Relative effect of hypertriglyceridemia on non-HDLC and apolipoprotein B as cardiovascular disease risk markers

•As TG increases, the correlation between non-HDLC and apoB decreases progressively. •In HTG, discordant non-HDLC and apoB causes divergence in CVD risk categorization. •Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in HTG. Background Non-high density lipoprotein cholesterol (non-HDLC) represents the cholesterol in triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL). Apolipoprotein B (apoB) reflects the number of TRL and LDL particles. In hypertriglyceridemia (HTG), there is triglyceride (TG) enrichment of TRLs, and also a substantial increase of cholesterol in larger TRLs that considerably augments the non-HDLC value. Therefore, in HTG, non-HDLC could increase disproportionately with respect to apoB. Objective We aimed to compare the relative effect of the full range of mild, moderate, and severe HTG on the status of non-HDLC and apoB as cardiovascular disease (CVD) risk markers. Methods Analysis of lipid profile data from 4347 patients in a Lipid Clinic cohort with baseline fasting lipid profiles documented prior to starting lipid-lowering medications. The correlation between non-HDLC and apoB was assessed in intervals of increasing TG. Non-HDLC and apoB were analyzed at each TG level using comparative CVD risk equivalent categories and assessed for divergence and discordance. Results With increasing TG levels: (1) the correlation between non-HDLC and apoB diminished progressively, (2) non-HDLC levels increased continuously, whereas apoB levels plateaued after an initial increase up to TG of ~ 4.0-5.0 mmol/L (~354-443 mg/dL), (3) there was divergence in the stratification of non-HDLC and apoB into CVD risk equivalent categories. Conclusions Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in the presence of severe HTG. This has never been tested. With increasing HTG severity, discordance between non-HDLC and apoB can cause clinically important divergence in CVD risk categorization. Non-high density lipoprotein cholesterol (non-HDLC) represents the cholesterol in triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL). Apolipoprotein B (apoB) reflects the number of TRL and LDL particles. In hypertriglyceridemia (HTG), there is triglyceride (TG) enrichment of TRLs, and also a substantial increase of cholesterol in larger TRLs that considerably augments the non-HDLC value. Therefore, in HTG, non-HDLC could increase disproportionately with respect to apoB. We aimed to compare the relative effect of the full range of mild, moderate, and severe HTG on the status of non-HDLC and apoB as cardiovascular disease (CVD) risk markers. Analysis of lipid profile data from 4347 patients in a Lipid Clinic cohort with baseline fasting lipid profiles documented prior to starting lipid-lowering medications. The correlation between non-HDLC and apoB was assessed in intervals of increasing TG. Non-HDLC and apoB were analyzed at each TG level using comparative CVD risk equivalent categories and assessed for divergence and discordance. With increasing TG levels: (1) the correlation between non-HDLC and apoB diminished progressively, (2) non-HDLC levels increased continuously, whereas apoB levels plateaued after an initial increase up to TG of ~ 4.0-5.0 mmol/L (~354-443 mg/dL), (3) there was divergence in the stratification of non-HDLC and apoB into CVD risk equivalent categories. Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in the presence of severe HTG. This has never been tested. With increasing HTG severity, discordance between non-HDLC and apoB can cause clinically important divergence in CVD risk categorization.