Table 2 Hemostatic parameters in patients with hyperlipidemic and normolipemic control subjects
a
Hyperlipidemia Controls n = 38
Variable IIa n = 20
IIb n = 12 165 130–206
Total TFPI ngml 151 140–197
113 96–141 31 27–34
Free-form TFPI ngml 41 38–45
21 17–27 93 77–130
90 50–116 103 70–147
TF pgml 92 79–100
FVIIc 112 97–118
121 109–128 1.00 0.67–1.21
0.74 0.56–0.92 0.94 0.79–1.71
F1+2 nmoll
a
TF, tissue factor; TFPI, tissue factor pathway inhibitor; FVIIc, factor VII activity; F1+2, prothrombin fragment 1+2. Values are shown as the median 25–75th percentiles.
PB0.05; PB0.01;
PB0.001, compared to normolipemic control subjects. Table 3
Serum lipids, apoprotein and hemostatic parameters in patients with hyperlipidemia before and after treatment with 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase inhibitors
a
After treatment n = 25 Variable
Statistical significance Before treatment n = 25
5.03 4.66–5.49 Total cholesterol mmoll
PB0.0001 7.07 6.52–7.29
2.75 2.41–3.49 LDL-cholesterol mmoll
PB0.0001 4.75 3.96–5.14
1.45 1.28–1.77 1.32 1.17–1.68
PB0.05 HDL-cholesterol mmoll
1.20 0.91–2.23 Triglycerides mmoll
PB0.01 1.73 1.31–2.59
142 130–173 138 123–163
NS Apoprotein AI mgdl
157 140–173 Apoprotein B mgdl
94 89–122 PB0.001
21.0 8.5–36.0 Lipoprotein a mgdl
30.0 3.8–38.3 NS
162 149–217 200 168–235
PB0.005 Total TFPI ngml
Free-form TFPI ngml 31 27–37
31 28–39 NS
118 105–124 128 112–150
PB0.005 FVIIc
0.89 0.72–1.21 PB0.05
F1+2 nmoll 1.13 0.94–1.27
a
TFPI, tissue factor pathway inhibitor; FVIIc, factor VII activity; F1+2, prothrombin fragment 1+2. Values are shown as the median 25–75th percentiles.
3. Results
3
.
1
. Patient characteristics Table 1 summarizes the clinical characteristics and
clinical data in patients with hypercholesterolemia and age- and sex-matched normolipemic control subjects
Study Group I. There were no statistically significant differences in age among the two patient groups and
control subjects. At base line, serum levels of total cholesterol, LDL-cholesterol, triglycerides, and apo B
were significantly higher in the two patients groups than in the control subjects. Patients with type IIb
hyperlipoproteinemia
exhibited significantly
higher body mass indices P B 0.05 and fasting blood sugar
P B 0.05 than control subjects.
3
.
2
. Assessment of hemostatic parameters Table 2 summarizes the hemostatic parameters in the
patients with hyperlipoproteinemia and in the age- and sex-matched normolipemic control group. The plasma
concentrations of tTFPI antigen were significantly higher in the patients with type IIa and type IIb hyper-
lipidemia compared with the control group P B 0.0001, P B 0.001, respectively. Compared with the control
group, fTFPI antigen was 2-fold higher in type IIb hyperlipidemia P B 0.0001 and 1.5-fold higher in type
IIa hyperlipidemia P B 0.001. With respect to the control group, the patients with type IIa and IIb hyper-
lipidemia had significantly higher levels of FVIIc P B 0.05, P B 0.001, respectively. F1 + 2 was significantly
higher in the two hyperlipidemic groups than in the control group type IIa; P B 0.05, type IIb; P B 0.05.
Although the median TF antigen was slightly higher in the patients with type IIb than in the control group,
this increase did not reach statistical significance.
3
.
3
. Effects of HMG-CoA reductase inhibitor on plasma hemostatic parameters
Before initiation of HMG-CoA reductase inhibitor therapy, serum lipids were highly elevated in 25 hyper-
lipidemic patients Study Group II, as shown in Table 3. During 6 months of treatment, serum total choles-
terol P B 0.0001, triglycerides P B 0.01, LDL-choles-
terol P B 0.0001, and apo B P B 0.005 decreased significantly, and HDL-cholesterol increased signifi-
cantly P B 0.05. However, serum apo AI and plasma Lp a did not show any significant change during
therapy. After therapy, the median value for plasma tTFPI 162 ngml decreased significantly compared to
the value before therapy 200 ngml, P B 0.005 Fig. 1A, although the plasma levels of fTFPI did not
change Fig. 1B. Significantly lower values for FVIIc Fig. 2 and F1 + 2 Fig. 3 were also observed follow-
ing therapy P B 0.005, P B 0.05, respectively.
Fig. 2. Changes in plasma levels of factor VII FVII activity in subjects taking 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA
reductase inhibitors.
Fig. 1. Changes in plasma concentrations of A total tissue factor pathway inhibitor tTFPI antigen and B free-form TFPI fTFPI
antigen in subjects taking 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase inhibitors.
Fig. 3. Changes in plasma concentrations of fragment 1 + 2 F1 + 2 in subjects taking 3-hydroxy-3-methylglutaryl coenzyme A HMG-
CoA reductase inhibitors.
3
.
4
. Relationships between serum lipids and tTFPI, fTFPI, and FVIIc
Simple regression analysis on correlations between tTFPI, fTFPI, and FVIIc and serum lipid concentra-
tions in hyperlipidemic patients are plotted in Figs. 4 – 6. Data from the hyperlipidemic patients at baseline
and after the different treatment regimens were in- cluded in the analysis. Plasma tTFPI was strongly
correlated with total cholesterol r = 0.57, P B 0.0001; Fig. 4A and LDL-cholesterol r = 0.53, P B 0.0005;
Fig. 4B, whereas no significant associations were found with HDL-cholesterol r = 0.16; Fig. 4C or triglyce-
rides r = 0.11; Fig. 4D. In contrast to the strong correlation between tTFPI and total cholesterol, the
correlation between plasma fTFPI and total cholesterol was relatively poor r = 0.31, P B 0.05; Fig. 5A. The
correlation between plasma fTFPI and LDL-cholesterol was also poor r = 0.30, P B 0.05; Fig. 5B. The plasma
level of FVIIc correlated with total cholesterol r = 0.35, P B 0.05; Fig. 6A and triglycerides r = 0.36,
P B 0.05; Fig. 6D, whereas no significant associations were found with LDL-cholesterol r = 0.03; Fig. 6B or
HDL-cholesterol r = 0.23; Fig. 6C. On the other hand, no correlations were found between plasma F1 +
2 and serum lipids data not shown. There were also no significant correlations between Lp a concentra-
tions and any of the hemostatic parameters data not shown.
4. Discussion
