Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field.

Dyslipidemia is one of the most common disorders worldwide, which, if left untreated, results in a multitude of complications. Thus proper diagnostics, which includes identifying of secondary causes of dyslipidemia is crucial. Endocrine disorders are an important cause of secondary dyslipidemia. This paper aims to review the publications on lipoprotein alterations in endocrine disorders from the past two years and provide an overview of the recent discoveries in this dynamically developing and large field. Significant changes in lipoprotein serum concentrations are present in most endocrinological diseases and can be modified with proper treatment. Some lipoproteins have also been proposed as markers in some endocrine diseases, e.g., thyroid carcinoma. From the scope of endocrine disorders, the largest number of studies explored the lipoprotein changes in polycystic ovary syndrome and in women during the menopausal and peri-menopausal period. Even though the association of thyroid disorders with dyslipidemia is already well studied, new research has delivered some exciting findings about lipoprotein alterations in euthyroid patients with either positive antithyroid peroxidase antibodies or reduced sensitivity to thyroid hormones. The problem of the adverse metabolic profile, including dyslipidemia in hypoprolactinemia has been recognized. Moreover, this review describes other significant discoveries encompassing lipoprotein alterations in disorders of the adrenals, thyroid, parathyroid glands, pituitary, and gonads. The up-to-date knowledge of the influence of endocrine disorders and hormonal changes on serum lipoproteins is prudent as it can significantly impact therapeutic decisions.

Sex Differences in the Association Between LDL/HDL with Cognitive Decline in Older Adults: National Health and Nutrition Examination Survey.

Background: Lipids have a significant impact on the development and functioning of the nervous system, but the sex differences between the association of LDL/HDL, which reflects lipid metabolic status, and cognitive impairment remains unclear. Objective: We aimed to determine if there were sex differences between the association of LDL/HDL and cognitive function in US older adults. Methods: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014 cycles. The main outcome was poor cognitive performance defined by the Digit Symbol Substitution Test (DSST) <  34 based on published literature. Results: A total of 1,225 participants were included in the study, with a cognitive impairment incidence of 25.6% (314/1,225). Multivariate regression models demonstrated a significant association between cognitive decline and each 1-unit increase in LDL/HDL, after adjusting for all covariates (adjusted odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.11-1.67). Furthermore, subgroup analysis revealed an interaction between LDL/HDL and cognitive impairment in sex subgroups. Conclusions: LDL/HDL was associated with cognitive impairment in the US older adult population in adjusted models, although the significance of this association was not observed in females.

Relationships of apolipoprotein E genotypes with a cluster of seven in persons with type 2 diabetes.

OBJECTIVE.: The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes (2/2, 2/3, 2/4, 3/3, 3/4, and 4/4) for each member of the cluster of seven associated with type 2 diabetes (T2D). The cluster of seven includes abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased plasma levels of triglycerides)), increased low-density lipoprotein (LDL) oxidation, and increased inflammation. METHODS.: Forty-six patients with well-controlled T2D participated in the study. Abdominal obesity (assessed by waist circumference), hypertension (measured by manual sphygmomanometry), platelet hyperaggregability (measured by bleeding time), hyperglycemia (by enzymatic kit and spectrophotometry), decreased plasma levels of HDL-C and increased plasma levels of triglycerides (by enzymatic kit and spectrophotometry), increased LDL oxidation (measured by LDL conjugated dienes using spectrophotometry) and increased inflammation measured by C-reactive protein (CRP) (by EIA kit) were determined. RESULTS.: All genotypes, except 2/2 were found in the population studied. Abdominal obesity did not vary significantly across the five genotypes. However, glucose levels trended progressively higher going from 2/3 to 2/4 to 3/4 to 4/4. Systolic blood pressure was higher in 3/4 compared to 2/4 and trended higher in 3/4 compared to 3/3. Diastolic blood pressure trended higher in 3/3 vs 2/4 and significantly higher in 3/4 compared to 2/4. Triglycerides trended higher in 3/4 vs 3/3 while HDL-C came close to trending downward in 4/4 compared to 2/4. Bleeding time was unaffected by genotype. Plasma LDL conjugated dienes trended higher in 3/4 vs 2/4 and were significantly higher in 3/4 vs 3/3. CRP trended higher in 4/4 vs 2/3. CONCLUSION.: We can conclude that those with at least one 4 allele in the presence of another allele being 2, 3 or 4 is potentially (in the case of trends) deleterious or is deleterious in terms of hyperglycemia, hypertension (systolic and diastolic blood pressure), dyslipidemia, LDL conjugated dienes and CRP levels.

Diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most frequent liver disease, closely related with metabolic risk factors such as obesity, insulin resistance, dyslipidemia, diabetes mellitus, and metabolic syndrome. In this context, γ-Glutamyl transpeptidase (GGT) and high-density lipoprotein cholesterol (HDL-C) have shown correlations with steatosis severity and metabolic syndrome, respectively. This positions the GGT/HDL-C ratio as a potential diagnostic indicator for NAFLD. OBJECTIVE: To assess the diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery. METHODS: We conducted an analytical cross-sectional study, designed as a diagnostic test evaluation. A secondary database of 249 adults with obesity was analyzed. The optimal cut-off point was ascertained using three methodologies, and five adjustment models were constructed for the total population, further stratified by sex. RESULTS: The optimal cut-off point was 20.5 U/mmol and the AUC of the ratio was 0.81 (95% CI: 0.64-0.98), with sensitivity and specificity being 82.5% and 77.8%, respectively. In the overall group with an elevated GGT/HDL-C ratio, the prevalence of NAFLD increased by 14% (PR: 1.14; 95% CI: 1.04-1.33). Specifically, women displaying this altered ratio showed a 19% increased prevalence (PR: 1.19; 95% CI: 1.07-1.42) compared to those with normal values. CONCLUSIONS: The GGT/HDL-C ratio is a promising biomarker for the diagnosis of NAFLD in an adult population living with obesity.

Predictive value of the serum uric acid to high-density lipoprotein cholesterol ratio for culprit plaques in patients with acute coronary syndrome.

BACKGROUND: Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). METHODS: A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. RESULTS: The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. CONCLUSIONS: An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.

Lipoprotein Ratios: Correlation With Glycated Hemoglobin (HbA1c) Among Thyroid Disorders' Patients.

INTRODUCTION: Thyroid disorders and diabetes mellitus are prevalent conditions in the modern era. Moreover, glycated hemoglobin (HbA1c) is the established (prognostic as well as diagnostic) marker for long-term glycemic control, whereas the lipid profile is the marker for cardiovascular risks. The association of hypothyroidism with dyslipidemia is also a well-established fact. The current study explores a correlation between thyroid profile, glycemic status, and various lipoprotein indices. OBJECTIVE: To look for an association between thyroid profile, glycemic status, and various lipoprotein indices. METHODOLOGY: The cross-sectional study conducted at AIIMS Gorakhpur included a total of 108 subjects, with 37 normal subjects (Group I) and 71 patients) with T2DM (Type-2 diabetes mellitus) (Group II). Baseline characteristics of the two groups were compared for age, sex, presence of hypertension, fasting blood glucose, and body mass index (BMI). Blood samples were collected from the patients. The sera were analyzed for HbA1c and lipid profile, which included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Serum samples were also used to estimate the thyroid stimulating hormone (TSH) and triiodothyronine (fT3). The association between thyroid profile, glycemic status, and various lipoprotein indices was calculated. STATISTICAL ANALYSIS:  Kolmogorov-Smirnov test for normality of the data. Spearmann correlation was used for nonparametric data. RESULTS: There were significantly higher levels of total cholesterol, triglycerides, and LDL-C levels in T2DM subjects than in non-diabetic subjects. There was also a significant positive correlation observed between TSH and TC among the normal control group (ρ =0.348, P=0.04). Similarly, significant positive correlations were found for TG (ρ =0.354, P=0.04) and LDL-C (ρ =0.431, P=0.03) among non-diabetic subjects. Among patients with T2DM, TSH was significantly correlated positively with TG (ρ =0.530, P=0.006) and LDL-C (ρ =0.443, P=0.03). Similarly, in the same group, among lipid ratios, TG/HDL-C (ρ =0.311, P=0.04) and LDL-C/HDL-C (ρ =0.227, P=0.05) were significantly correlated to TSH. Furthermore, there were significant positive correlations between TSH and HbA1c (ρ =0.301, P=0.04). fT3 was found to have a strong negative correlation with HbA1c among patients with T2DM (ρ =-0.454, P=0.02). CONCLUSION: Thyroid disorders exert significant effects on glycemic control and lipid metabolism, which may impact HbA1c levels and lipid profile parameters.

Are Higher Body Mass Index and Worse Metabolic Parameters Associated with More Aggressive Differentiated Thyroid Cancer? A Retrospective Cohort Study.

Obesity is a risk factor for differentiated thyroid cancer (DTC), but the association with DTC aggressiveness is controversial. To evaluate the association between preoperative body mass index (BMI)/other metabolic parameters and DTC aggressiveness in our surgical cohort, we retrospectively evaluated patients following thyroid surgery who were diagnosed with DTC between December 2013 and January 2021. Baseline characteristics, histopathological features, treatment modalities, and follow-up data were studied. We conducted logistic regression to analyze the association between BMI/other metabolic parameters and adverse DTC features. The final study cohort included 211 patients (79.6% women; mean age± standard deviation 48.7 ± 15.9 years): 66 (31.3%) with normal weight, 81 (38.4%) with overweight, and 64 (30.3%) with obesity. The median follow-up was 51 months (range 7-93). Complete versus partial thyroidectomy was more common among patients living with overweight or obesity than in normal weight patients (79.7% versus 61.7%, p = 0.017, respectively). Logistic regression demonstrated that higher BMI was associated with mildly increased risk for lymph nodes metastases (odds ratio [OR] 1.077, 95% CI: 1.013-1.145), and higher triglycerides/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was associated with aggressive histological variants of DTC (OR 1.269, 95% CI 1.001-1.61). To conclude, specific adverse clinical and histopathological DTC features were indeed associated with higher BMI and higher TG/HDL-C ratio.

Epigenetic age acceleration is associated with blood lipid levels in a multi-ancestry sample of older U.S. adults.

Background: Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. Methods: We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = and f) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether the relationships between epigenetic age acceleration and blood lipids differ by demographic factors including age, sex, and educational attainment. Results: After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjusting for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Conclusion: Epigenetic age acceleration, a powerful biomarker of cellular aging, is highly associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or the non-linear relationship between age and these lipids, as both TC and LDL-C decrease faster at older ages. More studies are needed to further understand the temporal relationships between epigenetic age acceleration on blood lipids and other health outcomes.

Fibrinogen to HDL-Cholesterol ratio as a predictor of mortality risk in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI. METHODS: A retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death. RESULTS: Over a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99-3.65) and 1.48 (1.26-1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05). CONCLUSION: AMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients. TRIAL REGISTRATION: The Cardiorenal ImprovemeNt II registry NCT05050877.

HOURS OF WORKING DAY AND CHOLESTEROL LEVEL IN LAND TRANSPORTATION DRIVERS IN A COMPANY IN LIMA / HORAS DE JORNADA LABORAL Y NIVEL DE COLESTEROL EN CONDUCTORES DE TRANSPORTE TERRESTRE EN UNA EMPRESA DE LIMA / HORAS DE JORNADA DE TRABALHO E NÍVEL DE COLESTEROL EM MOTORISTAS DE TRANSPORTE TERRESTRE DE UMA EMPRESA DE LIMA

Introduction: Ground transportation drivers face substantial risks to cardiovascular health, mainly hypercholesterolemia, possibly related to the hours of the workday.Objective. Determine the relationship between working hours and cholesterol level in land transport drivers in a company in Lima between the period from January 2022 to August 2023.Materials and methods. Correlational, cross-sectional research, which included 107 transport drivers. The main variables were: Hours of daily and weekly workday, total cholesterol and high-density lipoproteins (HDL), the instrument used was a data collection form. Spearman's Rho correlation test was used in the statistical analysis. The study was approved by the Ethics Committee of the Universidad Nacional Mayor de San Marcos.Results. It was observed that 47.02% of the workers worked between 9 and 10 hours a day, while 57.9% worked 61 to 72 hours a day. Furthermore, the majority of drivers had total cholesterol levels between 160 and 199 mg/dl (38.3%), and HDL cholesterol between 35 and 59 mg/dl (93.5%). A significant and direct correlation was determined between daily (p=0.026, Rho=0.216) and weekly (p=0.038, Rho=0.201) working hours with total cholesterol. No significant relationship was found with HDL cholesterol.Conclusions. It was identified that the hours of daily and weekly work hours were significantly related to the level of total cholesterol.

Introducción: Los conductores de transporte terrestre enfrentan riesgos sustanciales para la salud cardiovascular, principalmente hipercolesterolemia, posiblemente relacionadas a las largas horas de jornada laboral.Objetivo. Determinar la relación entre las horas de jornada laboral y nivel de colesterol en conductores de transporte terrestre en una empresa de Lima entre el periodo de enero 2022 hasta agosto de 2023.Materiales y métodos. Investigación correlacional, de corte transversal, que incluyó a 107 conductores de transporte. Las variables principales fueron: Horas de jornada laboral diaria y semanal, colesterol total y lipoproteínas de alta densidad (HDL), el instrumento empleado fue una ficha de recolección de datos. En el análisis estadístico se empleó la prueba de correlación Rho de Spearman. El estudio fue aprobado por el Comité de Ética de la Universidad Nacional Mayor de San Marcos.Resultados. Se observó que el 47,02% de los trabajadores laboraba entre 9 y 10 horas diarias, mientras que el 57,9% lo hacía de 61 a 72 horas. Además, la mayoría de los conductores presentaba niveles de colesterol total entre 160 y 199 mg/dl (38,3%), y colesterol HDL entre 35 a 59 mg/dl (93,5%). Se determinó correlación significativa y directa entre las horas de jornada laboral diaria (p=0,026, Rho=0,216) y semanal (p=0,038, Rho=0,201) con el colesterol total. No se encontró relación significativa con el colesterol HDL.Conclusiones. Se identificó que las horas de jornada laboral diaria y semanal se relacionaron significativamente con el nivel de colesterol total.

Reference Interval for Non-HDL-Cholesterol, Remnant Cholesterol and Other Lipid Parameters in the Southern Iranian Population; Findings From Bandare Kong and Fasa Cohort Studies.

BACKGROUND: Growing evidence shows the undisputable role of non-HDL-C and remnant cholesterol (remnant-C) in cardiovascular disease (CVD) risk assessment and treatment. However, the reference interval (RI) for these lipid parameters is not readily available. The aim of the present investigation was to determine the age and sex-specific RIs for non-HDL-C and remnant-C as well as other lipid parameters among a healthy population in southern Iran. We also report the RI of lipid parameters in rural and urban residents, smokers and post-menopausal women. METHODS: Among 14063 participants of Bandare Kong and Fasa cohort studies, 792 healthy subjects (205 men and 578 women) aged 35-70 years were selected. Fasting blood samples were used for determination of total cholesterol (TC), triglycerides (TG) and HDL-C using colorimetric methods. Non-HDL-C and remnant-C were calculated using the valid formula. The 2.5th and 97.5th percentiles were calculated and considered as RI. RESULTS: In the total population (n=792, age 35-70), RIs for non-HDL-C and remnant-C was 74.0-206.8 and 8.0-52.7 mg/dL, respectively. Age (35-44 and≥45 years) and gender-specific RIs for serum non-HDL-C and remnant-C were determined. Remnant-C and non-HDL-C level were different between sex and age categories. The mean value of all lipid parameters except HDL-C was higher in men, urban residents, subject with age≥45 years and smokers. CONCLUSION: This is the first study in which the RIs for non-HDL-C and remnant-C in southern Iran are reported. This may help physicians to conveniently use these lipid parameters for patient care and better cardiovascular risk assessment.

Reduced HDL-cholesterol in long COVID-19: A key metabolic risk factor tied to disease severity.

This controlled study investigated metabolic changes in non-vaccinated individuals with Long-COVID-19, along with their connection to the severity of the disease. The study involved 88 patients who experienced varying levels of initial disease severity (mild, moderate, and severe), and a control group of 29 healthy individuals. Metabolic risk markers from fasting blood samples were analyzed, and data regarding disease severity indicators were collected. Findings indicated significant metabolic shifts in severe Long-COVID-19 cases, mainly a marked drop in HDL-C levels and a doubled increase in ferritin levels and insulin resistance compared to the mild cases and controls. HDL-C and ferritin were identified as the leading factors predicted by disease severity. In conclusion, the decline in HDL-C levels and rise in ferritin levels seen in Long-COVID-19 individuals, largely influenced by the severity of the initial infection, could potentially play a role in the persistence and progression of Long-COVID-19. Hence, these markers could be considered as possible therapeutic targets, and help shape preventive strategies to reduce the long-term impacts of the disease.

Lipid parameters and depression in patients with chronic tinnitus: A cross-sectional observation.

BACKGROUND: Pathophysiological theories assume importance of metabolic abnormalities in patients with major depression - and possibly chronic tinnitus. Although chronic tinnitus frequently correlates with depression, links between high-density lipoprotein (HDL) and depression are uninvestigated. METHODS: Two-hundred patients with chronic tinnitus (Mage = 55; 51% female) were examined. Serum levels of total cholesterol (TC), triglycerides (TGs), HDL, low-density lipoprotein cholesterol (LDL), non-HDL, as well as LDL/HDL and TC/HDL ratios were analysed. Questionnaires included depression subscales of the ICD-10 Symptom Rating, the Hospital Anxiety and Depression Scale (HADS_D), and the Berlin Mood Questionnaire (BSF). Multivariate analyses of covariance and linear regression models - which controlled age, tinnitus-related distress and perceived stress - investigated between-subgroup differences (p < 0.05) and linear associations between HDL indices and depression (p < 0.01). RESULTS: HDL levels did not differ for tinnitus-symptom durations, smoking and alcohol use levels, statin or antihypertensive drug use, and body-mass indices. Relative to non-to-mildly depressed patients with chronic tinnitus, patients with moderate-to-severe depression (n = 45; 23%) had significantly lower HDL levels (d = -0.35) and higher LDL/HDL (d = 0.39) and TC/HDL ratios (d = 0.40). Across participants, HDL-levels were negatively associated with depression as measured by the HADS_D and BSF_indifference scales. CONCLUSIONS: In keeping with general depression research, low serum HDL levels correlate with depressive symptomatology in patients with chronic tinnitus. This association may be influenced by proximal (e.g. modulations of HPA-axis activity) or distal factors (e.g. maladaptive coping behaviours) - both of which should be conceptualized within psychological stimulus-processing frameworks.

Association between Serum Phytosterols and Lipid Levels in a Population-Based Study.

The association between phytosterols and lipid levels remains poorly assessed at a population level. We assessed the associations between serum levels of six phytosterols (campesterol, campestanol, stigmasterol, sitosterol, sitostanol and brassicasterol) and of lipids [total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipopoprotein A-IV and lipoprotein Lp(a)] in two cross-sectional surveys of a population-based, prospective study. Data from 910 participants (59.1% women, 70.4 ± 4.7 years) for the first survey (2009-2012) and from 721 participants (60.2% women, 75.1 ± 4.7 years) for the second survey (2014-2017) were used. After multivariable adjustment, all phytosterols were positively associated with total cholesterol: slope and (95% confidence interval) 1.594 (1.273-1.915); 0.073 (0.058-0.088); 0.060 (0.044-0.076); 2.333 (1.836-2.830); 0.049 (0.033-0.064) and 0.022 (0.017-0.028) for campesterol, campestanol, stigmasterol, sitosterol, sitostanol and brassicasterol, respectively, in the first survey, and 1.257 (0.965-1.548); 0.066 (0.052-0.079); 0.049 (0.034-0.063); 1.834 (1.382-2.285); 0.043 (0.029-0.057) and 0.018 (0.012-0.023) in the second survey, all p < 0.05. Similar positive associations were found between all phytosterols and LDL cholesterol. Positive associations were found between campesterol and sitosterol and HDL-cholesterol: slope and (95% CI) 0.269 (0.134-0.405) and 0.393 (0.184-0.602) for campesterol and sitosterol, respectively, in the first survey, and 1.301 (0.999-1.604) and 0.588 (0.327-0.849) in the second survey, all p < 0.05. No associations were found between phytosterols and triglyceride or lipoprotein Lp(a) levels, while a positive association between campesterol and apolipoprotein A-IV levels was found: 2.138 (0.454-3.822). Upon normal dietary intakes, serum phytosterol levels were positively associated with total and LDL cholesterol levels, while no consistent association with other lipid markers was found.

Hyperlipidaemia in diabetes: are there particular considerations for next-generation therapies?

Dyslipidaemias are major cardiovascular risk factors, especially in people with diabetes. In this area, next-generation therapies targeting circulating lipoparticle metabolism (LDL, VLDL, chylomicrons, HDL) have recently been approved by the European and US medical agencies, including anti- proprotein convertase subtilisin/kexin 9 (PCSK9) antibodies; an siRNA targeting PCSK9; bempedoic acid, which targets ATP citrate lyase; an antisense oligonucleotide targeting apolipoprotein C-III; an anti-angiopoietin-like 3 antibody; and a purified omega-3 fatty acid, icosapent ethyl. Other therapies are in different phases of development. There are several important considerations concerning the link between these new lipid-lowering therapies and diabetes. First, since concerns were first raised in 2008 about an increased risk of new-onset diabetes mellitus (NODM) with intensive statin treatment, each new lipid-lowering therapy is being evaluated for its associated risk of NODM, particularly in individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Second, people with diabetes represent a large proportion of those at high or very high cardiovascular risk in whom these lipid-lowering drugs are currently, or will be, prescribed. Thus, the efficacy of these drugs in subgroups with diabetes should also be closely considered, as well as any potential effects on glycaemic control. In this review, we describe the efficacy of next-generation therapies targeting lipoprotein metabolism in subgroups of people with diabetes and their effects on glycaemic control in individuals with diabetes and prediabetes and in normoglycaemic individuals.

Elevated remnant cholesterol and non-HDL cholesterol concentrations from real-world laboratory results: a cross-sectional study in Southeast Asians.

Introduction: Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. Aim: This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals. Methods: A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory. Results: The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L (n = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L (n = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated (n = 724), p < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia. Conclusions: An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

Alcohol Consumption, High-Density Lipoprotein Particles and Subspecies, and Risk of Cardiovascular Disease: Findings from the PREVEND Prospective Study.

The associations of HDL particle (HDL-P) and subspecies concentrations with alcohol consumption are unclear. We aimed to evaluate the interplay between alcohol consumption, HDL parameters and cardiovascular disease (CVD) risk. In the PREVEND study of 5151 participants (mean age, 53 years; 47.5% males), self-reported alcohol consumption and HDL-P and subspecies (small, medium, and large) by nuclear magnetic resonance spectroscopy were assessed. Hazard ratios (HRs) with 95% CIs for first CVD events were estimated. In multivariable linear regression analyses, increasing alcohol consumption increased HDL-C, HDL-P, large and medium HDL, HDL size, and HDL subspecies (H3P, H4P, H6 and H7) in a dose-dependent manner. During a median follow-up of 8.3 years, 323 first CVD events were recorded. Compared with abstainers, the multivariable adjusted HRs (95% CIs) of CVD for occasional to light, moderate, and heavy alcohol consumers were 0.72 (0.55-0.94), 0.74 (0.54-1.02), and 0.65 (0.38-1.09), respectively. These associations remained consistent on additional adjustment for each HDL parameter. For CVD, only HDL-C was associated with a statistically significant decreased risk of CVD in a fully adjusted analysis (HR 0.84, 95% CI 0.72-0.97 per 1 SD increment). For coronary heart disease, HDL-C, HDL-P, medium HDL, HDL size, and H4P showed inverse associations, whereas HDL-C and HDL size modestly increased stroke risk. Except for H6P, alcohol consumption did not modify the associations between HDL parameters and CVD risk. The addition of HDL-C, HDL size, or H4P to a CVD risk prediction model containing established risk factors improved risk discrimination. Increasing alcohol consumption is associated with increased HDL-C, HDL-P, large and medium HDL, HDL size, and some HDL subspecies. Associations of alcohol consumption with CVD are largely independent of HDL parameters. The associations of HDL parameters with incident CVD are generally not attenuated or modified by alcohol consumption.

Does Elevated High-Density Lipoprotein Cholesterol Protect Against Cardiovascular Disease?

High-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD.

Association of HDL-Cholesterol, hypertension and left ventricular hypertrophy in youths with overweight or obesity.

BACKGROUND AND AIM: To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional multicenter study was performed in 1469 youths (age 6-16 years) with OW/OB observed in the period 2016-2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56 > 51, Q3: ≤51 > 45, Q4: ≤45 > 41, Q5: ≤41 > 39, Q6: <39 mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33-3.16) (P < 0.01) in Q2, 1.67 (1.10-2.55) (P < 0.05) in Q3 and 1.59 (1.05-2.41) (P < 0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15-10.24) (P < 0.05) in Q2, 4.16 (1.58-10.91) (P < 0.05) in Q3 and 3.60 (1.44-9.02) (P < 0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. CONCLUSION: Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease.

Association of the monocytes to high-density lipoprotein cholesterol ratio with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

BACKGROUND: Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is an independent predictor of atherosclerosis and in-stent restenosis (ISR). However, the association between MHR and the incidence of in-stent neoatherosclerosis (ISNA) remains to be validated. METHODS: This study included 216 patients with acute coronary syndrome who had 220 ISR lesions and had undergone optical coherence tomography (OCT). All eligible patients were divided into three groups according to their MHR tertile level. OCT characteristics were comparatively analyzed between groups of different MHR levels, and univariate and multivariate logistic regression analyses were constructed to assess correlations between MHR level and ISNA as well as in-stent thin-cap fibroatheroma (TCFA). A receiver operating characteristic curve was used to determine the optimal MHR thresholds for predicting ISNA and in-stent TCFA. RESULTS: The incidence of ISNA (70.3% vs. 61.1% vs. 20.3%, P < 0.001) and in-stent TCFA (40.5% vs. 31.9% vs. 6.8%, P < 0.001) was the highest in the third tertile, followed by the second and first tertiles, respectively. Multivariate analysis revealed that MHR was independently associated with ISNA (odds ratio [OR], 7.212; 95% confidence interval [CI], 1.287-40.416; P = 0.025) and in-stent TCFA (OR, 5.610; 95% CI, 1.743-18.051; P = 0.004) after adjusting for other clinical factors. The area under the curve was 0.745 (95% CI, 0.678-0.811; P < 0.001) for the prediction of ISNA and 0.718 (95% CI, 0.637-0.778; P < 0.001) for the prediction of in-stent TCFA. CONCLUSION: MHR levels are an independent risk factor for ISNA.