Abstract
BackgroundElevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial.MethodsWe investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19–73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis.ResultsThe mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (β = 0.168, p < 0.001, R2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes.ConclusionsPUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.
Highlights
Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial
A report from the Framingham heart study suggested that every 60 μmol/l increase in uric acid resulted in a 0.04 m/s (p = 0.016) increase in carotid-to-femoral pulse wave velocity (PWV) when hypertensive subjects were excluded [10]
The present results suggest an independent relation between uric acid and large arterial stiffness, but no association between uric acid and blood pressure (BP), cardiac output, systemic vascular resistance, or wave reflection
Summary
Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial. In the Baltimore Longitudinal Study of Aging, higher serum uric acid was associated with greater increase in PWV in men but not in women during 6 years of follow-up [9]. This association was lost when men with PUA ≥ 370 μmol/l were excluded, suggesting a threshold for uric acid association with arterial stiffness [9]. The matter remains controversial, as serum uric acid was not, but uric acid-to-creatinine ratio in the urine was related to the risk of having higher PWV in 2296 Chinese subjects with a mean age of 43 years [12]
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