Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia.

Abstract

SUMMARY Haemostatic variables were measured in 61 patients with heterozygous familial hypercholesterolaemia, 32 of whom had evidence of coronary heart disease. Age adjusted mean concentrations of plasma fibrinogen and factor VIII were significantly higher in these patients than in the 29 patients without coronary heart disease, but there were no significant differences in serum lipid concentrations between the two groups. Comparisons in 30 patients taking and not taking lipid lowering drugs showed lower values for low density lipoprotein cholesterol, high density lipoprotein cholesterol and antithrombin III, and a higher high density lipoprotein ratio while receiving treatment. The results suggest that hypercoagulability may play a role in the pathogenesis of coronary heart disease in patients with familial hypercholesterolaemia.Premature coronary disease is a characteristic feature of heterozygous familial hypercholesterolaemia and up to 50% of male and 25% of female patients with familial hypercholesterolaemia develop symptoms of coronary ischaemia by the age of 50. 1 2 Increased concentrations of low density lipoprotein (LDL) play a major role in the pathogenesis of this premature atherosclerosis, but accelerated intravascular coagulation3 and increased plasma fibrinogen concentrations have also been reported.4 5 Preliminary results from the Northwick Park heart study have shown an association between high plasma concentrations of factor VII, factor VIII, and fibrinogen and an increased risk of subsequent cardiovascular death.6 We have therefore measured these and other haemostatic variables in patients with familial hypercholesterolaemia with or without overt coronary heart disease and in addition have studied the effects of hypolipidaemic drugs on these variables.

A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017

“…An earlier comparison of FH cases with and without CHD [16] found no significant differences in levels of plasma cholesterol and TG; however, levels of fibrinogen and coagulation factor VIII were significantly higher in the group with CHD. Among heterologous FH cases, high plasma lipid levels were not associated with CHD but hypercoagulability was a likely cause of CHD pathogenesis (Fig.…”

“…Data based on Surgrue et al [16]. CHD was associated with significantly increased levels of fibrinogen and coagulation factor VIII but not with increased levels of classical risk factors such as LDL-C, HDL-C, and TG.…”

“…The mechanisms by which inhibitors of VK2-dependent processes lead to atherosclerosis, DM, chronic kidney disease, and decreased bone mineral density have been reviewed elsewhere [16, 42], and will be addressed in section V below. Thus, the alternative measures predicted from Mendelian randomization studies (x-axis; Fig.…”

“…1). Therefore, genetic mutations in or near LDLR are expected to affect not only LDL receptor function, but also blood coagulability [16] through the coagulation factors IX, X, and protein C, inflammatory tone through tumor necrosis factor (TNF)-α, epidermal growth factor (EGF)-related physiology, and infectivity through complement C9. SNPs can cause gain or loss of function.…”

Chronic Alcohol Consumption Modulates the Clotting Time In Wistar Rats

“…Coagulation factors, specifically fibrinogen and factor VII, (serum prothrombin conversion accelerator) have been implicated as risk factors for atherosclerotic diseases (Wilhelmsen et al, 1984;Meade et al, 1986). Several cross-sectional studies also have suggested an association between factor VIII and von Willebrand factor (vWF) with atherosclerotic heart disease, but other studies have found no association with heart disease (Sugrue et al, 1985;Myreng et al, 1986). Thus, a reduction in the risk of CAD can be related to the prevention of clotting or thrombosis, especially because 90% of patients with fatal myocardial infarction have associated coronary thrombosis.…”