ORIGINAL

PAPER

Serum Uric Acid Is Associated With Coronary Artery Calcification Chagai Grossman, MD;1,* Joseph Shemesh, MD;2,* Nira Koren-Morag, PhD;3 Gil Bornstein, MD;4 Ilan Ben-Zvi, MD;5 Ehud Grossman, MD4 From the Rheumatology unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;1 Grace Ballas Research Unit of the Cardiac Rehabilitation Institute, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;2 Department of Epidemiology and Preventive Medicine, Tel Aviv University, TelAviv, Israel;3 Department of Internal Medicine D and the Hypertension unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;4 and Department of Internal Medicine F and Rheumatology unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel5 affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Israel

Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the association between UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 557 years) were evaluated for the presence of CAC. The study population was divided into three tertiles according to their UA levels, and the prevalence of CAC was compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of UA were significantly higher in those with

CAC than in those without CAC (5.6+1.2 vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs lowest UA tertile was 1.72 (95% confidence interval, 1.17– 2.51). The highest UA tertile remained associated with the presence of CAC after adjustment for known cardiovascular risk factors. The results show that high serum UA levels are associated with the presence of CAC. J Clin Hypertens (Greenwich). 2014;16:424–428. ª2014 Wiley Periodicals, Inc.

An association between uric acid (UA) and coronary heart disease (CHD) was found by Gertler and colleagues1 more than 50 years ago. Since then, several studies have attempted to establish whether UA is related to CHD events, independent of conventional CHD risk factors.2–4 High UA levels have been associated with carotid subclinical atherosclerosis and oxidative stress in a retrospective cohort of the Atherosclerosis Risk in Communities (ARIC) study.5 In a Japanese population, UA was found to be a marker of increased carotid intimal-media thickness, but only in patients without the metabolic syndrome.6 However, the association between UA levels and CHD events is still a subject of debate. Several studies have found an independent association between UA and CHD events,2,7 whereas other studies have failed to show any association.3–5 Coronary artery calcification (CAC) is well accepted as a surrogate marker of the total coronary atherosclerotic burden,8 as confirmed by histopathology9 and intravascular ultrasound studies.10 There is clear evidence that the presence and degree of CAC, as measured by computed tomography (CT), increases the risk of cardiac events11–19 and all-cause mortality.20–24 Several studies have demonstrated a relationship between serum UA levels and CAC score,25–27 but other studies do not support these findings.28,29

In light of the debatable association between UA and CAC, we aimed to investigate whether serum UA levels are independently associated with the presence of CAC in patients without known CHD.

*Both authors equally contributed to this study and are co-first authors of this manuscript. Address for correspondence: Ehud Grossman, MD, Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel E-mail: [email protected] Manuscript received: January 14, 2014; revised: February 13, 2014; accepted: February 17, 2014 DOI: 10.1111/jch.12313

424

The Journal of Clinical Hypertension

Vol 16 | No 6 | June 2014

PATIENTS AND METHODS Patient selection In this prospective, longitudinal observational study designed to evaluate the long-term prognostic value of CAC we screened healthy patients for the presence of CAC. Of 1850 patients examined in our annual checkup clinic between January 2001 and January 2002, we recruited 663 consecutive patients for the present study who fulfilled the inclusion criteria and consented to perform a screening cardiac CT for coronary calcium evaluation. The inclusion criteria for the screening were men older than 40 years and women older than 50 years who were free of cardiovascular (CV) disease and who had data on CV risk factors and levels of serum UA. Coronary CT All CT scans were performed on dual-detector spiral CT without electrocardiographic gating and without contrast injection. Scanning protocol and CAC measurements were performed according to a previously published protocol using the modified Agatston method.30,31 The reproducibility of calcification scoring by this method is high, with an intra-class correlation coefficient of 0.99 and an interobserver agreement of 0.94.31 Total CAC score (TCS) was the sum of all individual calcific lesions identified within the area of the coronary arteries. A TCS >0 was considered positive for the presence of CAC. Analysis was performed according to absence or presence of CAC.

Uric Acid and Coronary Calcification | Grossman et al.

Assessment of CV Risk Factors Height and weight were measured with participants wearing light clothing without shoes. Body mass index (BMI) was calculated as weight (kg) divided by height (m2). Blood pressure (BP) was measured in the seated position after 3 minutes of rest. Hypertension was defined when two separate BP readings were ≥140 mm Hg for systolic BP and/or ≥90 mm Hg for diastolic BP or a history of hypertension was reported or when the patient used antihypertensive medications. Diabetes mellitus (DM) was defined as a fasting serum glucose >126 mg/dL (7.0 mmol/L) on two separate readings, history of DM, or when the patient used insulin or oral hypoglycemic medications. Hypercholesterolemia was defined when measured total cholesterol was >250 mg/dL or when the patient reported using cholesterol-lowering medications. Smoking status was determined according to the questionnaire, and participants were divided into current smokers or nonsmokers. Estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.32

was divided into 3 tertiles according to their UA levels and the prevalence of CAC was compared between the tertiles. Statistical Analysis Data were analyzed with SPSS (IBM SPSS Statistics, Chicago, IL) software version 21.0. Continuous variables were expressed as meanstandard deviation. Categorical variables were expressed as frequencies (percentage). The clinical characteristics of study patients were compared with chi-square tests for categorical variables and independent t test or analysis of variance (ANOVA) for continuous variables between the following groups: patients with and without CAC and between the 3 tertiles of serum UA levels. Univariate and multivariate logistic regression modeling were performed to analyze the relationship between UA levels and the prevalence of CAC as well as other conventional CHD risk factors and clinical and laboratory parameters. A value of P0

N=663

N=314 (47%)

N=349 (53%)

P Value

Male sex, % Age, y

564 (85) 55.57.3

245 (78) 53.06.8

319 (91) 57.87.0

Serum uric acid is associated with coronary artery calcification.

Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the associati...
101KB Sizes 3 Downloads 4 Views