No association between increased high-density lipoprotein cholesterol and progressive cardiac damage in 1595 adolescents: a 7-year longitudinal study

Background The inverse relationships between high-density lipoprotein cholesterol (HDL-c) and subclinical atherosclerosis are well documented in the general population. However, recent studies among adults have reported paradoxical relationships in which high HDL-c levels were associated with cardiovascular morbidities and mortality. Purpose To investigate the longitudinal association of changes in HDL-c with progressive structural and functional cardiac damage in youth. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma HDL-c measured 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, low-density lipoprotein cholesterol, and triglyceride. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) HDL-c increased in males from 1.21 mmol/L to 1.42 mmol/L and in females from 1.38 mmol/L to 1.69 mmol/L, over 7 years. The prevalence of LVH 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 the fully adjusted model, a 1-mmol/L increase in HDL-c was not significantly associated with higher odds of LVH progression (odds ratio, 1.14; [95% CI, 0.97 – 1.33]), high RWT (0.99; [0.84 – 1.16]), LVD dysfunction (1.02 [0.86 – 1.20]), and high LVFP (1.08; [0.97 – 1.21]) over 7 years. Among males, a 1-mmol/L increase in HDL-c was associated with 1.15g/m2.7 [0.45 – 1.85], p=0.001) increase in LVMI and 0.008 cm [0.002 – 0.013], p=0.006) increase in RWT but not in females, after full adjustments. In both males and females, increased HDL-c was not significantly associated with changes in cardiac function. Conclusion Increased HDL-c had no association with cardiac structural and functional damage during growth from adolescence through young adulthood but was paradoxically associated with progressive LV structural remodelling in males.