Increasing lipids with risk of worsening cardiac damage in 1595 adolescents: A 7-year longitudinal and mediation study

Background and aims: Longitudinal evidence on the associations of changes in lipids level with changes in cardiac structure and function in youth is limited due to few repeated echocardiography measures. This study examined whether changes in lipid levels from adolescence through young adulthood associate with the risk of cardiac damage progression and potential mechanistic pathways.

Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and non-HDL-c measured at 17- and 24-year clinic visit were included. Echocardiography measured left ventricular mass indexed for height^2.7 (LVMI^2.7), and LV diastolic function from mitral E/A ratio (LVDF). LVMI^2.7 ≥51 g/m^2.7 and LVDF<1.5 were categorized as LV hypertrophy and LVD dysfunction, respectively. Multivariable adjusted associations were examined using generalized logit mixed-effect models and structural equation models for mediation analyses.

Results: The prevalence of LV hypertrophy increased from 3.6% at baseline to 11.6% at follow-up in males and increased from 1.6% to 4.0% in females. The prevalence of LVD dysfunction increased from 7.8% at baseline to 16.6% at follow-up in males and increased from 10.3% to 15.4% in females. Each 1 mmol increase in total cholesterol (OR, 1.18; [95% CI, 1.09-1.27]), triglyceride (2.89; [1.54-5.43]), LDL-c (1.19; [1.08-1.32]), and non-HDL-c (1.21; [1.11-1.33]) was associated with higher odds of worsening LV hypertrophy progression over 7 years. Increased triglyceride was associated with the odds of progressively worsening LVD dysfunction (1.98; [1.06-3.71]). Increased HDL-c was not associated with the odds of cardiac structural and functional damage. Systolic blood pressure (12% mediation) and fat mass (25% mediation) partly mediated the associations of LDL-c with increased LVMI^2.7.

Conclusions: Increased lipids may independently associate with the risk of progressively worsening structural and functional cardiac damage in youth but increased systolic blood pressure and fat mass explained circa forty percent of the relationship.