Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

 

Never smokers

Active smokers

P

N

1,178

777
 
Age (years)

65.3 ± 10.1

56.2 ± 10.3

<0.001

Male sex (%)

45.4

77.9

<0.001

BMI

27.4 ± 4.2

27.0 ± 4.2

0.833

LDL-C (mg/dl)

119.1 ± 36.4

117.5 ± 32.1

0.012

oxidized LDL-C (U/l)

73.5 ± 26.7

78.4 ± 25.4

<0.001

HDL-C (mg/dl)

41.2 ± 11.1

36.2 ± 10.2

0.002

Triglycerides (mg/dl)

136 (102–192)

154 (112–218)

<0.001

Galectin-3 (ng/ml)

15.8 ± 6.3

15.5 ± 7.3

0.496

hsC-reactive protein (mg/l)

2.72 (1.17–7.04)

4.93 (1.84–10.30)

<0.001

eGFR (ml/min/1.73 m2)

78.7 ± 19.1

88.2 ± 20.1

<0.001

INR

1.05 (1.00–1.10)

1.03 (0.98–1.08)

<0.001

ETP (%)

94.4 ± 28.5

99.1 ± 24.5

<0.001

Coronary artery disease (%)

68.1

80.1

<0.001

Diabetes mellitus (%)

38.3

36.0

0.314

Hypertension (%)

76.6

63.3

<0.001

Lipid lowering therapy (%)

42.4

52.8

<0.001


Data are means ± SD or median and 25–75th percentile

BMI body mass index, ETP endogenous thrombin potential, HDL-C high density lipoprotein cholesterol, INR international normalized ratio, LDL-C low density lipoprotein cholesterol



AS showed a higher thrombogenic potential demonstrated by a lower international normalized ratio (INR) and a higher endogenous thrombin potential (Table 1) as well as higher concentrations of fibrinogen and soluble fibrin (only men) (Table 2). Regarding the fibrinolytic system we found no difference in the concentration of D-dimers between AS and NS. While there were significant increases in PAI-1 activity and t-PA antigen as well as a decrease in t-PA activity for male AS, there was a small decrease in t-PA antigen for female AS. Regarding active protein C, only female AS showed a significant decrease.


Table 2
Parameters of the fibrinolytic and coagulation systems in non-smokers and active smokers














































































































 
Men
Women

Never smokers (n = 535)
Active smokers (n = 605)
P
Never smokers (n = 643)
Active smokers (n = 172)
P

D-dimers (mg/l)
0.33 (0.22–0.57)
0.35 (0.22–0.65)
0.323
0.38 (0.23–0.65)
0.39 (0.22–0.65)
0.362

PAI-1 (U/ml)
15.0 (9.0–29.0)
19.0 (10.0–35.0)
0.026
20.0 (10.0–36.0)
18.0 (10.0–33.0)
0.182

t-PA antigen (μg/l)
11.6 (8.9–14.6)
12.7 (9.65–16.3)
0.002
11.5 (8.80–15.0)
10.5 (8.30–13.9)
0.025

t-PA (U/l)
0.68 (0.42–1.10)
0.63 (0.30–1.05)
0.005
0.61 (0.32–1.01)
0.63 (0.38–0.95)
0.473

Protein C (%)
105.0 ± 22.4
106.0 ± 25.7
0.623
118.0 ± 25.7
108.0 ± 24.1
0.004

Protein S (%)
119.0 ± 34.0
124.0 ± 36.3
0.100
111.0 ± 31.2
107.0 ± 30.5
0.365

Factor V (U/dl)
109.0 ± 20.1
115.0 ± 22.0
0.001
116.0 ± 22.0
115.0 ± 23.4
0.816

Factor VIII (U/dl)
160 (122–206)
154 (116–198)
0.014
184 (144–226)
174 (116–216)
0.002

Fibrinogen (mg/dl)
381 ± 107
420 ± 114
<0.001
387 ± 93
405 ± 113
0.053

sol. fibrin (U/ml)
60.0 (35.0–87.1)
64.6 (42.5–97.9)
0.017
53.3 (33.8–82.1)
59.4 (37.9–79.5)
0.339

TFPI (μg/l)
1.21 ± 0.34
1.31 ± 0.37
<0.001
1.25 ± 0.39
1.27 ± 0.38
0.482


Data are means ± SD or median and 25–75th percentile

PAI-1 plasminogen activator inhibitor 1, TFPI tissue factor pathway inhibitor, t-PA tissue plasminogen activator antigen

We next examined whether fibrinolytic parameters were associated with mortality in AS and NS by Cox regression analysis. In NS the only parameter that showed a statistically significant association with mortality after adjustment for other cardiovascular risk factors was t-PA antigen with a HR (95 % CI) of 1.15 (1.05–1.25) per 1SD increase (Table 3). In the group of active smokers, D-dimers, t-PA antigen, and PAI-1 activity were associated with an increased risk of death with HR of 1.14 (1.04–1.25), 1.19 (1.06–1.34), and 1.29 (1.11–1.49), respectively.


Table 3
Cox regression analysis of all-cause mortality per 1SD increase


























































































 
n
Never-smokers
n
Active smokers

HR (95 % CI)
P
HR (95 % CI)
P

Model 1

 D-dimers
1,164
1.09 (1.01–1.16)
0.022
770
1.13 (1.04–1.24)
0.006

 t-PA antigen
1,175
1.21 (1.12–1.31)
<0.001
777
1.16 (1.04–1.30)
0.007

 PAI-1
1,175
1.08 (0.99–1.17)
0.082
777
1.23 (1.09–1.40)
0.001

 Protein C
383
0.95 (0.76–1.18)
0.629
294
1.09 (0.87–1.37)
0.453

Model 2

 D-dimers
1,162
1.07 (1.00–1.16)
0.068
766
1.14 (1.04–1.25)
0.006

 t-PA antigen
1,175
1.15 (1.05–1.25)
0.003
771
1.19 (1.06–1.34)
0.004

 PAI-1
1,175
1.03 (0.90–1.17)
0.668
771
1.29 (1.11–1.49)
0.001

 Protein C
382
0.91 (0.71–1.16)
0.434
292
1.15 (0.89–1.48)
0.275


Model 1, adjusted for age and gender; Model 2, adjusted for age, sex, LDL-C, HDL-C, logTG, BMI, diabetes, hypertension, and logCRP

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Oct 1, 2016 | Posted by in RESPIRATORY | Comments Off on Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

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