Elizabeth T Leary

Pacific Biomarkers, Seattle, Washington, United States

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Publications (11)36.28 Total impact

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    ABSTRACT: Background: Estimation of low density lipoprotein cholesterol (LDL-C) using the Friedewald (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle composition is altered. We hypothesized that LDL-C estimation by the FR formula and other measurement methods might also be inaccurate in individuals treated with a cholesteryl ester transfer protein (CETP) inhibitor. Methods and Results: An assay comparison study was conducted using pre- and post-treatment serum samples from 280 of the 811 patients treated with the CETP inhibitor anacetrapib in the DEFINE study (Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib). After 24 weeks of treatment with anacetrapib, mean LDL-C values by FR formula, Roche Direct Method and Genzyme Direct Method deviated from that measured by the β-quantification (BQ) reference method by -12.2 ± 7.5, -10.2 ± 6.6, -10.8 ± 8.8 mg/dL, respectively. Conclusions: After treatment with anacetrapib, the FR formula and detergent-based direct methods provided lower LDL-C values than those obtained by the BQ reference method. The bias by the FR formula appeared to be due to an overestimation of VLDL-C by the TG/5 component of the formula. Evaluation of the clinical significance of these findings awaits comprehensive lipid and cardiovascular outcome data from ongoing Phase III clinical studies of anacetrapib.
    The Journal of Lipid Research 11/2012; DOI:10.1194/jlr.M032615 · 4.73 Impact Factor
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    ABSTRACT: This position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers. Osteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. This need to advance the field of bone turnover markers has been recognized by a number of organizations, including the International Osteoporosis Foundation (IOF), National Osteoporosis Foundation, International Federation of Clinical Chemistry, and Laboratory Medicine (IFCC), and the NBHA. This position paper elucidates how this project will standardize bone turnover marker sample collection procedures in the USA, establish a USA reference range for one bone formation (serum procollagen type I N propeptide, s-PINP) and one bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) marker, and standardize bone turnover marker assays used in clinical laboratories. This effort will allow clinicians from the USA to have confidence in their use of bone turnover markers to help monitor osteoporosis treatment and assess future fracture risk. This project builds on the recommendations of the IOF/IFCC Bone Marker Standards Working Group by developing USA reference standards for s-PINP and s-CTX, the markers identified as most promising for use as reference markers. The goals of this project will be realized through the NBHA and will include its governmental, academic, for-profit, and non-profit sector stakeholders as well as major academic and commercial laboratories. Upon completion, a parallel effort will be pursued to make bone turnover marker measurements reliable and accepted by all health care professionals for facilitating treatment decisions and ultimately be reimbursed by all health insurance payers. Successful completion of this project will help assure health professionals from the USA of the clinical utility of bone turnover markers and ties in with the parallel effort of the IOF/IFCC to develop worldwide bone turnover reference ranges.
    Osteoporosis International 07/2012; 23(10):2425-33. DOI:10.1007/s00198-012-2049-z · 4.04 Impact Factor
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    ABSTRACT: To assess and validate the application of a non-radioactive assay for cholesteryl ester transfer protein (CETP) activity in clinical samples. In this Phase 0 study, CETP activity was measured following addition of the CETP inhibitor JNJ-28545595 to plasma samples from normolipidemic and three subgroups of dyslipidemic subjects with differing lipid profiles. CETP activity was elevated in plasma samples from dyslipidemic subjects compared to normolipidemic subjects. Increased triglyceride levels correlated with decreased CETP inhibition. The assay was found to have good analytical precision and high throughput potential as required for clinical trial sample analysis. The results demonstrate that pharmacological inhibition of CETP is affected by the dyslipidemic nature of plasma samples. In addition, since the optimal degree of CETP inhibition for maximal cardiovascular benefit in patients is not known, this assay may be used to help define optimal dosing of CETP inhibitors.
    International journal of clinical pharmacology and therapeutics 05/2012; 50(8):584-94. DOI:10.5414/CP201627 · 1.04 Impact Factor
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    ABSTRACT: Antecedentes: Nuestro objetivo fue evaluar la exactitud en el score de la clasificación del riesgo de enfermedad cardiovascular (ECV) por parte de la medida directa de colesterol de LDL (dc-LDL), del cálculo del colesterol LDL (cc-LDL), y del colesterol no HDL (no-c-HDL) en comparación a la clasificación por los métodos de referencia (MR) realizados en el CDC. Métodos: Se estudiaron 175 pacientes, entre ellos 138 con ECV u otras condiciones que puedan afectar a la medición de c-LDL. Las mediciones de dc-LDL se realizaron con reactivos Denka, Kyowa, Sekisui, Serotec, Sysmex, UMA y Wako. Se calculó cc-LDL mediante la ecuación de Friedewald, usando la respectiva medida directa del colesterol de HDL de cada fabricante y las mediciones de colesterol total y triglicéridos medidas por Roche y Siemens (Advia), respectivamente. Resultados: Para los participantes con triglicéridos <2,26 mmol / L (<200 mg / dL), la tasa de errores de clasificación global en el score de riesgo de ECV fue de 5% a 17% con los métodos de cc-LDL, y del 8% al 26% para los métodos dc-LDL en comparación con los MR. Sólo el dc-LDL realizado por Wako presentó menos errores de clasificación que su método de cc-LDL correspondiente (8% vs 17%, p<0,05). El no-c-HDL clasificó erróneamente a un menor número de pacientes que dc-LDL en 4 de los 8 métodos (P <0,05). Para los pacientes con triglicéridos >2,26 mmol / L (>200 mg / dL) y <4,52 mmol / L (<400 mg / dL), los métodos de dc-LDL, en general, presentaron mejores resultados que los métodos cc-LDL, y los métodos de no-c-HDL mostraron una mejor correspondencia con el MR en el score de clasificación de riesgo de ECV que los métodos de dc-LDL como de cc-LDL. Conclusiones: A excepción de las personas hipertrigliceridémicas, 7 de los 8 métodos de dc-LDL fallaron en mejorar el score de clasificación de riesgo de ECV sobre los correspondientes métodos de cc-LDL. No-c-HDL mostró en general la mejor concordancia con el MR en el score de clasificación de riesgo de ECV en individuos normales y con hipertrigliceridemia.
    Acta bioquímica clínica latinoamericana 12/2011; 45(4):773-784. · 0.09 Impact Factor
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    ABSTRACT: Our objective was to evaluate the accuracy of cardiovascular disease (CVD) risk score classification by direct LDL cholesterol (dLDL-C), calculated LDL cholesterol (cLDL-C), and non-HDL cholesterol (non-HDL-C) compared to classification by reference measurement procedures (RMPs) performed at the CDC. We examined 175 individuals, including 138 with CVD or conditions that may affect LDL-C measurement. dLDL-C measurements were performed using Denka, Kyowa, Sekisui, Serotec, Sysmex, UMA, and Wako reagents. cLDL-C was calculated by the Friedewald equation, using each manufacturer's direct HDL-C assay measurements, and total cholesterol and triglyceride measurements by Roche and Siemens (Advia) assays, respectively. For participants with triglycerides<2.26 mmol/L (<200 mg/dL), the overall misclassification rate for the CVD risk score ranged from 5% to 17% for cLDL-C methods and 8% to 26% for dLDL-C methods when compared to the RMP. Only Wako dLDL-C had fewer misclassifications than its corresponding cLDL-C method (8% vs 17%; P<0.05). Non-HDL-C assays misclassified fewer patients than dLDL-C for 4 of 8 methods (P<0.05). For participants with triglycerides≥2.26 mmol/L (≥200 mg/dL) and<4.52 mmol/L (<400 mg/dL), dLDL-C methods, in general, performed better than cLDL-C methods, and non-HDL-C methods showed better correspondence to the RMP for CVD risk score than either dLDL-C or cLDL-C methods. Except for hypertriglyceridemic individuals, 7 of 8 dLDL-C methods failed to show improved CVD risk score classification over the corresponding cLDL-C methods. Non-HDL-C showed overall the best concordance with the RMP for CVD risk score classification of both normal and hypertriglyceridemic individuals.
    Clinical Chemistry 02/2011; 57(3):490-501. DOI:10.1373/clinchem.2010.154773 · 7.77 Impact Factor
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    ABSTRACT: A randomized, double-blind, placebo-controlled study assessed the efficacy of acetaminophen or fluvastatin in preventing post-dose symptoms (increases in body temperature or use of rescue medication) following a single infusion of the intravenous (IV) bisphosphonate zoledronic acid (ZOL). Acetaminophen, but not fluvastatin, significantly reduced the incidence and severity of post-dose symptoms. Transient symptoms including myalgia and pyrexia have been reported post-infusion of IV bisphosphonates, typically starting the day after infusion and resolving within several days. The cause is unknown but may be related to transient cytokine elevations. Statins' potential to block release of these cytokines has been hypothesized. This study was aimed to evaluate efficacy of acetaminophen and fluvastatin in preventing/reducing post-dose symptoms following ZOL 5 mg infusion. Randomized, double-blind, placebo-controlled study of efficacy of acetaminophen or fluvastatin in preventing increases in body temperature or use of rescue medication (ibuprofen) following a single ZOL infusion. Bisphosphonate-naive postmenopausal women with low bone mass (N = 793) were randomized into three treatment groups and given 650 mg acetaminophen or 80 mg fluvastatin or placebo 45 min before ZOL infusion. The acetaminophen group continued taking 650 mg acetaminophen every 6 h over the next 3 days, and the other two groups took matching placebo according to the same schedule. Subjects recorded body temperature, symptoms in a diary. Inflammatory cytokines and C-reactive protein (CRP) were measured at baseline, 24, and 72 h in a study subset. Acetaminophen four times/day significantly reduced the incidence and severity of post-dose symptoms following ZOL infusion. Single-dose fluvastatin 80 mg prior to ZOL infusion did not prevent/reduce post-dose symptoms. Cytokine levels increased by 24 h and returned towards baseline by 72 h, similar to the pattern for post-infusion symptoms. CRP levels increased from baseline to 72 h. Acetaminophen four times/day for 3 days significantly reduced the incidence and severity of post-dose symptoms following ZOL infusion.
    Osteoporosis International 11/2010; 22(8):2337-45. DOI:10.1007/s00198-010-1448-2 · 4.04 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Methods from 7 manufacturers and 1 distributor for directly measuring HDL cholesterol (C) and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples. We performed each direct method according to the manufacturer's instructions, using a Roche/Hitachi 917 analyzer, and compared the results with those obtained with reference measurement procedures for HDL-C and LDL-C. Imprecision was estimated for 35 runs performed with frozen pooled serum specimens and triplicate measurements on each individual sample. Sera from 37 individuals without disease and 138 with disease (primarily dyslipidemic and cardiovascular) were measured by each method. Trueness and total error were evaluated from the difference between the direct methods and reference measurement procedures. Specificity was evaluated from the dispersion in differences observed. Imprecision data based on 4 frozen serum pools showed total CVs <3.7% for HDL-C and <4.4% for LDL-C. Bias for the nondiseased group ranged from -5.4% to 4.8% for HDL-C and from -6.8% to 1.1% for LDL-C, and for the diseased group from -8.6% to 8.8% for HDL-C and from -11.8% to 4.1% for LDL-C. Total error for the nondiseased group ranged from -13.4% to 13.6% for HDL-C and from -13.3% to 13.5% for LDL-C, and for the diseased group from -19.8% to 36.3% for HDL-C and from -26.6% to 31.9% for LDL-C. Six of 8 HDL-C and 5 of 8 LDL-C direct methods met the National Cholesterol Education Program total error goals for nondiseased individuals. All the methods failed to meet these goals for diseased individuals, however, because of lack of specificity toward abnormal lipoproteins.
    Clinical Chemistry 04/2010; 56(6):977-86. DOI:10.1373/clinchem.2009.142810 · 7.77 Impact Factor
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    ABSTRACT: This review evaluates the status of standardization of lipids and lipoproteins. Prerequisites and some basic principles for standardization are provided. The reference systems for cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and lipoprotein(a) (Lp[a]) are described. Brief descriptions of the standardization programs available for each of these analytes are also provided. Finally, the review addresses some of the challenges in standardizing these markers of cardiovascular disease (CVD). The standardization programs described have contributed to improvements in laboratory measurements of lipids and lipoproteins. Our intention is that clinical laboratory professionals and manufacturers of in vitro diagnostics will use these resources to standardize lipid and lipoprotein measurements. Manufacturers must take the initiative to thoroughly evaluate their products and ensure traceability to the reference systems.
    Laboratory Medicine 08/2008; 39(8):481-490. DOI:10.1309/6UL9RHJH1JFFU4PY · 0.49 Impact Factor
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    ABSTRACT: In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk. Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women. We conducted a prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial at 62 sites in the United States. Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), and lumbar (L1-L4) spine bone mineral density T-score between 0.0 and -2.5. Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin was administered. We assessed percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo. At 52 wk, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo. Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis.
    Journal of Clinical Endocrinology &amp Metabolism 01/2008; 92(12):4671-7. DOI:10.1210/jc.2006-1909 · 6.31 Impact Factor
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    ABSTRACT: The current analyses evaluated the effect of atorvastatin on biomarkers of renal function. Serum creatinine level and markers of tubular and glomerular function, including cystatin C, urine N-acetyl-beta-D-glucosaminidase, urine and serum beta2-microglobulin, and urine albumin, were assessed in osteopenic postmenopausal women with mild dyslipidemia who received atorvastatin 20 mg, atorvastatin 80 mg, or placebo for 1 year. During the study, changes in serum creatinine levels were the same in all 3 treatment groups. Cystatin C levels remained unchanged in all groups at all time points. For the additional markers of renal function, median values at baseline and weeks 26 and 52 in both of the atorvastatin and the placebo groups were similar. Neither moderate- nor high-dose atorvastatin treatment for 1 year altered markers of glomerular and renal tubular function compared with placebo. These data indicate that in this patient population, atorvastatin, even at a high dose, does not interfere with renal tubular reabsorption of protein, induce renal tubular dysfunction, or alter glomerular filtration rate in humans.
    Journal of the CardioMetabolic Syndrome 02/2007; 2(3):163-7. DOI:10.1111/j.1559-4564.2007.07295.x
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    ABSTRACT: 0.80 (0.70, 0.90) 0.80 (0.70, 0.90) 0.80 (0.70, 0.90) Week 26 0.80 (0.70, 0.90) 0.80* (0.80, 0.90) 0.80* (0.70, 0.90) Week 52 0.90* (0.80, 0.90) 0.90* (0.75, 1.00) 0.90* (0.80, 0.90) Cystatin C (mg/L) Baseline 0.82 (0.72, 0.94) 0.88 (0.76, 1.00) 0.80 (0.67, 0.90) Week 26 0.84 (0.76, 0.94) 0.87 (0.75, 0.98) 0.82 (0.68, 0.95) Week 52 0.83 (0.75, 0.95) 0.88 (0.78, 1.01) 0.80 (0.68, 0.94) Microalbumin, urine (µg/mg Cr) 0.082 (0.060, 0.132) 0.087 (0.064, 0.119) 0.074 (0.043, 0.109) Week 26 0.084 (0.059, 0.113) 0.082 (0.058, 0.111) 0.081 (0.043, 0.105) Week 52 0.077 (0.056, 0.110) 0.090 (0.059, 0.116) 0.081 (0.055, 0.109) *P

Publication Stats

156 Citations
36.28 Total Impact Points


  • 2010–2012
    • Pacific Biomarkers
      Seattle, Washington, United States
    • Virginia Commonwealth University
      • Department of Pathology
      Richmond, Virginia, United States
  • 2011
    • National Institutes of Health
      • Department of Laboratory Medicine
      Bethesda, MD, United States
  • 2007
    • University of Miami Miller School of Medicine
      Miami, Florida, United States