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Postprandial variations in fibrinolytic activity in middle-aged men are modulated by plasminogen activator inhibitor I 4G-675/5G genotype but not by the fat content of a meal^1,2,3

¹ From the Nutrition Food and Health Research Centre, King’s College London (TABS and TdG); the Medical Research Council Cardiovascular Research Group, Wolfson Institute, Royal London & St Bartholomew’s Hospital Medical School, London (GJM); and the Centre for the Genetics of Cardiovascular Disease, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London (JA and SEH).

Background: Decreased fibrinolytic activity is associated with an increased risk of ischemic heart disease and elevated plasma triacylglycerol concentrations.

Objective: The goal was to determine whether plasminogen activator inhibitor 1 (PAI-1) and fibrinolytic activities are influenced by 1) dietary fat intake from a test meal and 2) the PAI-1 4G allele.

Design: A parallel randomized controlled trial was used to compare the effect on fibrinolytic activity, measured as dilute clot lysis time, of high-oleate or high-palmitate test meals (both containing 50 g fat; both n = 18) with that of a low-fat test meal (15 g fat; n = 15) in men aged > 52 y. In a second study, postprandial changes in PAI-1 activity were measured in 32 men in response to a high-oleate meal containing 50 g fat. The results from both studies were analyzed according to PAI-1 4G-675/5G genotype.

Results: Fasting dilute clot lysis time was positively associated with body mass index (r = 0.326, P = 0.02) and was shortened postprandially (P < 0.00001) independent of the fat content of the meal. Fasting PAI-1 activity was higher in those carrying the 4G allele and was correlated with fasting plasma triacylglycerol concentrations (r = 0.48, P = 0.008) and factor VII coagulant activity (r = 0.46, P = 0.012) after adjustments for age, body mass index, and genotype. Plasma PAI-1 activity decreased significantly after a meal but was not associated with postprandial changes in plasma triacylglycerols after a high-fat meal. The postprandial increase in plasma triacylglycerols was higher in subjects carrying the 4G allele.

Conclusion: Fibrinolytic activity is not lower after meals rich in palmitate or oleate than after a low-fat meal.

Key Words: Plasminogen activator inhibitor 1 • PAI-1 • monounsaturated fatty acids • saturated fatty acids • PAI 4G-675/5G • fibrinolysis

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