Association of apolipoproteins C-I, C-II, C-III and E with coagulation markers and venous thromboembolism risk

Figures & data

Figure 1 Flow chart of participants selection. Patients and RDD controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (MEGA), the Netherlands, 1999–2004.

Abbreviations: RDD, random-digit-dialing; VTE, venous thromboembolism; apo, apolipoprotein.

Table 1 Clinical characteristics of patients and RDD controls randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study, the Netherlands, 1999–2004

Characteristic^a	Patients			RDD controls (n=299)
	All (n=127)	First VTE (n=63)	Recurrent VTE (n=64)
Age at enrollment^b, mean (SD)	46 (13)	45 (12)	47 (13)	47 (13)
Men, n (%)	59 (46)	20 (32)	39 (61)	138 (46)
Statin use, n (%)	3 (2.4)	3 (4.8)	0 (0)	22 (7)
BMI, kg/m^2, mean (SD)	27.4 (4.8)	27.6 (5.2)	27 (4.4)	25.3 (4.2)
Estrogen use, n (% in women)	43 (64.2)	26 (41.3)	17 (26.6)	40 (25.3)
Diabetes (self-reported), n (%)	3 (2.4)	1 (1.6)	2 3.1	5 (1.7)
Alcohol use, n (%)
No	26 (21)	15 (25)	11 (17)	35 (12)
Yes	96 (79)	45 (75)	52 (83)	263 (88)

Notes: ^aThere were some missing data on BMI, estrogen use, statin use, alcohol use and diabetes. ^bAge is expressed in years.

Abbreviations: BMI, body mass index; RDD, random-digit-dialing; VTE, venous thromboembolism.

Table 2 Association of apolipoproteins with levels of hemostatic factors and C-reactive protein in RDD controls randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis case–control study, the Netherlands, 1999–2004

Parameters	ApoC-I (n=292)^a		ApoC-II (n=286)^a		ApoC-III (n=292)^a		ApoE (n=292)^a
	per SD increase (5.33 mg/L)	(95%CI)	per SD increase (0.97 mg/L)	(95%CI)	per SD increase (37.11 mg/L)	(95%CI)	per SD increase (13.03 mg/L)	(95%CI)
Anticoagulant factors
Protein C (IU/dL)^b	8.21	(6.02; 10.40)	6.25	(3.77; 8.72)	8.00	(5.73; 10.26)	7.34	(5.00; 9.68)
Protein S antigen (IU/dL)^b	5.51	(3.52; 7.50)	5.26	(3.10; 7.42)	5.74	(3.71; 7.78)	3.86	(1.72; 5.99)
Antithrombin (IU/dL)	2.78	(1.56; 4.00)	2.12	(0.77; 3.46)	2.41	(1.19; 3.64)	1.74	(0.45; 3.02)
TFPI activity (IU/mL)	0.07	(0.01; 0.12)	0.04	(−0.02; 0.10)	0.00	(−0.05; 0.06)	0.04	(−0.01; 0.10)
Procoagulant factors
Fibrinogen (g/L)	−0.07	(−0.14; 0.00)	0.02	(−0.06; 0.10)	0.01	(−0.07; 0.08)	0.06	(−0.01; 0.14)
Factor II (IU/dL)^b	4.47	(3.07; 5.86)	3.10	(1.55; 4.65)	4.83	(3.41; 6.24)	3.42	(1.92; 4.92)
Factor VII (IU/dL)^b	8.10	(5.56; 10.63)	4.90	(2.07; 7.73)	9.87	(7.35; 12.39)	8.80	(6.17; 11.43)
Factor VIII (IU/dL)	1.07	(−3.72; 5.85)	2.83	(−2.37; 8.02)	6.60	(1.91; 11.30)	5.12	(0.23; 10.02)
VWF (IU/dL)	2.07	(−2.72; 6.85)	3.01	(−2.20; 8.21)	5.74	(1.02; 10.45)	6.08	(1.19; 10.96)
Factor IX antigen (IU/dL)^b	3.62	(1.62; 5.61)	2.80	(0.63; 4.96)	5.45	(3.46; 7.43)	2.74	(0.64; 4.84)
Factor X (IU/dL)^b	7.06	(5.22; 8.90)	4.81	(2.73; 6.90)	7.96	(6.11; 9.80)	4.70	(2.67; 6.73)
Factor XI (IU/dL)	3.67	(1.52; 5.82)	2.26	(−0.07; 4.58)	2.14	(−0.02; 4.31)	3.68	(1.46;5.89)
Fibrinolytic factor
Clot lysis time (min)^b	5.91	(3.71; 8.11)	3.40	(0.95; 5.85)	5.95	(3.69; 8.20)	6.36	(4.07; 8.64)
Inflammatory marker
hsCRP (mg/L)^c	−0.10	(−0.21; 0.02)	0.03	(−0.10; 0.16)	0.02	(−0.10; 0.14)	0.09	(−0.03; 0.21)

Notes: ^aAdjusted for age, sex, statin use, estrogen use, BMI, alcohol use and self-reported diabetes. ^bIndividuals using VKA are excluded when analyzing vitamin K-dependent coagulation factors (3 RDD were using anticoagulants). ^cValues were log-transformed.

Abbreviations: ApoC-I, apolipoprotein C-I; ApoC-II, apolipoprotein C-II; ApoC-III, apolipoprotein C-III; ApoE, apolipoprotein E; CI, confidence interval; RDD, random-digit-dialing; TFPI, tissue factor pathway inhibitor; VWF, von Willebrand factor.

Figure 2 Odds ratio of venous thromboembolism for apolipoproteins C-I, C-II, C-III and E levels when comparing patients and RDD controls randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis Case–control study, the Netherlands, 1999–2004. The models were adjusted for: (A) age and sex; (B) age, sex and statin use and (C) age, sex, statin use, estrogen use, alcohol intake, body mass index and self-reported diabetes adjusted model. Data show odds ratio (OR) and 95% confidence interval (CI).

Abbreviations: RDD, random digit dialing; VTE, venous thromboembolism; apo, apolipoprotein.