Very Long-Chain Saturated Fatty Acids Are Inversely Correlated with Thrombin Generation and Linked to a Reduced Risk of Coronary Artery Disease and Myocardial Infarction: Preliminary Findings from an Angiographically-Controlled Study

Background: The role of human plasma fatty acid (FA) composition in coagulation cascade has received limited attention so far, despite evidence that the coagulation is deeply influenced by lipid binding.

Aims: To assess the relationships between plasma FAs and thrombin generation parameters in a single-center, angiographically-controlled, cohort of subjects with or without coronary artery disease (CAD).

Methods: Plasma FA concentrations were measured by a gas-chromatographic method in clinically stable subjects undergoing to elective coronary angiography who were also characterized for thrombin generation assay. Thrombin generation was studied using the Calibrated Automated Thrombogram assay (CAT®, Diagnostica Stago, France) The following parameters of thrombogram were analyzed: the lag-time of thrombin generation, the time to reach the peak of thrombin (ttPeak), the thrombin peak (Peak), the endogenous thrombin potential (ETP) that reflects the total amount of thrombin activity. Subjects with any acute illness, including acute coronary syndrome, in the month before blood collection and coronary angiography were excluded from this study.

Results: The plasma FA profile was available for 245 subjects (males 73.9%; mean age 68.1±10.3 years): 54 with normal coronary arteries (CAD-free group) and 191 with coronary lesions with stenosis ≥50% (CAD group), of whom 51 with history of previous myocardial infarction (MI). Thirty-nine subjects taking oral anticoagulant therapies were excluded from further analysis on thrombin generation. In the 206 subjects not taking oral anticoagulants the saturated FAs 20:0, 22:0, and 24:0 were inversely correlated with peak of thrombin (R=-0.200 with P=0.004, R=-0.151 with P=0.031, and R=-0.182 with P=0.009, respectively) and endogenous thrombin potential (R=-0.217 with P=0.002, R=-0.170 with P=0.015, and R=-0.202 with P=0.004, respectively), while the saturated FA 26:0 correlated inversely with peak of thrombin (R=-0.208, P=0.003) and directly with time-to-peak (R=0.190, P=0.006).

Defining very long-chain saturated FAs (VLSFAs) as those with 20 carbons or more, the sum of their levels remained inversely associated with both peak of thrombin and endogenous thrombin potential after adjustment for gender, age, CAD diagnosis, renal function and other traditional cardiovascular risk factors by linear regression analysis (standardized beta coefficient=-0.465 with P<0.001 and standardized beta coefficient=-0.400 with P=0.001, respectively).

In the whole study population subjects with CAD with or without MI had lower levels of VLSFAs than CAD-free subjects (1.43±0.34, 1.58±0.40, and 1.68±0.43 g/100g, respectively, P=0.005 by ANOVA). Stratifying the study population on the basis of FA levels in CAD-free subjects, the prevalence of subjects within the highest VLSFA quartile (≥2.06 g/100g) decreased progressively from CAD-free to CAD without MI and CAD with MI (24.1%, 11.4%, and 3.9%, respectively, P=0.003).

Conclusions: This preliminary analysis showed an inverse correlation between VLSFA and thrombin generation, thereby indicating a potential antithrombotic effect of high VLSFA levels. Additionally, high VLSFA levels were linked to a lower prevalence of CAD and MI, consistently with the recent studies indicating that elevated VLSFA concentrations are associated with favourable cardiovascular outcomes.