Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood

Olli Raitakari; Noora Kartiosuo; Katja Pahkala; Nina Hutri-Kähönen; Lydia A. Bazzano; Wei Chen; Elaine M. Urbina; David R. Jacobs; Alan Sinaiko; Julia Steinberger; Trudy Burns; Stephen R. Daniels; Alison Venn; Jessica G. Woo; Terry Dwyer; Markus Juonala; Jorma Viikari

doi:10.1161/circulationaha.122.060667

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood

Olli Raitakari, Noora Kartiosuo, Katja Pahkala, Nina Hutri-Kähönen, Lydia A. Bazzano, Wei Chen, Elaine M. Urbina, David R. Jacobs, Alan Sinaiko, Julia Steinberger, Trudy Burns, Stephen R. Daniels, Alison Venn, Jessica G. Woo, Terry Dwyer, Markus Juonala, Jorma Viikari

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

1 Scopus citations

Abstract

Background: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). Methods: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. Results: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. Conclusions: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

Original language	English (US)
Pages (from-to)	23-31
Number of pages	9
Journal	Circulation
Volume	147
Issue number	1
DOIs	https://doi.org/10.1161/circulationaha.122.060667
State	Published - Jan 3 2023

Bibliographical note

Funding Information:
Both YFS and BHS have been supported by a grant (HL121230) from the National Institutes of Health. YFS has been supported by Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 255381, 256474, 283115, 319060, 320297, 314389, 338395, 330809, 104821, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere, and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; and the Cancer Foundation Finland. BHS has been supported by the National Institutes of Health (grants SCOR-A/P60 HL15103; U01 HL038844; R01s HL002942, HD032194, AG016592, HD069587, ES021724, AG062309; R03s HD047247, HD062783, AG060619; R21/R33 AG057983; RF1 AG041200) and the American Heart Association (grants 13SDG14650068 and 0160261B).

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

Keywords

atherosclerosis
epidemiology
lipoproteins
longitudinal studies
risk assessment
risk factors

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/circulationaha.122.060667

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Raitakari, O., Kartiosuo, N., Pahkala, K., Hutri-Kähönen, N., Bazzano, L. A., Chen, W., Urbina, E. M., Jacobs, D. R., Sinaiko, A., Steinberger, J., Burns, T., Daniels, S. R., Venn, A., Woo, J. G., Dwyer, T., Juonala, M., & Viikari, J. (2023). Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood. Circulation, 147(1), 23-31. https://doi.org/10.1161/circulationaha.122.060667

Raitakari, O, Kartiosuo, N, Pahkala, K, Hutri-Kähönen, N, Bazzano, LA, Chen, W, Urbina, EM, Jacobs, DR, Sinaiko, A, Steinberger, J, Burns, T, Daniels, SR, Venn, A, Woo, JG, Dwyer, T, Juonala, M & Viikari, J 2023, 'Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood', Circulation, vol. 147, no. 1, pp. 23-31. https://doi.org/10.1161/circulationaha.122.060667

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title = "Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood",

abstract = "Background: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). Methods: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. Results: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. Conclusions: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.",

keywords = "atherosclerosis, epidemiology, lipoproteins, longitudinal studies, risk assessment, risk factors",

author = "Olli Raitakari and Noora Kartiosuo and Katja Pahkala and Nina Hutri-K{\"a}h{\"o}nen and Bazzano, {Lydia A.} and Wei Chen and Urbina, {Elaine M.} and Jacobs, {David R.} and Alan Sinaiko and Julia Steinberger and Trudy Burns and Daniels, {Stephen R.} and Alison Venn and Woo, {Jessica G.} and Terry Dwyer and Markus Juonala and Jorma Viikari",

note = "Funding Information: Both YFS and BHS have been supported by a grant (HL121230) from the National Institutes of Health. YFS has been supported by Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 255381, 256474, 283115, 319060, 320297, 314389, 338395, 330809, 104821, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere, and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrj{\"o} Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; and the Cancer Foundation Finland. BHS has been supported by the National Institutes of Health (grants SCOR-A/P60 HL15103; U01 HL038844; R01s HL002942, HD032194, AG016592, HD069587, ES021724, AG062309; R03s HD047247, HD062783, AG060619; R21/R33 AG057983; RF1 AG041200) and the American Heart Association (grants 13SDG14650068 and 0160261B). Publisher Copyright: {\textcopyright} 2023 Lippincott Williams and Wilkins. All rights reserved.",

year = "2023",

month = jan,

day = "3",

doi = "10.1161/circulationaha.122.060667",

language = "English (US)",

volume = "147",

pages = "23--31",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "1",

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TY - JOUR

T1 - Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood

AU - Raitakari, Olli

AU - Kartiosuo, Noora

AU - Pahkala, Katja

AU - Hutri-Kähönen, Nina

AU - Bazzano, Lydia A.

AU - Chen, Wei

AU - Urbina, Elaine M.

AU - Jacobs, David R.

AU - Sinaiko, Alan

AU - Steinberger, Julia

AU - Burns, Trudy

AU - Daniels, Stephen R.

AU - Venn, Alison

AU - Woo, Jessica G.

AU - Dwyer, Terry

AU - Juonala, Markus

AU - Viikari, Jorma

N1 - Funding Information: Both YFS and BHS have been supported by a grant (HL121230) from the National Institutes of Health. YFS has been supported by Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 255381, 256474, 283115, 319060, 320297, 314389, 338395, 330809, 104821, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere, and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; and the Cancer Foundation Finland. BHS has been supported by the National Institutes of Health (grants SCOR-A/P60 HL15103; U01 HL038844; R01s HL002942, HD032194, AG016592, HD069587, ES021724, AG062309; R03s HD047247, HD062783, AG060619; R21/R33 AG057983; RF1 AG041200) and the American Heart Association (grants 13SDG14650068 and 0160261B). Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.

PY - 2023/1/3

Y1 - 2023/1/3

N2 - Background: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). Methods: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. Results: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. Conclusions: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

AB - Background: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). Methods: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. Results: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. Conclusions: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

KW - atherosclerosis

KW - epidemiology

KW - lipoproteins

KW - longitudinal studies

KW - risk assessment

KW - risk factors

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U2 - 10.1161/circulationaha.122.060667

DO - 10.1161/circulationaha.122.060667

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C2 - 36440577

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VL - 147

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JF - Circulation

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Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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