LDL-C Significance in ASCVD Challenged

Two studies suggest that low-density lipoprotein cholesterol (LDL-C) may not to be the main lipid contributor to atherosclerotic cardiovascular disease (ASCVD). The study in Spain included 6901 subjects in the high-risk primary prevention trial population (mean age: 67 years; body mass index: 30 kg/m²; 43% men; 48% with diabetes) with a median follow-up of 4.8 years. In multivariable-adjusted analyses, triglycerides (TG, hazard ratio [HR]: 1.04, per 10 mg/dl [0.11 mmol/l]), non−high-density lipoprotein cholesterol (HDL-C) (HR: 1.05, per 10 mg/dl [0.26 mmol/l]), and remnant cholesterol (remnant-C [all cholesterol except HDL-C and LDL-C], HR: 1.21, per 10 mg/dl [0.26 mmol/l]), but not LDL-C or HDL-C, were associated with major adverse cardiovascular events (MACEs, namely myocardial infarction [MI], stroke, or cardiovascular death). Atherogenic dyslipidemia (TG >150 mg/dl [1.69 mmol/l] and HDL-C <40 mg/dl [1.03 mmol/l] in men or <50 mg/dl [1.29 mmol/l] in women) was also associated with MACEs (HR: 1.44). Remnant-C ≥30 mg/dl (0.78 mmol/l) differentiated subjects at a higher risk of MACEs compared with those at lower concentrations, regardless of whether LDL-C levels were on target at ≤100 mg/dl (2.59 mmol/l). The Danish study included 25,480 subjects free of lipid-lowering therapy and MI at study entry. During a median 11 years of follow-up, 1,816 were diagnosed with MI. Per 1-mmol/l higher levels, multivariable-adjusted HRs for MI were 2.07 for very low-density lipoproteins cholesterol (VLDL-C), 1.19 for VLDL TG, 5.38 for intermediate-density lipoproteins cholesterol (IDL-C), and 1.86 for LDL-C. Per 1-g/l higher plasma apolipoprotein B (apoB, a composite measure of all apoB-containing lipoproteins), the corresponding value was 2.21. In a step-up Cox regression, VLDL-C explained 50% and IDL-C + LDL-C 29% of the risk of MI from apoB-containing lipoproteins, whereas VLDL TG did not explain risk. HDL-C is no longer an independent direct actor in ASCVD, although it remains a clinically valuable predictor of risk. The complementary findings of the 2 studies suggest that remnant-C (in TG-rich lipoproteins) and non-HDL-C (in apoB–containing lipoproteins) may be the predominant atherogenic agent. Source: https://www.jacc.org/