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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.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.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.Late adolescence is key to preventing, halting, and reversing dyslipidemic-related preclinical atherosclerosis progression, warranting universal lipid screening in the general pediatric population.

A rather common leucine7-to-proline7 (Leu7Pro) polymorphism in the preproneuropeptide Y (prepro-NPY) gene signal peptide may be important in blood pressure regulation, cholesterol metabolism and the pathogenesis of atherosclerosis in humans. We examined the associations of the Leu7Pro polymorphism with carotid atherosclerotic progression, blood pressure and serum lipids in a population-based sample of 966 men aged 42–60 years in Finland. The Pro7 substitution (carrier frequency 12.2%) was associated with accelerated four-year increase in the mean ( P =0.01) and maximal ( P =0.007) common carotid intima-media thickness (IMT) and with slightly increased systolic ( P =0.03) and diastolic ( P =0.02) blood pressures, adjusted for other major risk factors. Men with Pro7 substitution had 30.6% (95% CI 6.9–54.0%) greater increase in the mean IMT and 20.0% (95% CI 5.3–34.4%) greater increase in the maximal IMT than men with Leu7/Leu7 genotype. The Pro7 substitution was also related to increased serum total cholesterol ( P =0.01) and LDL cholesterol ( P =0.02) in obese (body mass index (BMI)>30 kg/m 2 ) men. This study provides important evidence suggesting that the Pro7 substitution in the prepro-NPY is an important risk factor for accelerated atherosclerotic progression, increased blood pressure and increased serum cholesterol in humans.