Table 1.

Pivotal clinical studies on the relationship between sUA level and cardiovascular disease.

Study	Study design	Population	No. of Subjects	Main findings/outcomes
Hypertension
Kuwabura et al., 2018b	Retrospective cohort	Prehypertension	3584	Increased sUA is a strong risk marker for developing hypertension from prehypertension
Sun et al., 2015	Prospective randomized	Adolescents	5478	A high level of UA indicated a higher likelihood of developing hypertension
Grayson et al., 2011	Meta-analysis (prospective)	Without hypertension	55607	Hyperuricemia is associated with an increased risk for incident hypertension, independent of traditional hypertension risk factors
Bjornstad et al., 2019	Follow-up RCT	Obese youth with T2D	539	Higher baseline sUA independently increased the risk for onset of hypertension
Tomiyama et al., 2018	Prospective	Men without hypertension	3274	Hyperuricemia may have a longitudinal association with the development of hypertension
Chen et al., 2018	Double-blind placebo RCT	Early Parkinson’s disease patients	75	Elevated urate is not association with high BP
Johnson et al., 2019	RCT	Chronic refractory gout	212	ULT can significantly reduce BP
Coronary heart disease
Braga et al., 2016	Meta-analysis (prospective)	Without CVD	457915	Hyperuricemia appears to increase the risk of CHD events in the general population
Dai et al., 2015	Retrospective	Under 45 years old diagnosed with EOCAD	786	sUA >8 mg/dl was independently associated with triple branches involvement, HF and LV enlargement
von Lueder et al., 2015	Meta-analysis	Four clinical trials	12677	Elevated sUA is associated with poor outcomes
Li M. et al., 2016	Systematic review (prospective)	Hyperuricemia or elevated sUA level	958410	Hyperuricemia was associated with increased risk of CHD morbidity and mortality
Wang R. et al., 2016	Meta-analysis	With suspected or definite CHD	25229	Elevated sUA levels are strongly and independently associated with greater risk of cardiovascular and all-cause mortality
Jun et al., 2018	Retrospective cohort	CT evaluation of CAC	9297	sUA was an independent predictor for development of moderate CAC in subjects with no or minimal calcification
Atrial fibrillation
Kuwabara et al., 2017c	Retrospective	Without general cardiovascular risk	49292	Hyperuricemia is an independent competing risk factor for AF
Zhang et al., 2016	Meta-analysis (prospective)	Hyperuricemia	426159	Hyperuricemia is associated with increased risk of AF
Pak et al., 2018	Meta-analysis	With and without AF	30609	The mean SUA level of patients with AF significantly is higher than those without AF
Canpolat et al., 2014	Prospective	Paroxysmal AF undergoing cryoablation	363	sUA levels were associated with a higher rate of AF recurrence
Zhao et al., 2016	Meta-analysis	AF undergoing cryoablation	1298	Elevated sUA is not associated with increased risk of AF recurrence after catheter ablation
Heart failure
Pavlusova et al., 2019	Prospective	Acute HF	3610	Hyperuricemia was associated with an unfavorable cardiovascular risk
Palazzuoli et al., 2017	Prospective	Acute HF	324	Hyperuricemia was the only independent predictor of HF hospitalization or death
Vaduganathan et al., 2014	Double-blind placebo RCT	Worsening chronic HF	3955	sUA is commonly elevated in patients hospitalized for worsening chronic HF
Huang et al., 2014	Meta-analysis	Chronic HF	427917	Elevated sUA is associated with an increased risk of incident HF and adverse outcomes in HF patients

Numerous clinical studies and meta-analysis have shown that UA levels are significantly positively correlated with cardiovascular diseases, including hypertension, coronary atherosclerosis, AF, and HF.

AF, atrial fibrillation; BP, blood pressure; CAC, coronary artery calcium; CHD, coronary heart disease; CT, computed tomography; CVD, cardiovascular disease; EOCAD, early-onset coronary artery disease; HF, heart failure; LV, left ventricle; RCT, randomized controlled trial; sUA, serum uric acid; T2D, type 2 diabetes; UA, uric acid; ULT, uric acid-lowering treatments.