Serum Uric Acid Is Associated with Carotid Plaques: The National Heart, Lung, and Blood Institute Family Heart Study

Abstract

Objective-To examine the association of serum uric acid (SUA) with a marker of preclinical cardiovascular disease (CVD), carotid atherosclerotic plaques (PLQ), where early evidence of risk may be evident, focusing on individuals without CV risk factors.Methods-The National Heart, Lung, and Blood Institute Family Heart Study is a multicenter study designed to assess risk factors for heart disease. PLQ were assessed with carotid ultrasound. We conducted sex-specific logistic regression to assess the association of SUA with presence of PLQ, including analyses among persons without risk factors related to both CVD and hyperuricemia.Results-In total, 4866 participants had both SUA and carotid ultrasound assessed (54% women, mean age 52 yrs, mean body mass index 27.6). The association of SUA with PLQ increased with increasing SUA levels, demonstrating a dose-response relation for men [OR 1.0, 1.29, 1.61, 1.75, for SUA categories < 5 (reference), 5 to < 6, 6 to < 6.8, ≥ 6.8 mg/dl, respectively; p = 0.002]. Similar associations were found in men without CV risk factors. We found no relation of SUA with PLQ in women. Studies examining the relation of hyperuricemia with cardiovascular disease (CVD) have had conflicting results. While many have found an independent association of higher serum uric acid (SUA) concentrations with increased risk of adverse cardiovascular outcomes 1-7 , others have not [8][9][10] . Biological mechanisms linking hyperuricemia to CVD risk exist, but direct effects of uric acid on the vasculature remain controversial 11,12 . Moreover, some have argued that the positive association between SUA and CVD may be due to the concurrent cardiovascular comorbidities seen in many persons with hyperuricemia, including diabetes, dyslipidemia, hypertension, and obesity [13][14][15] . Conclusion-In NIH Public AccessClarifying the relation of SUA to CVD risk has clinical implications and public health importance. First, there has been a secular increase in the incidence and prevalence of gout and hyperuricemia 16,17 . Second, asymptomatic hyperuricemia is presently not an indication for urate-lowering therapy. If hyperuricemia is indeed an independent risk factor for CVD, it might motivate a change in traditional treatment recommendations. [20][21][22][23][24][25][26] . Such conflicting results may in part be related to differences in analytic approaches and/or effectiveness of controlling for potential confounding.Further, prior studies have not examined SUA's effects in individuals who are free from comorbidities, which themselves can both increase SUA and increase risk for preclinical CVD. If SUA were associated with preclinical CVD in persons without any such comorbidities, it would constitute stronger evidence for SUA's association with CVD than has been presented in previous studies.We evaluated the association of SUA with carotid plaques in a large multicenter study, the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study, and further assessed these associations for the modifyi...

Prognostic Significance of Uric Acid Levels in Ischemic Stroke Patients

“…These may result from the uricosuric effect (i.e., the role of gender steroids in UA regulation) (Adamopoulos et al 1977) and the effect of the ''estrogen defense'' in premenopausal women. The association between UA levels and the prevalence of carotid plaques has been observed in men, however, not in women (Neogi et al 2009). Moreover, the prevalence of carotid plaques was reportedly higher in postmenopausal women aged C55 years than in younger women (Neogi et al 2009).…”

“…The association between UA levels and the prevalence of carotid plaques has been observed in men, however, not in women (Neogi et al 2009). Moreover, the prevalence of carotid plaques was reportedly higher in postmenopausal women aged C55 years than in younger women (Neogi et al 2009). On the other hand, the sample of women was about 50 % smaller than that of men, and thus, there was much less statistical observation power for testing UA levels' association with AIS prognosis in women.…”

Exposure to volatile organic compounds and kidney dysfunction in thin film transistor liquid crystal display (TFT-LCD) workers

“…Creatinine level was measured by a kinetic colorimetric assay based on a modified Jaffé method [18], and serum uric acid level was determined using a Kone Diagnostica reagent kit and a Kone autoanalyzer [19]. Subjects were defined as having kidney dysfunction if their serum creatinine level was >1.4 mg dl −1 or <0.8 mg dl −1 [20] or their serum uric acid level was >7.0 mg dl −1 or <3.0 mg dl −1 [21].…”

Uric acid transport and disease

“…In the Framingham cohort, investigators concluded that hyperuricemia was a covariable of other known cardiovascular risk factors for cardiac deaths and coronary heart disease (18). More recently, data appear to be swinging the interpretation the other way, indicating that hyperuricemia predisposes to plaque formation and endothelial dysfunction, as assessed by ultrasonography (19)(20)(21). Hyperuricemia was also reported to be an independent risk factor for cardiovascular mortality (22,23).…”