The relationship between blood lipids, fatty acids and plasma clot properties in black South Africans

Abstract

Introduction and aim: Cardiovascular disease (CVD) is the foremost cause of mortality worldwide and a major and steadily increasing cause of death among black South Africans. This increase is largely attributed to the nutrition transition the country is undergoing, driven by urbanisation, westernisation and cultural change. The associated dietary changes (including among others a higher total fat and lower ratio of polyunsaturated to saturated fat intake) contribute to the increase in CVD risk, specifically increased serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Certain individual plasma phospholipid fatty acids have also been linked to increased or decreased CVD risk. Most CVD events are caused by a blood clot obstructing blood flow to the heart or brain. Numerous factors influence clot properties including plasma fibrinogen concentration (being the structural protein of the clot) as well as certain blood lipids and individual plasma fatty acids. Studies on the relationship between serum lipids, plasma phospholipid fatty acids, fibrinogen and fibrin clot properties and how they affect CVD risk are, however, limited. With the increased CVD prevalence in black South Africans and the associated increase in atherogenic blood lipids in the presence of already high fibrinogen levels, black South Africans are an ideal population in which to investigate these associations. We therefore aimed to investigate the relationship of plasma fibrinogen concentration and fibrin clot properties with different blood lipid fractions and plasma phospholipid fatty acids in black South Africans. Participants and methods: Data for 1281 participants collected in 2010 for the first follow-up of the Prospective Urban and Rural Epidemiological Study in South Africa (PURE-SA) were included in this cross-sectional study. Participants were apparently healthy black South African men and women aged 35 to 70 years and residing in rural or urban areas in the North-West province. Biochemical analyses included determination of the plasma lipid and phospholipid fatty acid profile, total and ’ fibrinogen (a common fibrinogen splice variant demonstrating altered clot properties) concentration and clot properties (lag time, slope, maximum absorbance and clot lysis time) using a turbidity-based assay. Results: LDL-C, composite saturated fatty acids (driven by stearic (C18:0) and lignoceric (C24:0) acid) and composite n-3 and n-6 polyunsaturated fatty acids (driven by docosahexaenoic acid (DHA; C22:6n3) and arachidonic acid (C20:4n6), respectively) were associated with a higher fibrinogen concentration and the formation of prothrombotic clots, namely denser clots with a higher rate of lateral aggregation and a lower lysis rate. Despite palmitic acid (C16:0) contributing the largest proportion to the composite saturated fatty acids (27.3% of the total fatty acids), it did not drive the association observed with the composite saturated fatty acids. HDL-C and composite monounsaturated fatty acids (driven by oleic acid (C18:1n9) and palmitoleate (C16:1n7)), on the other hand, were associated with a lower fibrinogen concentration and a profibrinolytic clot phenotype, namely less dense clots with a lower rate of lateral aggregation and a higher lysis rate. Not all individual constituent fatty acids of a composite fatty acid group demonstrated the same relationship with fibrinogen concentration or clot properties as what was reported for their respective composite fatty acid group. For instance, in contrast with associations observed for composite monounsaturated fatty acids, nervonic acid (C24:1n9) was associated with a higher fibrinogen concentration and prothrombotic clots. Similarly, in contrast with associations observed for composite n-3 fatty acids, alpha-linolenic acid (ALA; C18:3n3) was associated with profibrinolytic clots but had no association with fibrinogen concentration. Eicosapentaenoic acid (EPA; C20:5n3) was associated with a lower fibrinogen concentration and profibrinolytic clots, while docosapentaenoic acid (DPA; C22:5n3) showed no associations with fibrinogen concentration or clot properties. The ratio total n-6/n-3 fatty acids was associated with a lower fibrinogen concentration and profibrinolytic clots. In many cases the associations with clot properties were fully or partially mediated by respective higher or lower fibrinogen concentrations. Associations that remained after adjustment for fibrinogen suggest these blood lipids and phospholipid fatty acids have direct effects on clot properties independent from fibrinogen concentration. No associations were found between blood lipids or fatty acids with ’ fibrinogen. Conclusion: Certain blood lipids and plasma phospholipid fatty acids were associated with a higher fibrinogen concentration and prothrombotic clot properties while others were associated with a lower fibrinogen concentration and profibrinolytic clot properties. Constituent fatty acids often did not have the same relationship with fibrinogen concentration and clot properties as their composite group. Conclusions regarding the relationship of individual fatty acids with fibrinogen concentration or clot properties should therefore not be drawn based on the relationship between composite fatty acids and these factors. The limited number of studies conducted on the topic thus far, along with differences in their study and experimental designs, prohibit the drawing of firm conclusions. Further investigation is necessary to elucidate the causal relationships and mechanisms involved.