Traditional LDL- and HDL-cholesterol measurements fall short of perfect prediction of cardiovascular risk. So, several academic and industry investigators have tried to identify supplementary advanced lipoprotein tests that can, at least in part, detect the “residual risk.” These include not only measurements of apolipoprotein B and A-I subcomponents, but also assays that identify LDL particles and their size. Accordingly, advanced lipoprotein analysis has garnered much attention during the past decade, and clinicians continue to wonder where and when they should request such analyses, if at all.
Results from existing studies vary to some degree (see Parish et al.), but several suggest that LDL particle number (LDL-P) might outperform LDL cholesterol (LDL-C) as a predictor of cardiovascular risk (see Greenland et al. and Otvos et al.). For example, in a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, although both LDL-C and LDL-P were associated with risk for incident cardiovascular disease, only LDL-P predicted incident CVD among people with discordant LDL-C and LDL-P. Given that evidence and assuming that advanced lipoprotein analysis would help to identify a larger group of at-risk patients, several insurance companies have agreed to pay for such tests. But does this additional information actually improve clinical outcomes?
Any recently introduced test has its proponents and critics, but the ultimate clinical value of the test’s results depends on the availability of high-quality evidence to guide practice. Some of the new cardiac biomarkers have recently been used as criteria for including patients in cardiovascular trials or for guiding management. Among those, perhaps use of D-dimer in algorithms to diagnose venous thromboembolism is the most well-known example of a widely available biomarker that has supportive evidence from multiple studies.
Advanced lipoprotein testing may ultimately prove helpful for appropriate risk stratification and guidance of therapy to improve outcomes. As a fan of tailored and “personalized” medicine, I would like to see this happen soon. However, for now, there is a dearth of evidence on clinically proven interventions that specifically target the increased risk identified by such advanced techniques. Therefore, conducting high-quality randomized controlled trials might be a prerequisite to widespread use of these tests.
In this era of a focus on real value to patients, I wonder if advocating for tests that have yet to make a difference to our patients is the best approach. Should insurers be paying for these tests? Please share your thoughts with me and with others here on CardioExchange.