Serum uric acid is a strong predictor of stroke [
Executed during the period between 1988 and 1994, the NHANES III consists of a representative sample of the noninstitutionalized civilian US population, which was selected by using a multistage, stratified sampling, and cluster sampling design [
The level of serum uric acid was measured by using the Hitachi 737 automated multichannel chemistry analyzer (Boehringer Mannheim Diagnostics, Indianapolis, IN, USA). Details concerning data quality control have been published elsewhere [
The information of daily intakes of cholesterol, total fat, saturated fatty acids, protein, carbohydrate, and total energy intake was based on Dietary Food Frequency Questionnaire [
All statistical analyses were computed using SPSS Complex Samples (Version 18.0 for Windows, SPSS, Inc., Chicago, IL, USA) to incorporate sample weights and adjust for clusters and strata of the complex sample design. We used quintile-based analysis by dividing serum uric acid levels into quintiles with the subjects in the lowest one as the reference group. The cut-off levels for serum uric acid levels quintiles were as follows:
The population’s mean age was 44 years. The mean serum uric acid level was 315.84
Characteristics of the study population by serum uric acid quintiles.
Serum uric acid levels ( |
|||||||
---|---|---|---|---|---|---|---|
Overall | 1st (≦238) | 2nd (239–286) | 3rd (287–327) | 4th (328–381) | 5th (≧382) |
|
|
|
14130 | 2749 | 2764 | 2674 | 2843 | 3100 | |
Uric acid ( |
315.84 | 205.11 | 265.21 | 308.72 | 355.69 | 442.53 | <0.001 |
Age (years) | 44.08 | 40.87 | 43.01 | 44.41 | 44.95 | 47.12 | <0.001 |
Sex (% male) | 49.10 | 10.40 | 30.30 | 53.80 | 70.50 | 79.00 | <0.001 |
Race (% white) | 84.90 | 85.50 | 84.40 | 85.60 | 85.80 | 83.20 | 0.21 |
Body mass index (Kg/m2) | 26.63 | 24.01 | 25.45 | 26.97 | 27.55 | 29.11 | <0.001 |
Waist (cm) | 92.07 | 82.69 | 88.20 | 92.95 | 95.84 | 100.59 | <0.001 |
History of hypertension (%) | 23.00 | 12.70 | 20.10 | 22.80 | 23.30 | 36.00 | <0.001 |
History of diabetes (%) | 5.00 | 6.20 | 4.70 | 5.00 | 3.70 | 6.20 | 0.49 |
Drink/month | 29.00 | 15.10 | 24.50 | 26.90 | 34.20 | 39.30 | <0.001 |
Serum cotinine (nmol/L) | 451.84 | 430.77 | 458.49 | 476.21 | 486.83 | 407.94 | 0.79 |
Antihyperlipidemic drug use (%) | 2.20 | 1.40 | 1.40 | 1.60 | 2.60 | 3.80 | <0.001 |
Average daily intakes | |||||||
Calories (kcal/d) | 2223.89 | 1909.78 | 2082.67 | 2340.35 | 2410.76 | 2378.32 | <0.001 |
Protein (g/d) | 83.28 | 70.46 | 76.84 | 87.74 | 90.32 | 91.09 | <0.001 |
Total carbohydrates (g/d) | 271.20 | 240.26 | 259.35 | 283.73 | 288.76 | 284.33 | <0.001 |
Total fats (g/d) | 85.37 | 74.00 | 80.09 | 91.46 | 92.68 | 88.89 | <0.001 |
Cholesterol (mg/d) | 288.26 | 254.80 | 265.24 | 301.18 | 312.09 | 307.88 | <0.001 |
Total saturated fatty acids (g/d) | 28.58 | 25.22 | 26.47 | 31.10 | 30.88 | 29.36 | <0.001 |
Serum lipids and apolipoproteins | |||||||
Total cholesterol (mmol/L) | 5.21 | 4.93 | 5.16 | 5.24 | 5.33 | 5.39 | <0.001 |
Total cholesterol (% of risk)* | 48.4 | 38 | 44.7 | 49.8 | 52.7 | 55.6 | |
Triglycerides (mmol/L) | 1.49 | 1.15 | 1.35 | 1.44 | 1.63 | 1.84 | <0.001 |
Triglycerides (% of risk)* | 16.6 | 7.9 | 12 | 14.5 | 18.5 | 27.4 | |
HDL cholesterol (mmol/L) | 1.25 | 1.38 | 1.32 | 1.25 | 1.18 | 1.13 | <0.001 |
HDL cholesterol (% of risk)* | 26.3 | 13.6 | 19.8 | 25.4 | 31.2 | 39.4 | |
LDL cholesterol (mmol/L) | 3.32 | 3.08 | 3.22 | 3.35 | 3.46 | 3.45 | <0.001 |
LDL cholesterol (% of risk)* | 76.6 | 68.5 | 74.1 | 78.9 | 81.6 | 80.1 | |
Apolipoprotein-B (g/L) | 1.05 | 0.96 | 1.01 | 1.05 | 1.09 | 1.14 | <0.001 |
Apolipoprotein-B (% of risk)* | 23.6 | 14.1 | 19.8 | 22.5 | 27.1 | 34.5 | |
Lipoprotein (a) (g/L) | 0.23 | 0.22 | 0.23 | 0.24 | 0.22 | 0.22 | 0.424 |
Lipoprotein (a) (% of risk)* | 32.6 | 30.3 | 32.5 | 33.2 | 32 | 34.7 | |
Apolipoprotein AI (g/L) | 1.40 | 1.46 | 1.44 | 1.39 | 1.36 | 1.36 | <0.001 |
Apolipoprotein AI (% of risk)* | 0.6 | 0.7 | 0.5 | 0.6 | 0.4 | 0.8 |
Data are survey-weighted means or percentages for continuous or categorical variables, respectively.
*Risk values of serum lipids and apolipoproteins: total cholesterol >5.18 mmol/L, triglycerides >2.26 mmol/L, HDL cholesterol <1.03 mmol/L, LDL cholesterol >2.59 mmol/L, serum apolipoprotein-B >1.25 g/L, serum lipoprotein (a) >0.3 g/L, and serum apolipoprotein AI <0.94 g/L.
Adjusted differences (95% CI) in serum lipids, triglycerides to HDL cholesterol ratio, and apolipoprotein-B to AI ratio comparing the four higher quartiles to the first quartile of serum uric acid.
Serum uric acid levels ( |
||||||
---|---|---|---|---|---|---|
1st (≦238) | 2nd (239–286) | 3rd (287–327) | 4th (328–381) | 5th (≧382) |
|
|
Total cholesterol (mmol/L) | ||||||
Model 1 | 0.00 (Reference) | 0.22 (0.17, 0.27) | 0.32 (0.26, 0.37) | 0.43 (0.37, 0.49) | 0.46 (0.41, 0.52) | <0.001 |
Model 2 | 0.00 (Reference) | 0.18 (0.10, 0.27) | 0.19 (0.10, 0.28) | 0.24 (0.15, 0.33) | 0.30 (0.20, 0.39) | <0.001 |
Model 3 | 0.00 (Reference) | 0.17 (0.09, 0.26) | 0.19 (0.10, 0.28) | 0.23 (0.14, 0.32) | 0.29 (0.19, 0.39) | <0.001 |
Triglycerides (mmol/L) | ||||||
Model 1 | 0.00 (Reference) | 0.18 (0.14, 0.22) | 0.28 (0.23, 0.32) | 0.46 (0.41, 0.50) | 0.66 (0.62, 0.71) | <0.001 |
Model 2 | 0.00 (Reference) | 0.12 (0.06, 0.18) | 0.11 (0.05, 0.18) | 0.25 (0.19, 0.32) | 0.33 (0.26, 0.40) | <0.001 |
Model 3 | 0.00 (Reference) | 0.12 (0.06, 0.18) | 0.10 (0.03, 0.17) | 0.27 (0.20, 0.33) | 0.33 (0.26, 0.41) | <0.001 |
HDL cholesterol (mmol/L) | ||||||
Model 1 | 0.00 (Reference) | −0.04 (−0.05, −0.02) | −0.08 (−0.09, −0.06) | −0.12 (−0.13, −0.10) | −0.16 (−0.17, −0.14) | <0.001 |
Model 2 | 0.00 (Reference) | −0.02 (−0.04, 0.00) | −0.05 (−0.08, −0.03) | −0.07 (−0.10, −0.05) | −0.08 (−0.11, −0.05) | <0.001 |
Model 3 | 0.00 (Reference) | −0.01 (−0.04, 0.01) | −0.05 (−0.07, −0.02) | −0.08 (−0.10, −0.05) | −0.08 (−0.11, −0.05) | <0.001 |
LDL cholesterol (mmol/L) | ||||||
Model 1 | 0.00 (Reference) | 0.10 (0.03, 0.18) | 0.19 (0.12, 0.27) | 0.28 (0.21, 0.36) | 0.24 (0.16, 0.32) | <0.001 |
Model 2 | 0.00 (Reference) | 0.08 (−0.04, 0.19) | 0.13 (0.01, 0.25) | 0.21 (0.09, 0.33) | 0.14 (0.01, 0.27) | 0.015 |
Model 3 | 0.00 (Reference) | 0.08 (−0.03, 0.20) | 0.13 (0.01, 0.24) | 0.20 (0.08, 0.33) | 0.14 (0.01, 0.27) | 0.022 |
Apolipoprotein-B (g/L) | ||||||
Model 1 | 0.00 (Reference) | 0.05 (0.03, 0.07) | 0.08 (0.06, 0.10) | 0.12 (0.10, 0.14) | 0.15 (0.13, 0.17) | <0.001 |
Model 2 | 0.00 (Reference) | 0.04 (0.01, 0.07) | 0.03 (0.00, 0.06) | 0.06 (0.03, 0.09) | 0.08 (0.05, 0.12) | <0.001 |
Model 3 | 0.00 (Reference) | 0.04 (0.02, 0.07) | 0.03 (0.00, 0.06) | 0.06 (0.03, 0.09) | 0.09 (0.05, 0.12) | <0.001 |
Lipoprotein (a) (g/L) | ||||||
Model 1 | 0.00 (Reference) | 0.01 (−0.12, 0.03) | 0.02 (0.00, 0.04) | 0.01 (−0.01, 0.03) | 0.00 (−0.02, 0.02) | 0.962 |
Model 2 | 0.00 (Reference) | 0.01 (−0.02, 0.04) | 0.02 (−0.02, 0.05) | 0.02 (−0.01, 0.05) | 0.02 (−0.02, 0.05) | 0.373 |
Model 3 | 0.00 (Reference) | 0.01 (−0.03, 0.04) | 0.01 (−0.03, 0.04) | 0.01 (−0.02, 0.05) | 0.00 (−0.03, 0.04) | 0.559 |
Apolipoprotein AI (g/L) | ||||||
Model 1 | 0.00 (Reference) | −0.01 (−0.02, 0.01) | −0.03 (−0.05, −0.01) | −0.04 (−0.06, −0.02) | −0.04 (−0.06, −0.02) | <0.001 |
Model 2 | 0.00 (Reference) | 0.03 (0.01, 0.05) | −0.03 (−0.05, 0.00) | −0.01 (−0.03, 0.02) | 0.02 (−0.01, 0.05) | 0.740 |
Model 3 | 0.00 (Reference) | 0.03 (0.00, 0.05) | −0.02 (−0.05, 0.00) | −0.01 (−0.04, 0.02) | 0.01 (−0.02, 0.04) | 0.738 |
Triglycerides to HDL cholesterol ratio | ||||||
Model 1 | 0.00 (Reference) | 0.16 (0.11, 0.21) | 0.27 (0.21, 0.32) | 0.48 (0.42, 0.53) | 0.72 (0.67, 0.78) | <0.001 |
Model 2 | 0.00 (Reference) | 0.09 (0.01, 0.17) | 0.10 (0.02, 0.18) | 0.27 (0.19, 0.36) | 0.33 (0.25, 0.42) | <0.001 |
Model 3 | 0.00 (Reference) | 0.08 (0.00, 0.17) | 0.08 (0.00, 0.17) | 0.29 (0.20, 0.37) | 0.35 (0.0.26, 0.44) | <0.001 |
Apolipoprotein-B to AI ratio | ||||||
Model 1 | 0.00 (Reference) | 0.04 (0.02, 0.05) | 0.07 (0.06, 0.09) | 0.11 (0.09, 0.12) | 0.14 (0.12, 0.15) | <0.001 |
Model 2 | 0.00 (Reference) | 0.02 (0.00, 0.04) | 0.04 (0.01, 0.06) | 0.05 (0.02, 0.08) | 0.06 (0.03, 0.09) | <0.001 |
Model 3 | 0.00 (Reference) | 0.02 (0.00, 0.05) | 0.03 (0.01, 0.06) | 0.05 (0.03.0.08) | 0.06 (0.03, 0.09) | <0.001 |
Adjusted covariates: model 1 = age, gender, and race; model 2 = model 1 + waist, hypertension, diabetes, alcohol drink, cotinine level, and antihyperlipidemic drug use; model 3 = model 2 + intake of total energy (kcal/day), protein (g/day), carbohydrates (g/day), total fats (g/day), cholesterol (mg/day), and total saturated fatty acids (g/day).
To the best of our knowledge, there are few studies which focused on the trend of the lipid panels at different levels of uric acid in a nationally representative sample of US adults. Our study illustrated the strong association between serum uric acid and lipid profiles by grading and comprehensively adjusting for confounders. In a survey of 60 patients, Sarmah and Sharma pointed out that serum uric acid levels were associated with the levels of LDL and HDL [
Several important implications can be drawn from our research. First, the level of serum uric acid increased accompanied with increment of serum LDL cholesterol, triglycerides, total cholesterol, and apolipoprotein-B levels. Second, ratios of triglycerides to HDL cholesterol and apolipoprotein-B to AI were also significantly associated with increased uric acid level. Third, there was a strongly inverse relationship between serum uric acid and HDL cholesterol levels regardless of adjustment for sex and several potential confounders, including dietary, hypertension, diabetes, and health related information, suggesting a crucial role of uric acid in the regulation of dyslipidemia. These finding strengthened on previous studies that showed a pathogenesis overlap among hyperuricemia and dyslipidemia [
LDL cholesterol, apolipoprotein-B, and ratio of apolipoprotein-B to AI showed linear correlation with serum uric acid even after adjusting covariants. According to earlier published data, apolipoprotein-B represented a better indicator of the truly LDL particle numbers and CAD [
In our study, serum HDL cholesterol, as a protective factor for CVD risk, is inversely related to uric acid level in line with previous study. It has been lately noted that elevated serum uric acid was a significant predictor of smaller, denser LDL cholesterol and HDL cholesterol particles, which offers a greater atherogenic ability [
It is now widely acceptable to receive antihyperlipidemic drugs to lower the CVD risk. The latest therapeutic strategies for hyperlipidemia attended to risk reduction, instead of the target of exactly lipid level such as LDL cholesterol level for 70 mg/dL [
The current analysis had few limitations. This study was performed in a nationally representative sample of US general population; therefore, the findings are likely to be generalizable to the US general population. Although previous reports and biological plausibility consistently suggest that lipid levels would be associated with the serum uric acid levels as observed, a cross-sectional study design tends to leave uncertainty regarding the temporal sequence of exposure, outcome relations. Thus, confirming the relation with prospective longitudinal data (e.g., relation between prior dyslipidemia and incident hyperuricemia) would be valuable. Further investigation of the potentially modifiable impact of apolipoprotein-B or lipoprotein (a) would also be warranted, including clinical trials.
From a nationally representative sample of US adults, our study demonstrated that serum LDL cholesterol, triglycerides, total cholesterol, apolipoprotein-B levels, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein-B to AI are significantly associated with serum uric acid levels, whereas serum HDL cholesterol levels are inversely associated. The more comprehensive strategic management to deal with dyslipidemia and hyperuricemia deserves further investigation.
The authors declare that there is no conflict of interests regarding the publication of this paper.