Lipoprotein Measurements Research Articles

Effect of Methadone on Lipid Profile, Serum Leptin and Liver Enzymes Levels in Male and Female Rats

Methadone Maintenance Therapy (MMT) has been accepted as a gold-standard treatment for opioid therapy. It may associate with adverse effects. This study aimed to affect methadone on serum lipid profile, leptin levels, and liver enzymes in male and female rats. 41 Wistar rats weighing 200-300gr were randomly assigned into four groups, including two methadone treatments and two control groups, both male and female, that received 5mg/kg methadone or 1cc normal saline daily for 8 weeks respectively by gavage method. All animals were weighed weekly. Fasting blood sugar (FBS) was measured by a glucometer, and blood samples were taken by cardiac puncture for triglyceride, low-density lipoprotein (LDL),high-density lipoprotein (HDL), total cholesterol, Aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) and leptin levels measurement after 12h fasting. One-way ANOVA showed no significant difference in mean FBS, total cholesterol, triglyceride, and LDL levels among the four groups. Moreover, there was a statistically significant difference in the mean of HDL, ALT, AST, and ALP levels. Furthermore, repeated measures ANOVA indicated a significant increase in body weight of rats during 8 weeks. Our findings indicated changes in some metabolic effects associated with methadone treatment in a gender-dependent manner.

Abstract 9971: Longitudinal Lipoprotein(a) Concentrations and Cardiovascular Risk: A Prospective Cohort Study

Introduction: When indicated, current guidelines recommend a single measurement of lipoprotein(a) for cardiovascular risk assessment. However, temporal variability in lipoprotein(a) concentration is not well understood, and it is unclear if repeat testing may help refine risk prediction of coronary artery disease (CAD). Hypothesis: We examined the longitudinal stability of lipoprotein(a) measurements and tested whether instability in lipoprotein(a) molar concentration was associated with incident CAD. Methods: We assessed the correlation between baseline and first follow-up measurements of lipoprotein(a) in the UK Biobank (molar concentration n=16,017) and Mass General Brigham cohorts (molar concentration n=271; mass n=1,748; cholesterol n=1,237). The association between change in lipoprotein(a) molar concentration and incident CAD was assessed among 15,432 UK Biobank participants using Cox proportional-hazards models. Results: Baseline and follow-up lipoprotein(a) molar concentration were significantly correlated in the UK Biobank over a median 4.42 years (IQR: 1.24 years) and Mass General Brigham cohorts over a median 0.94 years (IQR: 0.60 years) (Spearman correlations: 0.96 and 0.92, respectively; p-values <0.0001). Similar results were observed for lipoprotein(a) mass and cholesterol. Follow-up lipoprotein(a) molar concentration was significantly associated with risk of incident CAD (HR [95% CI] per 120 nmol/L: 1.31 [1.14-1.51], p-value=0.0002). However, delta lipoprotein(a) was not significantly associated with incident CAD independent of follow-up lipoprotein(a) (p-value=0.98). Conclusions: These findings suggest that, in the absence of therapies substantially altering lipoprotein(a) measures, longitudinal assessments of lipoprotein(a) are likely unnecessary for CAD risk assessment in the context of primary prevention.

Lipid measurements in the management of cardiovascular diseases: Practical recommendations a scientific statement from the national lipid association writing group

Lipoprotein measurements are pivotal in the management of patients at risk for atherosclerotic coronary heart disease (CHD) with myocardial infarction and coronary death as the main outcomes, and for atherosclerotic cardiovascular disease (ASCVD), which includes CHD and stroke. Recent developments and changes in guidelines affect optimization of using lipid measures as cardiovascular biomarkers. This scientific statement reviews the pre-analytical, analytical, post-analytical, and clinical aspects of lipoprotein measurements. Highlights include the following: i) It is acceptable to screen with nonfasting lipids. ii) non-high-density lipoprotein HDL-cholesterol (non-HDL-C) is measured reliably in either the fasting or the nonfasting state and can effectively guide ASCVD prevention. iii) low density lipoprotein cholesterol (LDL-C) can be estimated from total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) measurements. For patients with LDL-C>100 mg/dL and TG ≤150 mg/dL it is reasonable to use the Friedewald formula. However, for those with TG 150-400 mg/dL the Friedewald formula for LDL-C estimation is less accurate. The Martin/Hopkins method is recommended for LDL-C estimation throughout the range of LDL-C levels and up to TG levels of 399 mg/dL. For TG levels ≥400 mg/dL LDL-C estimating equations are currently not recommended and newer methods are being evaluated. iv) When LDL-C or TG screening results are abnormal the clinician should consider obtaining fasting lipids. v) Advanced lipoprotein tests using apolipoprotein B (apoB), LDL Particle Number (LDL-P) or remnant cholesterol may help to guide therapeutic decisions in select patients, but data are limited for patients already on lipid lowering therapy with low LDL-C levels. Better harmonization of advanced lipid measurement methods is needed. Lipid measurements are recommended 4-12 weeks after a change in lipid treatment. Lipid laboratory reports should denote desirable values and specifically identify extremely elevated LDL-C levels (≥190 mg/dL at any age or ≥160 mg/dL in children) as severe hypercholesterolemia. Potentially actionable abnormal lipid test results, including fasting triglycerides (TG) ≥500 mg/dL, should be reported as hypertriglyceridemia. Appropriate use and reporting of lipid tests should improve their utility in the management of persons at high risk for ASCVD events.

The Association of Metabolic Syndrome Components with Anthropometric Measurements

Aim: This study aims to research the association of metabolic syndrome components with anthropometric measurements like arm circumference, neck circumference, hip circumference, waist-hip ratio, and waist-to-height ratio, which are applied rarely. Methods: This cross-sectional study was conducted with 292 patients in November-December 2019. The arm circumference, neck circumference, waist circumference, hip circumference, waist-hip ratio, waist-to-height ratio, and body mass index measurements of the patients were made. Glucose, high-density lipoprotein, low-density lipoprotein, systolic, and diastolic blood pressure measurements were also recorded. The association between metabolic syndrome components and anthropometric measurements was analyzed. Results: Metabolic syndrome is diagnosed in 32.8% of the participants. According to body mass index, 18.6% of the patients were normal, 34.2% were overweight, and 47.2% were obese. There was a significant difference between the patients with and without metabolic syndrome in terms of laboratory parameters, blood pressure values, and anthropometric measurements. In the diagnosis of metabolic syndrome, optimal cut-off values for arm circumference, neck circumference, hip circumference, waist-hip ratio, and waist-to-height ratio were determined as 31.75 (AUC=0.703), 34.85 (AUC=0.763), 113.75 (AUC=0.757), 0.90 (AUC=0.701), 0.61 (AUC=0.769) for females while they were 35.75 (AUC=0.573), 39.75 (AUC=0.795), 111.5 (AUC=0.607), 0.96 (AUC=0.888), 0.61 (AUC=0.888) for males respectively. Conclusion: A significant correlation was detected between arm circumference, neck circumference, hip circumference, waist-hip ratio, and waist-to-height ratio, and metabolic syndrome components. However, low-density lipoprotein was not correlated with neck circumference and high-density lipoprotein with waist-to-height ratio. Keywords: metabolic syndrome, anthropometric measurement, body mass index, obesity, lipid profile

Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes.

We previously observed beneficial effects of a carbohydrate-reduced, high-protein (CRHP) diet on cardiovascular risk markers in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, when all food was provided to subjects as ready-to-eat meals. Here, we report the results from a 6-month open label extension: 28 patients with T2DM were instructed to self-prepare the CRHP diet with dietetic guidance. At weeks 0, 6, 12, and 36, fasting and postprandial (4-h meal test) blood samples were collected for measurements of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triacylglycerol (TG), apolipoproteins A1 and B, non-esterified fatty acids (NEFA), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6. Diurnal blood pressure and heart rate were also assessed. At the end of the study (week 36), concentrations of fasting total and LDL-cholesterol, fasting and postprandial NEFA and TG, and fasting apolipoprotein-B, CRP and TNF-α concentrations were significantly lower compared with week 0 (p < 0.05). A significant decrease in diurnal heart rate was also observed. From week 12 to 36, an increase in HDL-cholesterol and apolipoprotein-A1 concentrations and a further reduction in fasting and postprandial NEFA (p < 0.05) were found. These changes were independent of minor fluctuations in body weight. We conclude that the substitution of dietary carbohydrate for protein and fat has beneficial effects on several cardiovascular risk markers in patients with T2DM, which are maintained or augmented over the next 6 months when patients select and prepare the CRHP diet on their own in a dietitian-supported setting.

Lipid-modifying effects of lean fish and fish-derived protein consumption in humans: a systematic review and meta-analysis of randomized controlled trials.

Consumption of lean fish and fish-derived proteins were effective for improving lipid profiles in published studies; however, evidence remains inconclusive. To evaluate the effectiveness of lean fish or fish-derived protein on serum/plasma lipid and lipoprotein levels by conducting a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). Medline (Ovid), Scopus, CINAHL, and Food and Nutritional Sciences databases were searched from the start date of each database to September 2019 to identify RCTs determining the effect of lean fish on lipid profile. RCTs investigated lean fish and fish-derived proteins intake and determined at least 1 major lipid or lipoprotein measurement. Two reviewers independently evaluated 1217 studies against the inclusion and exclusion criteria. Relevant studies were assessed for risks of bias, and random-effects meta-analysis was conducted to generate average estimates of effect. A total of 24 studies met the inclusion criteria. Meta-analysis of data from 18 to 21 eligible crossover and parallel-design RCTs with a total of 1392 to 1456 participants found triacylglycerol-lowering effects for lean fish compared with no fish consumption. Lean fish intake showed no significant differences related to total cholesterol or lipoprotein levels. Subanalysis showed that parallel-group RCTs tended to find greater reduction effects on circulating triacylglycerol than did crossover RCTs. Additional better-designed, longer, and larger RCTs, particularly crossover RCTs, are needed to clarify the impact of lean fish and fish proteins on the serum/plasma lipid profile. Findings from such studies would enable practitioners to provide their patients evidence-based recommendations to meet the American Heart Association guidelines for fish consumption to reduce cardiovascular disease risk.

Early Childhood Fat Tissue Changes-Adipocyte Morphometry, Collagen Deposition, and Expression of CD163+ Cells in Subcutaneous and Visceral Adipose Tissue of Male Children.

Childhood obesity is a complex health problem, and not many studies have been done on adipose tissue remodeling in early childhood. The aim of this study was to examine extracellular matrix remodeling in the adipose tissue of healthy male children depending on their weight status. Subcutaneous and visceral adipose tissue was obtained from 45 otherwise healthy male children who underwent elective surgery for hernia repairs or orchidopexy. The children were divided into overweight/obese (n = 17) or normal weight groups (n = 28) depending on their body mass index (BMI) z-score. Serum was obtained for glucose, testosterone, triglyceride, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) measurements. Sections of adipose tissue were stained with hematoxylin and eosin to determine the adipocytes’ surface area, and Masson’s trichrome stain was used to detect the adipocytes’ collagen content. Immunohistochemistry for CD163+ cells was also performed. The results showed that male children in the overweight group had higher serum triglyceride levels, greater adipocyte surface area and collagen content in their subcutaneous adipose tissue, more crown-like structures in fat tissues, and more CD163+ cells in their visceral adipose tissue than males in the normal weight group. In conclusion, in male children, obesity can lead to the hypertrophy of adipocytes, increased collagen deposition in subcutaneous adipose tissues, and changes in the polarization and accumulation of macrophages.

Rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography

Background and aimsNovel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients. Methods and resultsThe patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG.The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04–1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04–1.96) and 1.39 (1.22–1.58) respectively]. Conclusionsrs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.

Low Volume in Vitro Diagnostic Proton NMR Spectroscopy of Human Blood Plasma for Lipoprotein and Metabolite Analysis: Application to SARS-CoV-2 Biomarkers.

The utility of low sample volume in vitro diagnostic (IVDr) proton nuclear magnetic resonance (1H NMR) spectroscopic experiments on blood plasma for information recovery from limited availability or high value samples was exemplified using plasma from patients with SARS-CoV-2 infection and normal controls. 1H NMR spectra were obtained using solvent-suppressed 1D, spin–echo (CPMG), and 2-dimensional J-resolved (JRES) spectroscopy using both 3 mm outer diameter SampleJet NMR tubes (100 μL plasma) and 5 mm SampleJet NMR tubes (300 μL plasma) under in vitro diagnostic conditions. We noted near identical diagnostic models in both standard and low volume IVDr lipoprotein analysis (measuring 112 lipoprotein parameters) with a comparison of the two tubes yielding R2 values ranging between 0.82 and 0.99 for the 40 paired lipoprotein parameters samples. Lipoprotein measurements for the 3 mm tubes were achieved without time penalty over the 5 mm tubes as defined by biomarker recovery for SARS-CoV-2. Overall, biomarker pattern recovery for the lipoproteins was extremely similar, but there were some small positive offsets in the linear equations for several variables due to small shimming artifacts, but there was minimal degradation of the biological information. For the standard untargeted 1D, CPMG, and JRES NMR experiments on the same samples, the reduced signal-to-noise was more constraining and required greater scanning times to achieve similar differential diagnostic performance (15 min per sample per experiment for 3 mm 1D and CPMG, compared to 4 min for the 5 mm tubes). We conclude that the 3 mm IVDr method is fit-for-purpose for quantitative lipoprotein measurements, allowing the preparation of smaller volumes for high value or limited volume samples that is common in clinical studies. If there are no analytical time constraints, the lower volume experiments are equally informative for untargeted profiling.

Lipoprotein(a) and Cardiovascular Disease.

High lipoprotein(a) concentrations present in 10%-20% of the population have long been linked to increased risk of ischemic cardiovascular disease. It is unclear whether high concentrations represent an unmet medical need. Lipoprotein(a) is currently not a target for treatment to prevent cardiovascular disease. The present review summarizes evidence of causality for high lipoprotein(a) concentrations gained from large genetic epidemiologic studies and discusses measurements of lipoprotein(a) and future treatment options for high values found in an estimated >1 billion individuals worldwide. Evidence from mechanistic, observational, and genetic studies support a causal role of lipoprotein(a) in the development of cardiovascular disease, including coronary heart disease and peripheral arterial disease, as well as aortic valve stenosis, and likely also ischemic stroke. Effect sizes are most pronounced for myocardial infarction, peripheral arterial disease, and aortic valve stenosis where high lipoprotein(a) concentrations predict 2- to 3-fold increases in risk. Lipoprotein(a) measurements should be performed using well-validated assays with traceability to a recognized calibrator to ensure common cut-offs for high concentrations and risk assessment. Randomized cardiovascular outcome trials are needed to provide final evidence of causality and to assess the potential clinical benefit of novel, potent lipoprotein(a) lowering therapies.

The nuclear magnetic resonance metabolic profile: Impact of fasting status

IntroductionMeasurement of lipoprotein subclass concentration (-c), particle number (-p), and size (-s) by nuclear magnetic resonance (NMR) has gained traction in the clinical laboratory due to associations between smaller lipid particle sizes and atherogenic risk, especially for LDL-p. The standard protocols for lipoprotein measurements by NMR require fasting blood samples; however, patients may not fast properly before sample collection. The study objective was to evaluate the impact of fasting status on the NMR-based lipid profile and to identify key parameters differentiating between fasting and post-meal specimens. MethodsForty-eight self-reported healthy male and female participants were recruited. Blood was collected after a 12 h fast and 4 h after a high fat meal. Samples were analyzed using the AXINON LipoFIT by NMR assay. The measurements included triglyceride, total cholesterol, IDL-c, and LDL, HDL, VLDL concentration, particle number, and size, as well as glucose, and four amino acids (alanine, valine, leucine and isoleucine). ResultsAs expected, triglycerides increased after the meal (58%, p < 0.0001). Significant changes were also observed for VLDL, LDL, and HDL parameters, and the branched chain amino acids. The ratio of Valine*VLDL-c/LDL-c or Isoleucine*VLDL-c/LDL-c provided equally effective differentiation of fasting and post-meal samples. The ratio cutoffs (79.1 and 23.6 when calculated using valine and isoleucine, respectively) had sensitivities of 86% and specificities of 93–95%. ConclusionsThe clinical impact on NMR results from post-meal samples warrants further evaluation. Algorithms to differentiate fasting and post-meal specimens may be useful in identifying suboptimal specimens.

A real-world assessment of the distribution of lipid levels across increasing lipoprotein(a) levels in patients with established cardiovascular disease in the United States

Abstract Background and purpose Measurements of lipid levels are frequently used to assess the risk of developing cardiovascular disease (CVD), including future myocardium infarction (MI) and ischemic stroke. Lipoprotein(a) [Lp(a)] has been established as an independent risk factor for developing CVD, however it is not widely measured. This real-world study assessed the distribution of lipid (Total Cholesterol [TC], low-density cholesterol [LDL-C], high-density cholesterol [HDL-C] and Triglycerides [TGs]) levels across different Lp(a) strata of patients with established CVD and at least one Lp(a) assessment. Methods This was a descriptive, non-interventional, retrospective cohort study of patients with established CVD and at least one Lp(a) assessment in the Optum® de-identified Electronic Health Record dataset (2007–2019). The index date was defined as the date of the first established CVD (MI, ischemic stroke or peripheral artery disease diagnosis) in the identification period (1/1/2008–30/6/2018) following one-year continuous enrollment. Patients were followed for up to one year, until death or transfer out of the dataset, whichever occurred first. Results 5,434 patients (55.5% males) with established CVD and at least one Lp(a) assessment having a mean (SD) age of 62.5 (12.6) years were evaluated. During the 12 months pre-index period, 49.9%, 46.1%, 48.1% and 49.8% of these patients had a measurement of TC, LDL-C, HDL-C and TGs, respectively. Overall, the mean (SD) TC, LDL-C, HDL-C and TGs levels were 182.1 (47.0) mg/dL [n=2,712], 102.6 (40.1) mg/dL [n=2,503], 52.7 (16.7) mg/dL [n=2,614], and 140.3 (108.8) mg/dL [n=2,707], respectively. More than half of these patients were treated with at least one lipid lowering drug (includes statins, ezetimibe, fibrates, niacin or PCSK9is) during the pre-index period. The mean (SD) levels of TC, LDL-C, HDL-C and TG in patients with Lp(a) &amp;lt;30 mg/dL, 30–50] mg/dL, 50–70 mg/dL, 70–90 mg/dL and ≥90 mg/dL are presented in Figure 1. Conclusions Overall, no trends in the levels of total cholesterol, LDL-C, HDL-C or triglycerides were observed across increasing levels of lipoprotein(a). These findings suggest the measurement of lipoprotein(a) is required to ensure a complete characterization of a patient lipid profile. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Lp(a): When and how to measure it.

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.

Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease

Lipoprotein(a) is a highly heritable biomarker independently associated with atherosclerotic cardiovascular disease (ASCVD). It is unclear whether measured lipoprotein(a) or genetic factors associated with lipoprotein(a) can provide comparable or additional prognostic information for primary prevention. To determine whether a genetic risk score (GRS) comprising 43 variants at the LPA gene, which encodes apolipoprotein(a), has clinical utility in assessing ASCVD risk compared with and in addition to lipoprotein(a) measurement. The UK Biobank is a prospective observational study of approximately 500 000 volunteers aged 40 to 69 years who were recruited from 22 sites across the United Kingdom between 2006 and 2010. Using externally derived weights, an LPA GRS was calculated for 374 099 unrelated individuals with array-derived genotypes and lipoprotein(a) measures. Data were analyzed from April 2020 to March 2020. Measured lipoprotein(a) and LPA GRS. We estimated the associations between measured lipoprotein(a) and LPA GRS with the incidence of ASCVD (peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality) using Cox proportional hazards models. To determine the utility of using measured lipoprotein(a) and LPA GRS as risk enhancers for ASCVD, we assessed the potential improvement in ASCVD risk discrimination by QRISK3 and Pooled Cohort Equations among individuals with borderline to intermediate risk (n = 113 703 and 144 350, respectively). The mean age of the overall study population was 57.6 years, and 204 355 individuals were female (54.6%). During a median follow-up of 11.1 years (interquartile range, 1.4 years), 15 444 individuals developed an incident ASCVD event (5.1%). The LPA GRS explained approximately 60% of the variation in measured lipoprotein(a) for White/European individuals. Independently, both lipoprotein(a) and LPA GRS were associated with incident, composite ASCVD (hazard ratio per 120 nmol/L increase, 1.26; 95% CI, 1.23-1.28 vs hazard ratio, 1.29; 95% CI, 1.26-1.33; P < .001). The association between LPA GRS and ASCVD was substantially attenuated after adjusting for measured lipoprotein(a). Adding measured lipoprotein(a) or LPA GRS to QRISK3 provided modest improvements to the risk discrimination of incident ASCVD events (area under the receiver operating curve, 0.640; 95% CI, 0.633-0.647 vs 0.642; 95% CI, 0.635-0.649 for both; P = .005 and P = .01, respectively). When indicated, cardiovascular risk assessment with lipoprotein(a) at middle-age may include direct measurement or an LPA GRS.

Validity of Anthropometric Cut-Offs for Early Diagnosis of Dyslipidemia Among Ethiopian Adults.

IntroductionLack of regional- and local-based cut-off points of lipid profile and/or anthropometric measurements remains one of the challenges in prevention, early detection and control of non-communicable diseases. This study aimed to validate anthropometric-based screening of lipid profiles to develop locally appropriate optimal cut-off points for metabolic syndrome screening.MethodsA community-based cross-sectional study was conducted among randomly selected 977 adults in Jimma Town, Ethiopia. Data were collected using structured questionnaire, anthropometric and biochemical measurements. Data were analyzed using SPSS windows version 21 and Kappa statistic was used to validate the agreement between anthropometric measurement and lipid profile. A p-value of <0.05 was considered statistically significant.ResultsBody mass index (BMI) at ≥24.5 was used as screening of dyslipidemia (TG≥150mg/dl) with slight Kappa coefficient of 0.138 (P<0.001) among females while it was ≥22.2 among males with fair (0.275) Kappa coefficient (P<0.001). Waist circumference-based screening of dyslipidemia (TG≥150mg/dl) at ≥78.0cm had negative (−0.005) Kappa coefficient (Pp<0.001) among females (sensitivity: 72.6% and specificity: 26.7%). Yet, waist circumference at ≥83.7cm had slight Kappa coefficient of 0.13 (P<0.005) among males (sensitivity: 38% and specificity: 74.9%). Waist hip ratio-based screening of dyslipidemia (TG≥150mg/dl) at ≥0.82 among females had negative (−0.001) Kappa coefficient (p=0.763), whereas among males at ≥0.88, there was a slight (0.105) Kappa coefficient of (p=0.002) (sensitivity:77.5% and specificity:36.8%). This study showed that anthropometric-based high-density lipoprotein measurement was not applicable.ConclusionThis study indicated that BMI-based screening of triglyceride was more applicable for both sexes than other anthropometric measurements. Waist circumference and waist-to-hip ratio-based screening of triglyceride were slightly applicable only for males. However, anthropometric-based screening of high-density lipoprotein measurement was not applicable for both sexes. In conclusion, researchers and policy makers need to consider locally validated cut-off points to be used for screening metabolic syndrome in the community.

Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?

BackgroundAn increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease.MethodsWe assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C.ResultsAfter adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios.ConclusionsHigh-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.

Risks of Incident Cardiovascular Disease Associated With Concomitant Elevations in Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-The Framingham Heart Study.

BackgroundElevated lipoprotein(a) is a well‐established risk factor for atherosclerotic vascular disease but is not measured in routine clinical care. Screening of high lipoprotein(a) in individuals with moderate elevations of low‐density lipoprotein cholesterol (LDL‐C) may identify individuals at high risk of cardiovascular disease.Methods and ResultsWe examined 2606 Framingham Offspring participants (median age, 54 years; 45% men) prospectively with a median follow‐up of 15 years (n=392 incident cardiovascular events). Individuals with higher (≥100 nmol/L) versus lower lipoprotein(a) were divided into groups based on LDL‐C <135 mg/dL versus ≥135 mg/dL. In Cox models, after adjustment for known risk factors, high lipoprotein(a) (≥100 nmol/L) and LDL‐C ≥135 mg/dL were each significant predictors of cardiovascular disease (LDL‐C ≥135 mg/dL: hazard ratio [HR], 1.34; 95% CI, 1.09–1.64; P=0.006; high lipoprotein (a): HR, 1.31; 95% CI, 1.03–1.66; P=0.026). Across the groups of high/low lipoprotein (a) and LDL‐C ≥135 mg/dL or <135 mg/dL, the absolute cardiovascular disease risks at 15 years were 22.6% (high lipoprotein(a)/LDL‐C ≥135 mg/dL, n=248), 17.3% (low lipoprotein(a)/LDL‐C ≥135 mg/dL, n=758), 12.7% (high lipoprotein(a)/LDL‐C <135 mg/dL, n=275) and 11.5% (low lipoprotein(a)/LDL‐C <135 mg/dL, n=1328, reference group). Among individuals with LDL‐C ≥135 mg/dL, those with high lipoprotein(a) had a 43% higher risk (HR, 1.43; 95% CI, 1.05–1.97; P=0.02). Presence of high lipoprotein(a) with moderate LDL‐C levels (135–159 mg/dL) yielded absolute risks equivalent to those with LDL‐C ≥160 mg/dL (23.5%, 95% CI, 17.4%–31.3%; and 20.7%, 95% CI, 16.8%–25.3%, respectively).ConclusionsConcomitant elevation of LDL‐C ≥135 mg/dL and lipoprotein(a) ≥100 nmol/L is associated with a high absolute risk of incident cardiovascular disease. lipoprotein(a) measurement in individuals with moderate elevations in LDL‐C, who do not otherwise meet criteria for statins, may identify individuals at high cardiovascular risk.

Quantitative In-Vitro Diagnostic NMR Spectroscopy for Lipoprotein and Metabolite Measurements in Plasma and Serum: Recommendations for Analytical Artifact Minimization with Special Reference to COVID-19/SARS-CoV-2 Samples.

Quantitative nuclear magnetic resonance (NMR) spectroscopy of blood plasma is widely used to investigate perturbed metabolic processes in human diseases. The reliability of biochemical data derived from these measurements is dependent on the quality of the sample collection and exact preparation and analysis protocols. Here, we describe systematically, the impact of variations in sample collection and preparation on information recovery from quantitative proton (1H) NMR spectroscopy of human blood plasma and serum. The effects of variation of blood collection tube sizes and preservatives, successive freeze–thaw cycles, sample storage at −80 °C, and short-term storage at 4 and 20 °C on the quantitative lipoprotein and metabolite patterns were investigated. Storage of plasma samples at 4 °C for up to 48 h, freezing at −80 °C and blood sample collection tube choice have few and minor effects on quantitative lipoprotein profiles, and even storage at 4 °C for up to 168 h caused little information loss. In contrast, the impact of heat-treatment (56 °C for 30 min), which has been used for inactivation of SARS-CoV-2 and other viruses, that may be required prior to analytical measurements in low level biosecurity facilities induced marked changes in both lipoprotein and low molecular weight metabolite profiles. It was conclusively demonstrated that this heat inactivation procedure degrades lipoproteins and changes metabolic information in complex ways. Plasma from control individuals and SARS-CoV-2 infected patients are differentially altered resulting in the creation of artifactual pseudo-biomarkers and destruction of real biomarkers to the extent that data from heat-treated samples are largely uninterpretable. We also present several simple blood sample handling recommendations for optimal NMR-based biomarker discovery investigations in SARS CoV-2 studies and general clinical biomarker research.

A sandwich-type aptasensor for point-of-care measurements of low-density lipoprotein in plasma based on aptamer-modified MOF and magnetic silica composite probes

Robust, rapid, and specific assays for point-of-care testing of plasma low-density lipoprotein (LDL) are needed for the early diagnosis of cardiovascular diseases (CVD). While immuno-sensors have been widely used for this purpose, they suffer from high costs and difficult sample preparation. Here, we designed a magnetically controllable sandwich-type aptasensor to detect LDL based on disposable screen-printed electrodes (SPE). First, Fe3O4@SiO2 was employed to rapidly capture and separate LDL in plasma. An aptamer (Apt) and ferrocene (Fc) co-immobilized UiO-66 metal–organic framework was used as a signal tag (MOF-Fc@Apt) and was conjugated with the LDL on Fe3O4@SiO2. The sandwich complex can be magnetically adsorbed on SPE for signal generation. At optimum conditions, the material could detect LDL in plasma with a linear range of 1.0 ng·mL−1–100 μg·mL−1 and low detection (LOD) limit of 0.3 ng·mL−1 (S/N = 3). The system exhibited many distinctive advantages: First, Fe3O4@SiO2 replaced expensive immunosorbent to capture and isolate LDL from complex plasma samples with acceptable selectivity. The MOF-based signal tags could encapsulate a large amount of Fc and Apt to increase the detection selectivity and sensitivity. Second, the LDL sandwich complex conjugated with the composite probes could be easily adsorbed on the SPE for signal development by the magnet and washed away after removing the magnet. Thus, the measurement platform is reusable. Third, the entire detection process was as quick as 20 min, and the sample volume was only 0.1 mL. These features made the assay a good candidate for point-of-care testing of LDL for early diagnosis of CVD.

A Pilot Study on the Effects of Nut Consumption on Cardiovascular Biomarkers.

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the United States and changes in lifestyle can minimize the likelihood of succumbing to heart disease. Anti-inflammatory agents are commonly used to reduce the chronic inflammatory state behind the pathogenesis of CVD. Multiple studies have been published correlating nut consumption with a reduction in both heart attacks and strokes. The goal of this study is to determine to what extent the consumption of almonds, hazelnuts, and walnuts have on the blood markers associated with cardiac disease and inflammation.Methods: This was a six-week study in which subject’s baseline values act as controls. Fasting blood draws occurred at week 0, week 2, and after four weeks of intervention (week 6). All participants had undesirable lipid profiles and no medications related to heart disease.Results: Total cholesterol (TC): high-density lipoprotein (HDL-C) ratio was lowered a statistically significant amount at the six-week time point (3.89 ± 0.74) compared to both the zero-week (4.93 ± 1.16, p < 0.01) and two-week (4.63 ± 1.20, p < 0.5) timepoints. Low-density lipoprotein (LDL) measurements were lowered a statistically significant amount at the six-week time point (135.6 ± 15.0 mg/dL) compared to the zero-week (159.7 ± 12.3 mg/dL, p < 0.01). Erythrocyte sedimentation rate (ESR) was lowered a statistically significant amount at six-week time point (10.44 ± 5.05 mm/h) compared to the zero-week (14.44 ± 5.12 mm/h, p < 0.01).Conclusions: Blood markers associated with CVD specifically and the general marker for inflammation associated with many chronic diseases can be favorably modified with the consumption of specific nuts as demonstrated by this study.