Direct HDL-cholesterol Research Articles

Income Inequality, Gender Disparities, and Ethnic Differences: Investigating Allostatic Load in American Adults.

To estimate the association between income inequality and allostatic load score (AL) in adults ages 20 years and older, with a particular focus on the differential impacts across racial and gender groups. By examining this association, the study seeks to inform targeted policy interventions to mitigate health disparities exacerbated by economic inequality. Utilizing data from the 1999-2016 National Health and Nutrition Examination Survey (NHANES), we assessed AL through eight biomarkers: systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), pulse rate (beats/min), body mass index (kg/m2), glycohemoglobin (%), direct HDL cholesterol (mg/dL), total cholesterol (mg/dL), and serum albumin (g/dL). Employing negative binomial regression (NBRG), we estimated incidence rate ratios (IRR) for a sample comprising 7367 men and 7814 women, adjusting for age, race/ethnicity, marital status, education, health insurance, comorbidity, and mental health professional utilization. Gini coefficients (GC) were calculated to assess income inequality among men and women. Findings revealed that men exhibited a higher poverty-to-income ratio (PIR) compared to women (3.12 vs. 2.86, p < 0.01). Yet, women experienced higher rates of elevated AL (AL > 4) (31.8% vs. 29.0%) and were more adversely affected by income inequality (GC: 0.280 vs. 0.333). NBRG results indicated that high PIR individuals had a lower IRR (0.96; CI:0.92-0.95) compared to their low PIR counterparts, a trend observed in women but not men. High PIR was notably protective among White non-Hispanic (WNH) men and women. Additionally, vigorous and moderate physical activity engagement was associated with lower AL (IRR: 0.89, CI: 0.85-0.93). The study emphasizes the importance of implementing policies that target AL in low-income populations across all racial groups, with a specific focus on Black non-Hispanic (BNH) and Hispanic communities. By prioritizing these groups, policies can more effectively target the nexus of income inequality, health disparities, and allostatic load, contributing to the reduction of health inequities.

Machine learning for the prediction of cognitive impairment in older adults.

The purpose of this study was to develop and validate a predictive model of cognitive impairment in older adults based on a novel machine learning (ML) algorithm. The complete data of 2,226 participants aged 60-80 years were extracted from the 2011-2014 National Health and Nutrition Examination Survey database. Cognitive abilities were assessed using a composite cognitive functioning score (Z-score) calculated using a correlation test among the Consortium to Establish a Registry for Alzheimer's Disease Word Learning and Delayed Recall tests, Animal Fluency Test, and the Digit Symbol Substitution Test. Thirteen demographic characteristics and risk factors associated with cognitive impairment were considered: age, sex, race, body mass index (BMI), drink, smoke, direct HDL-cholesterol level, stroke history, dietary inflammatory index (DII), glycated hemoglobin (HbA1c), Patient Health Questionnaire-9 (PHQ-9) score, sleep duration, and albumin level. Feature selection is performed using the Boruta algorithm. Model building is performed using ten-fold cross-validation, machine learning (ML) algorithms such as generalized linear model (GLM), random forest (RF), support vector machine (SVM), artificial neural network (ANN), and stochastic gradient boosting (SGB). The performance of these models was evaluated in terms of discriminatory power and clinical application. The study ultimately included 2,226 older adults for analysis, of whom 384 (17.25%) had cognitive impairment. After random assignment, 1,559 and 667 older adults were included in the training and test sets, respectively. A total of 10 variables such as age, race, BMI, direct HDL-cholesterol level, stroke history, DII, HbA1c, PHQ-9 score, sleep duration, and albumin level were selected to construct the model. GLM, RF, SVM, ANN, and SGB were established to obtain the area under the working characteristic curve of the test set subjects 0.779, 0.754, 0.726, 0.776, and 0.754. Among all models, the GLM model had the best predictive performance in terms of discriminatory power and clinical application. ML models can be a reliable tool to predict the occurrence of cognitive impairment in older adults. This study used machine learning methods to develop and validate a well performing risk prediction model for the development of cognitive impairment in the elderly.

Use of metabotyping for the delivery of personalised nutrition.

Personalised nutrition can be defined as dietary advice that is tailored to an individual. In recent years, the concept of targeted nutrition has evolved, which involves delivering specific dietary advice to a group of phenotypically similar individuals or metabotypes. This study examined whether cluster analysis could be used to define metabotypes and developed a strategy for the delivery of targeted dietary advice. K-means clustering was employed to identify clusters based on four markers of metabolic health (triacylglycerols, total cholesterol, direct HDL cholesterol and glucose) (n = 896) using data from the National Adult Nutrition Survey. A decision tree approach was developed for the delivery of targeted dietary advice per cluster based on biochemical characteristics, anthropometry and blood pressure. The appropriateness of the advice was tested by comparison with individualised dietary advice manually compiled (n = 99). A mean match of 89.1% between the methods was demonstrated with a 100% match for two-thirds of participants. Good agreement was found between the individualised and targeted methods demonstrating the ability of this framework to deliver targeted dietary advice. This approach has the potential to be a fast and novel method for the delivery of targeted nutrition in clinical settings.

Serum calprotectin levels in elderly males and females without bacterial or viral infections

ObjectivesCalprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker. MethodsSerum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated. ResultsThere was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol. ConclusionsThe reference interval for serum-calprotectin for all study subjects was 0.3–2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

Limitations of Direct Methods and the Reference Method for Measuring HDL and LDL Cholesterol

To the Editor: Miller and colleagues (1) compared the results obtained by direct measurements of HDL cholesterol (HDL-C) and LDL-C with those obtained with reference methods requiring ultracentrifugation. They used frozen pooled serum samples and fresh serum samples from 37 healthy controls and 138 individuals with dyslipidemia or heart disease that they had obtained from the NIH. Assay kits, calibrators, and controls were provided by 7 manufacturers. The authors reported CVs of <3.7% for HDL-C and <4.4% for LDL-C for the frozen serum pools, biases for fresh serum from the healthy controls of −5.4% to 4.4% for HDL-C and −6.8% to 1.1% for LDL-C. The biases for the patients with disease were −8.6% to 8.8% for HDL-C and −11.8% to 4.1% for LDL-C, compared with the reference method. The total error for the healthy controls ranged from −13.4% to 1.6% for HDL-C and from −13.3% to 13.5% for LDL-C. For the disease group, total errors ranged from −19.8% to 36.3% for HDL-C and from −26.6% to 31.9% for LDL-C. The authors concluded that 6 of 8 direct HDL-C …

The robustness of the Roche 2nd generation homogenous HDL cholesterol (PEGME) method: Assessment of the effect of serum sample storage for up to 8 years at − 80 °C

Background Low HDL-cholesterol (HDL-C) is a strong and independent cardiovascular risk factor. Clinical trials often necessitate storage of samples before assay. Results are lacking for longer-term storage with quantification of HDL-C using different methods before and after storage. Methods Serum samples ( n = 2936) from the Collaborative Atorvastatin Diabetes Study in which HDL-C had been determined on ‘fresh’ samples using the MnCl 2/heparin method before freezing and storage for up to 8 years at − 80 °C were thawed and HDL-C was determined using the Roche direct method. We participated in the Riqas QC programme and results obtained for the control serum samples using a CDC-approved method were used to generate a regression equation and thus to adjust both original results, obtained after precipitation and also to align the direct HDL-C results. Results CDC-aligned HDL-C results for stored samples were lower than CDC-aligned HDL-C results before storage (mean [S.E.M.]: 1.41 [0.01] vs. 1.43 [0.01] mmol/L; P < 0.0001, n = 2936). Although results after storage tended to be lower, there was no significant time-dependent change in the ratio of original to stored results for HDL-C. Conclusions The study establishes that the Roche 2nd generation PEGME method is robust and eminently suitable for determinations of HDL-C in stored serum samples.

Nightmares and Serum Cholesterol Level: A Preliminary Report

To examine whether there is a relation between nightmares and serum lipid levels. Fifteen subjects who met DSM-IV criteria for the diagnosis of nightmare disorder and 15 healthy control subjects participated in the study. We used an enzymatic colorimetric method for cholesterol and triglyceride determination. We measured high-density lipoprotien (HDL) cholesterol using the direct HDL-cholesterol method. Low-density lipoprotein (LDL) was calculated according to the Friedewald formula. Patients with nightmare disorder had lower serum triglyceride, lower total cholesterol, and lower LDL levels than healthy control subjects. These findings suggest that nightmares are associated with low serum lipid levels.

Overestimation of HDL-cholesterol using a homogeneous "direct" assay.

Direct HDL-cholesterol (HDLc) assays have several advantages over other assays that are more laborious and time-consuming. A recent College of American Pathologists (CAP) report indicates that at least 385 Beckman LX-20 analyzers use the selective detergent (homogeneous or direct) method for analyzing HDLc. There is no published evaluation of direct HDLc assays on the Beckman platform. Here we report our evaluation of a direct HDLc assay marketed by Beckman for the Beckman LX-20 analyzers. In general, the assay performed well; however, the total error was not within National Cholesterol Education Program (NCEP) guidelines. This was largely because of a significant positive bias that appeared to be due, at least in part, to triglycerides. This bias was worse at HDLc concentrations <40 mg/dL, which may make it difficult to identify a low HDLc concentration and consequently an increased risk for cardiovascular disease (CVD).

Case Study: A Woman With Type 2 Diabetes and Severe Hypertriglyceridemia Sensitive to Fat Restriction

L.S. is a 52-year-old Caucasian woman who was diagnosed with type 2 diabetes in 1988. She developed hypertriglyceridemia 3 years later and hypertension 9 years later. Other medical problems include obesity and diverticulosis. She presents now for screening to determine eligibility for a clinical research protocol using once-daily insulin. Physical exam reveals a height of 64 inches, a weight of 181 lb, a body mass index of 31 kg/m2, and a waist circumference of 40 inches. Blood pressure, well controlled on 20 mg lisinopril (Prinivil) daily, is 104/70 mmHg. Laboratory results reveal a fasting lipid panel as follows: total cholesterol 214 mg/dl, triglycerides 940 mg/dl, direct HDL cholesterol 24 mg/dl, an invalid LDL cholesterol unobtainable because of the hypertriglyceridemia, and a free fatty acid of 1.1 mEq/l (normal range 0.1–0.6 mEq/l). Hemoglobin A1c (A1C) is 9.5%, and fasting blood glucose (FBG) is 304 mg/dl. When called to discuss the finding of severe hypertriglyceridema, the patient commented that she had previously had fasting triglycerides as high as 3,000 mg/dl. L.S. is currently taking metformin (Glucophage), 1,000 mg twice daily, and glipizide (Glucatrol XL), 10 mg twice daily, to control her blood glucose. She is also on gemfibrizol (Lopid), 600 mg twice daily, for hypertriglyceridemia and estradiol (Estraderm) for menopause (topical estrogen does not induce hypertriglyceridemia). 1. What nutritional modification would be effective in rapidly lowering serum triglycerides when the patient is at risk of pancreatitis? 2. What treatment strategies can be employed to lower triglycerides, and how effective are they? 3. How can nutritional modifications improve insulin resistance? Type 2 diabetes carries a two- to fourfold excess risk of coronary heart disease. The most common pattern of dyslipidemia in patients with type 2 diabetes is elevated triglycerides and decreased …

Calculation of coronary risk in Type II diabetes: another cause for concern

We read with interest the paper by Stevens et al. [1], in which they described a new equation for calculating coronary heart disease (CHD) risk in patients with Type II diabetes mellitus. The new equation, which is based on the U.K. Prospective Diabetes Study (UKPDS) [2], utilizes HbA c as a continuous variable unlike the Framingham Figure 1 Comparison of the direct HDL cholesterol measurement method, marketed by Roche (Y) with the conventional precipitation method (X) using the method of Passing and Bablock for linear regression analysis The dashed lines indicate the 95% confidence limit. Similar results were obtained for methods marketed by the companies Sigma, Wako and Randox. (a) Patients with Type I diabetes, and (b) patients with Type II diabetes. risk equations [3], which are only interested in the presence or absence of diabetes. The inclusion of HbA c as a continuous risk factor for CHD in Type II diabetes resulted in a significant increase in the 10-year risk. The National Service Framework for CHD prevention proposed that statins should be limited to patients with a

Monoclonal Paraprotein May Interfere with the Roche Direct HDL-C Plus Assay

We report here the observation of a falsely decreased HDL-cholesterol (HDL-C) result obtained with the Roche HDL-C Plus assay (polyethylene glycol-modified enzymes, sulfated α-cyclodextrin, and dextran sulfate; cat no. 1930648) in an asymptomatic 78-year-old woman (1). The total cholesterol of the patient was 3.2 mmol/L, the triglycerides were 1.3 mmol/L, and the HDL-C was suppressed (<0) on a Roche Modular analyzer. The same analysis was repeated on the Johnson & Johnson Vitros (with magnetic separation of particles; cat. no. 1042523) and the Beckman LX-20 (with a polyanion-polymer/detergent reagent; cat. no. 650207) …

Inaccuracy of Calculated LDL-Cholesterol in Type 2 Diabetes: Consequences for Patient Risk Classification and Therapeutic Decisions

LDL-cholesterol (LDLc) is the main lipid marker in cardiovascular risk estimation and the principal therapeutic target in both diabetic and nondiabetic subjects (1)(2). The designated comparison method for the determination of LDLc, using ultracentrifugation and precipitation, known as “β-quantification” (3), is cumbersome and time-consuming and requires expensive instrumentation and trained personnel. The Friedewald equation (4) {LDLc = total cholesterol − HDLc − [triglycerides (in mmol/L)/2.17 or triglycerides (in mg/dL)/5]}, the most frequently used method for the calculation of LDLc, assumes that VLDL particles maintain a nearly constant cholesterol:triglyceride ratio. However, this assumption is invalid in the presence of chylomicronemia and increased VLDL or intermediate-density lipoprotein particles (4)(5)(6)(7). Because diabetic dyslipidemia includes quantitative and qualitative abnormalities in lipoprotein particles, including VLDL and their remnants (8)(9)(10), the use of the Friedewald equation in diabetic patients has been questioned (11)(12)(13). HDL-cholesterol (HDLc), often determined after chemical precipitation of apolipoprotein B (apoB)-containing lipoproteins, has technical drawbacks that could interfere with the accuracy of LDLc calculation (14). New homogeneous, direct methods have improved HDLc determination (15). However, the consequences on patient classification and therapy of using direct, more precise methods for HDLc in the estimation of LDLc by the Friedewald equation have, to our knowledge, not been assessed. We previously proposed an equation that included total triglycerides and cholesterol, and apoB that was more accurate than the Friedewald equation in estimating LDLc (16). Because diabetic dyslipidemia includes hyperapoB (17), an equation that includes apoB in the estimation of LDLc could be of special interest in these patients. Thus, our aims were to ascertain whether a direct HDLc method increases the accuracy of the Friedewald formula, to evaluate an equation that includes apoB in the estimation of LDLc, and …

Falsely Low Direct HDL-Cholesterol Results in a Patient with Dysbetalipoproteinemia

Direct methods for measuring HDL-cholesterol (HDL-C) are becoming more widely used because of their labor savings and favorable performance characteristics. We investigated three methodologies for direct HDL-C measurements. All three contain an initial reagent to block measurement of cholesterol in lipoproteins other than HDL, followed by a second reagent to measure HDL-C. The performance of each of these assays has been evaluated previously (1)(2)(3)(4)(5)(6)(7)(8). All of these direct assays appear to be relatively free of common interferences; however, triglycerides >10 g/L may affect recoveries. There are minimal published data on these new direct methods with patients who have a dyslipidemia or are receiving lipid-modifying drugs. In this report, we describe a patient with type III hyperlipidemia for whom three direct HDL-C assays yielded erroneously low results compared with traditional HDL-C methods. We analyzed a specimen from a 69-year-old man, using a direct HDL-C assay, and obtained a value that was less than the 40 mg/L detection limit of the assay. The patient had no signs or symptoms such as large orange tonsils, corneal opacities, or relapsing polyneuropathy, compatible with primary hypoalphalipoproteinemia. His medical history was remarkable for chronic obstructive pulmonary disease, peripheral vascular disease, recurrent deep vein thrombosis, congestive heart failure, coronary artery disease, hypertension, and an unspecified hyperlipidemia. His current medications included aspirin, coumadin, digoxin, diltiazem, furosemide, albuterol/ipratropium inhaler, and simvastatin, a hydroxymethylglutaryl-CoA reductase inhibitor. He had consumed no alcohol for at least 1 year. A review of results for hepatic disease tests for the past 4 years revealed serum concentrations of aspartate aminotransferase, alanine aminotransferase, and total bilirubin within the appropriate reference intervals. Alkaline phosphatase values were 1.3- to 1.9-fold higher than the upper limit of normal over this same time period. Additional …

Total Error Evaluation of Roche Direct HDL-Cholesterol Reagent and Calibrator across 31 Lot Combinations: A 2-Year Experience

Professionally set quality specifications are needed as major considerations in development of new reagents (1). Two years ago, the Dutch Lipid Reference Laboratory, a permanent international member of the CDC Cholesterol Reference Method Laboratory Network (2)(3), in collaboration with Roche Diagnostics Nederland B.V. (formerly Boehringer Almere, The Netherlands), began evaluating lot-to-lot differences of the new direct HDL-cholesterol (HDL-C) reagent from Kyowa Medex (cat. no. 1731157) and of the HDL-C/LDL-cholesterol cfas calibrator (cat. no. 1778501) before distribution on the Dutch market. To this end, a scaled down split-sample comparison protocol was used, essentially according to the design described in the HDL Cholesterol Method Evaluation Protocol for Manufacturers (4)(5). The accuracy platform was the CDC Designated Comparison Method (DCM) for HDL-C (2)(4); the test method was run …

Assessment of interlaboratory performance in external proficiency testing programs with a direct HDL-cholesterol assay

Direct assays for the determination of HDL-cholesterol (HDL-C) have recently become available. The methods are precise, require small sample volume, and appear to be less affected by increased triglycerides than traditional precipitation methods. In this study, we describe the inter- and intralaboratory variability of the Boehringer Mannheim Corporation direct HDL-C assay and its performance in external proficiency testing surveys. A comparison study among three laboratories, using different analyzers and 85 serum specimens, showed a correlation coefficient (r) of 0.99. The direct HDL-C assay also showed good agreement with the ultracentrifugation-dextran sulfate-Mg2+ method (r = 0.98) and the Cholesterol Reference Method Laboratory Network-Designated Comparison Method (a = 0.98x + 4.75 mg/L, r = 0.98). Total error at medical decision levels ranged from -0.8% to +11.1%. Furthermore, this assay performed adequately in the College of American Pathologists and the ALERT surveys as well as the CDC Lipid Standardization Program and met all performance criteria of regulatory agencies.

Evaluation of Homogeneous High-Density Lipoprotein Cholesterol Assay on a BM/Hitachi 747–200 Analyzer

Because of the inverse correlation that exists between serum HDL-C concentration and risk of atherosclerotic disease (1), monitoring of high-density lipoprotein cholesterol (HDL-C) in serum is clinically important. In 1993, the National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP II) revised its guidelines for diagnosis and treatment of hypercholesterolemia in adults to include HDL-C measurement at the initial screening stage when total cholesterol is measured (2). The enhanced role of HDL-C in clinical practice increases the need for reliable and readily performable HDL-C measurement. Most routine laboratories use a two-step method: chemical precipitation of lipoproteins containing apoprotein B, then quantification of HDL as cholesterol remaining in the supernate. Such precipitation-based methods are time-consuming, labor-intensive, require relatively large volumes of serum, and cannot be fully automated. Recently, several methods of direct HDL-C measurement have become commercially available, including the use of magnetically responsive particles with polyanion-metal combinations (3), the use of polyethylene glycol (PEG) with antibodies against apoprotein B and apoprotein CIII (4)(5), and the use of PEG-modified enzymes and sulfated α-cyclodextrin (6)(7). Okazaki et al. (8) also recently proposed the use of high-performance liquid chromatography (HPLC) as a tool to compare different methods for HDL-C. The goal of this study was to evaluate three assays for homogeneous HDL-C on BM/Hitachi 747–200 Automatic Analyzer (Boehringer Mannheim Corp.): the direct HDL-cholesterol reagent kit (Boehringer Mannheim Corp.), the N-geneousTM HDL cholesterol reagent kit (Genzyme Diagnostics), and EZ-HDLTM cholesterol reagent kit (Sigma Diagnostics). For each HDL-C assay, the reagent kit contains Reagent 1 and Reagent 2; Reagent 1 is liquid, and Reagent 2 is lyophilized. Reaction principles of these three methods are quite different; the direct-HDL uses PEG-modified cholesterol esterase and cholesterol oxidase as well as sulfated α-cyclodextrin to provide selective determination of HDL-C in serum; …

Automation and evaluation of direct HDL-cholesterol method on monarch 2000

Automation and evaluation of direct HDL-cholesterol method on monarch 2000