Uric Acid Variability as a Predictive Marker of Newly Developed Cardiovascular Events in Type 2 Diabetes

Abstract

Background: Cardiovascular disease (CVD) is associated with morbidity and mortality in patients with type 2 diabetes mellitus (T2D). However, the role of serum uric acid as a risk factor for developing cardiovascular disease is controversial. This study investigated whether uric acid variability was associated with new-onset symptomatic CVD in patients with T2D, requiring percutaneous coronary intervention.Methods: A total of 1,071 patients were enrolled in this retrospective cross-sectional study after propensity score matching. Patients with T2D and new-onset symptomatic CVD who received percutaneous coronary intervention for the first time, and with at least three consecutive 6-monthly measurements of serum uric acid were recruited from Severance Hospital between January 2015 and December 2019. Uric acid variability was measured by average successive variability (ASV) and analyzed to evaluate a possible correlation with the risk of developing CVD.Results: The patients were divided into quartiles based on the uric acid variability. Patients in the highest quartile were older and presented lower renal function and a higher mortality from CVD. There was a linear association between a high uric acid variability and the development of CVD. Compared to the lowest quartile, patients in the higher quartiles had a higher risk of CVD [quartile 3: adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI), 1.20–2.82; P = 0.019; quartile 4 aOR = 2.89; 95% CI, 1.74–4.80; P < 0.001].Conclusion: High uric acid variability is independently associated with an increased risk of new-onset symptomatic CVD requiring percutaneous coronary intervention in patients with T2D. Thus, maintaining serum uric acid in a narrow range by prescribing effective medications is essential to prevent new-onset CVD in patients with T2D. Nonetheless, the potential use of uric acid variability as a predictive marker of CVD in patients with T2D needs further validation.

Multicomponent prediction of 2‐year mortality and amputation in patients with diabetic foot using a random survival forest model: Uric acid, alanine transaminase, urine protein and platelet as important predictors

“…UA identified was as a predictor for mortality, which is consistent with previous studies 24–27 . It is thought that high concentrations of UA in T2DM facilitated insulin resistance, DPN and cardiovascular disease, which were associated with mortality 28–31 . ALT was ranked as the second‐best for predictor of mortality.…”

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

“…Besides, evidence from previous studies indicated that high uric acid is independently associated with an increased risk of new-onset CVD in patients with diabetes ( 21 , 22 ). Which is consistent with our finding that keeping or rising to hyperuricemia was significantly associated with the incidence of cardiovascular diseases among patients with diabetes (OR, 1.67; 95% CI, 1.15, 2.44, P = 0.007).…”

“…However, as for CVD, other studies demonstrated the associations between SUA and CVD, for example, a prospective study, found that compared with individuals in the bottom third of baseline measurements of serum uric acid in the Reykjavik study, those in the top third had an age- and sex-adjusted odds ratio for CHD of 1.39 (95% CI, 1.23–1.58) ( 20 ). Evidence from the Third National Health and Nutrition Examination Survey revealed an increased risk of CV mortality with increasing SUA levels, hazard ratio (95% CI) per 59.5 mmol/l of SUA was 1.32 (1.25–1.38), and remained 1.15 (1.08–1.21) even after adjusted for demographic factors, comorbidities and other risk factors ( 21 ). The role of SUA as a risk factor for developing cardiovascular disease is controversial ( 22 ), and the association between SUA and CVD may be explained by its complex relationship with other cardiovascular risk factors ( 23 ).…”

“…There is evidence that certain conditions are more likely to cluster due to shared pathological pathways or networks, whereby the onset of one condition increases the risk of another ( 24 ), previous studies showed that associations of diabetes with chronic disease outcomes are largely independent of major cardiovascular risk factors ( 25 , 26 ) and diabetes is a well-established risk factor for heart disease and stroke. Although the underlying mechanisms for higher risks of CVD among participants with diabetes remain unclear, previous studies have suggested hyperuricemia in patients with diabetes causes incremental variations in uric acid levels over time, thus increasing oxidative stress and generating free radicals, which contribute to endothelial dysfunction and RAAS activation, ultimately leading to CVD ( 13 , 21 ). But studies also suggested that the apparent association might be explained that SUA caused CVD is primarily a function of SUA being strongly collinear with established CVD risk factors ( 14 , 27 ).…”

Lower Serum Uric Acid Levels May Lower the Incidence of Diabetic Chronic Complications in U.S. Adults Aged 40 and Over

“…In addition, the statistical analysis, study population, and adjusted covariates differed in the above-mentioned research. For instance, age, sex, eGFR, HbA1C, and duration of DM were adjusted in Seok Kang’s research [ 33 ], while systolic/diastolic blood pressure, serum lipid, and waist circumference were adjusted in Liu’s study [ 30 ], and our study additionally adjusted race, education levels, and poverty income ratio, which might lead to the different results. Participants involved in the above-mentioned research had different characteristics.…”