LDL-C or apoB as the Best Target for Reducing Coronary Heart Disease

Should Apob be Implemented into Clinical Practice?

Helena Vaverkova

Disclosures

Clin Lipidology. 2011;6(1):35-48. 

In This Article

Abstract and Introduction

Abstract

LDL-C is considered to be the major lipid risk factor and the main target of lipid-lowering therapy. Nevertheless, as all potentially atherogenic lipoprotein particles contain only one molecule of apoB and various amounts of cholesterol, apoB is a better marker of atherogenic particle numbers. Many laboratory, prospective and interventional studies have proven that apoB is a better indicator of cardiovascular risk than LDL-C. Statins lower LDL-C and non-HDL-C more (and to lower population percentile levels) than apoB. As a result, many patients treated with statins to achieve LDL-C and non-HDL-C targets remain at high risk owing to high levels of apoB, especially subjects with the prevalence of small dense LDL. With the worldwide increasing prevalence of obesity and metabolic syndrome, the issue of appropriate risk markers and treatment goals is even more important. On the basis of evidence from many studies, this article proposes that apoB should be included in guidelines as a part of the routine lipid panel. ApoB should be measured in all subjects with abnormal lipid profiles or high cardiovascular risk. Furthermore, apoB should be the primary target of lipid-altering therapy or, at least for the interim period of time, an additional goal. ApoB should be measured in all prospective and interventional studies to further support this suggestion and to optimize apoB targets. ApoB is also the promising target of LDL-lowering therapy. Therapeutic strategies directed at the hepatic assembly of VLDL (the precursor of LDL) should be explored in detail.

Introduction

Cardiovascular diseases (CVDs) are the most common cause of death in all developed countries and in the near future will also become the leading cause of death in the developing world. Lipids play a key role in the development of atherosclerosis and its clinical manifestation. For more than 20 years, LDL-C has been considered to be a major lipid risk factor, and in most national guidelines, LDL-C is considered to be the main target of lipid-lowering therapy.[1,2] Large meta-analyses of interventional studies with statins have shown that reduction of LDL-C leads to reduction of the risk of coronary heart disease (CHD) and CVD both in nondiabetic[3] and diabetic populations.[4] However, even persons subjected to an active therapy in these trials display a high residual risk. One of the reasons for such a high residual risk may be the fact that LDL-C is not necessarily the best risk marker in all individuals.

At present, obesity and obesity-related insulin resistance, metabolic syndrome and Type 2 diabetes mellitus (T2D) is a worldwide phenomenon. It is expected that in the year 2030, the number of T2D patients worldwide will approximately double in comparison with the year 2000.[5] The most important demographic change to diabetes prevalence appears to be the increase in the proportion of people aged 65 years or older. This indicates that the 'diabetes epidemic' will continue even if levels of obesity remain constant. With the increasing prevalence of obesity, it is likely that these figures even underestimate the future diabetes prevalence.

Even in patients with metabolic syndrome and diabetes, lipids play the major role in the development of atherosclerotic macrovascular complications. However, LDL-C is not the major characteristic of lipid changes associated with the aforementioned states. These states are associated with atherogenic dyslipidemia, characterized especially by increased levels of triglycerides (TGs), reduced HDL-C and an increased prevalence of small dense LDL (sdLDL) at relatively normal levels of LDL-C. Low HDL-C and high plasma TGs are considered to represent an important residual risk besides LDL-C.[6] Nevertheless, normal LDL-C does not mean that the atherogenic particle number is normal, and this fact is often underestimated. The increased number of sdLDL associated with atherogenic dyslipidemia is reflected in increased concentrations of apoB, which is a better marker of atherogenic lipoprotein numbers than concentrations of LDL-C.[7,8] In fact, apoB is a key component of atherogenic dyslipidemia,[9] as will be discussed later.

Thus, in the future, changes in risk factors in the population will necessitate some changes in lipid-associated treatment targets, or at least additional goals.

In this article, we discuss the issue of apoB compared with LDL-C as lipid risk factors and treatment targets.

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