Among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), elevated uric acid (UA) in serum appears to be linked with a higher 10-year mortality incidence, study findings published in The American Journal of Cardiology suggest. However, UA was not linked with higher rates of nontarget vessel revascularization or target lesion revascularization.
“Population-based studies have suggested that subjects with CAD appear to have higher levels of UA in serum than subjects without CAD and the presence of CAD appears to strengthen the association between UA and mortality,” wrote lead study author Gjin Ndrepepa, MD, and colleagues. “However, studies with a short-term follow-up have reported an association between UA and mortality, whereas studies with a longterm follow-up have reported an attenuation of the association between UA and mortality.”
Assessing the Link Between UA & Adverse Outcomes
To better understand the link between UA and mortality, as well as investigate the association between UA and other adverse outcomes related to the progression of atherosclerosis, the researchers used two randomized trials as source samples. More than 5,000 adult patients with CAD underwent PCI with stent implantation between September 2007 and August 2009 following presentation with ischemic symptoms or evidence of myocardial ischemia.
Using blood samples taken before angiography, the study team measured UA concentration in serum with an enzymatic colorimetric test on a Cobas Integra 800 analyzer. “In the presence of the enzyme peroxidase, hydrogen peroxide reacts with a cromogen (amino-antipyrine and dichloro-hydrobenzen) to form quinoneimine, a red-colored product,” they wrote in their paper. Further, cardiovascular risk factors, including arterial hypertension, hyperlipidemia, diabetes mellitus, and smoking, were defined using guideline-recommended criteria.
Along with their primary endpoint of determining 10-year, all-cause mortality, the authors also sought to analyze cardiac mortality, noncardiac mortality, myocardial infarction, definite stent thrombosis, target lesion revascularization, target vessel revascularization, and nontarget vessel revascularization at 10 years. Follow-ups were performed by telephone or office visits at 1 and 12 months and annually for up to 10 years.
Identifying At-Risk Patients
For their study, Dr. Ndrepepa and colleagues included 3,998 patients who were placed in groups according to the tertile values of UA: tertile 1 (UA <5.80 mg/dl; n=1,347 patients), tertile 2 (UA 5.80 mg/dl to 7.04 mg/dl; n=1,340 patients), and tertile 3 (UA >7.94 mg/ dl to 18.0 mg/dl; n=1,311 patients). Follow-up intervals (median [25th–75th percentiles]) for patients in the 1st, 2nd, and 3rd tertiles were 10.6 [9.7–11.4] years, 10.8 [10.0–11.5] years, and 10.8 [10.0–11.6] years, respectively (P=0.073).
The researchers reported that 1,200 patients met the primary study endpoint. Specifically, 320 deaths occurred in patients with UA in the 1st tertile, 325 in the 2nd tertile, and 555 in the 3rd tertile (Table). There were 748 patients who experienced cardiac deaths—194 deaths occurred in patients with UA in the 1st tertile, 202 in the 2nd tertile, and 352 in the 3rd tertile. “Our study suggested that elevated UA levels appear to be a specific marker of increased risk of mortality,” wrote the study authors.
Dr. Ndrepepa and colleagues noted in their paper that patients’ risk for myocardial infarction was lowest in those with UA in the 2nd tertile. “In patients with CAD undergoing PCI, elevated UA in serum was associated with a higher incidence of 10-year mortality,” they wrote. “Based on the strong association between UA and 10-year mortality, measurement of UA may be used to improve the risk stratification of patients with CAD after treatment with PCI.”
