Elsevier

Mayo Clinic Proceedings

Volume 86, Issue 8, August 2011, Pages 762-780
Mayo Clinic Proceedings

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

https://doi.org/10.4065/mcp.2011.0128Get rights and content

Abstract

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) represent the cornerstone of drug therapy to reduce low-density lipoprotein (LDL) cholesterol and cardiovascular risk. However, even optimal statin management of LDL cholesterol leaves many patients with residual cardiovascular risk, in part because statins are more effective in reducing LDL cholesterol than apolipoprotein B (Apo B). Apo B may be a better marker of atherogenic risk than LDL cholesterol because Apo B measures the total number of all atherogenic particles (total atherosclerotic burden), including LDL, very low-density lipoprotein, intermediate-density lipoprotein, remnant lipoproteins, and lipoprotein(a). To determine whether Apo B is a better indicator of baseline cardiovascular risk and residual risk after lipid therapy compared with LDL cholesterol, a MEDLINE search of the literature published in English from January 1, 1975, through December 1, 2010, was conducted. On the basis of data from most population studies, elevated Apo B was more strongly associated with incident coronary heart disease than similarly elevated LDL cholesterol. Apo B was also a superior benchmark (vs LDL cholesterol) of statins' cardioprotective efficacy in both primary-prevention and secondary-prevention trials. To minimize cardiovascular risk among persons with hypercholesterolemia or dyslipidemia, the best available evidence suggests that intensive therapy with statins should be initiated to achieve the lowest possible Apo B level (with adequate drug toleration) and then other therapies (eg, niacin, bile acid resins, ezetimibe) added to potentiate these Apo B-lowering effects. In future consensus lipid-lowering treatment guidelines, Apo B should be considered as an index of residual risk, a potential parameter of treatment efficacy, and a treatment target to minimize risk of coronary heart disease.

Section snippets

METHODS

An English-language MEDLINE search of literature published from January 1, 1975, through December 1, 2010, was conducted. The title term *apo* was joined (using the Boolean operator “AND”) with terms including atheroscl*, cardiovasc*, *cholest*, dyslipidemia*,*trig*, *lip*, metabolism, and risk factors. The same title terms were also joined (using “AND”) with the title terms bile acid resin* (sequestrant*), docosahexaenoic acid, eicosapentaenoic acid, ezet*, *fibr*, hydroxymethylglutaryl-CoA

DEFINITIONS AND PATHOBIOLOGY

Apo B represents the total number of circulating atherogenic particles (ie, total atherogenic burden).19 Each VLDL, IDL, LDL, and lipoprotein(a) particle contains 1 molecule of Apo B100, and each chylomicron or chylomicron remnant contains 1 molecule of Apo B48.19, 20 Subendothelial trapping of Apo B is a key atherogenic trigger.21, 22

Article Highlights

  • Low-density lipoprotein (LDL) cholesterol measures may not adequately evaluate cardiovascular risk when other apolipoprotein B-containing atherogenic particles

EPIDEMIOLOGIC EVIDENCE

Many population studies have demonstrated the superior prognostic value of Apo B over LDL cholesterol and/or non-HDL cholesterol in predicting cardiovascular events (Table 1).24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 In the 52-country INTERHEART study, the Apo B:A-1 ratio accounted for 54% of the population-attributable risk of acute myocardial infarction (MI). Apo B was also superior to LDL cholesterol and non-HDL cholesterol in predicting coronary heart disease

Statin-Containing Treatments

Effects on Apo B Levels and Clinical/Angiographic/Imaging End Points. Statins are the most effective available medications to reduce Apo B levels. Statin monotherapy lowered Apo B levels in major randomized controlled trials (RCTs) by 19% to 42% (Table 2).4, 8, 9, 11, 43, 44, 45, 46, 47 On-treatment elevations of Apo B levels could serve as indices of statin efficacy and as treatment targets to maximize the cardioprotective benefits of statins.

In the AFCAPS/TexCAPS (Air Force/Texas Coronary

CURRENT GUIDELINES AND EXPERT PANEL RECOMMENDATIONS

Mounting evidence has led expert panels to recommend consideration of Apo levels, particularly in patients with either increased cardiometabolic risk, diabetic dyslipidemia, or CHD.55, 96 They have also recommended assessment of the adequacy of therapy for those already receiving treatment. A consensus panel of the American Diabetes Association/American College of Cardiology Foundation recommended a goal Apo B level of less than 80 mg/dL for patients at highest risk and less than 90 mg/dL for

Potential Pathways to Improved Outcomes

Increasingly aggressive statin and other cholesterol-lowering therapies have led to significant incremental reductions in absolute cardiovascular risk in RCTs.15, 98 Still, many clinicians justifiably contemplate which other atherogenic parameter needs to be altered to minimize atherosclerotic progression and cardiovascular events (Table 4).8, 23, 24, 26, 27, 28, 29, 30, 31, 35, 44, 47, 51, 54, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108

Levels of Apo B or non-HDL cholesterol are in general

CONCLUSION

Many patients have residual cardiovascular risk despite optimal LDL cholesterol management, in part because statins are more effective in reducing cholesterol in LDL, which is heterogeneous, than in reducing Apo B, which is present in each atherogenic particle. Apo B elevations provide a sound measure of residual cardiovascular risk on treatment, act as a parameter of treatment efficacy, and are a rational target for adding other lipid therapies. To minimize CHD risk, clinicians should

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  • Cited by (0)

    Research support was provided by Abbott Laboratories (Abbott Park, IL). Abbott had the opportunity to review and comment on the publication content; however, all decisions regarding content were made by the author.

    Individual reprints of this article are not available.

    1

    Dr Jacobson received no compensation from Abbott. Dr Jacobson discloses that he has served as a consultant for Abbott, Amarin, AstraZeneca, Glaxo-SmithKline, Kowa, and Merck.

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