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Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol
C Cimminiello1, P Vigorelli, T Piliego
1S Carlo Borr General Hospital, Milan, Italy.
Insights
Hypertriglyceridemia and low HDL-C increase coronary artery disease risk. Gemfibrozil improved lipid profiles and fibrinolysis in patients with high triglycerides and low HDL-C, suggesting a potential treatment benefit.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Hemostasis and Thrombosis
Background:
- Combined hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) are significant risk factors for coronary artery disease (CAD).
- High triglycerides (TG) are often associated with elevated plasminogen activator inhibitor (PAI), another CAD risk factor.
- Gemfibrozil has previously shown reduced coronary events and mortality, particularly in individuals with low HDL-C and high TG.
Purpose of the Study:
- To investigate if the combination of low HDL-C and high TG impairs fibrinolysis more than isolated conditions.
- To determine if gemfibrozil improves fibrinolysis in patients with both high TG and low HDL-C.
Main Methods:
- Assessed fibrinolytic parameters (tissue plasminogen activator, PAI antigen/activity, euglobulin fibrinolytic activity, plasminogen, alpha-2-antiplasmin) in four groups: combined low HDL-C/high TG, normal HDL-C, isolated low HDL-C, and healthy controls.
- Measurements were taken at baseline and after venous occlusion (vo).
- Evaluated the effect of 12-week gemfibrozil treatment (600 mg bid) on lipid profiles and fibrinolytic markers in the combined low HDL-C/high TG group.
Main Results:
- Patients with combined low HDL-C/high TG and normal HDL-C showed higher euglobulin fibrinolytic activity before venous occlusion and elevated PAI-1 antigen and alpha-2-antiplasmin levels after venous occlusion compared to controls or isolated low HDL-C.
- No consistent relationship was found between PAI antigen/activity and TG, or between PAI and HDL-C.
- Gemfibrozil treatment significantly improved lipid profiles, reduced PAI activity after venous occlusion, and significantly decreased PAI-1 antigen levels after venous occlusion.
Conclusions:
- The increased CAD risk associated with low HDL-C and high TG may be partly due to fibrinolytic impairment, similar to that seen in isolated high TG.
- Fibrinolytic activity is closely linked to TG and cholesterol levels, highlighting its crucial role in CAD development.
- Gemfibrozil demonstrates potential to improve fibrinolysis in individuals with combined dyslipidemia, suggesting a therapeutic benefit beyond lipid modification.
Abstract:
The combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) appears to be an excessively high risk factor for coronary artery disease (CAD). In the Helsinki study, both coronary events and mortality were decreased by gemfibrozil, especially in subjects with low HDL-C and high triglycerides (TG). On the other hand, it is known that high levels of TG can be associated with high levels of circulating plasminogen activator inhibitor (PAI), which is also a possible risk factor for CAD. The aim of the present study was to see: 1) whether the combination of low HDL-C and high TG is associated with a more impaired fibrinolytic response than in either isolated condition, and 2) whether gemfibrozil administration can improve fibrinolysis in patients with both high TG and low HDL-C. Twelve non-obese, non-diabetic subjects (eight men, four women; mean age 55 +/- 13 yrs) with low HDL-C (< 35 mg/dL men; < 45 mg/dL women) and high TG (mean 253.6 +/- 42.6 mg/dL) entered the study (Group A). Additionally fourteen comparable subjects with normal HDL-C were also investigated (Group B), plus 12 comparable subjects with isolated low HDL-C (Group C). Ten healthy people served as the control group. The following plasma fibrinolytic parameters were measured: tissue plasminogen activator antigen, PAI antigen and activity, euglobulin fibrinolytic activity (EFA) on fibrin plates, plasminogen and alpha-2-antiplasmin activities. All except the latter two values were also measured after venous occlusion (vo). In baseline conditions, patients in Groups A and B had higher EFA values before vo and higher PAI-1 antigen and alpha-2-antiplasmin levels after vo than those of controls or the subjects in Group C. The relationship between PAI antigen and PAI activity and TG was not confirmed in our population (n = 48). We also saw no interference due to HDL-C, while there was a significant relationship between EFA before vo and both TG and cholesterol. After gemfibrozil treatment (600 mg bid for 12 weeks), the lipid profiles of subjects with high TG and low HDL-C were significantly improved. There was also a slight reduction of PAI activity after vo, while the PAI-1 antigen had decreased significantly from baseline after vo (56.3 +/- 13 ng/mL before vo; 48.4 +/- 21 ng/mL after vo; P = 0.04). The higher risk of CAD in patients with low HDL-C and high TG might be in part related to impairment of fibrinolysis, which occurs in patients with isolated high TG. The close relationship existing between both TG and cholesterol levels and fibrinolytic activity confirm the key role of this latter process in the development of CAD.