Abstract 18433: Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators from Obesity to Ischemic Heart Disease
Introduction: Obesity leads to increased risk of ischemic heart disease(IHD), but the risk is probably mediated through intermediate variables and may not be caused by increased weight per se.
Hypothesis: We tested the hypothesis that the increased risk of IHD due to obesity is mediated through lipoproteins, blood pressure, glucose, and/or C-reactive protein.
Methods: 86,983 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index(BMI) and intermediate variables, and using genetic variants associated with these. During up to 22 years of follow-up 13,398 participants developed IHD.
Results: The increased risk of IHD due to obesity was mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein(LDL) cholesterol, and through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The three intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were LDL cholesterol with 10%, systolic blood pressure with 9%, and remnant cholesterol with 8% excess risk of IHD. Corresponding observational excess risks using conventional BMI were 20%, 10%, and 20%, respectively.
Conclusions: The increased risk of IHD due to obesity was primarily mediated through elevated levels of nonfasting remnant and LDL cholesterol, and through elevated blood pressure. Our results suggest there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss.
Author Disclosures: A. Varbo: None. M. Benn: None. G. Davey-Smith: None. N.J. Timpson: None. A. Tybjærg-Hansen: None. B.G. Nordestgaard: None.
- © 2014 by American Heart Association, Inc.