#5773 URINARY OROSOMUCOID IS ASSOCIATED WITH ALL-CAUSE MORTALITY IN THE GENERAL POPULATION

Abstract

Abstract Background and Aims Urinary albumin excretion (UAE) is considered a risk factor for cardiovascular (CV) disease and all-cause mortality, but the pathophysiological mechanisms are not known, and studies are not consistent with regards to the effect of pharmacological UAE reduction on endpoints. Another protein, orosomucoid (41-43kDa), is a non-specific acute inflammatory protein and is a part of the glycolax that covers the endothelium. Under normal conditions the concentration in urine is low, but a marked increase is demonstrated under both acute and chronic inflammation and in cardiovascular disease. In patients with diabetes urinary orosomucoid excretion (UOE), was an independent predictor of all-cause and cardiovascular mortality even in normoalbuminuric patients. In this longitudinal study, our aim was to study both UAE and UOE in a middle-aged cohort from the general population. We hypothesized that UOE, but not UAE, is an independent predictor for all-cause mortality. Method The Tromsø Study is a population-based, prospective study with repeated health surveys of inhabitants of Tromsø (Northern Norway), and the first took place in 1974. From the sixth wave (Tromsø6, 2007/2008) we included all participants with urinary samples. Follow-up time was assigned from the attendance date of Tromsø6 until 31.08.2022. The associations between urinary markers and all-cause mortality were assessed by Cox regression analysis. Results The cohort included 7180 subjects (4094 women and 3086 men) with a mean (SD) age 63.5 (±9.2) years. Median urinary orosomucoid to creatinine ratio (UOCR) was 0.44 g/g, median albumin to creatinine ratio (UACR) was 0.36 mg/mmol, mean (SD) eGFR was 88.1 (±14.0) ml/min/1.73m² and 1689 died during follow-up. UOCR was independently associated with all-cause mortality (hazard ratio (HR) per g/g increase 1.02, 95% CI 1.01,1.03, p<0.001) adjusted for sex, age, UACR, eGFR and CV risk factors (diabetes, hypertension, smoke, cholesterol, BMI). The HR for UOCR above vs. below median adjusted for the same variables was 1.13 (95% CI 1.01, 1.27, p = 0.032). UACR above median with the same adjustments was not associated to all-cause mortality (hazard ratio 1.04, 95%CI 0.93, 1.15, p = 0.484). Conclusion In this study, we showed for the first time that UOE, but not UAE, was an independent predictor of all-cause mortality in a large cohort from the general population. Thus, UOE may be an earlier marker of vascular damage than UAE. Whether UOE is clinically useful as an early marker of CV disease should be further studied.