Highlights
- •Serum uric acid is associated with microvascular peripheral endothelial dysfunction.
- •Uric acid threshold for vascular health is lower than the upper normal range limit.
- •Uric acid is associated with vascular health in apparently low risk individuals.
Abstract
Background and aims
Both elevated serum uric acid (SUA) and peripheral endothelial dysfunction (PED) are
associated independently with cardiovascular disease (CVD). However, the association
between SUA and PED is yet to be established. We hypothesized that high normal range
of SUA is associated with PED.
Methods
We performed a retrospective cross-sectional analysis of patients who were referred
to Mayo Clinic between 2006 and 2014 for routine cardiovascular evaluation and who
underwent evaluation of Reactive Hyperemia Peripheral Arterial Tonometry (index <2
consistent with PED). A high UA was defined as ≥5 mg/dL, in keeping with previous
studies evaluating the link between SUA and CVD outcomes.
Results
One hundred forty patients were included (mean age 50.7 ± 12.9 years, 86 (61.4%) female).
Twenty four patients (17.1%) had pre-existing CVD (8 (9.3%) in females). Thirty patients
(21.6%) had a Framingham score > 10% (8 (9.4%) in females). Fifty eight (41.4%) had
PED and 77 (55.0%) had an elevated SUA. SUA levels were higher in patients with PED
compared to those without (5.5 ± 1.4 vs 4.8 ± 1.2 mg/dL; p = 0.004). In an univariate analysis, elevated SUA levels were associated with PED (Odds
Ratio (OR): 2.7; 95% confidence interval [CI] 1.33–5.48; p = 0.005). In a multivariate analysis adjusting for age, sex, presence of obstructive
CVD and Framingham score>10, elevated SUA levels were associated with PED (OR 2.45;
95% CI 1.08–5.52; p = 0.031). After stratifying by sex, this association persisted in females only.
Conclusions
High normal SUA levels are associated with PED in women who are otherwise at low risk
for CVD. Thus, SUA is a promising circulating biomarker that could be used to assist
in risk stratification in female patients with chest pain and/or those undergoing
evaluation of CVD risk.
Keywords
Abbreviations:
SUA (serum uric acid), PED (peripheral endothelial dysfunction), RH-PAT (Reactive Hyperemia Peripheral Arterial Tonometry), eGFR (estimated glomerular filtration rate), FPG (fasting plasma glucose), FMD (flow-mediated vasodilatation), HBA1C (glycated hemoglobin), T. cholesterol (total cholesterol)To read this article in full you will need to make a payment
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References
- Hyperuricemia in primary and renal hypertension.N. Engl. J. Med. 1966; 275: 457-464
- Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents.Circulation. 2007; 115: 2526-2532
- Associations of serum uric acid with markers of inflammation, metabolic syndrome, and subclinical coronary atherosclerosis.Am. J. Hypertens. 2007 Jan; 20: 83-89
- Relation of uric acid levels to presence of coronary artery calcium detected by electron beam tomography in men free of symptomatic myocardial ischemia with versus without the metabolic syndrome.Am. J. Cardiol. 2007 Jan 1; 99: 42-45
- Serum uric acid levels predict the severity and morphology of coronary atherosclerosis detected by multidetector computed tomography.Atherosclerosis. 2010 Nov; 213: 178-183
- Uric acid and cardiovascular risk.N. Engl. J. Med. 2008; 359: 1811
- Uric acid in heart disease: a new C-reactive protein?.Curr. Opin. Rheumatol. 2011; 23: 174
- Endothelial dysfunction: a marker of atherosclerotic risk.Arterioscler. Thromb. Vasc. Biol. Feb 1 2003; 23: 168-175
- Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure.Circulation. 1998; 98: 2842-2848
- Association between high-sensitivity cardiac troponin levels and myocardial ischemia during mental stress and conventional stress.JACC Cardiovasc. Imaging. 2018; 11: 603-611
- Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction: results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study.Int. J. Cardiol. 2018; 251: 8-13
- Endothelial function and vascular response to mental stress are impaired in patients with apical ballooning syndrome.J. Am. Coll. Cardiol. 2010; 56
- Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia.J. Am. Coll. Cardiol. Dec 7 2004; 44: 2137-2141
- The assessment of endothelial function: from research into clinical practice.Circulation. 2012; 126: 753-767
- Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis.J. Am. Heart Assoc. 2015; 4: e002270
- Role of nitric oxide in the regulation of digital pulse volume amplitude in humans.J. Appl. Physiol. 1985; 101 (Aug 2006): 545-548
- Human vascular smooth muscle cells express a urate transporter.J. Am. Soc. Nephrol. : JASN (J. Am. Soc. Nephrol.). 2006; 17: 1791-1795
- Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4.PLoS One. 2014; 9: e115210
- Effects of uric acid on the NO production of HUVECs and its restoration by urate lowering agents.Drug Res. 2016; 66: 270-274
- Hyperuricemia and endothelial function: from molecular background to clinical perspectives.Atherosclerosis. 2018 Oct 6; 278: 226-231
- Hyperuricemia is independently associated with endothelial dysfunction in postmenopausal women but not in premenopausal women.BMJ Open. 2013 Nov 8; 3: e003659
- Uric acid is associated with inflammation, coronary microvascular dysfunction, and adverse outcomes in postmenopausal women.Hypertension. 2017 Feb; 69: 236-242
- Uric acid is closely linked to vascular nitric oxide activity. Evidence for mechanism of association with cardiovascular disease.J. Am. Coll. Cardiol. 2001; 38: 1850-1858
- Hemodynamics of hyperuricemia.Semin. Nephrol. 2005; 25: 19
- Asymptomatic hyperuricemia: cardiovascular and renal complications.in: Terkeltaub R. Gout and Other Crystal Arthropathies. Elsevier, Philadelphia2012: 226
- Endothelial function predicts 1-year adverse clinical outcome in patients hospitalized in the emergency department chest pain unit.Int. J. Cardiol. 2017; 240: 14-19
- Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects.Cardiovasc. Diabetol. 2016; 15: 36
- Sex differences in vascular and endothelial responses to acute mental stress.Clin. Auton. Res. Dec 2008; 18: 339-345
- Endothelial function: cardiac events.Circulation. 2005; 111: 363-368
- Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia.J. Am. Coll. Cardiol. Dec 7 2004; 44: 2137-2141
- Assessment of peripheral vascular endothelial function in the ambulatory setting.Vasc. Med. Feb 2007; 12: 13-16
- Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude.Am. Heart J. Jul 2003; 146: 168-174
- AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE.Endocr. Pract. 2017 Apr; 23: 1-87
- A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.Ann. Intern. Med. 1999; 130: 461
- Cross-sectional and longitudinal associations between serum uric acid and endothelial function in subjects with treated hypertension.Int. J. Cardiol. 2018 Dec 1; 272: 308-313
- Relation of elevated serum uric acid level to endothelial dysfunction in patients with acute coronary syndrome.J. Atheroscler. Thromb. 2019 Apr 1; 26: 362-367
- Recovery of endothelial function after minor-to-moderate surgery is impaired by diabetes mellitus, obesity, hyperuricemia and sevoflurane-based anesthesia.Int. Heart J. 2018 May 30; 59: 559-565
- Effects of uric acid on vascular endothelial function from bedside to bench.Hypertens. Res. 2018; 41: 923-931
- Relationships among hyperuricemia, metabolic syndrome, and endothelial function.Am. J. Hypertens. 2011 Jul; 24: 770-774
- Serum uric acid and cardiovascular disease: recent developments, and where do they leave us?.Am. J. Med. 2005 Aug; 118: 816-826
- Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.Purinergic Signal. 2018 Jun; 14: 191-199
- Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease.Am. J. Nephrol. 2011; 33: 298-304
- Serum uric acid and 11.5-year mortality of middle-aged women: findings of the Chicago heart association detection Project in industry.J. Clin. Epidemiol. 1989; 42: 257-267
- Lifestyle and biologic factors associated with atherosclerotic disease in middle aged men.Arch. Intern. Med. 1995; 155: 686-694
- Relation of serum uric acid to mortality and ischemic heart disease: the NHANES I Epidemiologic Follow-up Study.Am. J. Epidemiol. 1995; 141: 637-644
- Uric acid and cardiovascular risk.N. Engl. J. Med. 2008 Oct 23; 359: 1811-1821
Article info
Publication history
Published online: July 17, 2019
Accepted:
July 16,
2019
Received in revised form:
July 3,
2019
Received:
December 12,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
