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

Background and aims 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. Method 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/m(2), (dagger)g/L per kg/m(2), (double dagger)% per kg/m(2), and mu mol/L per kg/m(2). Results When adjusted for age, BMI was significantly related to nonHDL-cholesterol (males: 0.0238 +/- 0.0041, P=7.9x10(-9); females: 0.0330 +/- 0.0037, P<10(-16))*, LDL-particles (males: 0.0128 +/- 0.0024, P=2.1x10(-7); females: 0.0114 +/- 0.0022, P=3.2x10(-7))(*), apo B (males: 0.0053 +/- 0.0010, P=7.9x10(-8); females: 0.0073 +/- 0.0009, P=2.2x10(-16))(dagger), sdLDL (males: 0.0125 +/- 0.0015, P=2.2x10(-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))(double dagger), triglycerides (males: 0.0358 +/- 0.0049, P=2.0x10(-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=1.2x10(-13))* in both males and females. Age-adjusted BMI was significantly related to lbLDL in females (0.0098 +/- 0.0024, P=3.9x10(-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)(dagger), Lp(a) (-0.0091 +/- 0.0021, P=1.2x10(-5))(<section>), sdLDL (0.0001 +/- 0.0000, P=1.6x10(-11))(*) and %sdLDL (0.151 +/- 0.018, P<10(-16)) (double dagger). Conclusions Emerging apo B-containing risk factors show associations with weight change beyond those explained by the more traditional triglyceride and LDL-cholesterol measurements.