Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly
ObjectiveSmall and dense low-density lipoprotein (sdLDL) elevation may be among the most sensitive early biomarkers for nascent cardiovascular disease. This study, therefore, investigated the association between visit-to-visit changes in sdLDL and cerebral small vessel disease (CSVD) progression in...
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Frontiers Media S.A.
2022-06-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.851735/full |
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author | Weike Liu Jing Xu Huajing Song Huajing Song Chunju Zhang Chunju Zhang Yanli Yao Yanli Yao Hua Zhang Hua Zhang Yue-Chun Li Zhendong Liu Zhendong Liu |
author_facet | Weike Liu Jing Xu Huajing Song Huajing Song Chunju Zhang Chunju Zhang Yanli Yao Yanli Yao Hua Zhang Hua Zhang Yue-Chun Li Zhendong Liu Zhendong Liu |
author_sort | Weike Liu |
collection | DOAJ |
description | ObjectiveSmall and dense low-density lipoprotein (sdLDL) elevation may be among the most sensitive early biomarkers for nascent cardiovascular disease. This study, therefore, investigated the association between visit-to-visit changes in sdLDL and cerebral small vessel disease (CSVD) progression in older individuals, and the influence of Apolipoprotein E (APOE) genotype on this association.MethodsBetween April 2007 and July 2009, 1,143 participants ≥60 years old were recruited from the Shandong region of China, and sdLDL was measured at baseline and at each follow-up visit. White matter hyperintensities (WMHs), lacunes, microbleeds, and enlarged perivascular spaces (EPVSs) were assessed by magnetic resonance imaging. The APOE genotype was determined and participants were stratified as ε4-positive or ε4-negative.ResultsDuring an average follow-up of 86.0 months, 225 participants (19.7%) developed WMH progression, 193 (16.9%) lacune progression, 170 (14.9%) microbleed progression, and 185 (16.2%) EPVS progression. Compared with patients in the first (lowest) tertile of visit-to-visit mean sdLDL, those in the second and third tertiles demonstrated significantly greater risks of WMH progression (53.5 and 105.3% higher), lacune progression (53.3 and 60.8%), microbleed progression (47.2 and 127.6%), and EPVS progression (54.0 and 135.0%) after adjustment for confounders (all adjusted P values for trends <0.001). Compared with patients in the first tertile of visit-to-visit sdLDL SD, those in the second and third tertiles also demonstrated significantly greater risks of WMH progression (49.9% and 143.6%), lacune progression (75.3 and 178.0%), microbleed progression (12.7 and 64.7%), and EPVS progression (41.7 and 114.6%) after adjustment (all P < 0.001). There were significant and positive visit-to-visit mean sdLDL × visit-to-visit sdLDL SD, visit-to-visit mean sdLD×ε4-positive, visit-to-visit sdLDL SD×ε4-positive, and visit-to-visit mean sdLDL×visit-to-visit sdLDL SD×ε4-positive interactions influencing CSVD progression after confounder adjustment (all P < 0.05).ConclusionLarge and variable visit-to-visit changes in sdLDL are independent predictors of aggressive CSVD progression, and this association is strongly influenced by APOE ε4 allele genotype. |
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spelling | doaj.art-b212af4a438545d7ab4e039a880027fd2022-12-22T03:32:36ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-06-011310.3389/fneur.2022.851735851735Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the ElderlyWeike Liu0Jing Xu1Huajing Song2Huajing Song3Chunju Zhang4Chunju Zhang5Yanli Yao6Yanli Yao7Hua Zhang8Hua Zhang9Yue-Chun Li10Zhendong Liu11Zhendong Liu12Department of Cardiology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaSchool of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaSchool of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaSchool of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaSchool of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Cardiology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaSchool of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaObjectiveSmall and dense low-density lipoprotein (sdLDL) elevation may be among the most sensitive early biomarkers for nascent cardiovascular disease. This study, therefore, investigated the association between visit-to-visit changes in sdLDL and cerebral small vessel disease (CSVD) progression in older individuals, and the influence of Apolipoprotein E (APOE) genotype on this association.MethodsBetween April 2007 and July 2009, 1,143 participants ≥60 years old were recruited from the Shandong region of China, and sdLDL was measured at baseline and at each follow-up visit. White matter hyperintensities (WMHs), lacunes, microbleeds, and enlarged perivascular spaces (EPVSs) were assessed by magnetic resonance imaging. The APOE genotype was determined and participants were stratified as ε4-positive or ε4-negative.ResultsDuring an average follow-up of 86.0 months, 225 participants (19.7%) developed WMH progression, 193 (16.9%) lacune progression, 170 (14.9%) microbleed progression, and 185 (16.2%) EPVS progression. Compared with patients in the first (lowest) tertile of visit-to-visit mean sdLDL, those in the second and third tertiles demonstrated significantly greater risks of WMH progression (53.5 and 105.3% higher), lacune progression (53.3 and 60.8%), microbleed progression (47.2 and 127.6%), and EPVS progression (54.0 and 135.0%) after adjustment for confounders (all adjusted P values for trends <0.001). Compared with patients in the first tertile of visit-to-visit sdLDL SD, those in the second and third tertiles also demonstrated significantly greater risks of WMH progression (49.9% and 143.6%), lacune progression (75.3 and 178.0%), microbleed progression (12.7 and 64.7%), and EPVS progression (41.7 and 114.6%) after adjustment (all P < 0.001). There were significant and positive visit-to-visit mean sdLDL × visit-to-visit sdLDL SD, visit-to-visit mean sdLD×ε4-positive, visit-to-visit sdLDL SD×ε4-positive, and visit-to-visit mean sdLDL×visit-to-visit sdLDL SD×ε4-positive interactions influencing CSVD progression after confounder adjustment (all P < 0.05).ConclusionLarge and variable visit-to-visit changes in sdLDL are independent predictors of aggressive CSVD progression, and this association is strongly influenced by APOE ε4 allele genotype.https://www.frontiersin.org/articles/10.3389/fneur.2022.851735/fulllipidvariabilityApolipoprotein Erisk factorcerebral small vessel disease |
spellingShingle | Weike Liu Jing Xu Huajing Song Huajing Song Chunju Zhang Chunju Zhang Yanli Yao Yanli Yao Hua Zhang Hua Zhang Yue-Chun Li Zhendong Liu Zhendong Liu Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly Frontiers in Neurology lipid variability Apolipoprotein E risk factor cerebral small vessel disease |
title | Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly |
title_full | Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly |
title_fullStr | Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly |
title_full_unstemmed | Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly |
title_short | Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly |
title_sort | excessive visit to visit small and dense low density lipoproteins elevate cerebral small vessel disease progression risk in the elderly |
topic | lipid variability Apolipoprotein E risk factor cerebral small vessel disease |
url | https://www.frontiersin.org/articles/10.3389/fneur.2022.851735/full |
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