LDL Cholesterol Rises With BMI Only in Lean Individuals: Cross-sectional U.S. and Spanish Representative Data

Elevated LDL cholesterol (LDLc) is not strongly associated with obesity or metabolic syndrome (MS), but this relationship repeatedly has been examined assuming a linear association. This study aimed to assess the dose-response relationship between body mass index (BMI) or waist circumference (WC) and LDLc and to evaluate its link to metabolic impairment.

Participants in the continuous National Health and Nutrition Examination Survey (NHANES, 1999-2010) (n = 12,383) and the Study on Nutrition and Cardiovascular Risk (ENRICA, 2008-2010) (n = 11,765), representative samples of U.S. and Spanish noninstitutionalized populations, were cross-sectionally investigated. LDLc was modeled with age- and sex-adjusted regressions, with BMI and/or WC as explanatory variables included in models as two-segment linear and natural cubic splines.

In NHANES and ENRICA, slopes of the BMI-LDLc association changed (P < 0.001) at BMI 27.1 and 26.5 kg/m², respectively, forming an inverted U shape. Below these BMI inflection points, LDLc rose 2.30 and 2.41 mg/dL per kg/m² (both P < 0.001). However, above said points, LDLc declined -0.37 and -0.38 mg/dL per kg/m² (both P < 0.001). The WC-LDLc relationship was similar to the BMI-LDLc relationship. Accumulation of MS traits was associated with a weakening of the positive BMI-LDLc association among lean participants (below the BMI inflection point). Aging shifted the inflection point of the BMI-LDLc relationship to lower BMI values.

The BMI- and WC-LDLc relationships have inverted U shapes. Diminishing associations between BMI and LDLc might indicate metabolic impairment as a result of aging or other metabolic diseases. In lean individuals, small weight losses might help to lower LDLc for cardiovascular prevention.