Targets of Statin Therapy: LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B in Type 2 Diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS)

Abstract

BACKGROUND: LDL can vary considerably in its cholesterol content; thus, lowering LDL cholesterol (LDLC) as a goal of statin treatment implies the existence of considerable variation in the extent to which statin treatment removes circulating LDL particles. This consideration is particularly applicable in diabetes mellitus, in which LDL is frequently depleted of cholesterol.

Opening a New Lipid “Apo-thecary”: Incorporating Apolipoproteins as Potential Risk Factors and Treatment Targets to Reduce Cardiovascular Risk

“…11, 48,49 These changes in Apo B levels were associated with a 37% decline in the relative risk of major cardiovascular events. Hence, relative cardiovascular risk was reduced by approximately 1.5% for each 1% decrease in Apo B levels.…”

“…19 Each VLDL, IDL, LDL, and lipoprotein(a) particle contains 1 molecule of Apo B 100 , and each chylomicron or chylomicron remnant contains 1 molecule of Apo B 48 . 19,20 Subendothelial trapping of Apo B is a key atherogenic trigger.…”

“…The investigators concluded that "both Apo B and [non-HDL cholesterol] provide more consistent goals than [LDL cholesterol] for assessing the LDL particle response to statin therapy." 48 Finally, a pooled-data analysis of patients with a CHD history-stable CHD in TNT (Treating to New Targets) 17 and an MI history in IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering) 46 -showed that on-treatment (statin) Apo B and non-HDL cholesterol levels were more robustly predictive of cardiovascular outcomes than LDL cholesterol. 50 The investigators suggested that Apo B and non-HDL cholesterol levels were more accurate predictors of cardiovascular disease even in patients with largely normal levels of TGs.…”

ESC/EAS Guidelines for the management of dyslipidaemias

“…ApoB has not been evaluated as a primary treatment target in clinical trials, but several post hoc analyses of clinical trials suggest that apoB may be not only a risk marker, but also a treatment target. 100 A major disadvantage of apoB is that it is not included in algorithms for calculation of global risk, and it has not been a predefined treatment target in controlled trials. Recent data from a meta-analysis 83,90 indicate that apoB does not provide any benefit beyond non-HDL-C or traditional lipid ratios.…”

“…100,130 -apoB ,80 mg/dL and ,100 mg/dL in those at very high and high total CV risk, respectively (Class IIa, Level B). In patients at HIGH CV risk d , an LDL-C goal of <2.6 mmol/L (100 mg/dL), or a reduction of at least 50% if the baseline LDL-C e is between 2.6 and 5.2 mmol/L (100 and 200 mg/dL) is recommended.…”