Abstract

Background and aimsNon-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.MethodRegression 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.ResultsWhen 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) ‡.ConclusionsEmerging apo B-containing risk factors show associations with weight change beyond those explained by the more traditional triglyceride and LDL-cholesterol measurements.

Highlights

  • Background and aimsNon-high-density (HDL)-cholesterol, low-density lipoprotein (LDL)-particle number, apolipoprotein B, lipoprotein(a) (Lp(a)), and small-dense and large-buoyant LDL-subfractions are emerging apo B-containing atherosclerotic cardiovascular disease (ASCVD) risk factors

  • Lipoprotein management has historically focused on indirect low-density lipoprotein (LDL) and triglyceride concentrations [1]

  • Triglycerides are not thought to be atherosclerotic per se, but reflect high cholesterol concentrations in triglyceride-rich lipoproteins, and influence the metabolism of other lipoproteins more directly involved in the atherogenic process [1]

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Summary

Introduction

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. Lipoprotein management has historically focused on indirect low-density lipoprotein (LDL) and triglyceride concentrations [1]. Many individuals develop ischemic heart disease despite having had indirect LDLcholesterols within the normal range [1, 2]. Indirect LDL-cholesterol values are calculated using the Friedewald equation [3], which is subject to inaccuracy in the presence of high triglycerides and other conditions [4]. Current treatment guidelines do not target triglycerides concentrations under 500 mg/dL [1, 5]

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