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Lp(a) in Youth and Risk of ASCVD Outcomes in Adulthood
Quick Takes
- Elevated lipoprotein(a) [Lp(a)] identified in youth was related to a higher future risk for early-onset atherosclerotic cardiovascular disease (ASCVD) in White participants of the Young Finns and Bogalusa Heart studies.
- Individuals exposed to high Lp(a) and high LDL-C levels had a four times greater risk of developing an ASCVD outcome during follow-up than the nonexposed reference group.
- These data suggest that Lp(a) measured in youth may assist in identifying individuals at higher risk for future ASCVD.
Study Questions:
Is elevated lipoprotein(a) [Lp(a)] measured in youth associated with atherosclerotic cardiovascular disease (ASCVD) outcomes in adulthood?
Methods:
Two cohorts from the International Childhood Cardiovascular Cohort (i3C) were included in the present study. Data from the YFS (Cardiovascular Risk in Young Finns Study) (n = 3,596) were used for the current analysis. Lp(a) levels measured in youth 9–24 years of age were linked to adult ASCVD and carotid intima-media thickness. ASCVD outcomes were identified through linkages to the national registries, including the Care Register for Health Care and the National Death Index. As of 2018, 95 participants had been diagnosed with one or more ASCVD events and were included in this study. Results observed in YFS were replicated using 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. For BHS, ASCVD events were identified through self-report followed by adjudication with medical records and/or the National Death Index.
Results:
By 2018, 95 participants in the YFS cohort had a diagnosis of ASCVD (mean age, 48.4 years). The most common diagnosis was coronary artery disease (61%). Participants in the YFS who had elevated Lp(a) levels, defined as ≥30 mg/dL in youth, had an increased risk of developing ASCVD in adulthood (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4–2.6). Risk factors measured during youth that were independently associated with ASCVD outcomes in adulthood included Lp(a), low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), and smoking.
In BHS, in an age- and sex-adjusted model, White individuals 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 further adjusted for LDL-C and BMI, the risk associated with high Lp(a) remained unchanged (HR, 2.4; 95% CI, 0.8–7.3). In a multivariable model for pooled data, individuals exposed to high Lp(a) had a 2.0 times greater risk (95% CI, 1.0–3.7) of developing adult ASCVD compared with nonexposed individuals. Participants with both high Lp(a) and high LDL-C had over four times the risk of ASCVD as those without such elevations (HR, 4.30; 95% CI, 3.30–5.30). No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data.
Conclusions:
The authors concluded that elevated Lp(a) level identified in youth is a risk factor for adult ASCVD outcomes, but not for increased carotid intima-media thickness.
Perspective:
These data suggest that measuring Lp(a) in youth would identify individuals at higher risk of ASCVD events during adulthood. It should also be noted that those with the highest risk for ASCVD had a concomitant elevation of Lp(a) and LDL-C. Further work is needed to understand these associations in other populations and to understand the most effective preventive strategies for such individuals.
Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Echocardiography/Ultrasound, Smoking
Keywords: Atherosclerosis, Adolescent, Body Mass Index, Cardiovascular Diseases, Carotid Intima-Media Thickness, Cholesterol, LDL, Coronary Artery Disease, Delivery of Health Care, Heart Disease Risk Factors, Lipoprotein(a), Lipoproteins, Primary Prevention, Risk Factors, Smoking
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