This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (322)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Social Bookmarking   What's this?

The NHANES I Epidemiologic Follow-up Study, 1971-1992

Jing Fang, MD; Michael H. Alderman, MD

JAMA. 2000;283:2404-2410.

Context  Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for cardiovascular mortality, this relationship remains uncertain.

Objective  To determine the association of serum uric acid levels with cardiovascular mortality.

Design and Setting  Cross-sectional population-based study of epidemiological follow-up data from the First National Health and Nutrition Examination Survey (NHANES I) from 1971-1975 (baseline) and data from NHANES I Epidemiologic Follow-up Study (NHEFS).

Participants  A total of 5926 subjects who were aged 25 to 74 years and had serum uric acid level measurements at baseline.

Main Outcome Measures  Ischemic heart disease mortality, total cardiovascular mortality, and all-cause mortality, compared by quartiles of serum uric acid level.

Results  In an average of 16.4 years of follow-up, 1593 deaths occurred, of which 731 (45.9%) were ascribed to cardiovascular disease. Increased serum uric acid levels had a positive relationship to cardiovascular mortality in men and women and in black and white persons. Deaths due to ischemic heart disease in both men and women increased when serum uric acid levels were in the highest quartile compared with the lowest quartile (men, >416 vs <321 µmol/L; risk ratio, 1.77 [95% confidence interval {CI}, 1.08-3.98]; women, >333 vs <238 µmol/L; risk ratio, 3.00 [95% CI, 1.45-6.28]). Cox regression analysis showed that for each 59.48-µmol/L increase in uric acid level, cardiovascular mortality and ischemic heart disease mortality increased. Hazard ratios for men were 1.09 (95% CI, 1.02-1.18) and 1.17 (95% CI, 1.06-1.28), and for women were 1.26 (95% CI, 1.16-1.36) and 1.30 (95% CI, 1.17-1.45), respectively, after adjustment for age, race, body mass index, smoking status, alcohol consumption, cholesterol level, history of hypertension and diabetes, and diuretic use. Further analysis, stratifying by cardiovascular risk status, diuretic use, and menopausal status, confirmed a significant association of uric acid and cardiovascular mortality in all subgroups except among men using diuretics (n=79) and men with 1 or more cardiovascular risk factors (n=1140).

Conclusion  Our data suggest that increased serum uric acid levels are independently and significantly associated with risk of cardiovascular mortality.

Author Affiliations: Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

May 10, 2000
JAMA. ;283():2461-2462.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Elevated serum uric acid levels following heart transplantation predict all-cause and cardiac mortality
Arora et al.
Eur J Heart Fail 2009;11:1005-1013.
ABSTRACT | FULL TEXT  

Elevated Serum Uric Acid Concentrations Independently Predict Cardiovascular Mortality in Type 2 Diabetic Patients
Zoppini et al.
Diabetes Care 2009;32:1716-1720.
ABSTRACT | FULL TEXT  

Uric acid levels and outcome from coronary artery bypass grafting
Hillis et al.
J. Thorac. Cardiovasc. Surg. 2009;138:200-205.
ABSTRACT | FULL TEXT  

Oxidative stress and hyperuricaemia: pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure
Bergamini et al.
Eur J Heart Fail 2009;11:444-452.
ABSTRACT | FULL TEXT  

Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease
Navaneethan and Beddhu
Nephrol Dial Transplant 2009;24:1260-1266.
ABSTRACT | FULL TEXT  

Synergy Between Adiposity, Insulin Resistance, Metabolic Risk Factors, and Inflammation in Adolescents
Huang et al.
Diabetes Care 2009;32:695-701.
ABSTRACT | FULL TEXT  

Serum Uric Acid Is Associated with Carotid Plaques: The National Heart, Lung, and Blood Institute Family Heart Study
NEOGI et al.
The Journal of Rheumatology 2009;36:378-384.
ABSTRACT | FULL TEXT  

Genetics of Variation in Serum Uric Acid and Cardiovascular Risk Factors in Mexican Americans
Voruganti et al.
J. Clin. Endocrinol. Metab. 2009;94:632-638.
ABSTRACT | FULL TEXT  

Serum uric acid and cognitive function and dementia
Euser et al.
Brain 2009;132:377-382.
ABSTRACT | FULL TEXT  

Cum Hoc, Ergo Propter Hoc: Health Disparities Real and Imagined
Gadegbeku and Chertow
CJASN 2009;4:251-253.
FULL TEXT  

Serum uric acid and its association with metabolic syndrome and carotid atherosclerosis in obese children
Pacifico et al.
Eur J Endocrinol 2009;160:45-52.
ABSTRACT | FULL TEXT  

Elevated Uric Acid Increases the Risk for Kidney Disease
Obermayr et al.
J. Am. Soc. Nephrol. 2008;19:2407-2413.
ABSTRACT | FULL TEXT  

Association of Incident Gout and Mortality in Dialysis Patients
Cohen et al.
J. Am. Soc. Nephrol. 2008;19:2204-2210.
ABSTRACT | FULL TEXT  

Uric Acid and Cardiovascular Risk
Feig et al.
NEJM 2008;359:1811-1821.
FULL TEXT  

Serum uric acid concentration as non-classic cardiovascular risk factor in women with polycystic ovary syndrome: effect of treatment with ethinyl-estradiol plus cyproterone acetate versus metformin
Luque-Ramirez et al.
Hum Reprod 2008;23:1594-1601.
ABSTRACT | FULL TEXT  

Uric Acid Levels Are Associated With All-Cause and Cardiovascular Disease Mortality Independent of Systemic Inflammation in Men From the General Population: The MONICA/KORA Cohort Study
Meisinger et al.
Arterioscler. Thromb. Vasc. Bio. 2008;28:1186-1192.
ABSTRACT | FULL TEXT  

Predictors of new-onset decline in kidney function in a general middle-european population
Obermayr et al.
Nephrol Dial Transplant 2008;23:1265-1273.
ABSTRACT | FULL TEXT  

RE: "PLASMA URATE AND RISK OF PARKINSON'S DISEASE"
Wise et al.
Am J Epidemiol 2008;167:752-753.
FULL TEXT  

Serum uric acid levels of patients with multiple sclerosis and other neurological diseases
Fuhua Peng et al.
Mult Scler 2008;14:188-196.
ABSTRACT  

Serum Uric Acid: Novel Prognostic Factor in Primary Systemic Amyloidosis
Kumar et al.
Mayo Clin Proc. 2008;83:297-303.
ABSTRACT | FULL TEXT  

Serum Uric Acid and Risk of Cardiovascular Mortality: A Prospective Long-Term Study of 83 683 Austrian Men
Strasak et al.
Clin. Chem. 2008;54:273-284.
ABSTRACT | FULL TEXT  

Altered Uric Acid Levels and Disease States
Kutzing and Firestein
J. Pharmacol. Exp. Ther. 2008;324:1-7.
ABSTRACT | FULL TEXT  

Genome Scan for Determinants of Serum Uric Acid Variability
Nath et al.
J. Am. Soc. Nephrol. 2007;18:3156-3163.
ABSTRACT | FULL TEXT  

The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28 000 older Austrian women
Strasak et al.
Ann Oncol 2007;18:1893-1897.
ABSTRACT | FULL TEXT  

Serum uric acid and brain ischemia in normal elderly adults
Schretlen et al.
Neurology 2007;69:1418-1423.
ABSTRACT | FULL TEXT  

Association of serum uric acid with cardiovascular disease in rheumatoid arthritis
Panoulas et al.
Rheumatology (Oxford) 2007;46:1466-1470.
ABSTRACT | FULL TEXT  

Podagra, Uric Acid, and Cardiovascular Disease
Alderman
Circulation 2007;116:880-883.
FULL TEXT  

Independent Impact of Gout on Mortality and Risk for Coronary Heart Disease
Choi and Curhan
Circulation 2007;116:894-900.
ABSTRACT | FULL TEXT  

Morin (3,5,7,2',4'-Pentahydroxyflavone) Exhibits Potent Inhibitory Actions on Urate Transport by the Human Urate Anion Transporter (hURAT1) Expressed in Human Embryonic Kidney Cells
Yu et al.
Drug Metab. Dispos. 2007;35:981-986.
ABSTRACT | FULL TEXT  

Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease
Landmesser et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:943-948.
ABSTRACT | FULL TEXT  

Comparison of Clinical Characteristics of Acute Myocardial Infarction in Aborigines and Nonaborigines in Taitung Area of Taiwan
Wang et al.
ANGIOLOGY 2007;58:61-66.
ABSTRACT  

Comparison of Plasma Uric Acid Levels in Five Varieties of the Domestic Turkey, Meleagris gallopavo.
Hartman et al.
Poult. Sci. 2006;85:1791-1794.
ABSTRACT | FULL TEXT  

Uric Acid Is a Risk Factor for Myocardial Infarction and Stroke: The Rotterdam Study
Bos et al.
Stroke 2006;37:1503-1507.
ABSTRACT | FULL TEXT  

Uric acid and inflammatory markers
Ruggiero et al.
Eur Heart J 2006;27:1174-1181.
ABSTRACT | FULL TEXT  

Serum Uric Acid Is Associated With Microalbuminuria in Prehypertension
Lee et al.
Hypertension 2006;47:962-967.
ABSTRACT | FULL TEXT  

Vitamins C and E in adolescents and young adults with HIV infection.
Stephensen et al.
Am. J. Clin. Nutr. 2006;83:870-879.
ABSTRACT | FULL TEXT  

A longitudinal study of the influence of shift work on serum uric acid levels in workers at a telecommunications company
Uetani et al.
Occup Med (Lond) 2006;56:83-88.
ABSTRACT | FULL TEXT  

Uric Acid, Left Ventricular Mass Index, and Risk of Cardiovascular Disease in Essential Hypertension
Iwashima et al.
Hypertension 2006;47:195-202.
ABSTRACT | FULL TEXT  

Preexisting Morbidity as an Independent Risk Factor for Perioperative Acute Thromboembolism Syndrome
Kikura et al.
Arch Surg 2005;140:1210-1217.
ABSTRACT | FULL TEXT  

Effect of Smoking on Uric Acid and Other Metabolic Markers throughout Normal Pregnancy
Lain et al.
J. Clin. Endocrinol. Metab. 2005;90:5743-5746.
ABSTRACT | FULL TEXT  

Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy
Duncan et al.
Am. J. Physiol. Heart Circ. Physiol. 2005;289:H1512-H1518.
ABSTRACT | FULL TEXT  

Cigarette Smoking Among Spouses: Another Risk Factor for Stroke in Women
Qureshi et al.
Stroke 2005;36:e74-e76.
ABSTRACT | FULL TEXT  

Suboptimal physician adherence to quality indicators for the management of gout and asymptomatic hyperuricaemia: results from the UK General Practice Research Database (GPRD)
Mikuls et al.
Rheumatology (Oxford) 2005;44:1038-1042.
ABSTRACT | FULL TEXT  

The increase in serum uric acid concentration caused by diuretics might be beneficial in heart failure
Reyes
Eur J Heart Fail 2005;7:461-467.
ABSTRACT | FULL TEXT  

Serum Uric Acid and Target Organ Damage in Primary Hypertension
Viazzi et al.
Hypertension 2005;45:991-996.
ABSTRACT | FULL TEXT  

Gout epidemiology: results from the UK General Practice Research Database, 1990-1999
Mikuls et al.
Ann Rheum Dis 2005;64:267-272.
ABSTRACT | FULL TEXT  

Association of Soluble Markers with Various Stages and Major Events of Atherosclerosis
Wu and Wu
Annals of Clinical & Laboratory Science 2005;35:240-250.
ABSTRACT | FULL TEXT  

Relations of Serum Uric Acid to Longitudinal Blood Pressure Tracking and Hypertension Incidence
Sundstrom et al.
Hypertension 2005;45:28-33.
ABSTRACT | FULL TEXT  

Childhood Uric Acid Predicts Adult Blood Pressure: The Bogalusa Heart Study
Alper et al.
Hypertension 2005;45:34-38.
ABSTRACT | FULL TEXT  

Consumption of High-Pressurized Vegetable Soup Increases Plasma Vitamin C and Decreases Oxidative Stress and Inflammatory Biomarkers in Healthy Humans
Sanchez-Moreno et al.
J. Nutr. 2004;134:3021-3025.
ABSTRACT | FULL TEXT  

Role of Oxidative Modifications in Atherosclerosis
Stocker and Keaney
Physiol. Rev. 2004;84:1381-1478.
ABSTRACT | FULL TEXT  

Uric Acid Level as a Risk Factor for Cardiovascular and All-Cause Mortality in Middle-aged Men: A Prospective Cohort Study
Niskanen et al.
Arch Intern Med 2004;164:1546-1551.
ABSTRACT | FULL TEXT  

Serum uric acid levels in optic neuritis
Knapp et al.
Mult Scler 2004;10:278-280.
ABSTRACT  

Dietary Fat Type Affects Vitamins C and E and Biomarkers of Oxidative Status in Peripheral and Brain Tissues of Golden Syrian Hamsters
Sanchez-Moreno et al.
J. Nutr. 2004;134:655-660.
ABSTRACT | FULL TEXT  

Serum uric acid levels show a 'J-shaped' association with all-cause mortality in haemodialysis patients
Hsu et al.
Nephrol Dial Transplant 2004;19:457-462.
ABSTRACT | FULL TEXT  

Hyperuricaemia does not impair cardiovascular function in healthy adults
Waring et al.
Heart 2004;90:155-159.
ABSTRACT | FULL TEXT  

Pathogenesis of Hypertension
Oparil et al.
ANN INTERN MED 2003;139:761-776.
FULL TEXT  

Early Benefit from Structured Care with Atorvastatin in Patients with Coronary Heart Disease and Diabetes Mellitus: A Subgroup Analysis of the GREek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study
Athyros et al.
ANGIOLOGY 2003;54:679-690.
ABSTRACT  

Effect of orange juice intake on vitamin C concentrations and biomarkers of antioxidant status in humans
Sanchez-Moreno et al.
Am. J. Clin. Nutr. 2003;78:454-460.
ABSTRACT | FULL TEXT  

Hyperuricemia in Childhood Primary Hypertension
Feig and Johnson
Hypertension 2003;42:247-252.
ABSTRACT | FULL TEXT  

Serum Urate as an Independent Predictor of Poor Outcome and Future Vascular Events After Acute Stroke
Weir et al.
Stroke 2003;34:1951-1956.
ABSTRACT | FULL TEXT  

Gout
Rott and Agudelo
JAMA 2003;289:2857-2860.
FULL TEXT  

Two-Hour Insulin Determination Improves the Ability of Abdominal Fat Measurement to Identify Risk for the Metabolic Syndrome
Ribeiro-Filho et al.
Diabetes Care 2003;26:1725-1730.
ABSTRACT | FULL TEXT  

Fenofibrate and losartan
Bardin
Ann Rheum Dis 2003;62:497-498.
FULL TEXT  

Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?
Johnson et al.
Hypertension 2003;41:1183-1190.
ABSTRACT | FULL TEXT  

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2
Kanellis et al.
Hypertension 2003;41:1287-1293.
ABSTRACT | FULL TEXT  

Uric Acid and Survival in Chronic Heart Failure: Validation and Application in Metabolic, Functional, and Hemodynamic Staging
Anker et al.
Circulation 2003;107:1991-1997.
ABSTRACT | FULL TEXT  

The elevated prevalence of apolipoprotein E2 in patients with gout is associated with reduced renal excretion of urates
Cardona et al.
Rheumatology (Oxford) 2003;42:468-472.
ABSTRACT | FULL TEXT  

Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout
Feher et al.
Rheumatology (Oxford) 2003;42:321-325.
ABSTRACT | FULL TEXT  

Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers
Guthikonda et al.
Circulation 2003;107:416-421.
ABSTRACT | FULL TEXT  

Acetaminophen in the Post-ischemia Reperfused Myocardium
Golfetti et al.
Exp. Biol. Med. 2002;227:1031-1037.
ABSTRACT | FULL TEXT  

Effect of Aging on Serum Uric Acid Levels: Longitudinal Changes in a Large Japanese Population Group
Kuzuya et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2002;57:M660-664.
ABSTRACT | FULL TEXT  

Body Fat Distribution, Serum Leptin, and Cardiovascular Risk Factors in Men With Obstructive Sleep Apnea*
Schafer et al.
Chest 2002;122:829-839.
ABSTRACT | FULL TEXT  

Prognostic Significance of Renal Function in Elderly Patients with Isolated Systolic Hypertension: Results from the Syst-Eur Trial
de Leeuw et al.
J. Am. Soc. Nephrol. 2002;13:2213-2222.
ABSTRACT | FULL TEXT  

Allopurinol Improves Endothelial Dysfunction in Chronic Heart Failure
Farquharson et al.
Circulation 2002;106:221-226.
ABSTRACT | FULL TEXT  

Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study
Struthers et al.
Heart 2002;87:229-234.
ABSTRACT | FULL TEXT  

Uric acid is closely linked to vascular nitric oxide activity: Evidence for mechanism of association with cardiovascular disease
Maxwell and Bruinsma
J Am Coll Cardiol 2001;38:1850-1858.
ABSTRACT | FULL TEXT  

Elevated Uric Acid Increases Blood Pressure in the Rat by a Novel Crystal-Independent Mechanism
Mazzali et al.
Hypertension 2001;38:1101-1106.
ABSTRACT | FULL TEXT  

Bioavailability of Vitamin E as Function of Food Intake in Healthy Subjects: Effects on Plasma Peroxide-Scavenging Activity and Cholesterol-Oxidation Products
Iuliano et al.
Arterioscler. Thromb. Vasc. Bio. 2001;21 :e34-e37.
ABSTRACT | FULL TEXT  

Fenofibrate: a new treatment for hyperuricaemia and gout?
HEPBURN et al.
Ann Rheum Dis 2001;60:984a-986.
FULL TEXT  

Ultrasonography for the Evaluation of Visceral Fat and Cardiovascular Risk
Ribeiro-Filho et al.
Hypertension 2001;38:713-717.
ABSTRACT | FULL TEXT  

High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids, uric acid, and renal function
Jenkins et al.
Am. J. Clin. Nutr. 2001;74:57-63.
ABSTRACT | FULL TEXT  

Prognostic Significance of Serum Creatinine and Uric Acid in Older Chinese Patients With Isolated Systolic Hypertension
Wang et al.
Hypertension 2001;37:1069-1074.
ABSTRACT | FULL TEXT  

Relation Between Serum Uric Acid and Risk of Cardiovascular Disease in Essential Hypertension : The PIUMA Study
Verdecchia et al.
Hypertension 2000;36:1072-1078.
ABSTRACT | FULL TEXT  

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism
Mazzali et al.
Am. J. Physiol. Renal Physiol. 2002;282:F991-F997.
ABSTRACT | FULL TEXT