ApoB could be best predictor of future MI risk

Abstract

Apoprotein B (ApoB) was the only lipid parameter significantly associated with an increased risk of myocardial infarction (MI), according to results of a prospective cohort analysis presented at the 2021 American Heart Association (AHA) Scientific Sessions and published simultaneously in JAMA Cardiology. “We all know that cardiovascular disease has a link to cholesterol and cholesterol-containing compounds or particles,” said Manesh Raman Patel, MD, chief of cardiology and clinical pharmacology at Duke University in an interview with JAMA Medical News. “We traditionally haven’t used [ApoB] in clinical practice probably because we haven’t had therapies that have pushed that measure itself down, although some might be coming. So that was the key finding [from this study] to start to get our clinicians ready for therapies and predictors tied to ApoB.” ApoBs are atherogenic proteins found in lipoprotein particles. Since each of these particles has one ApoB molecule, measuring ApoB levels in fasting blood gives a good approximation of the total number of atherogenic lipoproteins in the blood. Examples of ApoB-containing lipoprotein particles include chylomicrons and low-, intermediate-, and very low-density lipoproteins. The greater the number, the greater the risk of a cardiovascular event. When compared to ApoB, which is a surrogate for the number of atherogenic particles, LDL cholesterol is a surrogate for the cholesterol concentration of the LDL particle. LDL cholesterol has long been the standard lipid marker for cardiovascular risk and the primary target of cholesterol-lowering therapies. Treatment guidelines have also focused on optimal LDL goals. There are scenarios, however, in which assessment of LDL cholesterol may underestimate the concentration, such as in patients with hypertriglyceridemia, diabetes, or those who are obese. In its 2018 lipid guidelines, the American College of Cardiology and AHA commented on ApoB levels and highlighted its association with cardiovascular disease. The guidelines stated that under certain circumstances, particularly in patients with hypertriglyceridemia, the measurement of ApoB may be advantageous. However, ApoB measurement carries an extra cost and its measurement in some laboratories may not be reliable. The 2019 European Society of Cardiology and the European Atherosclerosis Society lipid guidelines state that ApoB analysis is recommended for risk assessment, particularly in those with hypertriglyceridemia, diabetes, obesity or metabolic syndrome, or VLDL cholesterol levels. They note that it can be used as an alternative to LDL, if available, as the primary measurement for screening, diagnosis, and management, and may be preferred over non-HDL cholesterol in people with hypertriglyceridemia, diabetes, obesity, or VLDL. In an accompanying commentary to the JAMA Cardiology study, the authors write: “ApoB should be the primary measure of the atherogenic risk of the ApoB lipoproteins and the primary measure of the adequacy of therapy to lower the ApoB lipoproteins.” They note it can be used in combination with a conventional lipid panel to allow for an accurate diagnosis of all clinically significant lipid disorders. In their view, the debate on ApoB versus LDL and non-HDL cholesterol is over. The prospective cohort analysis was conducted using data from the UK Biobank and two interventional studies. A total of 389,529 patients who were not receiving lipid-lowering therapy (primary prevention cohort) were included from the UK Biobank, and 40,430 patients with established atherosclerosis disease who were receiving lipid-lowering therapy (secondary prevention cohort) were included from the two studies. The researchers used two models to calculate MI risk: a clinically adjusted model (i.e., for age, sex, BMI, smoking status, hypertension, diabetes, ethnicity, and kidney function, as well as prior MI, stroke, and peripheral artery disease for the secondary prevention cohort) and a model that was both clinically and lipid adjusted (i.e., ApoB, non-HDL, triglycerides, and HDL). In the primary prevention cohort, when adjusted clinically, increases in ApoB, non-HDL cholesterol, and triglycerides were all associated with an increased risk of MI, but once lipid parameters were also adjusted, only increases in ApoB remained significantly associated with an increased risk of MI. Similar results were seen in the secondary prevention cohort, with the clinically adjusted model showing increases in ApoB and non-HDL cholesterol associated with an increased risk of MI, and only increases in ApoB remaining significant once lipids were adjusted as well.