Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women

© 2019 Elsevier Inc. Metabolic profile and ApoE4 genotype have effects on coronary heart disease. We examined the interaction between these factors on subclinical atherosclerosis in postmenopausal women from the Early versus Late Intervention Trial with Estradiol (n = 497). Based on nine metabolic b...

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Main Authors: Intira Sriprasert, Wendy Jean Mack, Howard Neil Hodis, Hooman Allayee, Roberta Diaz Brinton, Roksana Karim
Format: Journal
Published: 2019
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/65830
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spelling th-cmuir.6653943832-658302019-08-05T04:41:55Z Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women Intira Sriprasert Wendy Jean Mack Howard Neil Hodis Hooman Allayee Roberta Diaz Brinton Roksana Karim Medicine © 2019 Elsevier Inc. Metabolic profile and ApoE4 genotype have effects on coronary heart disease. We examined the interaction between these factors on subclinical atherosclerosis in postmenopausal women from the Early versus Late Intervention Trial with Estradiol (n = 497). Based on nine metabolic biomarkers (fasting blood glucose, insulin sensitivity, ketones, triglycerides, high-density lipoprotein, low-density lipoprotein, hemoglobin A1c, and blood pressure), K-means clustering categorized women into three distinct phenotypes: healthy, high blood pressure, and poor metabolic. ApoE4 genotype was classified as either ApoE4+ or ApoE4−. General linear models tested whether the cross-sectional association between metabolic phenotypes and common carotid intima media thickness (CIMT) differed by ApoE4 genotype. Mixed effects linear models evaluated the modifying role of ApoE4 genotype on the association of metabolic phenotype with CIMT progression over a median follow-up of 4.8 years. In cross-sectional analysis, ApoE4+ women with poor metabolic phenotype had the highest CIMT compared with all other groups. In ApoE4− women, CIMT was significantly lower in those classified as healthy compared with high blood pressure phenotype (p = 0.004). In ApoE4+ women, CIMT was significantly higher in those with poor metabolic phenotype compared with healthy (p = 0.0003) and high blood pressure (p = 0.001) phenotypes. These results indicate that metabolic phenotype had a negative effect on CIMT in women with ApoE4+ but not ApoE4− (interaction p = 0.001). These effects were not observed on CIMT progression in longitudinal analysis. In conclusion, ApoE4+ women are more likely to have higher levels of subclinical atherosclerosis if their metabolic phenotype is poor compared with ApoE4+ women without poor metabolic profile and ApoE4− women. 2019-08-05T04:41:55Z 2019-08-05T04:41:55Z 2019-01-01 Journal 18791913 00029149 2-s2.0-85069653263 10.1016/j.amjcard.2019.06.022 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069653263&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/65830
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Medicine
spellingShingle Medicine
Intira Sriprasert
Wendy Jean Mack
Howard Neil Hodis
Hooman Allayee
Roberta Diaz Brinton
Roksana Karim
Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women
description © 2019 Elsevier Inc. Metabolic profile and ApoE4 genotype have effects on coronary heart disease. We examined the interaction between these factors on subclinical atherosclerosis in postmenopausal women from the Early versus Late Intervention Trial with Estradiol (n = 497). Based on nine metabolic biomarkers (fasting blood glucose, insulin sensitivity, ketones, triglycerides, high-density lipoprotein, low-density lipoprotein, hemoglobin A1c, and blood pressure), K-means clustering categorized women into three distinct phenotypes: healthy, high blood pressure, and poor metabolic. ApoE4 genotype was classified as either ApoE4+ or ApoE4−. General linear models tested whether the cross-sectional association between metabolic phenotypes and common carotid intima media thickness (CIMT) differed by ApoE4 genotype. Mixed effects linear models evaluated the modifying role of ApoE4 genotype on the association of metabolic phenotype with CIMT progression over a median follow-up of 4.8 years. In cross-sectional analysis, ApoE4+ women with poor metabolic phenotype had the highest CIMT compared with all other groups. In ApoE4− women, CIMT was significantly lower in those classified as healthy compared with high blood pressure phenotype (p = 0.004). In ApoE4+ women, CIMT was significantly higher in those with poor metabolic phenotype compared with healthy (p = 0.0003) and high blood pressure (p = 0.001) phenotypes. These results indicate that metabolic phenotype had a negative effect on CIMT in women with ApoE4+ but not ApoE4− (interaction p = 0.001). These effects were not observed on CIMT progression in longitudinal analysis. In conclusion, ApoE4+ women are more likely to have higher levels of subclinical atherosclerosis if their metabolic phenotype is poor compared with ApoE4+ women without poor metabolic profile and ApoE4− women.
format Journal
author Intira Sriprasert
Wendy Jean Mack
Howard Neil Hodis
Hooman Allayee
Roberta Diaz Brinton
Roksana Karim
author_facet Intira Sriprasert
Wendy Jean Mack
Howard Neil Hodis
Hooman Allayee
Roberta Diaz Brinton
Roksana Karim
author_sort Intira Sriprasert
title Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women
title_short Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women
title_full Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women
title_fullStr Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women
title_full_unstemmed Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women
title_sort effect of apoe4 genotype on the association between metabolic phenotype and subclinical atherosclerosis in postmenopausal women
publishDate 2019
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069653263&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/65830
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