Dr. Michael Fulks explores whether apoB should replace the cholesterol/HDL ratio as a measure of cardiovascular risk and its implications for individualized risk assessment.
In 2010 we published an article on lipids and mortality for 1.5 million life insurance applicants who were tested by the Clinical Reference Laboratory finding that the cholesterol/HDL ratio was the single best measure. It was cheap and because, decades ago, the total cholesterol value measured the risk well enough for most individuals and because higher levels of HDL reduces risk, the cholesterol/HDL ratio worked well. But research over the 12 years since then has documented the atherogenic potential of not just LDL but IDL (intermediate-density lipoproteins and VLDL (very low-density lipoproteins). The overall risk is more closely related to the total number of all such lipid particles (each of which have one apoB lipoprotein molecule), rather than to the amount of cholesterol or triglyceride which varies by particle type.
Some individuals have higher levels of adverse lipids other than LDL partly related to the epidemic of obesity and diabetes with favorable LDL levels or their LDL levels are well controlled by use of statins (which mostly treats LDL). These individuals still have substantial residual risk leading to the question of how to define overall cardiovascular risk more accurately on an individualized basis in the era of widespread statin use?
The answer may be the apoB lipoprotein molecule. Marston, et al. published an article in JAMA Cardiology using the large UK Biobank longitudinal cohort including almost 400,000 well participants not on lipid Rx and over 40,000 with established atherosclerosis looking at the best risk prediction measure for future MI (myocardial infarction) risk. For both those with no Rx and those with established history, apoB was the only measure still predictive after each lipid measure was adjusted for the others. This conclusion is supported by other (but not all) studies which has led to greater support of apoB use in Europe to evaluate risk but less so in the U.S.
Another question is: if we move to use apoB to assess risk, what happens to the HDL ratio? ApoA-1 is the lipoprotein component of HDL (instead of apoB) and the ratio of apoB to apoA-1 has been studied and is predictive of risk but whether such a ratio or just the independent use of apoB and apoA-1 or apoB and HDL is the best approach is unclear at this point.
In any event, it seems to be time to take a new look at measuring the risk associated with lipid levels on an individualized basis and decide if the venerable cholesterol/HDL ratio should be replaced.
About the Author
Michael Fulks, MD, Consulting Medical Director, is board-certified in internal and insurance medicine. After leaving practice, he served as a medical director, creating or editing several underwriting manuals and preferred programs. More recently, Mike has consulted for CRL participating in its mortality research on laboratory test results, BP and build, and in the development of risk-scoring tools for laboratory and non-laboratory data.