Urate is associated with both calcification and total atherosclerotic burden in coronary arteries: results from the SCAPIS study.
Drivelegka P 1, Jacobsson Lth 1, Forsblad D’elia H 1, Zverkova-Sandström T 1, Nilsson Pm 2, Fagman E 3, Söderberg S 4, Bergström G 5, Kapetanovic M 6, Dehlin M 1.
Affiliation(s):
1. department Of Rheumatology And Inflammation Research, Institute Of Medicine, Sahlgrenska Academy, University Of Gothenburg, Gothenburg, Sweden.
2. Department Of Clinical Sciences Malmö, Lund University, Sweden.
3. department Of Radiology, Institute Of Clinical Sciences, Sahlgrenska Academy, University Of Gothenburg, Gothenburg, Sweden.
4. Department Of Public Health And Clinical Medicine, Medicine, Umeå University, Umeå, Sweden
5. Department Of Clinical And Molecular Medicine, Sahlgrenska Academy, University Of Gothenburg, Sweden
6. Institution Of Clinical Sciences Lund, Section For Rheumatology And Skåne University Hospital Lund, Lund University, Sweden
Background: Elevated urate levels may promote atherosclerosis and cardiovascular disease (CVD) by inducing systemic inflammation, endothelial dysfunction, and proliferation of vascular smooth muscle cells (1). Coronary atherosclerosis can be assessed by computed tomography (CT) using the coronary artery calcification score (CACS). By adding coronary CT angiography (CCTA), the total burden of coronary atherosclerosis, including both calcified and non-calcified plaques, can be determined and described as the segment involvement score (SIS). SIS may improve the prediction of coronary events beyond traditional cardiovascular risk factors and CACS (2). While the association between elevated urate levels and CACS remains controversial (3, 4), the association between elevated urate levels and SIS has not been studied.
Objectives: To investigate the association between plasma urate and coronary atherosclerosis, assessed by CACS and SIS, in participants of the Swedish Cardiopulmonary bioimage study (SCAPIS).
Methodology: SCAPIS is a nationwide, population-based cohort of men and women aged between 50-64 years, randomly recruited from the general Swedish population (N=30,000). This study included participants with measured plasma urate no prior history of gout or CVD (N=11, 839). CACS was categorized as 0–9 (reference), 10–100, 101–300, and >300 Agatston units. Associations between urate and CACS were examined using ordinal logistic and negative binomial regression analyses. Urate was modeled as both a continuous variable and dichotomized (<405 vs ≥405 µmol/L). Associations with SIS were evaluated using logistic regression with two cutoffs: SIS=0 vs >0 and SIS 0–3 vs ≥4. Probability estimates and odds ratios (OR) with 95% confidence intervals (CI) were calculated in crude models and after adjustment for traditional cardiovascular risk factors.
Results: For the CACS analyses, 5,428 men and 6,083 women were included. In both men and women, plasma urate was associated with a significantly increased probability of having a higher CACS (CACS 10-100, 101-300, >300), compared to the reference group (CACS 0–9). These associations were consistent when urate was modeled as a continuous and as a dichotomous variable (urate <405 vs ≥405) and remained statistically significant even in the fully adjusted models (Table 1). For the SIS analyses, 4,345 men and 4,903 women were included. Similarly, in both men and women, urate was associated with a significantly increased probability of having SIS >0 and SIS ≥4 compared to the reference groups (SIS=0 and SIS 0-3, respectively). These associations remained significant even in the fully adjusted models (Table 2).
Conclusions: Among individuals without prior CVD, urate levels were independently associated with a higher burden of coronary atherosclerosis, as reflected by both CACS and SIS. These findings support urate as a potential biomarker of subclinical coronary atherosclerosis.
References
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2. Bergström G, Engström G, Björnson E, Adiels M, Andersson JSO, Andersson T, et al. Coronary Computed Tomography Angiography in Prediction of First Coronary Events. Jama. 2025.
3. Kiss LZ, Bagyura Z, Csobay-Novák C, Lux Á, Polgár L, Jermendy Á, et al. Serum Uric Acid Is Independently Associated with Coronary Calcification in an Asymptomatic Population. J Cardiovasc Transl Res. 2019;12(3):204-10.
4. Neogi T, Terkeltaub R, Ellison RC, Hunt S, Zhang Y. Serum urate is not associated with coronary artery calcification: the NHLBI Family Heart Study. J Rheumatol. 2011;38(1):111-7.
