Major adverse cardiovascular events and hyperuricemia as an effect-modifying factor in kidney transplant recipients

Table 1 Sociodemographic and disease-related characteristics of study participants, n (%)

Variable
Sociodemographic data
Male gender	283 (51.9)
Age, median (25%-75%), min-max (years)	55.0 (41.0–64.0), 15.0–89.0
body mass index, median (25%-75%), min-max (kg/m2)	24.5 (22.8–28.4), 15.4–42.6
Current smokers	165 (30.3)
Problems and treatments related to cardiovascular function
Having major adverse cardiovascular events (cardiovascular of cerebrovascular events)	145 (26.6)
Having hypertension	474 (87.0)
Having left ventricular hypertrophy	431 (79.1)
Having dyslipidemia	426 (78.2)
Having previous cardiovascular events	79 (14.5)
Problems and treatments related to the urine system
UA, median (25%-75%), min-max (μmol/L)	436.0 (357.0–514.5), 201.0–761.0
Having elevated UA	116 (21.3)
Having a very high level of UA	194 (35.6)
Having hyperuricemia	347 (63.7)
Glomerular filtration rate, median (25%-75%), min-max (mL/minute)	45.0 (24.0–64.0), 6.0–116.0
Having proteinuria	172 (31.6)
Using steroids for more than one year	411 (75.4)
Acute transplant rejection	182 (33.4)
Receiving hyperuricemia treatment	191 (35.0)
Calcineurin therapy-receiving cyclosporine therapy	111 (20.4)
Calcineurin therapy-receiving tacrolimus therapy	404 (74.0)
Other functions and diseases
New onset of diabetes mellitus	82 (15.0)
Length of hemodialysis, median (25%-75%), min-max (months)	12.0 (7.0–23.0), 0.0–131.0
HPT, median (25%-75%), min-max (pg/mL)	120.0 (73.0–180.0), 23.0-1023.0
Having secondary HPT (> 90 pg/mL)	375 (68.8)
Inflammation, median (25%-75%), min-max (mg/L)	3.6 (1.3–5.5), 0.0-130.0
Having inflammation (> 5 mg/L)	145 (26.6)
Having anemia (hemoglobin level < 13 g/dL in male and < 12 g/dL in female)	180 (33.0)

HPT: Hyperparathyroidism; Min: Minimum; Max: Maximum; UA: Uric acid.

Table 2 Univariate relationships between having major adverse cardiovascular events and independent variables, n (%)

Variable	Without MACEs (n = 400)	With MACEs (n = 145)	P value
Male gender	202 (71.4)	81 (28.6)	0.29
Age, mean (SD) (years)	50.7 (14.5)	60.9 (12.3)	< 0.01
Body mass index, mean (SD) (kg/m2)	25.4 (4.5)	26.7 (4.5)	< 0.01
Current smokers	106 (64.2)	59 (35.8)	< 0.01
Having hypertension	332 (70.0)	142 (30.0)	< 0.01
Having left ventricular hypertrophy	288 (66.8)	143 (33.2)	< 0.01
Having dyslipidemia	302 (70.9)	124 (29.1)	0.01
Having previous cardiovascular events	5 (1.3)	74 (93.7)	< 0.01
Uric acid,mean (SD) (μmol/L)	411.26 (89.6)	520.0 (102.5)	< 0.01
Glomerular filtration rate, mean (SD) (mL/minute)	49.6 (25.1)	37.7 (21.4)	< 0.01
Having proteinuria	103 (59.9)	69 (40.1)	< 0.01
Using steroids for more than one year	305 (74.2)	106 (25.8)	0.50
Acute rejection	135 (74.2)	47 (25.8)	0.84
Receiving hyperuricemia treatment	105 (55.0)	86 (45.0)	< 0.01
Receiving cyclosporine therapy	71 (64.0)	40 (36.0)	0.02
Receiving tacrolimus therapy	312 (77.2)	92 (22.8)	< 0.01
New onset of diabetes mellitus	55 (67.1)	27 (32.9)	0.32
Length of hemodialysis, mean (SD) (months)	16.9 (17.4)	20.2 (18.4)	< 0.01
Hyperparathyroidism, mean (SD) (pg/mL)	150.9 (137.5)	173.2 (112.1)	< 0.01
Inflammation, mean (SD) (mg/L)	4.3 (8.5)	5.9 (6.1)	< 0.01
Having anemia	110 (61.1)	70 (38.9)	< 0.01

MACEs: Major adverse cardiovascular events.

Table 3 Association between major adverse cardiovascular events and independent variables–main model

Variable	Odds ratio	95%CI	P value	Wald statistics
Age (years)	1.05	1.03–1.08	< 0.01	21.13
Receiving hyperuricemia treatment	4.29	2.44–7.57	< 0.01	25.42
Having previous cardiovascular events	70.6	24.9–200.1	< 0.01	64.03
Having left ventricular hypertrophy	12.6	2.74–58.3	< 0.01	10.56
Having anemia	5.32	2.89–9.80	< 0.01	28.82

Effect modification by a level of uric acid.

Table 4 Effect modification by a very high level of uric acid (> 475 μmol/L) of the associations in the main model

Variable	Not having elevated levels of UA			Having elevated levels of UA
	OR	95%CI	P value	OR	95%CI	P value
Age (years)	1.05	1.01–1.08	0.01	1.08	1.04–1.12	< 0.01
Receiving hyperuricemia treatment	1.76	0.66–4.69	0.26	2.09	0.86–5.08	0.10
Having previous cardiovascular events	63.07	16.14–246.40	< 0.01	72.82	9.09–583.34	< 0.01
Having left ventricular hypertrophy	10.97	1.28–94.06	< 0.01	6.48	0.74–56.58	0.09
Having anemia	6.08	2.32–15.92	< 0.01	6.46	2.46–16.95	< 0.01

OR: Odds ratio; UA: Uric acid.

Table 5 Effect modification by having hyperuricemia of the associations in the main model

Variable	Having hyperuricemia
	Odds ratio	95%CI	P value
Age (years)	1.06	1.03–1.09	< 0.01
Receiving hyperuricemia treatment	2.45	1.31–4.59	< 0.01
Having previous cardiovascular events	41.70	13.62–127.64	< 0.01
Having left ventricular hypertrophy	15.33	2.02–116.60	< 0.01
Having anemia	5.36	2.75–10.48	< 0.01

Table 6 Association between major adverse cardiovascular events and independent variables when parameters of uric acid included in the model

Variable	Odds ratio	95%CI	P value	Wald statistics
Age	1.06	1.03–1.08	< 0.01	22.73
Uric acid	1.01	1.00–1.01	< 0.01	40.39
Having previous cardiovascular events	69.01	22.15–215.05	< 0.01	53.32
Having left ventricular hypertrophy	9.22	2.05–41.54	< 0.01	8.36
Having anemia	4.97	2.65–9.30	< 0.01	25.12