The U-Shaped Relationship Between Serum Uric Acid and Long-Term All-Cause Mortality in Coronary Artery Disease Patients: A Cohort Study of 33,034 Patients

Abstract

BackgroundAssociations between high serum uric acid (SUA) and cardiovascular diseases have been reported. However, few studies have been conducted to explore the relationship between SUA and long-term all-cause mortality in coronary artery disease (CAD) patients. Our study aims to investigate the relationship between SUA and long-term all-cause mortality in patients with CAD.MethodsFrom January 2007 to December 2018, we divided 33,034 patients with CAD admitted in the Guangdong Provincial People's Hospital into five groups (quintile 1: SUA <5.05 mg/dl, quintile 2: 5.05 mg/dl ≤ SUA <5.59 mg/dl, quintile 3:5.59 mg/dl ≤ SUA <6.8 mg/dl, quintile 4, 6.8 mg/dl ≤ SUA <7.93 mg/dl, and quintile 5, SUA ≥7.93 mg/d;). This study used Kaplan–Meier survival analysis to evaluate patient outcomes with different ranges of SUA. Cox proportional hazards regression models and restricted cubic spline were applied to determine the association between serum uric and long-term all-cause mortality.ResultsA total of 33,034 participants were recruited, including 24,780 (75.01%) men and 8,254 (24.99) women in this cohort study. Median follow-up was 4.91 years. We found that SUA is an independent risk factor of long-term all-cause mortality according to the result of Cox proportional hazards models. This study also illustrated an approximate U-shape association between SUA and all-cause mortality when compared with 5.95 mg/lL ≤ SUA <6.8 mg/dl, SUA <5.0 5mg/dl (adjusted hazard ratio (aHR) =1.13, 95% CI: 1.01–1.26, p = 0.03), and SUA ≥8 mg/dL (aHR = 1.18, 95% CI: 1.06-1.32, p = 0.003).ConclusionOur study indicated a U-shaped relationship between SUA and long-term all-cause mortality in patients with CAD. No matter whether SUA is too high or too low, it increased the all-cause mortality in the CAD population, which deserves to be closely monitored.

U-shaped association of serum uric acid with all-cause mortality in patients with hyperlipidemia in the United States: a cohort study

“…It should be noted, however, that although these studies have confirmed a U-shaped relationship between SUA and all-cause mortality, the authors reported different optimal thresholds for SUA. For example, Weicheng et al found that in an older population aged >65 years, both low (<4 mg/dl) and high (>8 mg/dl) SUA levels were independently associated with an increased risk of all-cause mortality ( 19 ), and similarly in a cohort study of a Chinese population with coronary artery disease, the authors identified a U-shaped association in which the risk of all-cause mortality increased at both low (≤5.05 mg/dl) and high (≥8.0 mg/dl) levels of SUA ( 18 ). In addition, a cohort study including 375,163 Korean general medical examination population found that both low uric acid group (<3.5 mg/dl in men; <2.5 mg/dl in women) and high uric acid group (>9.5 mg/dl in men; >8.5 mg/dl in women) increased all-cause mortality compared to the sex-specific reference group ( 22 ).…”

“…A recent review of studies conducted on populations with different health conditions ( 9 ), including healthy individuals ( 16 , 17 ), patients with coronary heart disease ( 18 ), older patients ( 19 ), patients with hypertension ( 20 ), and patients with chronic kidney disease ( 21 ), summarized the U-shaped association between SUA and various adverse clinical outcomes, such as all-cause mortality and cardiovascular mortality. Our study confirmed the U-shaped relationship between SUA and all-cause mortality in patients with hyperlipidemia.…”

“…Although much of the previous research has focused on the pathophysiological effects of high levels of uric acid (hyperuricemia), more recently, the focus of research has extended to examining the effects of hypouricemia, with the findings of several studies indicating that abnormally low levels of SUA may have potentially severe effects. In this regard, it has been suggested that SUA may act as an important antioxidant molecule, accounting for 50% of the body's total antioxidant capacity ( 7 ), and it has been demonstrated that low SUA levels are associated with a loss of free radical scavenging capacity, which may in turn contribute to an increase in vascular endothelial cell damage and thus higher cardiovascular-associated mortality ( 18 ). Similarly, in a retrospective cohort study of hypertensive patients, low values of uric acid were found to be associated with an increase in cardiovascular mortality, and is potentially a causal factor for stroke and heart-specific mortality ( 20 ).…”

The potential relationship of coronary artery disease and hyperuricemia: A cardiometabolic risk factor

“…A cohort study concluded that blood uric acid level reached a minimum risk of all-cause mortality in patients with CAD at 6.52 mg/dL in men and 5.83 mg/dL in women, with a subsequent increase in the risk of mortality regardless of whether uric acid concentrations increased or decreased. The results of the study showed that CAD with serum uric acid level in the interval (5.59 mg/dL ≤ SUA < 6.8 mg/dL) had a better prognosis [ 93 ]. However, the result of the EPOCH-JAPAN study differed, with low uric acid levels (<4.6 mg/dL in men and <3.9 mg/dL in women) increasing mortality from CAD, heart failure, and stroke [ 90 ].…”

“…Is it the drug or the uric acid concentration that makes uric acid-lowering therapy effective in reducing the risk of poor prognosis in CAD, given its effect on improving the risk of poor prognosis in CAD? Clinical studies have shown a U-shaped relationship between serum uric acid and all-cause mortality in CAD in the group using uric acid-lowering drugs, with low and high levels of serum uric acid still associated with increased long-term all-cause mortality in patients with CAD, and the use of uric acid-lowering drugs did not reduce all-cause mortality [ 93 ]. Based on the available studies, it is believed that there are harmful effects of uric acid-lowering drugs that increase the risk of death from CAD and that a sharp decrease in uric acid concentration may be responsible for the harmful effects of uric acid-lowering drugs [ 110 , 111 ].…”