Lipoprotein (a) and coronary artery calcification: prospective study assessing interactions with other risk factors

Kwok Leung Ong; Robyn L. McClelland; Matthew A. Allison; Mary Cushman; Parveen K. Garg; Michael Y. Tsai; Kerry Anne Rye; Fatiha Tabet

doi:10.1016/j.metabol.2021.154706

Lipoprotein (a) and coronary artery calcification: prospective study assessing interactions with other risk factors

Kwok Leung Ong, Robyn L. McClelland, Matthew A. Allison, Mary Cushman, Parveen K. Garg, Michael Y. Tsai, Kerry Anne Rye, Fatiha Tabet

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. Methods: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. Results: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm³/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm³/year in quartile 4, compared to −3.44, −0.59 and 1.91 mm³/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. Conclusions: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.

Original language	English (US)
Article number	154706
Journal	Metabolism: clinical and experimental
Volume	116
DOIs	https://doi.org/10.1016/j.metabol.2021.154706
State	Published - Mar 2021

Bibliographical note

Funding Information:
Kwok Leung Ong was supported by the Australian National Health and Medical Research Council Career Development Fellowship ( 1122854 ). The MESA study was supported by contracts 75N92020D00001 , HHSN268201500003I , N01-HC-95159 , 75N92020D00005 , N01-HC-95160 , 75N92020D00002 , N01-HC-95161 , 75N92020D00003 , N01-HC-95162 , 75N92020D00006 , N01-HC-95163 , 75N92020D00004 , N01-HC-95164 , 75N92020D00007 , N01-HC-95165 , N01-HC-95166 , N01-HC-95167 , N01-HC-95168 , and N01-HC-95169 from the National Heart, Lung, and Blood Institute , and by grants UL1-TR-000040 , UL1-TR-001079 , and UL1-TR-001420 from National Center for Advancing Translational Sciences . This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the U.S Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication.

Keywords

Blood coagulation
Coronary artery calcification
Inflammation
Lipoprotein (a)
Multi-Ethnic Study of Atherosclerosis

PubMed: MeSH publication types

Journal Article

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Lipoprotein (a) and coronary artery calcification : prospective study assessing interactions with other risk factors. / Ong, Kwok Leung; McClelland, Robyn L.; Allison, Matthew A.; Cushman, Mary; Garg, Parveen K.; Tsai, Michael Y.; Rye, Kerry Anne; Tabet, Fatiha.

In: Metabolism: clinical and experimental, Vol. 116, 154706, 03.2021.

Research output: Contribution to journal › Article › peer-review

@article{dc16405b5c3b46b3b95a80517fb21e7f,

title = "Lipoprotein (a) and coronary artery calcification: prospective study assessing interactions with other risk factors",

abstract = "Background: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. Methods: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. Results: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to −3.44, −0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. Conclusions: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.",

keywords = "Blood coagulation, Coronary artery calcification, Inflammation, Lipoprotein (a), Multi-Ethnic Study of Atherosclerosis",

author = "Ong, {Kwok Leung} and McClelland, {Robyn L.} and Allison, {Matthew A.} and Mary Cushman and Garg, {Parveen K.} and Tsai, {Michael Y.} and Rye, {Kerry Anne} and Fatiha Tabet",

note = "Funding Information: Kwok Leung Ong was supported by the Australian National Health and Medical Research Council Career Development Fellowship ( 1122854 ). The MESA study was supported by contracts 75N92020D00001 , HHSN268201500003I , N01-HC-95159 , 75N92020D00005 , N01-HC-95160 , 75N92020D00002 , N01-HC-95161 , 75N92020D00003 , N01-HC-95162 , 75N92020D00006 , N01-HC-95163 , 75N92020D00004 , N01-HC-95164 , 75N92020D00007 , N01-HC-95165 , N01-HC-95166 , N01-HC-95167 , N01-HC-95168 , and N01-HC-95169 from the National Heart, Lung, and Blood Institute , and by grants UL1-TR-000040 , UL1-TR-001079 , and UL1-TR-001420 from National Center for Advancing Translational Sciences . This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the U.S Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. ",

year = "2021",

month = mar,

doi = "10.1016/j.metabol.2021.154706",

language = "English (US)",

volume = "116",

journal = "Metabolism: Clinical and Experimental",

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TY - JOUR

T1 - Lipoprotein (a) and coronary artery calcification

T2 - prospective study assessing interactions with other risk factors

AU - Ong, Kwok Leung

AU - McClelland, Robyn L.

AU - Allison, Matthew A.

AU - Cushman, Mary

AU - Garg, Parveen K.

AU - Tsai, Michael Y.

AU - Rye, Kerry Anne

AU - Tabet, Fatiha

N1 - Funding Information: Kwok Leung Ong was supported by the Australian National Health and Medical Research Council Career Development Fellowship ( 1122854 ). The MESA study was supported by contracts 75N92020D00001 , HHSN268201500003I , N01-HC-95159 , 75N92020D00005 , N01-HC-95160 , 75N92020D00002 , N01-HC-95161 , 75N92020D00003 , N01-HC-95162 , 75N92020D00006 , N01-HC-95163 , 75N92020D00004 , N01-HC-95164 , 75N92020D00007 , N01-HC-95165 , N01-HC-95166 , N01-HC-95167 , N01-HC-95168 , and N01-HC-95169 from the National Heart, Lung, and Blood Institute , and by grants UL1-TR-000040 , UL1-TR-001079 , and UL1-TR-001420 from National Center for Advancing Translational Sciences . This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the U.S Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication.

PY - 2021/3

Y1 - 2021/3

N2 - Background: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. Methods: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. Results: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to −3.44, −0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. Conclusions: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.

AB - Background: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. Methods: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. Results: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to −3.44, −0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. Conclusions: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.

KW - Blood coagulation

KW - Coronary artery calcification

KW - Inflammation

KW - Lipoprotein (a)

KW - Multi-Ethnic Study of Atherosclerosis

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U2 - 10.1016/j.metabol.2021.154706

DO - 10.1016/j.metabol.2021.154706

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