-at-baseline individuals were also mostly older, more often male, nonwhite, and more commonly had a history of myocardial infarction (MI), coronary revascularization, congestive heart failure, cerebrovascular disease, peripheral vascular disease, diabetes mellitus, hypertension, and renal disease compared with those without gout. In general, the majority of subjects included in this study received optimal medical therapy for CVD. In this context, Pagidipati et al further revealed that over a median follow-up of 6.4 years after catheterization, a diagnosis of gout at the time of catheterization was not primarily associated with cardiovascular death, MI, or stroke, but significantly correlated with higher overall mortality and was associated with cardiac and noncardiac deaths. An initial (baseline) gout diagnosis was particularly associated with a more than 2-fold increase in the risk of death from heart failure. Overall, these data suggest that long-term cardiovascular mortality is increased despite medical therapy of obstructive CAD in patients with clinical manifestations of gout and that current standard therapies do not address that residual cardiovascular risk. As noted before, gout and hyperuricemia have been identified as risk factors for atherosclerosis and CAD (for example, in the Framingham Study or in the US National Health and Nutrition Examination Survey). Both studies report an 60% increase in coronary heart disease or cardiovascular mortality in men with gout, but not in women, regardless of traditional risk factors or diuretic medications. The survey also revealed a gradual increase in cardiovascular mortality dependent on blood uric acid levels. In line with this, a prospective study of the Health Professionals Follow-Up Study confirmed these data by also revealing an 60% increase in the risk of fatal coronary heart disease in men with diagnosed gout and a history of CVD. Additional new independent meta-analyses have confirmed these correlations of gout and CVD risk. However, the most conclusive studies have only been conducted in men, most likely because risk factors and development of gout in women follow different patterns since serum estrogen levels play a significant role in the control of uric acid levels. Therefore, extrapolation of data on gout from men to The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany (Y.D., E.P.C.v.d.V.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (Y.D.). Correspondence to: Emiel P. C. van der Vorst, PhD, or Yvonne D€oring, PhD, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 8a und 9, D-80336 M€unchen, Germany. E-mail: emiel.van_der_vorst@med.uni-muenchen.de or ydoering@med.lmu.de J Am Heart Assoc. 2018;7:e010322. DOI: 10.1161/JAHA.118.010322. a 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.