Cor Vasa 2004, 45(2):60-67

The relationship of selected fibrinolytic markers to early atherosclerosis in dyslipidemic middle-aged subjects

Martin Hutyra^1,*, Luděk Slavík², Dalibor Novotný³, David Karásek¹, Milan Halenka¹, Helena Vaverková¹

¹ III. interní klinika

² Hemato-onkologická klinika

³ Oddělení konsolidovaných biochemických laboratoří, Fakultní nemocnice Olomouc a Lékařská fakulta Univerzity Palackého, Olomouc, Česká republika

Objective:
The aim of the present study was to examine the association of carotid intima-media thickness (IMT) as a marker of early atheroslerosis to the plasma concentrations of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) antigens in middle-aged dyslipidemic subjects without clinically manifest atherosclerosis.

Methods:
In the period from January 2001 through October 2002, we studied the association of tPA and PAI-1 with carotid IMT in 111 individuals (65 women/46 men, mean age 43.4 ± 13.25 years). Furthermore, we investigated the plasma concentrations of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A, B, as well as markers of systemic inflammation, i. e., high-sensitivity C-reactive protein (hs-CRP), fibrinogen, BMI and waist. The exclusion criteria were presence of any cardiovascular disease (coronary artery disease, heart failure, stroke, intermittent claudication, arterial hypertension or other established disease), diabetes mellitus, cigarette smoking, trauma, acute infectious disease, and any treatment with cardiovascular drugs including estrogens. Mean values ± SD of total cholesterol were 6.36 ± 2.22 mmol/L, HDL-C 1.58 ± 0.43 mmol/L, LDL-C 3.82 ± 1.26 mmol/L, TG 2.09 ± 2.85 mmol/L, and BMI 25.59 ± 3.87 kg/m². We used linear correlation analysis in the study cohort and cross-sectional case-control substudy analysis (control vs. hyperlipidemic individuals).

Results:
There was a significant correlation between carotid IMT and tPA (r = 0.251, p = 0.008) and PAI-1 (r = 0.225, p = 0.018). IMT correlated with total cholesterol (r = 0.266, p = 0.005), LDL-C (r = 0.425, p < 0.0001), TG (r = 0.222, p = 0.019), apolipoprotein B (r = 0.431, p < 0.0001), BMI (r = 0.396, p < 0.0001), waist (for women r = 0.397, p < 0.0001, for men r = 0.373, p = 0.005), systolic blood pressure (r = 0.334, p < 0.0001). There was no significant correlation of IMT with diastolic blood pressure, HDL-C, apolipoprotein A1, hs-CRP and fibrinogen concentrations. We found a significant correlation of tPA with total cholesterol (r = 0.299, p = 0.001), LDL-cholesterol (r = 0.205, p = 0.033), TG (r = 0.357, p < 0.0001), hs-CRP (r = 0.2, p = 0.048), BMI (r = 0.295, p = 0.003) and waist (for women r = 0.302, p = 0.008, for men r = 0.241, p = 0.048). PAI-1 was significantly associated with concentrations of total cholesterol (r = 0.322, p = 0.001), LDL-C (r = 0.339, p < 0.0001), TG (r = 0.38, p < 0.0001), HDL (r = -0.263, p = 0.007), apolipoprotein A-1 (r = -0,296, p = 0.003), apolipoprotein B (r = 0.329, p < 0.0001), hs-CRP (r = 0.18, p = 0.05), BMI (r = 0.491, p < 0.0001), waist (for women r = 0.281, p = 0.012, for men r = 0.508, p < 0.0001) and systolic blood pressure (r = 0.334, p < 0.0001). When comparing the two age- and sex--matched groups of hyperlipidemic patients and healthy controls, significant differences in values of carotid IMT and concentrations of total cholesterol and LDL-C, TG, apolipoprotein B, hs-CRP, PAI-1, BMI, and waist were demonstrated.

Conclusions:
The findings of this study support the hypothesis that impaired fibrinolytic activity contributes to early atherogenesis. The atherogenic effects of tPA and PAI-1 may be influenced by insulin resistance and chronic systemic inflammation.

Keywords: Early atherosclerosis; Intima-media thickness; Fibrinolysis; Endothelial dysfunction; Insulin resistance; Chronic systemic inflammation

Published: February 1, 2004  Show citation