Effects of weight change on apolipoprotein B-containing emerging atherosclerotic cardiovascular disease (ASCVD) risk factors

Non-high-density (HDL)-cholesterol, low-density lipoprotein (LDL)-particle number, apolipoprotein B, lipoprotein(a) (Lp(a)), and small-dense (sdLDL) and large-buoyant (lbLDL) LDL-subfractions are emerging apo B-containing atherosclerotic cardiovascular disease (ASCVD) risk factors. Current guidelines emphasize lifestyle, including weight loss, for ASCVD risk management. Whether weight change affects these emerging risk factors beyond that predicted by traditional triglyceride and LDL-cholesterol measurements remains to be determined. Regression analyses of fasting ∆apo B-containing lipoproteins vs. ∆BMI were examined in a large anonymized clinical laboratory database of 33,165 subjects who did not report use of lipid-lowering medications. Regression slopes (±SE) were estimated as: *∆mmol/L per ∆kg/m2, †∆g/L per ∆kg/m2, ‡∆% per ∆kg/m2, and §∆μmol/L per ∆kg/m2. When adjusted for age, ∆BMI was significantly related to ∆nonHDL-cholesterol (males: 0.0238 ± 0.0041, P = 7.9 × 10− 9; females: 0.0330 ± 0.0037, P < 10− 16)*, ∆LDL-particles (males: 0.0128 ± 0.0024, P = 2.1 × 10− 7; females: 0.0114 ± 0.0022, P = 3.2 × 10− 7)*, ∆apo B (males: 0.0053 ± 0.0010, P = 7.9 × 10− 8; females: 0.0073 ± 0.0009, P = 2.2 × 10− 16)†, ∆sdLDL (males: 0.0125 ± 0.0015, P = 2.2 × 10− 16; females: 0.0128 ± 0.0012, P < 10− 16)*, ∆percent LDL carried on small dense particles (%sdLDL, males: 0.296 ± 0.035, P < 10− 16; females: 0.221 ± 0.023, P < 10− 16)‡, ∆triglycerides (males: 0.0358 ± 0.0049, P = 2.0 × 10− 13; females: 0.0304 ± 0.0029, P < 10− 16)*, and ∆LDL-cholesterol (males: 0.0128 ± 0.0034, P = 0.0002; females: 0.0232 ± 0.0031, P = 1.2 × 10− 13)* in both males and females. Age-adjusted ∆BMI was significantly related to ∆lbLDL in females (0.0098 ± 0.0024, P = 3.9 × 10− 5)* but not males (0.0007 ± 0.0026, P = 0.78)*. Female showed significantly greater increases in ∆LDL-cholesterol (P = 0.02) and ∆lbLDL (P = 0.008) per ∆BMI than males. ∆BMI had a greater effect on ∆LDL-cholesterol measured directly than indirect estimate of ∆LDL-cholesterol from the Friedewald equation. When sexes were combined and adjusted for age, sex, ∆triglycerides and ∆LDL-cholesterol, ∆BMI retained residual associations with ∆nonHDL-cholesterol (0.0019 ± 0.0009, P = 0.03)*, ∆LDL-particles (0.0032 ± 0.0010, P = 0.001)*, ∆apo B (0.0010 ± 0.0003, P = 0.0008)†, ∆Lp(a) (− 0.0091 ± 0.0021, P = 1.2 × 10− 5)§, ∆sdLDL (0.0001 ± 0.0000, P = 1.6 × 10− 11)* and ∆%sdLDL (0.151 ± 0.018, P < 10− 16) ‡. Emerging apo B-containing risk factors show associations with weight change beyond those explained by the more traditional triglyceride and LDL-cholesterol measurements.