Uric Acid for Cardiovascular Risk: Dr. Jekyll or Mr. Hide?

Abstract

Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA “biological shift” from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient’s hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an “alarm” for increased CV risk.

Low concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in overweight or obesity

“…16 UA is a potent antioxidant, although at higher levels may acquire pro-oxidant activity and an adverse role as cardiometabolic risk factor. 13,17 In the present study, UA highest levels were found in subjects with positivity for both tests, and intermediate in those with one test positive, respect to patients with negativity for both tests, possibly reflecting a progressively increased cardiometabolic risk. 18 In our population, concordance between OGTT and HbA1c test to diagnose pre-T2D and T2D was similar in the two genders.…”

“…Moreover, increased oxidative stress promotes the autoxidation of glucose to dicarbonyl intermediates in an early step of the Maillard reaction, through which takes place the haemoglobin glycation . UA is a potent antioxidant, although at higher levels may acquire pro‐oxidant activity and an adverse role as cardiometabolic risk factor . In the present study, UA highest levels were found in subjects with positivity for both tests, and intermediate in those with one test positive, respect to patients with negativity for both tests, possibly reflecting a progressively increased cardiometabolic risk …”

Relationship between Inflammatory Parameters and Cardiovascular and Lifestyle Factors in the Mugello Study Oldest Old

“…Another interesting point is that although UA is not included between criteria for diagnosing metabolic syndrome (MetS), many studies have evidenced a positive association between UA and MetS in patients of various ages and ethnicities [3,27]. However, the lack of this relationship observed in our population is in agreement with the previous results, evidencing a higher MetS risk in the population ranging 65-74 years, but not in the oldest old subgroup (85 and over) [26].…”

Sex‐dependent effects of uric acid on cerebral microbleed: a cross‐sectional study in the general population

“…The precise mechanism underlying the sex differences in association between UA and CMB remains unclear. Recent studies focused on a dual effect of UA, as its role switches from antioxidant to oxidant in environments characterized by high oxidative stress, which is mediated by urate redox shuttle [23,24]. In this context, one of the mechanisms that we propose is that female subjects are less susceptible to vascular oxidative stress because female sex hormones suppress the activity and expression of enzymes related to vascular reactive oxygen species [25].…”