Cumulative dyslipidemia with arterial stiffness and carotid IMT progression in asymptomatic adolescents: A simulated intervention longitudinal study using temporal inverse allocation model
Elevated lipids and dyslipidemia are associated with subclinical atherosclerosis progression in asymptomatic adolescents.
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Simulated treatment intervention at age 17 years neutralizes the effect of dyslipidemia on atherosclerosis progression.
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Optimal timing for reversing dyslipidemia-related atherosclerosis progression in asymptomatic youths is late adolescence.
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Total cholesterol, non-HDL-C and HDL-C may be the main targets of lipid intervention in asymptomatic youths, but not LDL-C.
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A universal pediatric lipid screening is highly recommended for the primary prevention of subclinical atherosclerosis.
Abstract
Background 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, halting, and reversing dyslipidemic-related preclinical atherosclerosis progression, warranting universal lipid screening in the general pediatric population.
