The risk of clinically diagnosed gout by serum urate levels: results from 30 years follow-up of the Malmö Preventive Project cohort in southern Sweden

Meliha C. Kapetanovic, Peter Nilsson, Carl Turesson, Martin Englund, Nicola Dalbeth, Lennart Jacobsson

Hyperuricemia (HU) is in the causal pathway for developing clinical gout. There are few population-based assessments of the absolute and relative risk of clinically diagnosed incident gout in subjects with HU. We aimed to explore the long-term risk of developing incident gout among asymptomatic adults with different levels of serum urate (SU). Malmö Preventive Project was a population-based screening program for cardiovascular risk factors, alcohol abuse, and breast cancer in Malmö, Sweden. The study population was screened between 1974 and 1992. At baseline, subjects were assessed with a questionnaire, physical examination, and laboratory tests. Follow-up ended at first gout diagnosis, death, moving from area, or December 31, 2014. Incident gout (using ICD10 codes) was diagnosed based on national registers for specialized inpatient and outpatient care, and from 1998 onward in the Skåne Healthcare Register including primary healthcare. Incidence rates, absolute risk, hazard ratios (HRs) and potentially associated factors were analyzed by baseline SU levels, i.e. normal levels (≤ 360 μmol/L); 361-405 (levels below tissue solubility of SU), and > 405 (HU), overall, and by sex. Overall, 1275 individuals [3.8%; 1014 men (4.5%) and 261 women (2.4%)] of the 33,346 study participants (mean age: 45.7 (SD: 7.4), 67% men), developed incident gout during follow-up (mean 28.2 years). Of those with HU, 14.7% of men and 19.5% of women developed gout. Compared to subjects in the lowest SU category, the age-adjusted HR in men increased from 2.7 to 6.4, and in women from 4.4 to 13.1 with increasing baseline SU category, and with a statistically significant interaction of sex (p < 0.001). Body mass index, estimated glomerular filtration rate (negative), triglycerides, alcohol risk behavior (only in men), and comorbidities such as hypertension, cardiovascular disease, and diabetes were strongly associated with SU at baseline in both sexes. The absolute risk for developing clinically diagnosed gout over 30 years in middle-aged subjects was 3.8%, and increased progressively in both men and women in relation to baseline SU. This risk increase was significantly higher in women than in men, whereas the associations between baseline risk markers and SU levels were similar in both sexes.