Increased Impact of Serum Uric Acid on Arterial Stiffness and Atherosclerosis in Females

Abstract

Aims: Serum uric acid increases with metabolic disorders; however, whether the effects of uric acid on atherosclerosis are different in females and males has not been sufficiently evaluated. Therefore, this study compared the impact of uric acid on arterial stiffness and atherosclerosis between females and males.

Methods: We enrolled 10196 untreated middle-aged subjects (46±8 years, 3021 females and 7175 males) who underwent periodic health check-ups. Serum uric acid levels were measured and arterial stiffness and atherosclerosis were assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and plaque, using ultrasound imaging.

Results: Females with increased arterial stiffness (CAVI ≥ 8.0) or carotid plaques had higher uric acid than those without (P＜0.0001), but males did not. In multivariable regression analyses including overall participants, uric acid was significantly associated with the CAVI, where sex interacted with uric acid. In sex-specific analyses, uric acid was significantly associated with the CAVI, but not with carotid IMT, in both sexes. However, logistic regression analyses revealed that serum uric acid was independently associated with the presence of carotid plaques in females. The exclusion of subjects with abdominal obesity or metabolic syndrome from the analysis did not alter the results in females.

Conclusions: Serum uric acid was significantly associated with the CAVI in both sexes, but the interaction of sex was confirmed and associated with a carotid plaque only in females. These findings support the increased impact of serum uric acid on arterial stiffness and atherosclerosis in females.

Keywords: Atherosclerosis; Carotid plaque; Female; Sex difference; Uric acid.

Fig.1.

Impacts of having (a) abdominal obesity, (b) metabolic syndrome, (c) alcohol drinking, (d) current smoking, (e) increased arterial stiffness (CAVI value ≥ 8.0), and (f) the presence of carotid plaques, on serum uric acid levels in each sex

Fig.2.Impacts of quartiles of serum uric on the CAVI value and carotid IMT in females (a, c) and males (b, d

Q1: uric acid levels below the lower quartile (≤ 3.6 mg/dL in females and ≤ 5.1 mg/dL in males). Q2: uric acid levels above the lower quartile and below the median (3.7–4.1 mg/dL in females and 5.2–5.8 mg/dL in males). Q3: uric acid levels above the median and below the upper quartile (4.2–4.8 mg/dL in females and 5.9–6.6 mg/dL in males). Q4: uric acid levels above the upper quartile (≥ 4.9 mg/dL in females and ≥ 6.7 mg/dL in males). ANOVA, one-way analysis of variance. ^＊P＜0.0001 vs. Q1 (ANOVA, followed by Scheffe’s post hoc test).