In our cohort, 6,424 individuals were included, and the mean baseline age was 61.7±13.7 years. Baseline characteristics of subjects by combining hyperuricemia and HTG status were shown in Table1. Combination of hypertension and HTG tended to have higher serum uric acid levels, body mass index, serum creatinine, fasting plasma glucose, alanine aminotransferase and more proteinuria.
Table 1. Baseline characteristics of subjects by combining hypertension and hypertriglyceridemia status
Variables
|
Normotension and normal TG
|
Hypertension and normal TG
|
Normotension and HTG
|
Hypertension and HTG
|
P-value*
|
N (%)
|
2515(39.2)
|
2028(31.6)
|
907(14.1)
|
974(15.2)
|
|
Age (years)
|
57.3±13.5
|
68.4±12.5
|
56.8±11.6
|
64.1±12.4
|
<0.001
|
Men (%)
|
1704(67.8)
|
1659(81.8)
|
711(78.4)
|
974(79.8)
|
<0.001
|
TG (mmol/L)
|
1.1±0.3
|
1.1±0.3
|
2.6±1.3
|
2.6±1.3
|
<0.001
|
TC (mmol/L)
|
4.7±0.8
|
4.8±0.8
|
5.1±0.9
|
5.1±0.9
|
<0.001
|
FPG (mmol/L)
|
5.1±0.9
|
5.5±1.3
|
5.3±1.4
|
5.7±1.7
|
<0.001
|
SBP (mmHg)
|
120.9±11.1
|
153.8±19.9
|
123.0±10.6
|
152.6±14.4
|
<0.001
|
DBP (mmHg)
|
69.8±8.7
|
81.7±11.8
|
72.5±8.5
|
84.6±12.0
|
<0.001
|
SUA (µmol/L)
|
298.0±60.9
|
308.6±60.7
|
325.1±56.1
|
332.5±55.9
|
<0.001
|
BUN(mmol/L)
|
5.1±1.3
|
5.4±1.3
|
5.1±1.2
|
5.3±1.2
|
<0.001
|
SCR (µmol/L)
|
75.8±15.7
|
81.3±17.1
|
78.7±14.1
|
81.4±16.3
|
<0.001
|
eGFR (ml/min/1.73 m2)
|
92.9±18.3
|
86.4±19.6
|
91.3±16.6
|
86.8±18.0
|
<0.001
|
proteinuria (%)
|
62(2.5)
|
80(3.9)
|
33(3.6)
|
53(5.4)
|
<0.001
|
TP (g/L)
|
73.4±3.9
|
74.3±4.3
|
74.7±4.0
|
75.8±4.1
|
<0.001
|
ALT (IU/L)
|
21.2±12.4
|
21.8±12.8
|
26.4±12.2
|
27.4±16.0
|
<0.001
|
TBIL (µmol/L)
|
13.7±5.3
|
14.1±5.0
|
13.3±4.6
|
13.6±4.4
|
0.057
|
BMI (kg/m2)
|
23.5±2.9
|
24.8±3.1
|
25.0±2.7
|
26.1±2.8
|
<0.001
|
Abbreviations: TG, plasma triglyceride level; TC, total cholesterol; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; SUA, serum uric acid; BUN, blood urea nitrogen; SCR, serum creatinine; eGFR, estimated glomerular filtration rate; TP, plasma total protein; ALT, alanine aminotransferase; TBIL, total bilirubin; BMI, body mass index; HTG, hypertriglyceridemia.
*P< 0.05 was considered statistically significant.
Over a period of 8 years, 1259 individuals diagnosed with hyperuricemia and the cumulative incidence of hyperuricemia was 20.2%, 21.3% for men and 16.6% for women. Furthermore, regardless of men or women, the incidence of hyperuricemia among individuals with a combination of hypertension and HTG (37.8%, 95% CI: 34.8-40.9%) was significantly higher than that of those with hypertension alone (18.7%, 95%CI:17.0-20.4%), HTG alone (24.5%, 95%CI:21.7-27.3%) and neither hypertension nor HTG group (13.0%, 95% CI: 11.7%-14.3%) (Additional file 1: Figure 2).
Our results revealed that there existed positive relationships between blood pressure and triglyceride level and the incidence of hyperuricemia assessed by the restricted cubic spline fitting Cox model (Additional file 1: Figure 3). After adjusted age, with the increase of blood pressure, the risk of hyperuricemia increases gradually (Additional file 1: Figure 3a, b, d). Our results also suggested that with the increase of triglyceride levels, the risk of hyperuricemia increases gradually and then stabilizes (Additional file 1: Figure 3g, h, i), and triglyceride level at around2.5 mmol/l cut-off point has the greatest hyperuricemia risk.
Cox regression model assessed the impact of comorbid hypertension and HTG on the risk of hyperuricemia (Table 2). In an unadjusted model of overall participant, the HRs (95% CIs) for hyperuricemia in the combination of hypertension and HTG, HTG alone and hypertension alone groups, compared with the normal control group (normotension and normal TG), were 1.48 (1.28-1.71), 1.84 (1.55-2.18), and 3.02 (2.60-3.50), respectively; after adjusting for sex and age, the HRs (95% CIs) were 1.39 (1.19-1.63), 1.80 (1.52-2.14), and 2.88(2.48-3.36), respectively. After further adjustment for other confounders, the association also found to be significant, with HRs (95% CIs) of 1.24 (1.05-1.46), 1.61 (1.34-1.93), and 2.36 (2.00-2.78), respectively. Additionally, after fully adjustment for potential confounders, the HRs for hyperuricemia in the combination of hypertension and HTG, HTG alone and hypertension alone groups, compared with the normal control group, for men, were 1.17(0.98-1.40), 1.43(1.17-1.76), 2.22(1.85-2.67), respectively; and for women, were 1.57(1.07-2.32), 2.36(1.60-3.47), 2.76(1.87-4.07), respectively.
Table 2. Hazard ratio for the incidence of hyperuricemia by combining hypertension and hypertriglyceridemia status.
|
Hazard Ratio (95% CI)
|
|
Normotension and normal TG
|
Hypertension and normal TG
|
Normotension and HTG
|
Hypertension and HTG
|
P-value for trend
|
Overall†
|
|
Model 1
|
1(Ref.)
|
1.48 (1.28-1.71)
|
1.84 (1.55-2.18)
|
3.02 (2.60-3.50)
|
<0.001
|
Model 2
|
1(Ref.)
|
1.39 (1.19-1.63)
|
1.80 (1.52-2.14)
|
2.88 (2.48-3.36)
|
<0.001
|
Model 3
|
1(Ref.)
|
1.24 (1.05-1.46)
|
1.61 (1.34-1.93)
|
2.36 (2.00-2.78)
|
<0.001
|
Men‡
|
|
Model 1
|
1(Ref.)
|
1.28(1.09-1.52)
|
1.58(1.30-1.91)
|
2.63(2.23-3.11)
|
<0.001
|
Model 2
|
1(Ref.)
|
1.28(1.08-1.51)
|
1.57(1.29-1.91)
|
2.63(2.22-3.11)
|
<0.001
|
Model 3
|
1(Ref.)
|
1.17(0.98-1.40)
|
1.43(1.17-1.76)
|
2.22(1.85-2.67)
|
<0.001
|
Women‡
|
|
Model 1
|
1(Ref.)
|
2.06(1.48-2.87)
|
2.77(1.93-3.98)
|
4.16(3.00-5.76)
|
<0.001
|
Model 2
|
1(Ref.)
|
1.77(1.23-2.56)
|
2.62(1.82-3.78)
|
3.60(2.52-5.16)
|
<0.001
|
Model 3
|
1(Ref.)
|
1.57(1.07-2.32)
|
2.36(1.60-3.47)
|
2.76(1.87-4.07)
|
<0.001
|
† Model 1 was unadjusted baseline values of variables. Model 2 was adjustment for age and sex. Model 3 was further adjustment for body-mass index, eGFR, blood urea nitrogen and proteinuria.
‡ Model 1 was unadjusted baseline values of variables. Model 2 was adjustment for age. Model 3 was further adjustment for body-mass index, eGFR, blood urea nitrogen and proteinuria.
Survival analysis of the risk of hyperuricemia for men and women in four groups during the 8-year period were showed in Fig. 1. Kaplan-Meier survival curve showed that hypertension combined with HTG could predict the highest risk of hyperuricemia in four groups of men and women.
To explore effect of obesity and impaired renal function on hypertension and HTG correlations, this cohort stratified by BMI (<24, 24-27.9, ≥28 kg/m2) and eGFR (<60, ≥60 ml/min/1.73 m2). The Cox regression results with hyperuricemia risk were relatively unchanged in individuals of normal-weight and normal-eGFR (Table 3).
Table 3. Stratified Analysis of multivariate hazard ratios for hyperuricemia among 6424 individuals according to combining hypertension and hypertriglyceridemia status. §
|
Hazard Ratio (95% CI)
|
|
|
Normotension and normal TG
|
Hypertension
and normal TG
|
Normotension and
HTG
|
Hypertension
and HTG
|
P-Value for trend
|
P-Value for
Interaction
|
Body-mass index
|
|
|
<24
|
1
|
1.46(1.12-1.92)
|
1.96 (1.45-2.64)
|
2.49(1.81-3.44)
|
<0.001
|
0.80
|
24~27.9
|
1
|
1.16 (0.92-1.47)
|
1.51(1.17-1.95)
|
2.24 (1.79-2.82)
|
<0.001
|
|
≥28
|
1
|
1.06 (0.68-1.66)
|
1.30(0.78-2.17)
|
2.40 (1.58-3.66)
|
<0.001
|
|
eGFR (ml/min/1.73 m2)
|
|
0.60
|
<60
|
1
|
1.17(0.37-3.78)
|
1.70(0.75-3.86)
|
3.63(1.58-5.33)
|
<0.001
|
|
≥60
|
1
|
1.24(1.04-1.48)
|
1.65(1.37-2.00)
|
2.34(1.96-2.78)
|
<0.001
|
|
|
|
|
|
|
|
|
|
§The Cox regression analysis was adjusted, if not stratified, for age, body-mass index, and blood urea nitrogen, as continuous variables; eGFR (<60 or ≥60 ml/min/1.73 m2 or missing information); and proteinuria (positive, negative, or missing information).
ROC analysis showed an AUC of 0.634 in the total cohort, 57.6% for sensitivity and 63.4 % for specificity. For men, the AUC was 0.626, 59.1% for sensitivity and 61.7% for specificity. For women, the AUC was 0.695, 71.3% for sensitivity and 57.5% for specificity (Fig. 2a–c). All the above models were significantly different from the random predictor (AUC > 0.500, P < 0.001).