Circulating total and H-specific GDF15 levels are elevated in subjects with MASLD but not in hyperlipidemic but otherwise metabolically healthy subjects with obesity.

BACKGROUND: Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD. METHODS: Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT). Exploratory correlations of total and H-specific GDF15 with clinical, hormonal and metabolomic/lipidomic parameters were also performed. RESULTS: In study 1, 15 individuals were included per weight group. Fasting and postprandial total and H-specific GDF15 were similar between groups, whereas GIP was markedly higher in leaner individuals and was upregulated following a MMT. Baseline and postprandial C-peptide were markedly elevated in people with obesity compared with lean subjects. GIP was higher in leaner individuals and was upregulated after a MMT, while C-peptide and its overall AUC after a MMT was markedly elevated in people with obesity compared with lean subjects. In study 2, 27 individuals were evaluated. Fasting total GDF15 was similar, but postprandial total GDF15 levels were significantly higher in MASLD patients compared to controls. GIP and C-peptide remained unaffected. The postprandial course of GDF15 was clustered among those of triglycerides and molecules of the alanine cycle, was robustly elevated under MASLD, and constituted the most notable differentiating molecule between healthy and MASLD status. We also present robust positive correlations of the incremental area under the curve of total and H-specific GDF15 with a plethora of lipid subspecies, which remained significant after adjusting for confounders. CONCLUSION: Serum GDF15 levels do not differ in relation to weight status in hyperlipidemic but otherwise metabolically healthy individuals. In contrast, GDF15 levels are significantly increased in MASLD patients at baseline and they remain significantly higher compared to healthy participants during OGTT, pointing to a role for GDF15 as a mitokine with important roles in the pathophysiology and possibly therapeutics of MASLD. Trial registration ClinicalTrials.gov NCT03986684, NCT04430946.

Pediatric hyperlipidemia.

The leading cause of mortality worldwide is atherosclerotic cardiovascular disease. Atherosclerotic plaques are well known to originate early in the childhood. Identifying hyperlipidemia in early childhood creates an opportunity to prevent major cardiovascular events in adults. Children with identified risk factors are at an increased risk of developing cardiovascular incidents in later life. This article emphasizes the diagnosis and management of pediatric hyperlipidemia with reference to the recent guidelines. In terms of etiology pediatric hyperlipidemia are divided into primary and secondary causes. The mainstay of management includes high-risk target screening, early risk factor identification and lifestyle modifications in vulnerable population. Drug therapy is recommended in primary hyperlipidemia and in children with no response to lifestyle changes.

The effect of hyperlipidemia and body fat distribution on subclinical left ventricular function in obesity: a cardiovascular magnetic resonance study.

BACKGROUND: Obesity is often associated with multiple comorbidities. However, whether obese subjects with hyperlipidemia in the absence of other complications have worse cardiac indices than metabolically healthy obese subjects is unclear. Therefore, we aimed to determine the effect of hyperlipidemia on subclinical left ventricular (LV) function in obesity and to evaluate the association of cardiac parameters with body fat distribution. MATERIALS AND METHODS: Ninety-two adults were recruited and divided into 3 groups: obesity with hyperlipidemia (n = 24, 14 males), obesity without hyperlipidemia (n = 25, 13 males), and c ntrols (n = 43, 25 males). LV strain parameters (peak strain (PS), peak diastolic strain rate (PDSR), peak systolic strain rate) derived from cardiovascular magnetic resonance tissue tracking were measured and compared. Dual-energy X-ray absorptiometer was used to measure body fat distribution. Correlations of hyperlipidemia and body fat distribution with LV strain were assessed by multivariable linear regression. RESULTS: Obese individuals with preserved LV ejection fraction showed lower global LV longitudinal, circumferential, and radial PS and longitudinal and circumferential PDSR than controls (all P < 0.05). Among obese patients, those with hyperlipidemia had lower longitudinal PS and PDSR and circumferential PDSR than those without hyperlipidemia (- 12.8 ± 2.9% vs. - 14.2 ± 2.7%, 0.8 ± 0.1 s-1 vs. 0.9 ± 0.3 s-1, 1.2 ± 0.2 s-1 vs. 1.4 ± 0.2 s-1; all P < 0.05). Multivariable linear regression demonstrated that hyperlipidemia was independently associated with circumferential PDSR (ß = - 0.477, P < 0.05) in obesity after controlling for growth differences, other cardiovascular risk factors, and central fat distribution. In addition, android fat had an independently negative relationship with longitudinal and radial PS (ß = - 0.486 and ß = - 0.408, respectively; all P < 0.05); and visceral fat was negatively associated with longitudinal PDSR (ß = - 0.563, P < 0.05). Differently, gynoid fat was positively correlated with circumferential PS and PDSR and radial PDSR (ß = 0.490, ß = 0.481, and ß = 0.413, respectively; all P < 0.05). CONCLUSION: Hyperlipidemia is independently associated with subclinical LV diastolic dysfunction in obesity. Central fat distribution (android and visceral fat) has a negative association, while peripheral fat distribution (gynoid fat) has a positive association on subclinical LV function. These results suggest that appropriate management of hyperlipidemia may be beneficial for obese patients, and that the differentiation of fat distribution in different regions may facilitate the precise management of obese patients. Clinical trials registration Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).

Pragmatic Trial of Messaging to Providers About Treatment of Hyperlipidemia (PROMPT-LIPID): A Randomized Clinical Trial.

BACKGROUND: Lipid-lowering therapy (LLT) is underutilized for very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID (PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia) sought to determine whether electronic health record (EHR) alerts improve 90-day LLT intensification in patients with very high-risk atherosclerotic cardiovascular disease. METHODS: PROMPT-LIPID was a pragmatic trial in which cardiovascular and internal medicine clinicians within Yale New Haven Health (New Haven, CT) were cluster-randomized to receive an EHR alert with individualized LLT recommendations or no alert for outpatients with very high-risk atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol), ≥70 mg/dL. The primary outcome was 90-day LLT intensification (change to high-intensity statin and addition of ezetimibe or PCSK9i [proprotein subtilisin/kexin type 9 inhibitors]). Secondary outcomes included LDL-C level, proportion of patients with LDL-C of <70 or < 55 mg/dL, rate of major adverse cardiovascular events, ED visit incidence, and 6-month mortality. Results were analyzed using logistic and linear regression clustered at the provider level. RESULTS: The no-alert group included 47 clinicians and 1370 patients (median age, 71 years; 50.1% female, median LDL-C, 93 mg/dL); the alert group included 49 clinicians and 1130 patients (median age, 72 years; 47% female, median LDL-C 91, mg/dL). The primary outcome was observed in 14.1% of patients in the alert group as compared with 10.4% in the no-alert group. There were no differences in any secondary outcomes at 6 months. Among 542 patients whose clinicians (n=46) did not dismiss the EHR alert recommendations, LLT intensification was significantly greater (21.2% versus 10.4%, odds ratio, 2.33 [95% CI, 1.48-3.66]). CONCLUSIONS: With a real-time, targeted, individualized EHR alert as compared with usual care, the proportion of patients with atherosclerotic cardiovascular disease with LLT intensification was numerically higher but not statistically significant. Among clinicians who did not dismiss the alert, there was a > 2-fold increase in LLT intensification. EHR alerts, coupled with strategies to reduce clinician dismissal, may help address persistent gaps in LDL-C management. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04394715, https://www.clinicaltrials.gov/ct2/show/study/NCT04394715.

Statin treatment in stroke patient with low-density lipoprotein cholesterol levels below 70 mg/dL.

BACKGROUND AND PURPOSE: The effectiveness of hyperlipidemia treatment in strokes secondary prevention has been established. However, whether pretreatment with statins could confer protective effects when a patient's baseline low-density lipoprotein cholesterol (LDL-C) level is <70 mg/dL remains uncertain. Additionally, the ability of statin treatment to reduce poststroke complications, mortality, and recurrence in this patient group is unclear. METHODS AND RESULTS: In this retrospective observational study, we enrolled patients who had experienced an ischemic stroke with LDL-C levels <70 mg/dL. We analyzed the association of statin use with baseline characteristics, stroke severity, in-hospital complications, mortality rates, stroke recurrence rate, and mortality rate. Patients who used and patients who did not use statins were similar in terms of age and sex. Patients using statins had higher rates of diabetes mellitus, hypertension, prior stroke, and coronary artery disease but a lower incidence of atrial fibrillation. Stroke severity was less pronounced in those using statins. We also evaluated the relationship between in-hospital statin use and complications. We noted that in-hospital statin use was associated with lower rates of infection, hemorrhagic transformation, gastrointestinal hemorrhage, and mortality, as well as higher rates of positive functional outcomes. The 1-year recurrence rate was similar in both groups. CONCLUSIONS: Statin use is associated with milder strokes and improved poststroke outcomes, even in patients with well-controlled LDL levels. Neurologists may consider prescribing statins for patients with ischemic stroke who do not overt hyperlipidemia. Further research into potential underlying mechanisms is warranted.

55-year-old woman • Myalgias and progressive symmetrical proximal weakness • History of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia • Dx?

► myalgias and progressive symmetrical proximal weakness ► history of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia.

Socioeconomic and behavioral determinants of non-compliance with physician referrals following community screening for diabetes, hypertension and hyperlipidemia: a mixed-methods study.

Early detection of undiagnosed diabetes, hypertension or hyperlipidemia through screening could reduce healthcare costs resulting from disease complications. To date, despite ample research on the factors linked to the uptake of community health screening programs, little attention has been directed at delayed or incomplete follow-up after positive outcomes are identified in community screening tests. This study aimed to investigate the socioeconomic and behavioral factors that influence non-compliance with recommendations for primary care physician referrals, following community-based screening for diabetes, hypertension and hyperlipidemia. A parallel mixed-methods study was conducted. For quantitative data, we performed multivariable analysis on community-based chronic disease screening data. The qualitative component involved semi-structured interviews with individuals with both non-compliance and compliance with referral recommendations. Thematic data analysis was undertaken using the Theoretical Domains Framework (TDF). The quantitative analysis showed that older age (OR = 0.92, 95%CI [0.89-0.96]), non-Chinese ethnicity (OR = 0.24; 95% CI [0.08-0.44]) and residing in 5-room public/ private housing (OR = 0.40; 95% CI [0.14-0.74]) were associated with lower odds of non-compliance with referral recommendations. Thematic analysis identified multiple behavioral-level determinants acting as enablers or barriers within 7 TDF domains: awareness of health risks after receiving screening results, self-management orientation and behavioral control, fear of formal diagnosis and concerns about healthcare cost, optimistic belief driven by the lack of symptoms, interpersonal relationship and social obligations, aversion to medication, communication at the result collection and sense of uncertainty regarding self-scheduling of appointment. Findings provide valuable implications for the development of interventions aimed at improving adherence to referral recommendation. Future endeavors should include culturally sensitive outreach, evidence-based information dissemination, family-centered education, positive public health messaging, brief counseling during result collection and an opt-out appointment system to enhance follow-up care.

Comparison between oral and enteral tube refeeding in hyperlipidemic acute pancreatitis.

OBJECTIVE: Hyperlipidemic acute pancreatitis (HLAP) remains one of the major digestive emergencies with increasing health risks. Oral refeeding tolerant (ORT) and enteral tube feeding tolerant (ETFT) are commonly used for nutritional management in HLAP. However, the differences between ORT and ETFT are yet to be characterized. PATIENTS AND METHODS: This study included consecutive patients admitted to the Ordos Central Hospital between January 2019 and April 2023, with predefined inclusion criteria. RESULTS: A total of 335 HLAP patients were recruited according to the inclusion criteria. 268 patients were diagnosed with moderately severe acute pancreatitis (MSAP), of which 193 were in the OFT group and 75 in the ETFT group. In the ETFT group, abdominal pain and abdominal distension were significantly higher than that in the OFT group. No significant result was identified in the laboratory data. However, the OFT group showed a higher hospitalization and cost, as well as exocrine insufficiency and newly onset diabetes, than the ETFT group. CONCLUSIONS: Based on the incidence of HLAP retrieved in this study, MSAP is the major type with increasing clinical value. From the nutritional management sense, patients who received OFT showed higher hospitalization and cost, as well as lower exocrine insufficiency and newly onset diabetes.

Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia.

BACKGROUND: Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. METHODS: This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. RESULTS: In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia. CONCLUSION: The TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.

Delayed diagnosis and exacerbation of hyperlipidemia in idiopathic nephrotic syndrome in children during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, there was a lack of access to outpatient facilities for other diseases. Conversely, few studies have reported changes in clinical features of idiopathic nephrotic syndrome (INS) in children before and after the COVID-19 pandemic. METHODS: Thirty-two children with primary INS, who were admitted to four Showa University-affiliated hospitals between January 2017 and December 2022, were enrolled in this retrospective study. Children were divided according to the onset of INS into a post-COVID-19 group (onset in 2020-2022, n = 25) and a pre-COVID-19 group (onset in 2017-2019, n = 32). We compared the clinical characteristics and features of initial INS between two groups. RESULTS: In the post-COVID-19 group, these patients had interval between noticing symptoms of INS, such as edema and INS diagnosis was significantly longer (7 days versus 3.5 days; p = 0.0047), and had significantly raised serum LDL cholesterol levels at the time of INS diagnosis than in the pre-COVID-19 group (314 mg/dL versus 260 mg/dL; p = 0.028). Likewise, steroid-resistant nephrotic syndrome was significantly more common in the post-COVID-19 group [32% (n = 8) versus 6% (n = 2); p = 0.016]. A correlation analysis revealed a moderate positive correlation between the interval from symptom to diagnosis and LDL cholesterol (r = 0.460015, p = 0.0003). CONCLUSIONS: Children with INS after the COVID-19 pandemic showed a longer time between noticing symptoms of INS and diagnosis, increased serum LDL cholesterol and more steroid resistance than before the pandemic.

Xanthoma of rib: a case report and review of the literature.

BACKGROUND: Xanthomas are well-circumscribed benign proliferative lesions seen mainly in soft tissues. Usually, they are found in hyperlipidemia and familial hyperlipoproteinemia. Histologically, are characterized by macrophage-like mononuclear cells, multinucleated giant cells and abundant foam cells. The bone involvement, however, is notoriously rare and rib localization is extremely rare. CASE PRESENTATION: A 55-year-old man performed a chest X-ray and a subsequent chest Computed Tomography scan showing a rib lesion that was surgically removed and a diagnosis of rib xanthoma was made. The patient presented an unknown condition of hyperlipidemia. CONCLUSION: Rib xanthoma can be discovered accidentally and can be helpful in identifying an unrecognized condition of hyperlipidemia.

Análisis clínicos en pediatría: la necesidad de minimizar las horas de ayuno / Clinical analysis in pediatrics: the need to minimize fasting hours

Los informes de laboratorio tienen impacto en las decisiones médicas. El ayuno es un factor preanalítico "controlable" que influye en los distintos parámetros bioquímicos. El objetivo del presente trabajo es poner en discusión la realización en pediatría de análisis clínicos con la indicación de un ayuno fisiológico , analizando resultados obtenidos por diferentes autores y evaluando las diferencias clínicas encontradas según los criterios de calidad establecidos por el laboratorio de Química Clínica. La mayoría de los individuos durante el día se encuentran en estado postprandial. Los resultados del perfil lipídico en ayunas no representan las concentraciones reales promedios de los lípidos plasmáticos de un paciente. El ayuno no sería crítico en la etapa de pesquisa , pero puede ser relevante para establecer un diagnóstico certero o inicio de tratamiento. En el caso de la glucemia si se indica en el control rutinario del paciente, y no hay sospecha de alteraciones en el metabolismo de los hidratos de carbono la glucemia sin ayuno puede ser solicitada comparando la misma con valores de corte adecuado. Las diferentes guías nacionales e internacionales recomiendan que la elección de la métrica para la evaluación, control y seguimiento de pacientes con diagnóstico de diabetes se realicen según el objetivo terapéutico. En los trabajos analizados, observamos que varios parámetros bioquímicos presentaron diferencias estadísticas, aunque las diferencias clínicas no fueron relevantes y permanecieron dentro de los intervalos de referencia. El factor limitante para evaluar parámetros bioquímicos sin ayuno es la falta de valores de referencia adecuados. Hay evidencia suficiente para que tanto el perfil lipídico, la glucemia como el resto de los parámetros bioquímicos del laboratorio de química clínica, sean solicitados con la indicación de un ayuno fisiológico de 2, 4 o 6 horas, dependiendo siempre del motivo de consulta y/o la edad del paciente. Es esencial extender la evaluación a otros analitos en población pediátrica, así como evaluar nuevos puntos de corte para parámetros bioquímicos sin ayuno (AU)

Laboratory reports have an impact on medical decision-making. Fasting is a "controllable" preanalytical factor that influences the different biochemical parameters. The aim of this study is to discuss the performance of clinical analyses in pediatrics with the indication of physiological fasting, analyzing results obtained in different disciplines, and evaluating the clinical differences found according to the quality criteria established by the clinical chemistry laboratory. During the day, most patients are in a postprandial state. Fasting lipid profile results do not represent the actual average plasma lipid concentrations of a patient. Fasting would not be critical in the screening stage, but it may be relevant to establish an accurate diagnosis or initiate treatment. Regarding glycemia, if it is indicated in the routine control of the patient and there is no suspicion of alterations in carbohydrate metabolism, non-fasting glycemia can be requested, comparing it with adequate cut-off values. Different national and international guidelines recommend that the choice of metrics for the evaluation, control, and follow-up of patients with diabetes should be made according to the therapeutic objective. In the studies analyzed, we found that several biochemical parameters presented statistical differences, although the clinical differences were not relevant and remained within the reference range. The limiting factor in the evaluation of biochemical parameters without fasting is the lack of adequate reference values. There is sufficient evidence that the lipid profile, glycemia, and the remaining biochemical parameters of the clinical chemistry laboratory should be requested with the indication of a physiological fast of 2, 4, or 6 hours, always depending on the reason for consultation and/or the patient's age. It is essential to extend the evaluation to other analytes in the pediatric population, as well as to evaluate new cut-off points for biochemical parameters without fasting (AU)

Development of a Nomogram That Predicts the Risk of Coronary Heart Disease in Patients With Hyperlipidemia.

BACKGROUND: Hyperlipidemia is one of the independent risk factors for the onset of coronary heart disease (CHD), and our aim is to construct a coronary risk prediction model for patients with hyperlipidemia based on carotid ultrasound in combination with other risk factors. METHODS: The nomogram risk prediction model is based on a retrospective study on 820 patients with hyperlipidemia. The predictive accuracy and discriminative ability of the nomogram were determined by receiver operating characteristic (ROC) curves and calibration curves. The results were validated using bootstrap resampling and a prospective study on 39 patients with hyperlipidemia accepted at consenting institutions from 2021 to 2022. RESULT: In the modeling cohort, 820 patients were included. A total of 33 variables were included in univariate logistic regression. On multivariate analysis of the modeling cohort, independent factors for survival were sex, age, hypertension, plaque score, LVEF, PLT, and HbAlc, which were all selected into the nomogram. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The area under the curve (AUC) of the nomogram model was 0.881 (95% CI 0.858∼0.905), with a sensitivity of 79% and a specificity of 81.7%. In the validation cohort, the AUC was 0.75, 95% CI (0.602∼0.906). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 54.16%, 80%, 81.25%, 52.17% and 64.1%. This model showed a good fitting and calibration and positive net benefits in decision curve analysis. CONCLUSION: A nomogram model for CHD risk in patients with hyperlipidemia was developed and validated using 7 predictors, which may have potential application value in clinical risk assessment, decision-making, and individualized treatment associated with CHD.

Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype.

BACKGROUND: Familial dysbetalipoproteinemia (FDBL) is a monogenic disease due to variants in APOE with a highly variable phenotype. Current diagnostic lipid-based methods have important limitations. The objective is twofold: to define characteristics of dysbetalipoproteinemia (DBL) based on the analysis of APOE in patients from a lipid unit and in a sample from the general population, and to propose a screening algorithm for FDBL. METHODS: Lipids and APOE genotype from consecutive unrelated subjects from Miguel Servet University Hospital (MSUH) (n 3603), subjects from the general population participants of the Aragon Workers Health Study (AWHS) (n 4981), and selected subjects from external lipid units (Ext) (n 390) were used to define DBL criteria and to train and validate a screening tool. RESULTS: Thirty-five subjects from MSUH, 21 subjects from AWHS, and 31 subjects from Ext were APOE2/2 homozygous. The combination of non high-density lipoprotein cholesterol (non-HDLc)/apoB 1.7 plus triglycerides/apoB 1.35, in mg/dL (non-HDLc [mmol/L]/apolipoprotein B (apoB) [g/L] 4.4 and triglycerides [mmol/L]/apoB [g/L] 3.5), provided the best diagnostic performance for the identification of subjects with hyperlipidemia and APOE2/2 genotype (sensitivity 100 in the 3 cohorts, and specificity 92.8 [MSUH], 80.9 [AWHS], and 77.6 [Ext]). This improves the performance of previous algorithms. Similar sensitivity and specificity were observed in APOE2/2 subjects receiving lipid-lowering drugs. CONCLUSIONS: The combination of non-HDLc/apoB and triglycerides/apoB ratios is a valuable tool to diagnose DBL in patients with hyperlipidemia with or without lipid-lowering drugs. FDBL diagnosis requires DBL and the presence of a compatible APOE genotype. Most adult APOE2/2 subjects express DBL, making FDBL as common as familial hypercholesterolemia in the population.

Evaluation of hemolysis, lipemia, and icterus interference with common clinical immunoassays.

OBJECTIVES: Hemolysis, icterus, and lipemia (HIL) are common sources of endogenous interference in clinical laboratory testing. Defining the threshold of interference for immunoassays enables appropriate reporting of their results when they are affected by HIL. METHODS: Pools of residual patient serum samples were spiked with a known amount of interferent to create samples with varying concentrations of hemolysate, bilirubin, and Intralipid that mimicked the effects of endogenous HIL. Samples were analysed on the Alinity i analyser (Abbott Diagnostics) for more than 25 immunoassays. The average recovery relative to the non-spiked sample was calculated for each interference level and was compared to a predefined allowable bias. RESULTS: C-peptide, estradiol, serum folate, free T4, homocysteine, insulin, and vitamin B12 were found to be affected by hemolysis, at hemoglobin concentrations between 0.3 to 20 g/L. Immunoassays for BNP, estradiol, free T3, and homocysteine were affected by icterus at conjugated bilirubin concentrations between 50 to 1,044 µmol/L. BNP, serum folate, and homocysteine were affected by Intralipid with measured triglyceride concentrations between 0.8 to 10 mmol/L. Lastly, serological immunoassays for HIV and hepatitis A, B and C were also affected by interferences. CONCLUSIONS: Immunoassays are impacted by varying degrees of HIL interference. Some measurands, in the presence of interference, are affected in a manner not previously indicated. The data presented herein provide an independent evaluation of HIL thresholds and will be of aid to resource-limited clinical laboratories that are unable to internally verify endogenous interferences when implementing the Alinity i analyser.

Polygenic risk in Type III hyperlipidaemia and risk of cardiovascular disease: An epidemiological study in UK Biobank and Oxford Biobank.

BACKGROUND: Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL. METHODS: The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB. RESULTS: One TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0-14.0%) greater TG in OBB and 15.2% (15.0-15.4%) in UKB. APOE22 carriers had 19.0% (1.0-39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0-6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3-1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; -0.35 (-0.29 to -0.40)g/L, UKB; -0.41 (-0.405 to -0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers. In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76-1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69-0.95); no differences were observed in CVD incidence. CONCLUSIONS: TG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers.

Guidelines for the management of hyperlipidemia: How can clinicians effectively implement them?

Guidelines support lowering cholesterol to decrease atherosclerotic cardiovascular disease (ASCVD) risk across the entire lifespan with intensive lifestyle intervention, as well as statin and non-statin pharmacotherapy for those at highest risk. Modest improvements in the initiation, use, and adherence to statin therapy in patients with ASCVD have occurred over the past decades. However, studies continue to document a less than desired implementation of guidelines highlighting a substantial and persistent treatment gap. The success of implementation depends on the consideration of a variety of barriers that exist throughout the healthcare delivery system. Further research is needed to comprehensively evaluate these barriers in order to develop appropriate and sustainable interventions to improve guideline implementation.

Protocol to evaluate hyperlipidemia in zebrafish larvae.

In this report, we describe an approach to generate a zebrafish larval model of lipid accumulation that can be used as an in vivo system to study hyperlipidemic conditions such as atherosclerosis. Furthermore, we detail steps on staining techniques, lipid estimation assays, RNA isolation, and utilization of ImageJ to evaluate larval dimensions and to explore the model in the context of hyperlipidemia. Researchers should be aware of context specificity of the proposed protocols and interpret results accordingly. For complete details on the use and execution of this protocol, please refer to Balamurugan et al., (2022).