The association between cholesterol remnants and cardiac structure and function

Abstract Background Cardiac disease is the most common cause of death in Europe and is a rising problem globally. Recently, a causal relationship between ischemic heart disease and cholesterol remnants has been suggested by genetic studies. Additionally, new studies have shown that cholesterol remnants were independently related to later development of ischemic disease in individuals free of known heart disease. Finally, in patients suffering from type 1 diabetes, one study demonstrated an association between cholesterol remnants and cardiac function indicating early signs of cardiac pathology. Purpose To investigate whether cholesterol remnants are associated with alterations in cardiac structure and function, as evaluated by sensitive echocardiographic measures, in individuals from the general population without known heart disease. Methods The study sample consisted of 3,792 participants from a general population cohort without known heart disease. All participants had blood samples withdrawn for analysis and were examined with comprehensive echocardiography including both conventional measurements and two-dimensional speckle tracking analysis. Cholesterol remnant levels were calculated from lipid analyses in non-fasting venous blood samples using the following formula: cholesterol remnants = total-cholesterol − HDL-cholesterol − LDL-cholesterol. Results In multivariable analyses increasing levels of cholesterol remnants were associated with significant alterations in cardiac function, demonstrated as a decrease in left ventricular ejection fraction (β=−0.686, P=0.001), a decrease in E/A ratio (β=−0.109, P<0.001) and a decrease in global longitudinal strain (β=−1.195 P=0.014) (Figure 1). The multivariable model was adjusted for age, sex, body mass index, hypertension, diabetes and smoking status. This association was significantly stronger than the association with cardiac alterations and LDL levels with the most significant difference regarding LVEF (cholesterol remnants: β=−0.158, P<0.001) and (LDL: β=−0.016, P=0.353). Additionally, increasing levels of cholesterol remnants were associated with alterations in cardiac structure (IVSd, LVIDd, LVPWd, LVMi and RWT) in the univariable analysis, but these associations were attenuated after multivariable adjustment. Conclusion In a general population sample without known heart disease, alterations in cardiac function expressed as both impaired systolic and impaired diastolic function were present with increasing levels of cholesterol remnants. This association was stronger than the association between the cardiac alterations and LDL-cholesterol levels. The findings support the need for testing treatment options aimed specifically at cholesterol remnants, also in the general population. Funding Acknowledgement Type of funding sources: None.