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Triglyceride association with coronary disease strengthened
It is uncertain whether conditions characterised by increased circulating triglyceride concentrations are causal in coronary heart disease. Although epidemiological associations have suggested a positive correlation between triglyceride levels and coronary risk, these associations disappear after controlling for high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol.
In this study the authors assessed a promoter polymorphism (rs662799) of the apolipoprotein A5 (APOA5) gene that is known to lead to triglyceride-rich very low-density lipoprotein (VLDL). The promoter polymorphism was studied in relation to triglyceride concentrations, several other cardiac risk factors and the risk of coronary heart disease. In addition, the authors compared disease risk for patients with genetically raised triglyceride concentration (20 842 patient with coronary heart disease, 35 206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12 785 incident cases of coronary heart disease). Lastly, to provide mechanistic insights, the rs662799 polymorphism was also analysed in 1795 people without a history of cardiovascular disease, for whom information about lipoprotein concentration and diameter was obtained by nuclear magnetic resonance spectroscopy.
The rs662799 polymorphism was not significantly associated with non-lipid risk factors or LDL cholesterol, and was only modestly associated with lower HDL cholesterol, lower apolipoprotein A1, and higher apolipoprotein B (figure 1). However, for each C allele inherited, mean triglyceride concentration was 0.25 mmol/l higher. The rs662799 polymorphism was significantly associated with higher VLDL particle concentration, and smaller HDL size, factors that might mediate the effects of triglyceride.