No association between LDL cholesterol levels and cellular membrane integrity assessed with phase angle: Insights from the MALIPID study.

Background: Although aggressive low-density lipoprotein cholesterol (LDL-C) reduction has demonstrated significant cardiovascular benefits, concerns have emerged regarding potential adverse effects of very low LDL-C on cellular functions, particularly membrane integrity as cholesterol constitutes an essential component of cellular membranes. The phase angle (PhA), derived from bioelectrical impedance analysis (BIA) reflects cellular membranes integrity and nutritional status. The MALIPID study aimed to assess if LDL-C levels are associated with PhA in high cardiovascular risk patients.

Methods: A cross-sectional study was conducted in 140 patients matched 1:1 for age, sex, and body mass index, stratified by LDL-C levels (<55 vs. ≥55mg/dL). Laboratory parameters, anthropometry, and BIA measurements were collected with PhA at 50kHz as the primary outcome.

Results: Median PhA values were comparable between LDL-C groups (4.88 vs. 4.93; p=0.67). LDL-C was not significantly associated with PhA multivariable regression models adjusted for age, sex, fat-free mass, and biochemical parameters. PhA significantly inversely correlated with age (R=-0.60, p<0.0001) and positively with eGFR (R=0.38, p<0.0001), but not with LDL-C. Subgroup analyses in patients aged >75 years also presented lack of relationship between LDL-C and PhA.

Conclusions: No association was found between LDL-C levels and cellular membrane integrity assessed by PhA. These findings potentially support the physiological safety of intensive LDL-C reduction and highlight the dominant role of age and body composition in determining PhA. Larger, prospective studies are needed to confirm these results.