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Serum lipoproteins and hemostatic function in intermittent claudication
J Johansson1, N Egberg, H Johnsson
1Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Insights
Men with intermittent claudication show altered lipoprotein profiles, including lower high-density lipoprotein (HDL) and elevated lipoprotein(a) [Lp(a)]. Hemostatic factors like plasminogen activator inhibitor-1 (PAI-1) and fibrinogen are also increased, indicating coagulation system activation.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Lipidology
Background:
- Intermittent claudication (IC) is a manifestation of peripheral artery disease, often linked to systemic atherosclerosis.
- Lipoprotein metabolism and hemostatic function are critical in cardiovascular health and disease progression.
Purpose of the Study:
- To compare plasma lipoprotein and hemostatic variables between normoglucemic men with IC and matched controls.
- To investigate correlations between lipoprotein(a) [Lp(a)] and coagulation markers.
- To identify independent predictors of IC.
Main Methods:
- Comparison of plasma lipoprotein profiles (including HDL subclasses and Lp(a)) and hemostatic variables (PAI-1, antiplasmin, fibrinogen, beta-thromboglobulin) between IC patients (n=41) and controls (n=75).
- Correlation analyses between Lp(a), coagulation factors, and HDL subclasses.
- Multiple regression analysis to identify independent predictors of IC.
Main Results:
- IC patients exhibited lower levels of large HDL particles (HDL2b, HDL2a, HDL3a) and higher Lp(a) concentrations compared to controls.
- Elevated levels of plasminogen activator inhibitor-1 (PAI-1), plasma antiplasmin, plasma fibrinogen, and urine beta-thromboglobulin were observed in IC patients.
- Lp(a) correlated with plasma fibrinogen and urine fibrinopeptide A, while PAI-1 activity correlated with HDL3b and inversely with HDL2b.
- PAI-1, plasma fibrinogen, and HDL3a were identified as independent predictors of IC (R2 = .36).
- A subgroup of IC patients on beta-blockers/thiazides showed higher coronary heart disease frequency, elevated triglycerides, lower HDL cholesterol, and a shift towards smaller HDL particles.
Conclusions:
- Normoglucemic men with intermittent claudication display dyslipidemia characterized by reduced large HDL particles and increased Lp(a).
- Abnormalities in hemostatic variables, particularly PAI-1 and fibrinogen, are associated with intermittent claudication.
- These findings highlight the complex interplay of lipid and hemostatic factors in the pathophysiology of intermittent claudication.
Abstract:
Normoglucemic men with intermittent claudication (n = 41), mean age of 63 years, and sex-, age-, body mass index-, and smoking habit-matched controls (n = 75) were compared for plasma lipoprotein and hemostatic variables. The patients had significantly lower levels of large high-density lipoprotein (HDL) particles (HDL2b, HDL2a, and HDL3a) and elevated lipoprotein(a) [Lp(a)] concentrations than the control subjects. Of the hemostatic variables, plasminogen activator inhibitor-1 (PAI-1), plasma antiplasmin, plasma fibrinogen, and urine beta-thromboglobulin concentrations were significantly elevated in patients. In intermittent claudication patients Lp(a) correlated significantly with activation of the coagulation system, ie, with the levels of plasma fibrinogen and urine fibrinopeptide A. No correlations between the values for Lp(a) and PAI-1 or plasma alpha 2-antiplasmin were seen. The PAI-1 activity showed significant univariate correlations to the levels of HDL3b, HDL2b (inverse), and very-low-density lipoprotein triglycerides, of which the positive correlation to HDL3b persisted in multivariate analysis (r = .48, P < .001). Independent characteristics for intermittent claudication estimated by multiple regression analysis were PAI-1, plasma fibrinogen, and HDL3a, with a combined R2 of .36. The intermittent claudication subgroup that was being treated with beta-blockers/thiazides had a higher frequency of coronary heart disease compared with the other patients. In addition, the patients taking beta-blockers/thiazides had elevated triglyceride concentrations, lower HDL cholesterol with a size shift toward smaller particles, and a tendency toward raised PAI-1 and plasma alpha 2-antiplasmin levels compared with the patient group that did not take these medications.