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Background <p>Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor, traditionally considered stable across the lifespan, supporting a single lifetime measurement strategy. However, its longitudinal behaviour during childhood and adolescence remains poorly characterised, particularly in individuals with type 1 diabetes who face a markedly increased lifetime risk of coronary artery disease. We therefore aimed to characterise intra- and inter-individual trajectories of Lp(a) in a paediatric type 1 diabetes cohort and to assess the implications of Lp(a) variability for cardiovascular risk classification.</p> Methods <p>We conducted a retrospective single-centre cohort study of children and adolescents with type 1 diabetes attending Geneva University Hospitals between 2012 and 2023. Annual fasting Lp(a) concentrations were analysed longitudinally. Variability was assessed in participants with ≥ 2 measurements. Clinically relevant thresholds were used to evaluate cardiovascular risk reclassification. Paired Wilcoxon tests, Pearson and Kendall correlations, and Holm-adjusted <i>p</i>-values (<i>P</i> &lt; 0.05) were applied. Analyses were conducted in R.</p> Results <p>A total of 286 participants contributed 1403 Lp(a) measurements, with observation periods varying across individuals (median 6.2&#xa0;years, IQR 2.9–9.6) and between 1 and 13 measurements per participant. At baseline, 26% had elevated Lp(a) (≥ 300&#xa0;mg/l). Among participants with serial measurements, 32% showed intraindividual fluctuations exceeding 50% of their individual maximum value. Reclassification across the 300&#xa0;mg/l cardiovascular risk threshold occurred in 11.9% of participants. Lp(a) concentrations peaked between ages 10 and 13&#xa0;years and declined thereafter. Modest seasonal variation was observed, with higher concentrations in autumn and winter (<i>P</i> &lt; 0.05).</p> Conclusions <p>In youth with type 1 diabetes, Lp(a) is not as stable as previously assumed, exhibiting clinically relevant variability over time. These findings challenge the current paradigm of a single lifetime Lp(a) measurement and suggest that repeated assessment, particularly during adolescence, may improve early cardiovascular risk stratification.</p> Graphical abstract <p></p>

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Longitudinal variability of lipoprotein(a) in youth-onset type 1 diabetes: implications for cardiovascular risk stratification

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Fanny Iafrate-Luterbacher,
  • Cecilia Jimenez-Sanchez,
  • Maria Loukia Anastasiadou,
  • Julien Prados,
  • Frida Renström,
  • Michael Brändle,
  • Stefan Bilz,
  • Valerie M. Schwitzgebel

摘要

Background

Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor, traditionally considered stable across the lifespan, supporting a single lifetime measurement strategy. However, its longitudinal behaviour during childhood and adolescence remains poorly characterised, particularly in individuals with type 1 diabetes who face a markedly increased lifetime risk of coronary artery disease. We therefore aimed to characterise intra- and inter-individual trajectories of Lp(a) in a paediatric type 1 diabetes cohort and to assess the implications of Lp(a) variability for cardiovascular risk classification.

Methods

We conducted a retrospective single-centre cohort study of children and adolescents with type 1 diabetes attending Geneva University Hospitals between 2012 and 2023. Annual fasting Lp(a) concentrations were analysed longitudinally. Variability was assessed in participants with ≥ 2 measurements. Clinically relevant thresholds were used to evaluate cardiovascular risk reclassification. Paired Wilcoxon tests, Pearson and Kendall correlations, and Holm-adjusted p-values (P < 0.05) were applied. Analyses were conducted in R.

Results

A total of 286 participants contributed 1403 Lp(a) measurements, with observation periods varying across individuals (median 6.2 years, IQR 2.9–9.6) and between 1 and 13 measurements per participant. At baseline, 26% had elevated Lp(a) (≥ 300 mg/l). Among participants with serial measurements, 32% showed intraindividual fluctuations exceeding 50% of their individual maximum value. Reclassification across the 300 mg/l cardiovascular risk threshold occurred in 11.9% of participants. Lp(a) concentrations peaked between ages 10 and 13 years and declined thereafter. Modest seasonal variation was observed, with higher concentrations in autumn and winter (P < 0.05).

Conclusions

In youth with type 1 diabetes, Lp(a) is not as stable as previously assumed, exhibiting clinically relevant variability over time. These findings challenge the current paradigm of a single lifetime Lp(a) measurement and suggest that repeated assessment, particularly during adolescence, may improve early cardiovascular risk stratification.

Graphical abstract