Deborah Winegar

Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children

BackgroundGlycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses.MethodsNuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (nu2009=u200975), post-treatment subacute (nu2009=u200936) and convalescent (nu2009=u200963) KD, as well as febrile controls (nu2009=u200948), and age-similar healthy controls (nu2009=u200948).ResultsGlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUCu2009=u20090.789–0.884), the combinations of GlycA and LDL-P (AUCu2009=u20090.909) or GlycA and the LDL-P/HDL-P ratio (AUCu2009=u20090.910) were best at discerning KD in patients 6–10 days after illness onset.ConclusionsHigh levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients.

Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle Number Versus Low-Density Lipoprotein Cholesterol Level

A recent analysis of a commercially insured US population found fewer cardiovascular disease (CVD) events in high-risk patients attaining low levels of low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL-lowering therapy guided by LDL-P. Patients were selected from the HealthCore Integrated Research Database and followed for 12 to 36xa0months. Patients who achieved LDL-P <1,000xa0nmol/l were placed into the LDL-P cohort, whereas those without LDL-P tests, but who achieved LDL-C <100xa0mg/dl, were placed into the LDL-C cohort. CVD-related costs included all health plan paid amounts related to CVD events or lipid management. Cost effectiveness was assessed through incremental cost-effectiveness ratios, defined as difference in total costs across the cohorts divided by difference in CVD events, measured over follow-up. Each cohort included 2,094, 1,242, and 705 patients over 12-, 24-, and 36-month follow-up. Patients in the LDL-P cohort received more aggressive lipid-lowering therapy and had fewer CVD events during follow-up compared to patients in the LDL-C cohort. This led to greater pharmacy costs and lower medical costs over time. Incremental cost-effectiveness ratio estimates ranged from

DISCORDANCE IN LOW-DENSITY LIPOPROTEIN PARTICLE NUMBER (LDL-P) AND APOLIPOPROTEIN B (APO B) LEVEL

23,131 per CVD event avoided at 12xa0months to

NMR-BASED LIPOPROTEIN PARTICLE PROFILING IDENTIFIES NOVEL SIGNATURES FOR CARDIOVASCULAR DISEASE

3,439 andxa0-

Lipoprotein Measurements in Patients Infected with HIV: Is Cholesterol Content of HDL and LDL Discordant with Particle Number?

4,555 at 24- and 36-month follow-up, suggesting a high likelihood that achieving LDL-P <1,000xa0nmol/l is cost effective. In conclusion, LDL-lowering therapy guided by LDL-P was demonstrated to be cost effective, with greater clinical and economic benefit seen over longer time horizons and with the increased use of generic statins.

Heterogeneity of LDL and HDL Particle Concentrations in Subjects Meeting LDL-Cholesterol Goals

Many subjects with relatively normal levels of LDL cholesterol have increased numbers of atherogenic lipoproteins, hence exhibiting discordance. There are few data comparing the relationship between an individuals LDL-P and Apo B levels and whether discordance exists between these values.nnTo

Discordance Between LDL Particle Number (LDL-P) and LDL-cholesterol (LDL-C) Among Patients Treated at Two Medical Systems

The standard lipid panel routinely performed for cardiovascular risk assessment measures the cholesterol and triglyceride content of lipoproteins. Lipoprotein particle concentrations measured by NMR spectroscopy more strongly associate with coronary artery disease (CAD) risk. We hypothesized that