fibrin and Dyslipidemias

This article reports current evidence on the association between Lp(a) and cardiovascular (CV) disease and on pathophysiological mechanisms. The available information on therapy for reduction of lipoprotein(a) is also discussed.. Although some evidence is conflicting, Lp(a) seems to increase CV risk through stimulation of platelet aggregation, inhibition of tissue factor pathway inhibitor, alteration of fibrin clot structure and promotion of endothelial dysfunction and phospholipid oxidation. Lp(a) 3.5-fold higher than normal increases the risk of coronary heart disease and general CV events, particularly in those with LDL cholesterol ≥ 130 mg/dl. High Lp(a) values represent also an independent risk factor for ischemic stroke (more relevant in young stroke patients), peripheral artery disease (PAD) and aortic and mitral stenosis. Furthermore, high Lp(a) levels seem to be associated with increased risk of cardiovascular events in patients with chronic kidney disease, particularly in those undergoing percutaneous coronary intervention.. Lipoprotein (a) (Lp[a]) seems to significantly influence the risk of cardiovascular events. The effects of statins and fibrates on Lp(a) are limited and extremely variable. Nicotinic acid was shown effective in reducing Lp(a) but, due to its side effects and serious adverse events during clinical trials, it is no longer considered a possible option for treatment. To date, the treatment of choice for high levels of Lp(a) in high CV risk patients is represented by LDL-Apheresis. Thanks to innovative technologies, new selectively inhibiting LPA drugs are being developed and tested.

Topics: Biomarkers; Blood Component Removal; Blood Platelets; Cardiovascular Diseases; Dyslipidemias; Endothelium, Vascular; Fibrin; Humans; Hypolipidemic Agents; Lipoprotein(a); Lipoproteins; Oxidation-Reduction; Phospholipids; Platelet Aggregation; Risk Assessment; Risk Factors

Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia.. Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured.. During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001).. Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.

Topics: Adult; Aged; Atorvastatin; Biomarkers; Blood Platelets; C-Reactive Protein; Cell-Derived Microparticles; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Dyslipidemias; Fibrin; Fibrinolytic Agents; Glycated Hemoglobin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Integrin beta3; Middle Aged; P-Selectin; Plasminogen Activator Inhibitor 1; Pyrroles; Sweden; Thrombin; Thromboplastin; Thrombosis; Time Factors; Treatment Outcome

Topics: Atorvastatin; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Dyslipidemias; Fibrin; Fibrinolytic Agents; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Poland; Pyrroles; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thromboembolism

Individuals with hypertension, dyslipidemia or diabetes are at a higher risk to suffer cardiovascular disease than other people; while impaired fibrin structure/function may contribute to further raise the cardiovascular risk in the former. The purpose of this work was to study the fibrin network and fibrin degradation properties in hypertensive (HT) patients, pharmacologically treated, 124 +/- 11 mmHg, systolic blood pressure, and 70 +/- 10 mmHg, diastolic blood pressure, n = 12; metabolic dyslipidemic patients (DL), cholesterol: 5.7 +/- 1.5 mmol/L, n = 10; patients with type 2 diabetes mellitus (T2D), fasting plasma glucose: 8.8 +/- 2.2 mmol/L, n = 10; and a control group of healthy individuals, n = 9. The fibrinogen concentration was determined by the gravimetric method. Fibrin network formation and porosity were assessed by turbidity and permeation techniques, respectively; fibrin elastic properties were evaluated by compaction and fibrin lysis, by turbidity after addition of external tPA prior to plasma clotting. Fibrinogen concentration was significantly higher only in T2D patients (p = 0.004), compared to the control group. The fibrin polymerization and lysis processes were similar for all patient and control groups. Permeation was significantly slower in DL and T2D patients, p = 0.022 and 0.0002, respectively, whereas the compaction coefficient was significantly smaller in T2D patients, p = 0.0015. Our results suggest that the fibrin structure was altered in DL and T2D patients, probably due to the increased cholesterol and glycation, respectively.

Topics: Diabetes Mellitus, Type 2; Dyslipidemias; Female; Fibrin; Humans; Hypertension; Male; Middle Aged; Structure-Activity Relationship