Change of serum uric acid and progression of cardiometabolic multimorbidity among middle aged and older adults: A prospective cohort study

Abstract

BackgroundHyperuricemia is prevalent and associated with individual cardiometabolic diseases, highlighting the potential role of serum uric acid (SUA) in the development and progression of cardiometabolic multimorbidity (CMM, the coexistence of diabetes, heart disease, or stroke). This study aimed to examine the role of SUA change in the progression of CMM.MethodsThis prospective cohort study used data from the China Health and Retirement Longitudinal Study, included 4,820 participants aged 45 years or above with three complete surveys at 2011 (baseline), 2015, and 2018. SUA level at survey 2011 and 2015 was used to measure SUA change as keeping or rising to hyperuricemia, and keeping or declining to non-hyperuricemia. CMM progression was defined as the first report of CMM or additional report of cardiometabolic diseases during survey 2015 and 2018. We used logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of SUA change on CMM progression.ResultsDuring the follow-up of around 7 years, 519 (10.8%) of the participants kept or rose to hyperuricemia from survey 2011 to 2015, and 311 (6.5%) experienced CMM progression from survey 2015 to 2018. Participants who kept or rose to hyperuricemia had 1.86 (95% CI, 1.29, 2.68) increased odds of CMM progression compared with those who kept or declined to non-hyperuricemia. Specifically, keeping or rising to hyperuricemia (vs. keeping or declining to non-hyperuricemia) was associated with 2.01 times higher odds (95% CI, 1.18, 3.43) of incident diabetes and 1.67 times higher odds (OR:1.67; 95% CI, 1.15, 2.43) of incident cardiovascular diseases following diabetes.ConclusionKeeping or rising to hyperuricemia was associated with CMM progression, particularly with incident cardiovascular diseases following diabetes. These findings suggest that monitoring SUA change may provide innovative insights into the prevention of CMM, especially in the secondary prevention of CMM (i.e., preventing further progression to cardiovascular diseases among patients with diabetes).

Genome‐wide association study of cardiometabolic multimorbidity in the UK Biobank

“…Furthermore, our MR analysis showed the application value of the GWAS results in the causal inference of CMM risk factors. Consistent with previous studies, 2,9 we observed potential causal effect of total cholesterol, serum urate, smoke, and BMI. Cholesterol, BMI and unhealthy lifestyles are known causal factors of CMDs.…”

“…However, although there is association between elevated uric acid and increased CMDs risk, the mechanism is still inconclusive. 9,44 Currently, prooxidant activity, depletion of nitric oxide and endothelial dysfunction, promotion of inflammation and potentiation of vasoconstrictor and proliferative vascular stimuli are the most accepted mechanisms. 44 Besides, depression was found an independent risk factor for CMM by Qiao et al, 8 but we did not found evidence for causal association.…”

“…Cholesterol, BMI and unhealthy lifestyles are known causal factors of CMDs. However, although there is association between elevated uric acid and increased CMDs risk, the mechanism is still inconclusive 9,44 . Currently, pro‐oxidant activity, depletion of nitric oxide and endothelial dysfunction, promotion of inflammation and potentiation of vasoconstrictor and proliferative vascular stimuli are the most accepted mechanisms 44 .…”

“…To show the application value of our GWAS in the causal analysis of CMM, we performed two‐sample MR analysis testing previously reported risk factors including total cholesterol, 24 serum urate, 9 body mass index, 2 smoke (cigarettes per day), 2 alcohol consumption (drinks per week), 2 and depression 8 as examples. The statistical analysis was implemented in R package TwoSampleMR (v0.5.7) 25 .…”

“…Previous studies have demonstrated several environmental risk factors associated with CMM, including unhealthy lifestyles, 2 body mass index (BMI), 2 depression, 8 serum uric acid, 9 and so forth. However, these studies have mainly adopted survival analysis methods.…”