Increased low-density lipoprotein cholesterol predict the risk of progressive structural but not functional cardiac damage in youth: a 7-year follow-up study

Background Childhood low-density lipoprotein cholesterol (LDL-c) has been associated with cardiovascular events in mid-adulthood. Recent evidence suggests that cumulative LDL-c may not contribute to sub-clinical atherosclerosis progression during growth from mid-adolescence through young adulthood. However, whether increasing LDL-c associate with premature cardiac damage in youth remains unclear. Purpose To investigate the longitudinal association of changes in LDL-c with the risk of progressive structural and functional cardiac damage in youth. Methods From Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma LDL-c estimated with Friedewald equation 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, moderate-to-vigorous physical activity, high-density lipoprotein cholesterol, and triglyceride. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) LDL-c increased in males from 1.97 mmol/L to 2.37 mmol/L and in females from 2.23 mmol/L to 2.37 mmol/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, a 1-mmol/L increase in LDL-c was significantly associated with higher odds of LVH progression (odds ratio 1.19; [95% CI, 1.08 – 1.32]) and high RWT (1.14; [1.01 – 1.29]), but not LVD dysfunction (0.96 [0.85 – 1.09]) and high LVFP (1.07; [0.97 – 1.19]) over 7 years. Among females, a 1 mmol/L increase in LDL-c was associated with 0.005cm [0.002 – 0.007], p<0.001) increase in RWT but not in males after full adjustments. In both males and females, increased LDL-c was not significantly associated with changes in LVMI and cardiac function. Conclusion Increased LDL-c was associated with progressive structural but not functional cardiac damage during growth from adolescence through young adulthood.