Lipoprotein Measurements Research Articles

Patient demographics and clinical characteristics among patients with a premature myocardial infarction and lipoprotein(a) measurement: a retrospective analysis of the South Tyneside and Sunderland NHS Foundation Trust in the UK

Patient demographics and clinical characteristics among patients with a premature myocardial infarction and lipoprotein(a) measurement: a retrospective analysis of the South Tyneside and Sunderland NHS Foundation Trust in the UK

The current status of lipoprotein (a) measurement in clinical biochemistry laboratories in the UK: Results of a 2021 national survey.

Lipoprotein(a) (Lp(a)) is now established as a causal risk factor for cardiovascular disease (CVD) and accurate laboratory measurement is of pivotal importance in reducing Lp(a) associated risk. The consensus statement by HEART UK in 2019 included recommendations to improve standardisation of clinical laboratory measurement and reporting of Lp(a). A 16 question, electronic audit survey was circulated to 190 accredited clinical biochemistry laboratories to assess the adoption of these recommendations in the UK. Responses were received from 65 of 190 laboratories (34%). Only 5 (8%) did not offer Lp(a) measurement. Of those providing the test, 23% (n = 14) offered an in-house service (IHS), the remaining laboratories (77%; n = 46) used an external referral service (ERS). The majority (10 of 14 or 71%) of IHS laboratories responded with details of their method, stating whether it minimised sensitivity to the effect of Lp(a) isoform size and used calibrators certified for traceability to the WHO/IFCC reference material, however, only a minority ERS laboratories (13 of the 46 or 28%) were able to specify the method used by their referral laboratory. Of the laboratories who specified their reporting units, 6 of 10 IHS and 7 of 23 ERS laboratories reported in nmol/L. Among the 60 laboratories who responded, the HEART UK recommendations appear to have been adopted in full by only 3 IHS laboratories. Further efforts are needed to standardise the measurement and reporting of Lp(a) so that results and interpretation are comparable across clinical biochemistry laboratories in the UK.

Abstract 14601: Increased Risk of Major Adverse Cardiovascular Events Attributed to Lipoprotein(a) Across Current Atherosclerotic Cardiovascular Disease Risk Categories

Introduction: AHA guidelines recommend measurement of lipoprotein(a) [Lp(a); an inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD)] in individuals with a family or personal history of premature ASCVD. Lp(a) measurement is also recommended for recalibrating the 10-year risk score for borderline or intermediate risk individuals. However, there is limited evidence on the risk of MACE attributed to elevated Lp(a) across ASCVD risk categories. Hypothesis: To assess the impact of elevated Lp(a) levels on MACE across ASCVD 10-year risk categories. Methods: This observational, retrospective study included a primary prevention cohort of Caucasian and Black ethnicities from the UK Biobank (2006-2020). Associations of Lp(a) level (categories of 105-150, 150-190, 190-215, and 215-260 nmol/L were compared to Lp(a) <105 nmol/L) with time to first MACE and MI were assessed using Cox proportional hazard models adjusted for age, sex, and ethnicity, stratified by ASCVD 10-year risk score category. Results: The cohort (N=362,061) included 55.2% female, 94.3% Caucasian and 1.6% Black. MACE incidence rates (IR, per 100 person/years) increased with 10-year ASCVD risk score: low risk IR=0.14 (n=161,183), intermediate risk IR=0.72 (n=121,272) and high-risk IR=1.52 (n=27,733). Within and across these risk categories, elevated Lp(a) conferred a significant increase in risk of MACE and myocardial infarction (MI). In the low-risk category, HRs ranged from 1.15-1.55 (MACE) and 1.32-1.72 (MI), in the intermediate risk category HRs ranged from 1.19-1.51 (MACE) and 1.37-1.77 (MI), and in the high-risk category HRs ranged from 1.12-1.55 (MACE) and 1.14-1.76 (MI) (Figure 1). Conclusions: Our study demonstrates that elevated Lp(a) increases the risk of MACE independently of ASCVD risk score. Measuring and considering elevated Lp(a) levels as part of individual ASCVD risk assessment in routine clinical practice may help improve the risk predication.

Effect Of Tamoxifen On Plasma Lipid Profile In Patients Of Breast Cancer.

To evaluate the effect of Tamoxifen on plasma lipid profile in breast cancer patients presenting at tertiary care hospitals. It was a longitudinal study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from December 2018 to November 2019. Eighty-eight females aged 26-66 years diagnosed with breast cancer were included in the study using a non-probability consecutive sampling technique. Detailed gynaecological and clinical investigations and detailed history were taken. The blood samples of all the patients were collected and the plasma lipid profile was measured before initiation of Tamoxifen treatment and three- and six-months post-treatment at the clinical laboratory. The plasma lipid profile includes the measurement of Total cholesterol (mg/dl), Triglyceride(mg/dl), High-density Lipoprotein (mg/dl) & Low-density Lipoprotein (mg/dl). SPSS version 23 was used to analyse data. After treatment, there was a significant reduction in serum cholesterol & Low-density Lipoprotein level by 20.54 mg/dl & 16.46 mg/dl at 3 months (p<0.05), moreover there was a significant increase in Triglyceride by 22.14 at 3 months (p<0.05). No significant difference was observed in High density lipoprotein level at 3 months after using Tamoxifen. At 6 months there was a significant reduction in serum cholesterol and low-density lipoprotein by 32.29mg/dl and 24.11 mg/dl at 6 months (p<0.05), moreover there was a significant increase in Triglyceride level by 42.19 mg/dl at 6 months (p<0.05). No significant difference was observed in High-density lipoprotein level at 6 months after using Tamoxifen. Total cholesterol and Low-density Lipoprotein levels showed significant reduction over the period of six months from the baseline with the use of Tamoxifen. Hence Tamoxifen should be considered to have an added advantage on lipid metabolism and therefore, can reduce the risk of cardiovascular events.

Prevalence of lipoprotein(a) measurement in patients with or at risk of cardiovascular disease

Prevalence of lipoprotein(a) measurement in patients with or at risk of cardiovascular disease

Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.

Frequency of lipoprotein(a) measurements in patients with or at risk of cardiovascular disease

Knowledge of lipoprotein(a) measurement in community practice is limited. The objective of this study is to evaluate the frequency of Lp(a) screening across the University of Rochester Medical Center (URMC). Descriptive data were collected for all URMC patients >= 18 years old who have had at least one Lp(a) measurement from January 2011 to August 2022 from the URMC electronic health record (EHR). Cardiovascular diagnoses were queried to define yearly frequency and demographic information. We identified 2,698 patients with at least one Lp(a) result. An increasing number of patients were tested per year. There were more women than men, and about 11% having more than one Lp(a) measured with the majority having a level <30mg/dL (the normal-range in the UMRC lab). The majority do not have a listed diagnosis of cerebral infarction, peripheral vascular disease, myocardial infarction, coronary artery disease, or aortic stenosis. Across URMC, there has been a steady increase of Lp(a) measurements in the past several years.

Lipoprotein(a) and carotid intima-media thickness in children with familial hypercholesterolaemia in the Netherlands: a 20-year follow-up study

Elevated lipoprotein(a) and familial hypercholesterolaemia are both independent risk conditions for cardiovascular disease. Although signs of atherosclerosis can be observed in children with familial hypercholesterolaemia, it is unknown whether elevated lipoprotein(a) is an additional risk factor for atherosclerosis in these young patients. Therefore, we aimed to assess the contribution of lipoprotein(a) concentrations to arterial wall thickening (as measured by carotid intima-media thickness) in children with familial hypercholesterolaemia who were followed up into adulthood. We conducted a 20-year follow-up study of 214 children (aged 8-18 years) with heterozygous familial hypercholesterolaemia who were randomly assigned in a statin trial in Amsterdam (Netherlands) between Dec 7, 1997, and Oct 4, 1999. At baseline, and at 2, 10, and 20 years thereafter, blood samples were taken and carotid intima-media thickness was measured. Linear mixed-effects models were used to evaluate the association between lipoprotein(a) and carotid intima-media thickness during follow-up. We adjusted for sex, age, corrected LDL-cholesterol, statin use, and BMI. Our study population comprised 200 children who had a carotid intima-media thickness measurement and a measured lipoprotein(a) concentration from at least one visit available. Mean age at baseline was 13·0 years (SD 2·9), 106 (53%) children were male, and 94 (47%) were female. At baseline, median lipoprotein(a) concentration was 18·5 nmol/L (IQR 8·7-35·5) and mean carotid intima-media thickness was 0·4465 mm (SD 0·0496). During follow-up, higher lipoprotein(a) concentrations contributed significantly to progression of carotid intima-media thickness (β adjusted 0·0073 mm per 50 nmol/L increase in lipoprotein(a) [95% CI 0·0013-0·0132]; p=0·017). Our findings suggest that lipoprotein(a) concentrations contribute significantly to arterial wall thickening in children with familial hypercholesterolaemia who were followed-up until adulthood, suggesting that lipoprotein(a) is an independent and additional risk factor for early atherosclerosis in those already at increased risk. Lipoprotein(a) measurement in young patients with familial hypercholesterolaemia is crucial to identify those at potentially highest risk for cardiovascular disease. Silence Therapeutics.

Diagnosis and management of hypertension understanding imperative role of various biomarkers

As hypertension, almost 90% of cases of hypertension with an unknown origin called essential hypertension, continue to be one of the most important risk factors for various fatal health conditions, its early diagnosis using trustworthy biomarkers to predict, diagnose, and monitor the therapeutic progress of hypertension is proving to be of utmost importance for the preventive as well as curative purpose of various health hazards. A rise in the activity of biochemical markers of endothelial dysfunction and blood lipids, notablyLow-density lipoprotein (LDL) andverylow-density lipoprotein(VLDL)measurements, and inflammation markers including C-reactive protein(CRP), cytokines, and adhesion molecules are linked to the development of hypertension. Growth and differentiation factor-15, red cell distribution width, uric acid, creatinine, inflammatory markers including interleukin-6, angiopoietins, and microRNAs are prognostic indicators in individuals with pulmonary arterial hypertension (PAH).The most extensively used blood markers for portal hypertension (PH) are the fibrosis-4 index and the improved liver fibrosis test. Likewise, Hepatic venous pressure gradient (HVPG), liver/SSMs and Plasma cyclic guanosine monophosphate (cGMP) being clinically significant tools to assess for PH. Along with Copeptin, serum levels of uric acid, potassium, and sodium may be crucial for the identification and monitoring of hypertension in pediatrics.Similarly, the severity of gestational hypertension correlates with hyperuricemia, elevated CRP, and interleukin-1 serum levels. Here, in this study, literature on biomarkers has been reviewed which are versatile diagnostic tools posing that influence healthcare professionals’ judgment and assist in patient education regarding diagnosis, prognosis, early detection, and treatment intervention.

Prevalence of Lipoprotein(a) Measurements in Patients with or at Risk of Cardiovascular Disease

Prevalence of Lipoprotein(a) Measurements in Patients with or at Risk of Cardiovascular Disease

Abdominal magnetic resonance imaging assessment and quantification of pancreatic and liver adipose tissues in obesity before and after laparoscopic sleeve gastrectomy

ObjectivesTo investigate the changes of liver and pancreas fat fraction after laparoscopic sleeve gastrectomy (LSG) by magnetic resonance imaging (MRI). MethodsOur study included morbid obesity with normal blood glucose and underwent abdominal MRI before and after LSG. In total, 21 patients were included, 10 underwent abdominal MRI before and 3 months after LSG, 11 underwent abdominal MRI before and 1–2 years after LSG. Liver fat fraction (LFF), pancreas fat fraction(PFF) were measured on proton density fat fraction (PDFF) maps at different time points. Fasting blood samples were collected for measurement of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), plasma glucose and insulin levels. Homeostasis model assessment (HOMA) was used to evaluate insulin resistance (HOMA-IR). Pearson correlation was used to analyze the correlation between different parameters. ResultsLFF and PFF were significantly decreased at 3 months and 1–2 years after LSG along with weight loss, decreased body mass index (BMI) and waist circumference. Though these parameters showed a decreasing trend from 3 months to 1–2 years, but there was no statistical difference. 81.0% patients had fatty liver and 38.1% patients had fatty pancreas at baseline. However, all patients had no fatty liver at 3 months and no fatty pancreas at 1–2 years after LSG. HDL levels were increased, but LDL, TG and insulin levels were decreased 1–2 years after LSG but not at 3 months. LFF was related to fasting insulin and HOMA-IR at baseline but not after LSG. There was no association of PFF with fasting plasma glucose, fasting insulin or HOMA-IR, but ΔPFF was related to Δinsulin and ΔHOMA-IR at 1–2 years after LSG. ConclusionChanges of liver and pancreas fat content in obesity before and after LSG can be quantified by IDEAL-IQ. Treatment with LSG can reverses fatty liver and fatty pancreas in obese patients. In addition, the lipid profile and insulin sensitivity are also improved after LSG along with the decreased of LFF and PFF.

Lipid profile after omega-3 supplementation in neonates with intrauterine growth retardation: a randomized controlled trial

BackgroundNeonates with intrauterine growth restriction (IUGR) have a high lipid profile that predisposes them to cardiovascular disease later in life. We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR.MethodsThis clinical trial was conducted on 70 full-term neonates with IUGR. Neonates were randomly divided into two equal groups; the treatment group: received omega 3 supplement (40 mg/kg/day) for 2 weeks after the establishment of full feeding, and the control group, who were followed up to full feeding without any supplementation. Serum leptin level, total cholesterol (TC), high-density lipoprotein (HDL), triglycerides (TG), low-density lipoprotein (LDL), and anthropometric measurement were evaluated at admission and after 2 weeks of omega 3 supplementation in both groups.ResultsAfter treatment, HDL significantly increased, unlike TC, TG, LDL, LDL, and serum leptin levels, which significantly decreased in the treatment group compared to the control group after treatment. Interestingly, weight, length, and ponderal index greatly increased in omega 3-treated neonates compared to the control group.ConclusionOmega 3 supplementations lowered serum leptin level, TG, TC, LDL, and VLDL but increased HDL and growth in neonates with IUGR.Clinical trial registrationThe study was registered at clinicaltrials.gov (NCT05242107).ImpactNeonates with intrauterine growth retardation (IUGR) were reported to have a high lipid profile that predisposes them to cardiovascular disease later in life. Leptin is a hormone that adjusts dietary intake and body mass and has a significant role in fetal development. Omega 3 is known to be essential for neonatal growth and brain development.We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR.We found that omega 3 supplementations lowered serum leptin level and serum lipid profile but increased high density lipoprotein and growth in neonates with IUGR.

Characterization of Lipoprotein(a) Measurement in a Large US Healthcare Dataset

Characterization of Lipoprotein(a) Measurement in a Large US Healthcare Dataset

Racial/Ethnic Variation in White Matter Hyperintensity Progression in the ACCORDION MIND Study.

White matter hyperintensities (WMHs) are linked to cognitive decline and stroke. We investigate the impact of race on WMH progression in the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORDION MIND) trial. The primary outcome is WMH progression in milliliters, evaluated by fitting linear regression to WMH volume on the month 80 magnetic resonance imaging (MRI) and including the WMH volume on the baseline MRI. The primary predictor is patient race, with the exclusion of patients defined as "other" race. We also derived predicted probabilities of our outcome for systolic blood pressure (SBP) levels. We included 276 patients who completed the baseline and month 80 MRI, of which 207 (75%) were White, 48 (17%) Black, and 21 (8%) Hispanic. During follow-up, the mean number of SBP, low-density lipoprotein (LDL), and A1c measurements per patient was 21, 8, and 15. The median (IQR) WMH progression was 1.5mL (0.5 to 3.9) for Black patients, 1.0mL (0.4 to 4.0) for Hispanics, and 1.3mL (0.5 to 2.7) for Whites (Kruskal-Wallis test, P =0.59). In the multivariate regression model, Black, compared with White, patients had significantly more WMH progression (β Coefficient 1.26, 95% confidence interval 0.45 to 2.06, P =0.002). Hispanic, compared with White, patients neither have significantly different WMH progression ( P =0.392), nor was there a difference when comparing Hispanic to Black patients ( P =0.162). The predicted WMH progression was significantly higher for Black compared with White patients across a mean SBP of 117 to 139mmHg. Black diabetic patients in Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORDION MIND) have a higher risk of WMH progression than White patients across a normal range of SBP.

Abstract 6486: Single nucleotide polymorphisms that predict serum cholesterol as a prostate cancer prognostic factor - a Mendelian randomization study

Abstract Introduction: Intracellular cholesterol metabolism plays an important role in prostate cancer progression and emergence of treatment resistance. However, it remains unclear whether serum cholesterol and lipoproteins are associated with prostate cancer outcomes. Studies on serum cholesterol and cancer are often confounded by lifestyle factors such as diet and obesity. A possible solution is to use instrumental variables, such as SNPs predicting serum cholesterol. According to the Mendelian randomization theory, germline SNP distribution is unaffected by confounding variables such as diet and lifestyle factors. Objective: To estimate whether SNPs that predict serum cholesterol and lipoproteins also predict mortality among a cohort of men with prostate cancer. Methods: Our study cohort consisted of 3,241 men diagnosed with prostate cancer between 1996-2015, using data collected by the Finnish Randomized Study of Screening for Prostate Cancer. Blood samples were genotyped by PRACTICAL consortium. A UCSC genome browser was utilized for selecting 85 SNPs in lipid metabolism-associated genes. Dates and causes of deaths between 1996-2015 were obtained from the Statistics Finland's statistics on causes of death. Information on serum cholesterol and lipoprotein measurements were obtained from a regional laboratory database.Scores predicting serum cholesterol, LDL, HDL and triglyceride level by SNP genotype were created using linear regression and lasso regression. Risk of prostate cancer death and overall mortality by level of the SNP risk score were evaluated with multivariable-adjusted Cox regression. Follow-up started at prostate cancer diagnosis and continued until death, emigration or common closing date of Dec 31, 2015.Results: SNP score predicting total cholesterol stratified prostate cancer patients both for disease-specific (HR 1.27, 95% CI 0.49-3.28 for highest tertile vs. lowest) and overall survival (HR 1.43, 95% CI 0.94-2.20, p for trend = 0.077), albeit statistical significance was not reached. Similar survival differences were observed for SNP score predicting triglyceride level, but not for scores predicting LDL or HDL.Conclusions: SNPs predicting serum cholesterol and triglycerides are likely prognostic factors for survival of prostate cancer patients. This suggest serum cholesterol and lipoproteins areimportant in prostate cancer progression. Total cholesterol SNP scoreProstate-cancer specific survival Overall survival Citation Format: Sebastian Boele, Aino Siltari, Paavo Raittinen, Johanna Schleutker, Kimmo Taari, Kirsi Talala, Teuvo Tammela, Anssi Auvinen, Teemu J. Murtola. Single nucleotide polymorphisms that predict serum cholesterol as a prostate cancer prognostic factor - a Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6486.

Risk Factors of Hyperglycemia After Treatment With the AKT Inhibitor Ipatasertib in the Prostate Cancer Setting: A Machine Learning-Based Investigation.

Hyperglycemia is a major adverse event of phosphatidylinositol 3-kinase/AKT inhibitor class of cancer therapeutics. Machine learning (ML) methodologies can identify and highlight how explanatory variables affect hyperglycemia risk. Using data from clinical trials of the AKT inhibitor ipatasertib (IPAT) in the metastatic castrate-resistant prostate cancer setting, we trained an XGBoost ML model to predict the incidence of grade ≥2 hyperglycemia (HGLY ≥ 2). Of the 1,364 patients included in our analysis, 19.4% (n = 265) of patients had HGLY ≥2 events with a median time of first onset of 28 days (range, 0-753 days), and 30.0% (n = 221) of patients on an IPAT regimen had at least one HGLY ≥2 event compared with 7.0% (n = 44) of patients on placebo. An 11-variable XGBoost model predicted HGLY ≥2 events well with an AUROC of 0.83 ± 0.02 (mean ± standard deviation). Using SHapley Additive exPlanations analysis, we found IPAT exposure and baseline HbA1c levels to be the strongest predictors of HGLY ≥2, with additional predictivity of baseline measurements of fasting glucose, magnesium, and high-density lipoproteins. The findings support using patients' prediabetic status as a key factor for hyperglycemia monitoring and/or trial exclusion criteria. Additionally, the model and relationships between explanatory variables and HGLY ≥2 described herein can help identify patients at high risk for hyperglycemia and develop rational risk mitigation strategies.

A Review Paper on Lipoprotein(a) and its Biochemical Relevance as a Risk Factor in the Assessment of Cardiovascular Disease

The accumulation of lipids in the forms of increased total cholesterol (High Density Lipoprotein), Triglycerides, Low Density Lipoprotein) in the blood stream is significant of several health conditions such as coronary congestive heart disease, atherosclerosis, heart failure and several other forms of cardiovascular diseases. Although several blood tests such as lipid profiling of individuals with diabetes type II as well as stroke has been the gold standard for the detection of increased total cholesterol in the arteries but this review paper revealed significant levels of the concentration of lipoprotein(a) (p&lt;0.05) when measured in the assessments of individuals with diabetes. The ultimate reason for this research work is that measurements of lipoprotein(a) has proved to be more sensitive, accurate and specific in the detection of cholesterol especially with the measurement of low -density (LDL) lipoprotein as indicated in this research compared to the conventional methods of lipid profiling.

Congruence and Complementarity of Differential Mobility Spectrometry and NMR Spectroscopy for Plasma Lipidomics.

The lipid composition of lipoprotein particles is determinative of their respective formation and function. In turn, the combination and correlation of nuclear magnetic resonance (NMR)-based lipoprotein measurements with mass spectrometry (MS)-based lipidomics is an appealing technological combination for a better understanding of lipid metabolism in health and disease. Here, we developed a combined workflow for subsequent NMR- and MS-based analysis on single sample aliquots of human plasma. We evaluated the quantitative agreement of the two platforms for lipid quantification and benchmarked our combined workflow. We investigated the congruence and complementarity between the platforms in order to facilitate a better understanding of patho-physiological lipoprotein and lipid alterations. We evaluated the correlation and agreement between the platforms. Next, we compared lipid class concentrations between healthy controls and rheumatoid arthritis patient samples to investigate the consensus among the platforms on differentiating the two groups. Finally, we performed correlation analysis between all measured lipoprotein particles and lipid species. We found excellent agreement and correlation (r > 0.8) between the platforms and their respective diagnostic performance. Additionally, we generated correlation maps detailing lipoprotein/lipid interactions and describe disease-relevant correlations.

Particle Size Distribution of Plasma Lipoproteins in Donkeys from Death Valley Compared to a Sampling of Horses.

Simple SummaryDonkeys, like horses, belong to the Equidae family. Though they share some physical attributes, much of their physiology is quite different from horses. Both horses and donkeys can develop clinical issues associated with obesity; insulin dysregulation; and altered lipid metabolism, often termed equine metabolic syndrome or donkey metabolic syndrome, respectively. Unlike large breed horses, however, donkeys, ponies, and miniature horses are more susceptible to developing dyslipidemias. This study aimed to use a novel Lipoprint® assay to compare the lipid profiles of apparently healthy donkeys and large-breed horses to establish a baseline for future work that may lead to the use of this test methodology for the evaluation and monitoring of equids with endocrine disorders.The clinical evaluation of lipid metabolism in equids is often limited to the measurement of total cholesterol and triglyceride concentrations. This provides a limited picture of metabolic state and general health, given the continuous exchange of lipid species between various lipoproteins. Major lipoprotein classes in equids include high-density lipoprotein (HDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and chylomicrons (CM). Unlike large breed horses, donkeys are highly susceptible to hepatic lipidosis. Currently, serum triglyceride concentrations serve as a surrogate marker of hepatic lipid exportation. Both VLDL, indicative of hepatic exportation, and its metabolic end-product, LDL, are rich in triglycerides, and contribute to this value. Diagnostic assays that distinguish VLDL from LDL could be useful in better recognizing the hepatic pathology in donkeys. The compositional differences of lipoproteins across species limit the use of commercially available assays developed for the measurement of human lipoproteins in domestic animals. In this study, we evaluated a high-resolution polyacrylamide gel electrophoresis method (Lipoprint®) for separating major lipoprotein classes and sub-fractionating LDL and HDL based on particle size in a large group of donkeys, and compared the pattern to a representative set of horses. Donkeys proved an HDL-rich species, with HDL accounting for the bulk of all lipoproteins (average 78.45%, SD 6.6%, range 92.2–55%). VLDL accounted for a large portion of the total (average 21.6%, SD 6.6%, range 37.1–7.8%), with minimal amounts of LDL detected. The horses tested had higher proportions of VLDL as compared to donkeys (31.7% and 21.6%, respectively p = 0.00008). The later finding draws into question the purported relationship between VLDL, high triglycerides, and hepatic lipidosis, given the incidence of the disease in donkeys is far higher than in horses.

Elevated Lipoprotein(a) levels increase Major Adverse Limb Event

Abstract Background High lipoprotein(a) levels are involved in the development of cardiovascular events, as particularly in myocardial infarction, stroke, and peripheral artery disease. Studies assessing prognostic values of lipoprotein(a) levels on the lower limbs are lacking. Purpose The aim of our study was to look after a relationship between the lipoprotein(a) level and the incidence of major adverse limb events (MALE) defined as major amputation, peripheral artery endovascular revascularization or peripheral artery bypass. Methods We included 16,513 patients with lipoprotein(a) measurements from our clinical information system. Normal lipoprotein(a) level was under 50 mg/dL and we defined: high lipoprotein(a) level as a lipoprotein(a) level between 50 mg/dL and 134 mg/dL and very high lipoprotein(a) level as a lipoprotein(a) levels over 134 mg/dL, i.e the 95th percentile in this cohort. Accelerated Failure Time models were used to assess the relationship between the lipoprotein(a) level and the incidence of MALE retrieved from the patient's electronic record during a median (interquartile range) follow-up of 3.74 (1.07; 7.30) years after the lipoprotein(a) measurement. MALE was defined as the occurrence of one of the following during follow-up: aortofemoral bypass surgery, limb bypass surgery, percutaneous transluminal angioplasty revascularization of the iliac, or infrainguinal arteries; or major amputation above the forefoot. Secondary outcomes included individual components of the primary Results Median lipoprotein(a) level was 24 mg/dL (10; 60), with 70.3%; 24.7%; and 5.0% within normal; high and very high lipoprotein(a) level respectively. The 1-year MALE incidence was 2.2% [95% CI: 1.96; 2.51]; 2.60% [95% CI: 2.09; 3.10] and 4.54% [95% CI: 3.08; 5.98] among the normal, high and very high lipoprotein(a) level patients respectively. High and very high lipoprotein(a) levels were independently associated with an increased risk of MALE (adjusted Accelerated Failure Time Exponential Estimate) 0.43 [95% CI: 0.24; 0.78], p=0.01 and 0.17 [95% CI: 0.07; 0.40], p&amp;lt;0.001, respectively. Conclusion In this large cohort of unselected real-world hospital inpatients, higher lipoprotein(a) levels were independently associated with an increased risk of MALE. Though, lipoprotein(a) measurement shall be taken into account not only to refine the cardiovascular risk but also the lower limb risk of revascularization or amputation. Funding Acknowledgement Type of funding sources: None.