Elevated Uric Acid Mediates the Effect of Obesity on Hypertension Development: A Causal Mediation Analysis in a Prospective Longitudinal Study

Abstract

Conglin Hong,1,* Qiu Zhang,2,* Yan Chen,3,* Ying Lu,1 Linan Chen,1 Yan He,1 Jing Li,1 Shengqi Ma,1 Jun Jiang,4 Xiaolong Zhang,4 Jianwei Hu,5 Yi Ding,6 Mingzhi Zhang,1 Hao Peng1,7 1Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Chronic Disease, Gusu Center for Disease Prevention and Control, Suzhou, People’s Republic of China; 3Department of Nephrology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, People’s Republic of China; 4Department of Tuberculosis Control, Suzhou Center for Disease Control and Prevention, Suzhou, People’s Republic of China; 5Department of Central Office, Maternal and Child Health Bureau of Kunshan, Suzhou, People’s Republic of China; 6Department of Preventive Medicine, College of Clinical Medicine, Suzhou Vocational Health College, Suzhou, People’s Republic of China; 7Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao Peng; Mingzhi Zhang, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, 215123, People’s Republic of China, Tel [phone], Email [email protected]; [email protected]: Although elevated uric acid is associated with obesity and considered a predictor of hypertension, the causal linkage between the three metabolic conditions is not very clear. We aim to examine whether elevated uric acid mediates the effects of obesity on hypertension development.Methods: A total of 1984 participants (mean aged 53 years, 62.10% female) with repeated measurements of obesity, blood pressure, and uric acid 4 years apart in the Gusu cohort were included. We first applied cross-lagged panel analysis and bidirectional association analysis to delineate the temporal association between obesity and hyperuricemia. Then, a causal mediation model was constructed to further examine the causal role of hyperuricemia in the linkage between obesity and hypertension. Age, sex, education, cigarette smoking, alcohol consumption, fasting blood glucose, and lipids were adjusted.Results: The cross-lagged panel analysis demonstrated that the relationship from baseline obesity to follow-up hyperuricemia was stronger than that from baseline hyperuricemia to follow-up obesity (β: 0.09 vs 0.06, P 0.05). The causal mediation analysis found that hyperuricemia partially mediated the association of baseline BMI (mediate proportion: 3.09%, 95% CI: 0.97%∼ 6.00% for SBP, 3.74%, 95% CI: 1.55%∼ 7.00% for DBP) and baseline WC (mediate proportion: 5.56%, 95% CI: 2.01%∼ 11.00% for SBP, 5.81%, 95% CI: 2.59%∼ 10.00% for DBP) with follow-up blood pressures.Conclusion: Obesity preceded hyperuricemia and the latter partially mediated the relationship between obesity and hypertension, independent of behavioral and other metabolic factors.Keywords: bidirectional association analysis, causal mediation analysis, cross-lagged panel analysis, blood pressures, temporal relationship, uric acid, obesity

Keywords

• bidirectional association analysis
• causal mediation analysis
• cross-lagged panel analysis
• blood pressures
• temporal relationship
• uric acid
• obesity