Cumulative dyslipidemia with arterial stiffness and carotid IMT progression in asymptomatic adolescents: A simulated intervention longitudinal study using temporal inverse allocation model

Elsevier

Available online 12 November 2022

AtherosclerosisHighlights•

In the pediatric population free of familial hypercholesterolemia, cumulative elevated lipids and dyslipidemia from mid-adolescence through early adulthood was associated with worsening subclinical atherosclerosis progression from late adolescence through early adulthood.

A simulated treatment intervention in late adolescence but not in early adulthood appears to neutralize the effect of dyslipidemia on worsening subclinical atherosclerosis progression.

The optimal timing for reversing and attenuating dyslipidemia-related subclinical atherosclerosis progression in a large asymptomatic pediatric population is late adolescence.

Total cholesterol, non-HDL-C, and HDL-C may be the main targets of lipid intervention in a general adolescent population, rather than LDL-C to prevent early atherosclerosis progression.

AbstractBackground and aims

We aimed to examine the longitudinal associations of total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) progression.

Methods

We studied 1779, 15-year-old participants from the Avon Longitudinal Study of Parents and Children, UK birth cohort, followed up for 9 years. Fasting TC, non–HDL-C, HDL-C, triglyceride, and LDL-C were measured at 15, 17, and 24 years and age-categorized as normal, elevated, and dyslipidemia based on National Heart, Lung, and Blood Institute lipid guidelines. cfPWV and cIMT were measured at 17 and 24 years. Associations were examined using linear mixed-effect models. To simulate the treatment of dyslipidemia we conducted temporal inverse allocation model analyses.

Results

Among 1779 [49.9% female] participants, mean lipid levels and proportions at elevated or dyslipidemia categories increased from ages 15 through 24 years. Persistently elevated TC: effect estimate 0.026 mm; [95% CI 0.004 to 0.049; p = 0.024], elevated non–HDL-C, and elevated LDL-C were cumulatively associated with cIMT progression. Persistent borderline-low HDL-C: −0.027 mm; [-0.050 to −0.005; p = 0.019] and very-low HDL-C −0.035 mm; [-0.057 to −0.013; p = 0.002] levels were associated with cIMT progression. A temporal inverse allocation of elevated and dyslipidemic levels with normal lipid levels at age 17 years attenuated the associations of cumulative elevated TC, non–HDL-C, LDL-C, and low HDL-C with cIMT progression. Cumulative elevated lipids or dyslipidemia were not associated with cfPWV progression.

Conclusions

Late adolescence is key to preventing dyslipidemic-related preclinical atherosclerosis.

Keywords

Lipoproteins

Cardiovascular diseases

Atherosclerosis

Pediatrics

Arteriosclerosis

Health promotion

© 2022 The Authors. Published by Elsevier B.V.

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