Fasting Plasma Ketone Bodies Are Associated with NT-proBNP: A Potential Mechanism to Provide Fuel for the Failing Heart.

Background: Heart failure (HF) features a shift in metabolism towards enhanced utilization of ketone bodies. While elevations in plasma natriuretic peptides represent a biochemical hallmark of HF, natriuretic peptides may promote lipolysis, thereby contributing to fatty acid availability for ketogenesis. Methods: We cross-sectionally tested to what extent fasting plasma total ketone bodies (measured using nuclear magnetic resonance spectroscopy) are associated with N-terminal pro-BNP (NT-proBNP; electrochemiluminescent sandwich immunoassay) in individuals with and without HF. Results: Among 6217 participants from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, 203 were identified with HF. NT-proBNP was four-fold and total ketone bodies were 25% higher in HF participants (each p < 0.001). In both participants with and without HF, total ketone body levels correlated with NT-proBNP (r = 0.116 and 0.185, respectively; p < 0.001). In multivariable linear regression analysis adjusted for relevant covariates, total ketone bodies remained associated with NT-proBNP in the whole cohort (std ß = 0.08, p < 0.001), without a difference in participants with and without HF (p interaction: 0.52). Conclusion: This general population-based study reveals an independent association of fasting total body ketone bodies with plasma NT-proBNP. Our findings suggest that a metabolic defense mechanism could be operative, providing the myocardium with ketone bodies to meet its energy demands.

A High-Throughput NMR Method for Lipoprotein-X Quantification.

Lipoprotein X (LP-X) is an abnormal cholesterol-rich lipoprotein particle that accumulates in patients with cholestatic liver disease and familial lecithin-cholesterol acyltransferase deficiency (FLD). Because there are no high-throughput diagnostic tests for its detection, a proton nuclear magnetic resonance (NMR) spectroscopy-based method was developed for use on a clinical NMR analyzer commonly used for the quantification of lipoproteins and other cardiovascular biomarkers. The LP-X assay was linear from 89 to 1615 mg/dL (cholesterol units) and had a functional sensitivity of 44 mg/dL. The intra-assay coefficient of variation (CV) varied between 1.8 and 11.8%, depending on the value of LP-X, whereas the inter-assay CV varied between 1.5 and 15.4%. The assay showed no interference with bilirubin levels up to 317 mg/dL and was also unaffected by hemolysis for hemoglobin values up to 216 mg/dL. Samples were stable when stored for up to 6 days at 4 °C but were not stable when frozen. In a large general population cohort (n = 277,000), LP-X was detected in only 50 subjects. The majority of LP-X positive cases had liver disease (64%), and in seven cases, had genetic FLD (14%). In summary, we describe a new NMR-based assay for LP-X, which can be readily implemented for routine clinical laboratory testing.

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score: Associations with subclinical atherosclerosis and incident cardiovascular disease.

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated. METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study). RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized ß = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR. CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.