Low-Density Lipoprotein, Non-High-Density Lipoprotein, and Apolipoprotein B as Targets of Lipid-Lowering Therapy

Abstract

A lthough low-density lipoprotein (LDL) is widely recognized as the major atherogenic lipoprotein and the primary target of lipid-lowering therapy, 1 other lipoprotein species nonetheless appear to be involved in atherogenesis. These include very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and highdensity lipoproteins (HDL). Both VLDL and IDL are triglyceride-rich lipoproteins (TGRLP). Thus, in the aftermath of unequivocal evidence that LDL lowering reduces risk for major coronary events and stroke, 2 the field of lipid study is turning more of its attention to the other lipoproteins that appear to be involved in atherosclerosis. The recent Adult Treatment Panel III (ATP III) report 1 of the National Cholesterol Education Program has summarized our current understanding of the relationship between other lipoprotein species and risk for coronary heart disease (CHD). See p 2537ATP III 1 placed more emphasis on TGRLP and HDL as secondary targets of lipid-modifying therapy than did previous ATP reports. 3 There is an emerging consensus that among TGRLP, cholesterol-rich remnant lipoproteins carry atherogenic potential. This view led ATP III to designate LDLϩIDLϩVLDL cholesterol (called non-HDL cholesterol) as "atherogenic cholesterol" and to identify it as a secondary target of therapy, after LDL cholesterol. In the ATP III report, however, non-HDL cholesterol as a secondary target is limited to persons who have elevated serum triglyceride levels (Ն200 mg/dL). In the majority of people who have lower triglyceride levels, LDL cholesterol contains the bulk of "atherogenic cholesterol" and thus is a sufficient target alone.The designation of elevated non-HDL cholesterol as a treatment target depended strongly on increasing data showing that high levels of cholesterol-rich TGRLP raise risk for CHD. Several reviews summarize the evidence for atherogenicity of triglyceride-rich remnants. 4 -6 On the other hand, only a limited number of studies 7,8 have examined the strength of association between non-HDL cholesterol and risk for CHD. The current report of Bittner et al 9 contributes to a growing body of information on the predictive power for major coronary events of non-HDL cholesterol. In the discussion to follow, the current status of non-HDL cholesterol as predictor of major coronary events and as a target of lipid-lowering therapy will be examined. Predictive Power of LipoproteinsEpidemiological studies reveal a strong independent relation between serum cholesterol levels and risk for CHD. 10 Since LDL is the major cholesterol-carrying lipoprotein of serum, it too is widely accepted as an independent risk factor. 1 Prospective surveys 11 further document that reduced serum levels of HDL cholesterol independently predict CHD incidence. The case for high serum triglycerides as a marker for TGRLP has been less robust. 11 Since HDL cholesterol and triglycerides are inversely correlated, when HDL is entered into multivariate predictive models, triglycerides are generally found to be weak pr...

Ezetimibe: cholesterol lowering and beyond

“…Non-HDL-C sums cholesterol carried by atherogenic lipoproteins such as ApoB-100-containing LDL, VLDL, IDL, RLP, lipoprotein [Lp(a)] and, in certain instances, ApoB-48-containing chylomicrons [72]. Thus, non-HDL-C, a measure of total cholesterol minus HDL, is thought to be a better predictor of CHD risk than LDL-C alone [72].…”

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

“…This residual risk may be attributed in part to atherogenic dyslipidemia, characterized by high levels of triglycerides, low levels of high‐density lipoprotein (HDL) cholesterol (HDL‐C), and high LDL‐particle (LDL‐P) numbers in these patients 1. In addition to LDL‐C lowering, non–HDL‐C and apolipoprotein B (apoB) have been recommended as treatment targets for assessment of individuals with diabetic dyslipidemia 1, 7, 12, 13, 14, 15…”

“…Several international guidelines endorse statin uptitration, switching to a more‐potent statin therapy, and/or combination therapy for high‐risk individuals in need of additional cholesterol lowering 7, 12, 13, 14, 15. US guidelines recommend using the maximum tolerated statin dose with consideration given to the addition of a nonstatin cholesterol‐lowering drug if the clinical benefit outweighs the safety risk in these patients 16.…”

Targeting Low HDL-Cholesterol to Decrease Residual Cardiovascular Risk in the Managed Care Setting

“…The NCEP ATP III guidelines indicate that an elevated non-HDL-C level in patients with hypertriglyceridemia (i.e., TG ≥ 200 mg per dL) imparts an increased risk for cardiovascular events even after the LDL-C goal has been reached. 19,52 For this reason, non-HDL-C is considered to be a secondary therapeutic target (after LDL-C) that may provide additional risk reduction. 52 A 2004 update to the NCEP ATP III guidelines emphasized the increasing evidence for the benefits of combination therapy, compared with monotherapy, by recommending the possibility of adding a fibrate or niacin to LDL-lowering therapy in high-risk patients who have elevated TG or low HDL-C levels.…”

“…19,52 For this reason, non-HDL-C is considered to be a secondary therapeutic target (after LDL-C) that may provide additional risk reduction. 52 A 2004 update to the NCEP ATP III guidelines emphasized the increasing evidence for the benefits of combination therapy, compared with monotherapy, by recommending the possibility of adding a fibrate or niacin to LDL-lowering therapy in high-risk patients who have elevated TG or low HDL-C levels. 19 In 2007, the American Diabetes Association (ADA) and the American Heart Association (AHA) collaborated on a joint statement outlining treatment guidelines in the Primary Prevention of Cardiovascular Disease in Patients with Diabetes.…”