Association between hyperuricemia and hypertension and the mediatory role of obesity: a large cohort study in China

Wang, Changyi; Qin, Pei; Liu, Yinxing; Wang, Li; Xu, Shan; Chen, Hongen; Dai, Shuhong; Zhao, Ping; Hu, Fulan; Lou, Yanmei

doi:10.1590/1806-9282.20220241

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ORIGINAL ARTICLE • Rev. Assoc. Med. Bras. 69 (8) • 2023 • https://doi.org/10.1590/1806-9282.20220241 copy

Association between hyperuricemia and hypertension and the mediatory role of obesity: a large cohort study in China

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

This study aimed to investigate the sex-specific association between hyperuricemia and the risk of hypertension and whether obesity mediates this association.

METHODS:

This study included 31,395 (47.0% women) adults without hypertension, cardiovascular disease, or cancer at baseline who completed at least one follow-up annual examination between 2009 and 2016. Cox regression models were performed to calculate hazard ratios and 95% confidence intervals. Mediation analysis was conducted to estimate the effect of body mass index on the association between hyperuricemia and hypertension.

RESULTS:

During a median 2.9-year follow-up, hyperuricemia was significantly associated with a higher risk of hypertension (HR 1.15, 95%CI 1.07-1.24 for all participants; HR 1.12, 95%CI 1.03-1.22 for men; and HR 1.23, 95%CI 1.02-1.48 for women) after adjustment for potential confounders. Additional adjustment for body mass index attenuated this association (HR 1.09, 95%CI 1.08-1.10 for all participants; HR 1.07; 95%CI 0.98-1.16 for men; HR 1.18; 95%CI 0.96-1.44 for women). Mediation analysis showed that BMI partially mediated the relationship between hyperuricemia and incident hypertension (indirect effect HR 1.09, 95%CI 1.08-1.10; direct effect: HR 1.08, 95%CI 1.02-1.15). The percentage of the mediation effect was 53.2% (95%CI 37.9-84.5).

CONCLUSION:

Hyperuricemia is associated with a risk of hypertension in both sexes, and BMI partially mediates hyperuricemia-related incident hypertension.

KEYWORDS:
Uric acid; Hypertension; Obesity; Mediation analysis

	Hyperuricemia			Hypertension
	Yes (n=4,943)	No (n=26,452)		Yes (n=5,023)	No (n=26,372)
Men
n	4,043	12,587		3,729	12,901
Age (years)	40.76 (12.48)	41.63 (12.04)	<0.001	45.78 (13.27)	40.16 (11.51)	<0.001
Heart rate (beats/min)	75.44 (9.83)	74.69 (9.53)	<0.001	76.17 (9.57)	74.50 (9.59)	<0.001
BMI (kg/m²)	26.53 (3.03)	25.07 (3.05)	<0.001	26.69 (3.09)	25.06 (3.02)	<0.001
Weight (kg)	79.24 (10.65)	74.35 (10.16)	<0.001	78.93 (10.83)	74.56 (10.18)	<0.001
Blood pressure (mmHg)
Systolic	118.07 (10.11)	116.64 (10.53)	<0.001	122.42 (8.87)	115.43 (10.34)	<0.001
Diastolic	75.00 (7.21)	73.37 (7.48)	<0.001	78.52 (6.12)	72.41 (7.23)	<0.001
SUA (mg/dL)	7.88 (0.78)	5.69 (0.82)	<0.001	6.40 (1.32)	6.17 (1.22)	<0.001
FPG (mmol/L)	5.42 (0.92)	5.47 (1.21)	0.002	5.76 (6.12)	5.38 (7.23)	<0.001
TC (mmol/L)	5.04 (0.94)	4.78 (0.89)	<0.001	5.06 (1.41)	4.78 (1.04)	<0.001
TG (mmol/L)	2.22 (1.76)	1.63 (1.26)	<0.001	2.10 (0.93)	1.68 (0.89)	<0.001
HDL-C (mmol/L)	1.21 (0.26)	1.28 (0.28)	<0.001	1.25 (1.73)	1.27 (1.31)	<0.001
LDL-C (mmol/L)	3.13 (0.75)	2.97 (0.73)	<0.001	3.13 (0.27)	2.97 (0.28)	<0.001
Albumin (g/L)	45.69 (3.02)	45.35 (3.06)	<0.001	45.24 (3.01)	45.49 (3.06)	<0.001
ALT (IU/L)	26.6 (19.0-39.1)	21.2 (16.0-30.0)	<0.001	25.0 (18.4-35.8)	22.0 (16.0-31.0)	<0.001
Women
n	900	13,865		1,294	13,471
Age (years)	42.83 (14.75)	38.01 (10.6)	<0.001	48.34 (13.27)	37.34 (11.51)	<0.001
Heart rate (beats/min)	76.12 (9.9)	76.33 (9.74)	0.522	76.67 (9.57)	76.29 (9.59)	<0.001
BMI (kg/m²)	25.48 (3.66)	22.83 (3.11)	<0.001	25.28 (3.09)	22.78 (3.02)	<0.001
Weight (kg)	65.61 (10.01)	59.02 (8.39)	<0.001	64.38 (10.83)	58.95 (10.18)	<0.001
Blood pressure (mmHg)			<0.001			<0.001
Systolic	113.79 (11.64)	108.79 (11.48)	<0.001	120.6 (8.87)	108 (10.34)	<0.001
Diastolic	72.08 (7.93)	68.24 (7.85)	<0.001	76.67 (6.12)	67.69 (7.23)	<0.001
SUA (mg/L)	6.62 (0.62)	4.28 (0.78)	<0.001	4.84 (1.32)	4.38 (1.22)	<0.001
FPG (mmol/L)	5.36 (0.91)	5.08 (0.65)	<0.001	5.43 (1.41)	5.06 (1.04)	<0.001
TC (mmol/L)	5.18 (1.05)	4.63 (0.88)	<0.001	5.12 (0.93)	4.62 (0.89)	<0.001
TG (mmol/L)	1.65 (1.15)	1.05 (0.68)	<0.001	1.42 (1.73)	1.06 (1.31)	<0.001
HDL-C (mmol/L)	1.4 (0.3)	1.54 (0.34)	<0.001	1.47 (0.27)	1.54 (0.28)	<0.001
LDL-C (mmol/L)	3.2 (0.86)	2.73 (0.72)	<0.001	3.11 (0.74)	2.72 (0.73)	<0.001
eGFR (mL/min/1.73 m²)	95.66 (23.63)	106.97 (24.18)	<0.001	95.49 (17.25)	107.32 (17.92)	<0.001
Albumin (g/L)	44.51 (3.04)	44.37 (3.18)	0.245	43.9 (3.01)	44.43 (3.06)	<0.001
ALT (IU/L)	18.0 (13.0-26.0)	13.7 (11.0-18.0)	<0.001	16.7 (13.0-22.58)	13.5 (11.0-18.0)	<0.001

	Whole cohort		Sensitivity analysis^d		Sensitivity analysis^e
	Hazard ratio (95%CI)	P-value	Hazard ratio (95%CI)	P-value	Hazard ratio (95%CI)	P-value
Overall
Model 1^a	1.43 (1.34-1.52)	<0.001	1.44 (1.35-1.54)	<0.001	1.44 (1.31-1.59)	<0.001
Model 2^b	1.15 (1.07-1.24)	<0.001	1.17 (1.09-1.27)	<0.001	1.19 (1.06-1.33)	0.003
Model 3^c	1.10 (1.02-1.19)	0.018	1.11 (1.03-1.20)	0.007	1.14 (1.01-1.28)	0.032
Men
Model 1^a	1.34 (1.25-1.44)	<0.001	1.36 (1.27-1.46)	<0.001	1.40 (1.26-1.56)	<0.001
Model 2^b	1.12 (1.03-1.22)	0.007	1.14 (1.05-1.24)	0.002	1.20 (1.06-1.36)	0.004
Model 3^c	1.07 (0.98-1.16)	0.131	1.08 (0.99-1.18)	0.066	1.15 (1.01-1.31)	0.034
Women
<50 years
Model 1^a	1.37 (1.27-1.47)	<0.001	1.37 (1.27-1.47)	<0.001	1.20 (1.10-1.31)	<0.001
Model 2^b	1.26 (1.16-1.37)	<0.001	1.26 (1.16-1.37)	<0.001	1.29 (1.16-1.43)	<0.001
Model 3^c	1.18 (1.07-1.29)	<0.001	1.18 (1.07-1.29)	<0.001	1.25 (1.11-1.40)	<0.001
≥50 years
Model 1^a	1.17 (1.09-1.27)	<0.001	1.19 (1.10-1.30)	<0.001	1.42 (1.27-1.59)	<0.001
Model 2^b	1.12 (1.02-1.24)	0.017	1.13 (1.02-1.25)	0.018	1.23 (1.07-1.41)	0.003
Model 3^c	1.12 (1.01-1.24)	0.031	1.13 (1.02-1.26)	0.023	1.16 (1.00-1.34)	0.052

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[1] *Corresponding author: hitila@sina.com