NIST BMD/IBBR Seminar: Investigating lipoproteins using electrospray-differential mobility analysis and quantitative LC-MS/MS
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Multiple lipoproteins are known to be causal risk factors for cardiovascular disease (CVD). While LDL cholesterol (LDL-C) has been causally linked to CVD risk, the link of HDL-C, the “good cholesterol”, to CVD is much more complicated and the HDL-C as a metric of HDL’s antiatherogenic properties has been put in question both by genetics studies and by failure of pharmacologic elevation of HDL-C to lower CVD risk. We’ve developed a novel measurement of HDL that directly measures concentration of HDL particles (including individual subspecies) as opposed to the HDL cholesterol content. We have now shown that this metric is not only associated with prevalent CVD, but also an independent predictor of incident CVD. In addition to LDL and HDL, lipoprotein(a) (Lpa) is a strong and independent genetic risk factor for CVD, but because of its complex structure, accurate quantification has been a major challenge and a primary reference method is lacking. We have developed an LC-MS/MS based candidate reference method and demonstrated its precision, robustness and agreement with current gold standard method for Lpa – monoclonal antibody based ELISA.
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