Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk.
BACKGROUND
Cohort studies evaluating increased uric acid level as a cardiovascular disease (CVD) risk factor have shown variable results; studies are particularly lacking in lower risk populations.


METHODS
Prospective cohort study.


METHODS
484,568 adults participating in a medical screening program in Taiwan since 1994 were followed up for a median of 8.5 years. Two subgroups were constructed: the first (n = 246,697; 51%) excluded participants with either overt CVD or overt CVD risk factors (including hypertension, diabetes, obesity, and hypertriglyceridemia) and the second (n = 157,238; 32%) further excluded individuals with early-stage CVD risk factors (including prehypertension, prediabetes, overweight, and borderline hypertriglyceridemia).


METHODS
Serum uric acid.


METHODS
All-cause and CVD mortality risk assessed using Cox proportional hazards models for categorical and continuous serum uric acid levels. As applicable, models adjusted for 14 variables. Population-attributable fraction was applied to compare contributions to mortality between high uric acid level and other CVD risk factors.


RESULTS
In the total cohort, mean age was 41.4 +/- 14.0 years and 26.2% had serum uric acid levels >or=7 mg/dL. Through 2007, there were 16,246 deaths (3.4% of all participants), with 35.2% of deaths occurring in individuals with hyperuricemia. Adjusted HRs associated with serum uric acid levels >or=7 mg/dL for all-cause and CVD mortality were 1.10 (95% CI, 1.04-1.17) and 1.38 (95% CI, 1.20-1.58), respectively. In individuals with hyperuricemia, 64.3% had overt CVD risk factors and 82.5% had either overt or early-stage CVD risk factors. Individuals with serum uric acid levels >or=8 mg/dL without overt CVD risk factors constituted 13.5% of the total study population with hyperuricemia; in analyses excluding those with overt CVD risk factors, serum uric acid level >or=8 mg/dL was significantly associated with all-cause and CVD mortality, with HRs of 1.37 (95% CI, 1.18-1.60) and 2.30 (95% CI, 1.51-3.49), respectively. In the subgroup of those with serum uric acid levels >or=8 mg/dL but who lacked both overt and early-stage CVD risk factors, the HRs for all-cause and CVD mortality were also significant and were 1.39 (95% CI, 1.08-1.78) and 2.38 (95% CI, 1.24-4.54), respectively. HRs for individuals with the same risk profiles but with serum uric acid of 7.0-7.9 mg/dL were not significant. In all groups, inclusion of proteinuria and glomerular filtration rate in models substantially attenuated the association between uric acid level and outcomes. High uric acid levels contributed a relatively insignificant portion to mortality (1.2%) and CVD deaths (4.5%) in this population.


CONCLUSIONS
A single measurement of uric acid was used.


CONCLUSIONS
Increased serum uric acid level is a minor, but significant, risk factor for all-cause and CVD mortality. However, except for a small proportion (13.5%), increased serum uric acid level is more a risk marker than a target for treatment and is not an independent risk. Determining appropriate groups to target in clinical trials for uric acid-lowering therapy is critical.
Wen
Chi Pang
CP
Division of Health Policy Research and Development, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan. cwengood@nhri.org.tw
David Cheng
Ting-Yuan
TY
Chan
Hui Ting
HT
Tsai
Min Kuang
MK
Chung
Wen-Shen Isabella
WS
Tsai
Shan Pou
SP
Wahlqvist
Mark L
ML
Yang
Yi Chen
YC
Wu
Shiuan Be
SB
Chiang
Po Huang
PH
Wen
Sung Feng
SF
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000401:mortality*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
D001786:Blood Glucose; D014527:Uric Acid