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 journalArticlepeer-review

13 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 languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalCirculation
Volume147
Issue number1
DOIs
StatePublished - 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

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