Response to Letter Regarding Article, “Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared With Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women”
We thank Dr Ala-Korpela and colleagues for their interest and their thoughtful comments on our study.1 We agree that different uses may be made of the nuclear magnetic resonance (NMR) spectroscopy signals that arise from the lipids carried in plasma by lipoprotein subclass particles of varying size. In our study, subclass signal amplitudes were converted to particle concentrations using calculations that account for the amount of lipid that fits into a lipoprotein particle of given diameter, as previously described.2 Using a different set of conversion factors that account for the mass of cholesterol and triglycerides found in subclass particles of normal lipid content, we calculated NMR estimates of high-density lipoprotein (HDL) cholesterol and triglycerides. These NMR-derived estimates assume that the lipoprotein particles have a normal lipid content, whereas they sometimes do not, and hence there may be a certain amount of disagreement between chemically measured and NMR-derived lipid concentrations.
Adjusting for nonlipid risk factors (age, randomized treatment assignment, smoking status, menopausal status, hormone use, blood pressure, diabetes mellitus, and body mass index), hazard ratios and 95% confidence intervals for quintiles 2 to 5 versus quintile 1 of NMR-derived triglycerides were 1.51 (1.13–2.01), 1.71 (1.30–2.26), 1.61 (1.23–2.11), and 2.31 (1.79–3.00), respectively, P for trend <0.001, whereas for chemically measured triglycerides they were 1.34 (0.98–1.83), 1.87 (1.39–2.50), 1.89 (1.42–2.52), and 2.58 (1.95–3.41), respectively, P for trend <0.001. Similarly adjusted hazard ratios and 95% confidence intervals for NMR-derived HDL cholesterol quintiles 2 to 5 versus quintile 1 were 0.84 (0.69–1.02), 0.78 (0.64–0.96), 0.63 (0.51–0.77), and 0.66 (0.54–0.81), respectively, P for trend <0.001, and for chemically measured HDL cholesterol they were 0.85 (0.71–1.03), 0.70 (0.58–0.86), 0.59 (0.48–0.73), and 0.52 (0.42–0.64), respectively, P for trend <0.001. In sum, NMR-derived HDL cholesterol and triglycerides predicted incident cardiovascular disease in this large study of initially healthy women to a magnitude that was comparable with, but not superior to, the chemical lipid measurements.
Dr Otvos in employed by, is a stockholder of and serves on the board of directors of LipoScience, Inc., a diagnostic laboratory company that performed the lipoprotein subclass analyses described in the manuscript. Dr Rosenson is a stockholder of LipoScience, Inc., and serves as a member of its Scientific Advisory Board.