Prospective associations of non-HDL cholesterol with premature structural and functional cardiac damage progression in British youth: the ALSPAC study

Abstract

Abstract Background Non high-density lipoprotein (non-HDL) cholesterol from childhood has been associated with signs of cardiac damage and subclinical atherosclerosis in middle age adults. Cumulative non-HDL cholesterol has been associated with subclinical atherosclerosis during growth from mid-adolescence through young adulthood. Due to the scarcity of repeated measures of cardiac structure and function, there is limited knowledge regarding the independent associations of non-HDL cholesterol with premature cardiac damage in youth. Purpose To investigate the longitudinal association of changes in non-HDL cholesterol with structural and functional cardiac damage progression during growth from adolescence through young adulthood. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma non-HDL cholesterol computed from the difference between total cholesterol and HDL cholesterol at 17- and 24-year clinic visits were included. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e´ ratio (LVFP) were available at baseline and follow-up. LVMI2.7 ≥51g/m2.7, RWT ≥0.44, LVDF <1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively. Multivariable adjusted associations were examined using generalized linear mixed-effect models and generalized logit mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, sedentary time, light physical activity, and moderate to vigorous physical activity. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) mean non-HDL cholesterol values increased in males from 2.34mmol/L to 2.82mmol/L and in females from 2.60mmol/L to 2.77mmol/L, over 7 years. The prevalence of LV hypertrophy increased in males from 3.6% to 11.9% and in females from 1.6% to 4% over 7 years. The prevalence of LVD dysfunction increased in males from 7.8% to 16.6% and in females from 10.3% to 15.4%. In a fully adjusted model, 1 mmol increase in non-HDL cholesterol was significantly associated with higher odds of LV hypertrophy progression (odds ratio 1.21; [95% CI, 1.11 – 1.33], p<0.0001), high RWT (1.16; [1.07 – 1.29], p=0.005), and high LVFP (1.15; [1.06 – 1.25], p=0.001) but not LVD dysfunction (1.05 [0.95 – 1.18], p=0.342), over 7 years. Conclusion Increased non-HDL cholesterol during growth from adolescence through young adulthood was prospectively associated with worsening structural and functional cardiac damage in asymptomatic youth.