Soluble TWEAK may predict carotid atherosclerosis in treated HIV infection

Figures & data

Table 1 Baseline characteristics. Median values (interquartile range)

	HIV positive ≥50 copies/mL (n = 100)	HIV positive <50 copies/mL (n = 174)	HIV negative (n = 59)	P value
Demographics
Age, years	41 (31,49)	43 (25,51)	35 (23,44)	0.01
Male sex	79%	78%	64%	0.08
African-American	65%	70%	41%	<0.01
Metabolic and cardiovascular risk factors
Family history of MI	29%	25%	19%	0.64
Family history of diabetes	34%	40%	15%	0.01
BMI, kg/m^2	27 (23,31)	25 (22,29)	28 (25,31)	<0.01
Waist hip ratio	0.89 (0.77,0.92)	0.86 (0.75,0.92)	0.86 (0.73,0.92)	0.90
Active hepatitis C	8%	4%	0%	0.04
Systolic blood pressure, mm Hg	122 (110,131)	122 (114,133)	120 (110,128)	0.18
Hypertensive medication	26%	32%	10%	<0.01
HDL cholesterol, mg/dL	43 (37,53)	46 (38,56)	47 (42,58)	0.03
LDL cholesterol mg/dL	99 (78,120)	95 (75,112)	118 (91,135)	<0.01
HOMA-IR	1.54 (0.72,2.31)	1.99 (1.21,4.07)	1.32 (0.65,2.38)	<0.01
Current smoking	59%	55%	19%	<0.01
HIV parameters
Current CD4+ count, cells/mm3	538 (461,709)	653 (451,860)		0.06
Nadir CD4+ count, cells/mm3	107 (322,524)	198 (80,300)		<0.01
HIV RNA, copies/mL	1860 (160,10322)	20 (20,48)		<0.01
Current protease inhibitor use	19%	46%		<0.01
Measures of subclinical vascular disease
Mean–Mean common carotid artery IMT, mm	0.64 (0.59,0.69)	0.64 (0.57,0.73)	0.59 (0.56,0.68)	0.02
Mean–Max common carotid artery IMT, mm	0.80 (0.75,0.90)	0.81 (0.72,0.91)	0.78 (0.69,0.88)	0.22
Mean–Mean carotid bulb IMT, mm	0.72 (0.65,0.81)	0.74 (0.64,0.89)	0.67 (0.61,0.79)	0.06
Mean–Max carotid bulb IMT, mm	1.03 (0.92,1.17)	0.81 (0.72,0.91)	0.78 (0.69,0.88)	0.14
Inflammation and immune activation
hsCRP, μg/mL	1.15 (0.59,3.50)	2.15 (0.56,2.30)	0.86 (0.34,1.82)	<0.01
D-dimer, μg/mL	0.20 (0.11,0.36)	0.21 (0.11,0.71)	0.19 (0.11,0.28)	0.15
Interleukin 6, pg/mL	2.61 (1.88,4.14)	2.16 (1.33,3.76)	1.81 (1.10,2.72)	<0.01
TNFα- receptor I, pg/mL	1261 (1053,1445)	1253 (944,1762)	1243 (1087,1394)	0.79
TNFα- receptor II, pg/mL	2888 (2474,3515)	2332 (1848,2859)	2295 (2052,2662)	<0.01
VCAM, ng/mL	843 (653,1069)	670 (562,812)	570 (467,714)	<0.01
CD4 + CD38 + HLADR + T-cells, %	18 (13,21)	13 (10,17)
CD8 + CD38 + HLADR + T-cells, %	43 (31,52)	29 (21,38)
CD14 + CD16 + monocytes, %	20 (18,42)	23 (18,32)
CD14dimCD16 + monocytes, %	12 (8,18)	11 (8,14)
sCD14, ng/mL	1558 (1289,1883)	1997 (1572,2401)	1221 (1031,1494)	<0.01
sTWEAK, pg/mL	638 (500,1096)	850 (541,2539)	1707 (629,4780)	<0.01
sCD163, ng/mL	867 (373,1291)	607 (363,901)	449 (265,651)	<0.01
sCD163/sTWEAK	0.92 (0.33,2.19)	0.52 (0.17,1.24)	0.17 (0.06,0.61)	<0.01

Figure 1 sTWEAK, sCD163, and sCD163/sTWEAK ratio in HIV-infected participants and controls

Table 2 Multivariable analysis for relationship between inflammatory markers between sTWEAK, sCD163, sTWEAK/sCD163 and inflammatory and cardiovascular markers for HIV-infected patients with VL < 50 copies/mL.

	sTWEAK		sCD163		sCD163/sTWEAK
	β (SE)	P value	β (SE)	P value	β (SE)	P value
Demographics
Age, years	−125.42 (55.9)	0.03	120.02 (26.80)	<0.01	0.20 (0.34)	<0.01
Male sex	53.19 (217.8)	0.80	16.44 (67.90)	0.81	−0.02 (0.23)	0.91
Metabolic and cardiovascular risk factors
Waist hip ratio	−439.67 (972.10)	0.65	988.36 (383.75)	0.01	1.46 (0.74)	0.05
BMI, kg/m^2	−8.81 (10.59)	0.41	9.31 (6.10)	0.13	0.011 (0.01)	0.18
Hypertensive medication	602.42 (266.75)	0.03	−233.96 (137.86)	0.10	−0.56 (0.38)	0.14
HOMA-IR	−6.00 (14.20)	0.67	1.144 (9.09)	0.90	0.15 (0.01)	0.21
Cholesterol, mg/dL	26.46 (97.51)	0.79	−61.43 (38.32)	0.11	−0.04 (0.05)	0.41
LDL, mg/dL	96.84 (90.19)	0.28	−59.68 (35.58)	0.09	−0.06 (0.05)	0.28
HIV parameters
Nadir CD4+ count, cells/mm3	193.16 (116.58)	0.10	0.033 (38.89)	0.99	−0.07 (0.06)	0.20
HIV RNA, copies/mL	−83544.14 (99169.93)	0.40	62948.01 (44852.87)	0.16	127.89 (63.99)	0.05
Measures of subclinical vascular disease
Mean–Mean common carotid artery IMT, mm	1806.50 (685.16)	<0.01	678.82 (304.98)	0.03	−0.75 (0.37)	0.05
Mean–Max common carotid artery IMT, mm	1128.18 (555.64)	0.04	776.63 (199.34)	<0.01	−0.13 (0.33)	0.70
Mean–Mean carotid bulb IMT, mm	65.76 (281.92)	0.82	165.53 (106.64)	0.12	0.15 (0.22)	0.52
Mean–Max carotid bulb IMT, mm	371.17 (289.68)	0.20	99.20 (94.18)	0.29	0.04 (0.18)	0.81
Inflammation and Immune activation
hsCRP, μg/mL	36.62 (55.62)	0.51	13.31 (22.69)	0.56	0.01 (0.04)	0.82
D-dimer, μg/mL	−10.61 (74.61)	0.89	−69.54 (34.62)	0.05	−0.00 (0.05)	0.92
Interleukin 6, pg/mL	29.21 (7.06)	<0.01	6.59 (2.67)	0.015	−0.01 (0.00)	0.11
TNFα-receptor I, pg/mL	−60.59 (54.96)	0.27	91.07 (25.49)	<0.01	0.10 (0.05)	0.06
TNFα-receptor II, pg/mL	89.60 (96.40)	0.35	87.78 (30.48)	<0.01	−0.00 (0.06)	0.90
VCAM	−0.04 (100.10)	1.00	72.46 (36.30)	0.05	0.05 (0.07)	0.45
CD4 + CD38 + HLADR + T-cells, %	17.86 (14.33)	0.22	5.08 (6.00)	0.40	−0.00 (0.01)	0.77
CD8 + CD38 + HLADR + T-cells, %	172.72 (118.55)	0.15	5.48 (52.81)	0.92	−0.13 (0.13)	0.31
CD14 + CD16 + monocytes, %	−11.77 (5.15)	0.02	7.93 (2.00)	<0.01	0.01 (0.01)	0.06
CD14dimCD16 + monocytes, %	−30.14 (21.82)	0.17	2.50 (8.35)	0.77	0.04 (0.02)	0.03
sCD14, ng/mL	11.73 (35.82)	0.74	14.26 (16.23)	0.38	0.2 (0.02)	0.44
sCD163, ng/mL	0.54 (0.21)	0.01

Note: All regression coefficients were adjusted for age, sex, and race.