Crystal-proven gout patients have an increased mortality due to cardiovascular diseases, cancer, and infectious diseases especially when having tophi and/or high serum uric acid levels: a prospective cohort study
To investigate the cause-specific mortality and the possible involved clinical characteristics with increased mortality in a cohort of 700 patients with crystal-proven gout. The cause-specific mortality of gout was compared to the mortality of the general population.
Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers Cohort (GOAL). Joint fluid analysis was performed in all patients and only crystal-proven gout patients were included in this study. At inclusion clinical characteristics and laboratory values were collected. At follow-up patients who died were identified. Standardized mortality ratios (SMRs) were calculated for all-causes, cardiovascular diseases, cancer, and infectious diseases using indirect standardization methods for mortality outcomes and compared with the general population. The clinical characteristics of the patients who died were compared with those of the survivors and were analyzed by a logistic regression analysis to identify any associations with mortality.
The study population at inclusion contained 573 (81.9%) men and 127 (18.1%) females with an average age of 62.0 (SD 13.4). During 3500 person-years from inclusion visit till 31 May 2016, in 700 gout patients, 66 deaths (27 cardiovascular deaths, 15 cancer-related deaths, 8 infectious deaths, 16 various other causes) occurred in this cohort. The all-cause standardized mortality ratio in gout patients was 2.21 (95% CI 1.68–2.74). In this cohort, gout patients had a higher SMR for death attributed to cardiovascular diseases (6.75; 95% CI 4.64–8.86), infectious diseases (4.66; 95% CI 1.51–7.82) and cancer (3.58; 95% CI 1.77–5.39). Corrected for confounders high serum uric acid levels (SUA; > 0,56 mmol/L), tophaceous gout, a history of peripheral vascular disease, myocardial infarction, and heart failure at the inclusion visit were associated with increased mortality during follow-up.
Compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases. This association is strongest in hyperuricemic (uric acid levels > 0,56 mmol/l) and tophaceous patients and in those with a history of peripheral vascular disease, myocardial infarction, and heart failure. Preventive measures like treatment of high SUA levels and treatment of cardiovascular risk factors need to be considered and evaluated.
KeywordsCancer Cardiovascular diseases Crystal-proven gout Infectious diseases Mortality Standardized mortality ratios (SMR)
We wish to thank E.P. Martens (Statisticor) for the assistance by the statistical calculations.
Compliance with ethical standards
- 7.Knoema (2015) World and Regional Statistics. Netherlands—mortality—crude death rate. https://knoema.com
- 8.Eurostat (2015) Major causes of death for persons aged 65 and over (standardized date rates per 100.000 inhabitants). https://ec.europa.eu
- 9.Disveld IJM, Fransen J, Rongen GA, Kienhorst LBE, Zoakman S, Janssens HJEM et al Crystal-proven gout and characteristic gout severity factors are associated with cardiovascular disease. J Rheumatol 45(6):858–863Google Scholar
- 13.Jing J, Kielstein JT, Schultheiss UT, Sitter T, Titze SI, Schaeffner ES, McAdams-DeMarco M, Kronenberg F, Eckardt KU, Kottgen A, for the GCKD Study Investigators, GCKD Study Investigators, Eckardt KU, Titze S, Prokosch HU, Barthlein B, Reis A, Ekici AB, Gefeller O, Hilgers KF, Hubner S, Avendano S, Becker-Grosspitsch D, Hauck N, Seuchter SA, Hausknecht B, Rittmeier M, Weigel A, Beck A, Ganslandt T, Knispel S, Dressel T, Malzer M, Floege J, Eitner F, Schlieper G, Findeisen K, Arweiler E, Ernst S, Unger M, Lipski S, Schaeffner E, Baid-Agrawal S, Petzold K, Schindler R, Kottgen A, Schultheiss U, Meder S, Mitsch E, Reinhard U, Walz G, Haller H, Lorenzen J, Kielstein JT, Otto P, Sommerer C, Follinger C, Zeier M, Wolf G, Busch M, Paul K, Dittrich L, Sitter T, Hilge R, Blank C, Wanner C, Krane V, Schmiedeke D, Toncar S, Cavitt D, Schonowsky K, Borner-Klein A, Kronenberg F, Raschenberger J, Kollerits B, Forer L, Schonherr S, Weissensteiner H, Oefner P, Gronwald W, Zacharias H, Schmid M (2015) Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German chronic kidney disease (GCKD) study. Nephrol Dial Transplant 30(4):613–621CrossRefPubMedGoogle Scholar
- 18.Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA (2010) Hyperuricemia and coronary heart disease: a systemic review and meta-analysis. Arthritis Care Res 62(2):170–180Google Scholar
- 20.Kienhorst LBE, van Lochem E, Kievit W, Dalbeth M, Merriman ME, Phipps-Green A et al (2015) Gout is a chronic inflammatory disease in which high levels of interleukin 8 (CXCL8) , myeloid-related protein 8/myoloid related protein 14 complex, and an altered proteome associated with diabetes mellitus and cardiovascular disease. Arthritis Rheum 67(12):3303–3313CrossRefGoogle Scholar
- 22.Kienhorst LBE, Janssens H, Radstake T, van Riel P, Jacobs J, van Koolwijk E, van Lochem E, Janssen M (2017) A pilot study of CXCL8 levels in crystal proven gout patients during allopurinol treatment and their association with cardiovascular disease. Joint Bone Spine 84(6):709–713CrossRefPubMedGoogle Scholar
- 24.Vazirpanah N, Kienhorst LBE, Van Lochem E, Wichers C, Rossato M, Shiels PG et al (2017) Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout. Ann Rheum Dis 76(7):1313–1319CrossRefPubMedGoogle Scholar