Dense LDL Research Articles

Impact of measured or calculated small dense LDL cholesterol compared with apolipoprotein B or non-HDL cholesterol for long-term secondary prevention in patients with stable coronary artery disease

Abstract Background This study was aimed to investigate whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with LDL-C, non–high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated sdLDL-C (E-sdLDL-C) determined by Sampson’s equation in patients with stable CAD. Methods D-sdLDL-C measured at Showa University, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization were monitored for 12 years. Cut-points of D-sdLDL-C, E-sdLDL-C, LDL-C, non-HDL-C, and apoB were determined by receiver operating characteristic curves. Results CAD events were observed in 238 male and 67 female patients. The Kaplan–Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL had an increased risk for CAD events (chi-square from log-rank test = 7.23), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL was not. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47, 95% confidence interval (CI) 1.15-1.89, and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB. These results remained significant in the patients treated with statin. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. The high D-sdLDL-C enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73, 95%CI 1.27-2.37). Conclusions: High D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C by distinguishing the patients at high risk. D-sdLDL-C is an independent risk-enhancer for secondary CAD prevention whereas E-sdLDL-C is not.Figure

7093 Atherogenic Index of Plasma Is Strongly Correlated With Cardiovascular Disease Independent of LDL level in the US Population

Abstract Disclosure: H. Ayesh: None. K.D. Niswender: None. B.G. Carranza Leon: None. Introduction: Cardiovascular disease (CVD) poses a global health challenge, prompting exploration of risk factors. The Atherogenic Index of Plasma (AIP), calculated as the readily available TG/HDL-C ratio, stands out as a promising avenue for investigation. Previous studies have reported an independent association between AIP and cardiovascular disease across diverse populations. Despite this recognized significance, there exists a gap in understanding its relevance in the US. This research aims to bridge this gap by examining the AIP-CVD relationship within the US population, utilizing data from the National Health and Nutrition Examination Survey (NHANES). Methods: The study included 4,784 NHANES subjects, with AIP values calculated using the established formula. The outcome was assessed using a combined variable (stroke, myocardial infarction, and CAD). Statistical analysis employed logistic regression to evaluate the AIP-CVD relationship, controlling for age, BMI, hemoglobin A1c, blood pressure, smoking, and LDL levels. Results/Discussion: We observed a significant correlation between AIP and CVD (odds ratio: 1.77, P = 0.026, 95% CI: 1.07-2.94), which persisted after controlling for common risk factors, including HbA1c, BMI, blood pressure, smoking, and LDL levels. Importantly, our findings highlighted the independence of this association from LDL levels—a pivotal observation with implications for healthcare strategies. Our study suggests that even with optimized LDL levels, AIP maintains an independent association with CVD. Existing literature supports the notion that AIP levels are strongly correlated with small dense LDL and remnant cholesterol levels. The pragmatic utility of AIP as a cardiovascular risk marker is evident due to the impracticality and costliness of testing for small dense LDL and remnant cholesterol. Given AIP is based on routine lipid profiles, our data underscores the potential integration of AIP into clinical practice, streamlining risk assessment. As we delve into our findings, the optimization of cardiovascular risk beyond LDL levels emerges as a tangible goal, with AIP emerging as a valuable tool. Larger studies are needed to validate and generalize these findings in the US population. Presentation: 6/2/2024

6366 Elevated Baseline Triglycerides As an Independent Risk Factor For Coronary Artery Disease

Abstract Disclosure: E. Askar: None. H. Moran: None. D. Bleich: None. Introduction: Diabetes is considered a coronary artery disease (CAD) risk equivalent. Studies have shown that the baseline level of triglycerides plays a role in cardiovascular risk independent of LDL levels lowered with statins. Numerous studies demonstrate that, in the general population, coronary artery calcium (CAC) scoring predicts and reclassifies cardiovascular disease (CVD) events, even in the absence of other risk factors. Here, we present a case of a 65 -year-old Caucasian male with elevated baseline triglycerides and a high CAC score, increasing his CVD risk despite the normalization of his triglycerides with statin therapy.Case presentation: A 65-year-old Caucasian male with a history of hypertension, hyperlipidemia, and diabetes presented to our endocrinology clinic for the management of hyperlipidemia and diabetes. His medications included empagliflozin 10 mg daily, repaglinide 1 mg three times a day, atorvastatin 20 mg daily, and amlodipine 10 mg daily. He had no complaints, and the physical examination was unremarkable. His recent HbA1c was 7.4%. Six months prior to presentation, he was found to have elevated triglycerides of 253 mg/dL (normal range: 10-149 mg/dL), low HDL of 34 mg/dL (normal range: >39 mg/dL), LDL of 84 mg/dL (normal range: 0-99 mg/dL), and total cholesterol of 167 mg/dL (normal range: 100-200 mg/dL). At that time, he was started on atorvastatin, and his recent triglycerides and HDL levels normalized. He was referred for CAC scoring, and the result was 2733 , which is above the 90th percentile for men between the ages of 65 and 69. As a result, he was further referred to a coronary angiogram. Conclusion: McGarry at the University of Texas Southwestern Medical Center was the first to describe the elevated triglyceride along with low HDL phenotype associated with insulin resistance. They explained this phenotype as a result of hepatic insulin resistance. Elevated insulin levels reduce the activity of lipoprotein lipase (LPL). As a result of that, the VLDL triglycerides rise, forming small dense LDL with a strong atherogenic potential.In the 2010 published ACCORD study, the effects of simvastatin alone versus simvastatin and fenofibrate were compared in 5500 Patients with type 2 diabetes. The experimental group did not exhibit any significant adverse cardiovascular events after eight years. However, the mean triglyceride was only 162 mg/dL. Consequently, no assumptions about the impact of the treatment on cardiovascular events in a more pertinent subset of people with greater baseline triglycerides could be made.While there has been controversy on the role of triglycerides in CVD, the idea of lowering triglycerides in diabetes patients with high triglycerides and low HDL to lower the risk of CVD is well supported. Presentation: 6/2/2024

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

Relationship between LDL-cholesterol, small and dense LDL particles, and mRNA expression in a cohort of African Americans.

Understanding the characteristics and behavior of low-density lipoprotein (LDL) particles provides insights into the atherogenic risk of elevated LDL cholesterol in hypercholesterolemia, cardiovascular disease risks. Studying LDL particles helps identify specific LDL subtypes [e.g., small dense LDL particles (sdLDL)] that may be atherogenic and, consequently, potential targets for therapeutics. This study cohort consists of African Americans (AAs), a population disproportionately affected by cardiovascular diseases, thereby accentuating the importance of the investigation. Differential expression (DE) analysis was undertaken using a dataset comprising 17,947 protein-coding mRNAs from the whole blood transcriptomes of 416 samples to identify mRNAs associated with low-density lipoprotein cholesterol (LDL-C) and sdLDL plasma levels. Subsequently, mediation analyses were used to investigate the mediating role of sdLDL particles on the relationship between LDL-C levels and mRNA expression. Finally, pathway enrichment analysis was conducted to identify pathways involving mRNAs whose relationship with LDL-C is mediated by sdLDL. DE analysis revealed 1,048 and 284 mRNA transcripts differentially expressed by LDL-C and sdLDL levels, respectively. Mediation analysis revealed that the associations between LDL-C and 33 mRNAs were mediated by sdLDL. Of the 33 mRNAs mediated by sdLDL, 18 were mediated in both males and females. Nine mRNAs were mediated only in females, and six were mediated only in males. Pathway analysis showed that 33 mRNAs are involved in pathways associated with the immune system, inflammatory response, metabolism, and cardiovascular disease (CVD) risk. In conclusion, our study provides valuable insights into the complex interplay between LDL-C, sdLDL, and mRNA expression in a large sample of AAs. The results underscore the importance of incorporating sdLDL measurement alongside LDL-C levels to improve the accuracy of managing hypercholesterolemia and effectively stratify the risk of CVD. This is essential as differences in sdLDL modulate atherogenic properties at the transcriptome level.NEW & NOTEWORTHY The study investigated the interplay between LDL-C and mRNA expression, focusing on the role of small dense LDL (sdLDL) particles and sex differences. Differential expression analysis identified 1,048 and 284 mRNAs associated with LDL-C and sdLDL levels, respectively. Mediation analysis revealed that sdLDL mediates the relationship between LDL-C and 33 mRNAs involved in immune, inflammatory, and metabolic pathways. These findings highlight the significance of sdLDL in cardiovascular disease risk assessment and underscore sex-specific differences in lipid metabolism.

Impact of circulatory microRNA-126 &122 in severity of coronary artery disease correlation with small dense LDL: A case control study

Impact of circulatory microRNA-126 &122 in severity of coronary artery disease correlation with small dense LDL: A case control study

Lipoprotein (a) and the Occurrence of Lipid Disorders and Other Cardiovascular Risk Factors in Patients without Diagnosed Cardiovascular Disease.

Background: Elevated lipoprotein (a) [Lp(a)] concentrations are linked mainly to genetic factors. The relationship between Lp(a) and other lipid disorders or cardiovascular (CV) risk factors has been less investigated. The aim of this study was to assess the occurrence of lipid disorders and other CV risk factors according to Lp(a) concentrations. Methods: A cross-sectional analysis of 200 primary-care patients who had not been diagnosed with CV disease was conducted. The following risk factors were assessed: older age, history of hypertension, diabetes mellitus or dyslipidemia, smoking, lack of physical activity, body mass index (BMI), and waist circumference. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and small, dense LDL (sdLDL-C). Patients were divided into two groups based on their Lp(a) concentrations: <30 mg/dL and ≥30 mg/dL. Results: In 70% of patients, the Lp(a) concentration was <30 mg/dL. The concentrations of lipid parameters did not differ between the groups. The rate of patients with sdLDL-C >1.0 mmol/L was higher in the low-Lp(a) group (10.0 vs. 1.7%, p = 0.04), with no significant differences regarding the other analyzed lipid disorders (p > 0.05). Both in the low- and high-Lp(a) group, most patients had two other abnormal lipid factors (45.0% and 60.0%, respectively). The distribution of impaired lipid parameters (p = 0.41) and other CV risk factors (p = 0.16) was similar in both groups. There was a lower rate of patients >60 years old (15.0% vs. 32.9%, p = 0.01) and with a BMI ≥ 25 kg/m2 (46.7% vs. 63.6%, p = 0.026) in the high-Lp(a) group, and previously diagnosed hyperlipidemia was more prevalent in this group (65.0% vs. 47.1%, p = 0.02). The occurrence of other cardiovascular risk factors did not differ significantly between the Lp(a) groups (p > 0.05). In the high-Lp(a) group, the highest proportion (25.0%) had two CV risk factors, and in the low-Lp(a) group, 31.4% had four CV risk factors. Conclusions: An elevated Lp(a) concentration is not related to the number of conventional CV risk factors or other impairment major lipid parameters.

Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05–1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67–0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49–0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065–1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.

Lipid profile in patients with acute coronary syndrome undergoing cardiac rehabilitation. Characteristics and effects of the program. The importance of small and dense LDL (LDLpd)

Abstract Funding Acknowledgements None. Introduction Recently it has been shown that not all lipid risk for atherosclerosis is due to LDL cholesterol. Both remnant particles and small and dense LDL (LDLpd) have been associated with a higer risk of the first cardiovascular events and recurrences. Methods We analyzed the lipid profile at admission of patients undergoing a cardiac rehabilitation (CR) program in a tertiary referral hospital, in association with other analytical parameters, clinical characteristics and outcomes of CR in these patients. We collected data from patients who completed the programme between January 2022 and March 2023 on admission and at the end of the programme. Clinical and anthropometric data and the results of the stress tests were collected. We defined a TG/HDL ratio greater than 2 as being associated with the presence of small and dense LDL. Results 170 patients who had complete analytical profiles at hospital admission were included, 80.5% were male with a mean age 57.9+/-9 years, 92.5% were referred after an acute coronary syndrome, 25.6% were diabetic, 56.6% were smokers and 37.7% were obese. LDLpd at hospital admission was present in 73.4% of the patients. Male gender was more likely (86.3 vs. 68.9%, p=0.01, p=0.01) as well as being obese (83.9 vs 68.8%, p=0.04). No differences were found in terms of age, presence of DM, smoking or peripheral arterial disease. Nor did functional capacity or baseline quality of life. Less improvement was found in the SF 36 questionnaire (-6 vs +20, p=0.011), but similar in ergometry. Basal lipid profile was associated with higher total Ch values (173 vs 149, p=0.002), Ch LDL (104 vs 79, p=0.000), remnants (32 vs 14, p=0.000). As for baseline LDL, 51.6% with LDLpd,had it high LDL Ch&amp;gt;100 mg/dl, compared to 22.2% of those without LDLpd (P=0.002). As for the profile at discharge, we found that 63.5% still had LDLpd at discharge from the CR program ( vs. 15.9% of those without elevated LDLpd, P=0.000) and 22% had elevated remnants (P=0.002). After CR, these patients still had higher TG values (128 vs 81, p=0.000), lower HDL-C (44 vs 56, p=0.003) and higher remnants (24 vs 17, p=0.000) despite the fact that a greater decrease in remnants and TG/HDL in this group. Conclusions More than one third of the patients who undergo a Cardiac Rehabilitation Program in our centre have LDLpd. Initially, male and obese patients have higher LDL and remnants. A weaker effect of the CR program in improving the lipidic profile has been observed in those patients. Consideration should be given to enhance lipid-lowering and intensive weight-loss treatments to decrease cardiovascular risk in this population.

The importance of remnant cholesterol particles.Lipid profile in patients with acute coronary syndrome undergoing cardiac rehabilitation

Abstract Funding Acknowledgements None. Main funding source(s): Ninguno. Introduction Recently it has been shown that not all lipid risk for atherosclerosis is due to LDL cholesterol. Both, remnant and small particles have been proposed as risk factors for the first cardiovascular event and recurrences. Methods This is an observational, descriptive, prospective, single-centre, descriptive study. We set out to analyse the lipid profile on admission of patients undergoing a cardiac rehabilitation (CR) program in a tertiary hospital. In addition, we studied the association with other analytical parameters, clinical characteristics and CR results in these patients. For this purpose, data were collected from patients who completed the program between January 2022 and March 2023. We compared analytical variables at hospital admission and at the end of the program, as well as clinical and anthropometric data and stress test results. In our study we defined elevated remnants as &amp;gt;30 mg/dl. Results We included 170 patients who had a complete analytical profile at hospital admission. In our cohort, 80.5% were male, with a mean age of 57.9+/-9 yrs. A total of 92.5% were referred after acute coronary syndrome. There were 25.6% diabetic, 56.6% smokers and 38.1% obese patients. Patients with elevated remnants were more likely to be men (90.3 vs 79.8%, p=0.039). No differences were found in age, presence of DM, smoking, obesity or peripheral arterial disease. Functional capacity, quality of life and improvement in these parameters did not differ either. As for baseline lipid profile, it was associated with higher total Ch (190 vs 152, p=0.0), LDL Ch (109 vs 90, p=0.0), TG (227 vs 104, p=0.0) and TG/HDL ratio (6.8 vs 2.5, p=0.0) and lower HDL Ch (37 vs 45, p=0.0). 66.1% of patients with high remnants have an LDL-Ch greater than 100 mg/dl, compared with 29.6% of those with low remnants.(P=0,000). Regarding the profile at discharge, we found that 34.4% still had elevated remnants at discharge from the CR program (vs 22.2% of those without elevated remnants, P=0.000) and that 75.9% had TG/HDL greater than 2. After CR, these patients still had higher TG values (156 vs 93, p=0.000), lower HDL-C (43 vs 50, p=0.003) and higher TG/HDL ratio (4 vs 2, p=0.000), despite a greater decrease in remnants and TG/HDL in this group. Conclusions More than one third of patients undergoing a Cardiac Rehabilitation Program in our hospital have elevated cholesterol remnants. These particles predominate in male patients and initially, they have a higher prevalence of small and dense LDL and lower HDL cholesterol. In addition, the effect of the cardiac rehabilitation program on the improvement of lipid risk parameters is lower. More powerful intensive treatments are needed to improve cardiovascular risk in this population.

Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease

Background and aimsInflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients’ cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT). MethodsCross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out. ResultsMost of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71–14.92) and female sex (OR=3.32, CI 95%=1.03–10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07–12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04–50) but not total LDL cholesterol were associated with CIMT alterations. ConclusionsMASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.

Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients.

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710-0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.

Effects of portable pedal machines at work on lipoprotein subfraction profile in sedentary workers – the REMOVE study

BackgroundSedentary behaviour at work is a major cause of atherosclerosis, particularly in tertiary workers. However, no studies have ever assessed the effect of active workstation on lipoprotein subfraction profile. This study aimed to evaluate the effect of 12-week portable pedal machines (PPMs) on lipoprotein subfraction profile among healthy sedentary workers.MethodsHealthy administrative workers were randomized into an intervention group using PPMs for 12 weeks or a control group using normal-desk. Lipoprotein subfractions were assessed using Lipoprint® electrophoresis. Main outcomes were explored using mixed models with sensitivity analyses (four models).ResultsWe included 40 participants (43.7 ± 8.6 years old, 100% women, BMI 23.8 ± 3.4 kg/m2; sedentary time at work 7.7 ± 1.8 h/day). Groups did not differ at baseline in any outcomes. 32 participants finished the trial. Changes in lipoprotein subfractions were especially marked for LDL profile. There was an interaction time x group for all parameters related to LDL and their subfractions: total LDL-cholesterol (p = 0.012), LDL particle size (p = 0.027), large LDL subfractions 1 and 2 (p = 0.001), and small dense LDL subfractions 3 to 7 (p = 0.046), using the crude model. The interaction reflects difference in the direction of changes between groups. The LDL particle size significantly increased in the intervention group (from 271.9 ± 2.5 at t0 to 272.8 ± 1.9 Ångström at t1, p = 0.037) while it did not change in the control group (272.5 ± 1.7 at t0 to 271.8 ± 1.5Å at t1, p = 0.52). All interactions were constantly significant whatever the models. Influencing variables were mainly stress at work that was associated with an increase in total LDL-cholesterol (coefficient 3.15, 95CI 0.20 to 6.11 mg/dl, p = 0.038), and BMI that was associated with Large-LDL, Large-HDL, IDL-C and triglycerides.ConclusionsLipoprotein profile was improved after a 12-week PPMs intervention at work in healthy administrative workers. Changes were mainly showed for LDL and LDL subfractions. Lipoprotein profile was worsened by stress at work, BMI and age.Trial registrationNCT04153214.

Guidelines of the Polish Society of Laboratory Diagnosticsand the Polish Lipid Association on laboratory diagnosticsof lipid metabolism disorders. 2024

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area – the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

2024 Guidelines of the Polish Society of Laboratory Diagnostics and the Polish Lipid Association on laboratory diagnostics of lipid metabolism disorders.

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area - the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

The effects of saturated fat intake from dairy on CVD markers: the role of food matrices.

CVD is the leading cause of death worldwide, and is commonly associated with modifiable risk factors. Most studies to date examining link between food intake and risk of CVD, have focused on modulation of plasma cholesterol concentrations (total cholesterol (TC), LDL-C). However, recent studies suggest LDL particle size is a more sensitive risk marker for CVD with smaller, dense LDL particles reported as more atherogenic than larger, more buoyant LDL. Although dietary guidelines recommend SFA intake of < 10 % of total energy, this does not consider food source, with recent evidence suggesting differing, sometimes beneficial, lipid responses following consumption of SFA from dairy compared to other food sources. This may be from differences in the physical food matrices, the nutrient content of the foods, and/or how these components interact with each other, described as a 'dairy matrix effect'. Dietary fat not only raises LDL-C, but also HDL cholesterol (HDL-C), associated with reduced CVD risk. HDL particles are complex emulsions of lipids, proteins and microRNAs that exhibit atheroprotective properties. In addition, HDL particles exhibit a very heterogeneous proteomic composition, dependent on a person's disease state - with a more pro-inflammatory proteome evident in patients with established CVD. This review will discuss the evidence to date on the importance of the food matrix in modulating response to dietary SFA and impact on CVD risk factors. A focus on potential biomarker properties of lipoprotein particles beyond cholesterol and current use of such biomarkers in human nutrition research will be considered.

New Advances in Rapid Pretreatment for Small Dense LDL Cholesterol Measurement Using Shear Horizontal Surface Acoustic Wave (SH-SAW) Technology.

Atherosclerosis is an inflammatory disease of the arteries associated with alterations in lipid and other metabolism and is a major cause of cardiovascular disease (CVD). LDL consists of several subclasses with different sizes, densities, and physicochemical compositions. Small dense LDL (sd-LDL) is a subclass of LDL. There is growing evidence that sd-LDL-C is associated with CVD risk, metabolic dysregulation, and several pathophysiological processes. In this study, we present a straightforward membrane device filtration method that can be performed with simple laboratory methods to directly determine sd-LDL in serum without the need for specialized equipment. The method consists of three steps: first, the precipitation of lipoproteins with magnesium harpin; second, the collection of effluent from a 100 nm filter; and third, the quantification of sd-LDL-ApoB in the effluent with an SH-SAW biosensor. There was a good correlation between ApoB values obtained using the centrifugation (y = 1.0411x + 12.96, r = 0.82, n = 20) and filtration (y = 1.0633x + 15.13, r = 0.88, n = 20) methods and commercially available sd-LDL-C assay values. In addition to the filtrate method, there was also a close correlation between sd-LDL-C and ELISA assay values (y = 1.0483x - 4489, r = 0.88, n = 20). The filtration treatment method also showed a high correlation with LDL subfractions and NMR spectra ApoB measurements (y = 2.4846x + 4.637, r = 0.89, n = 20). The presence of sd-LDL-ApoB in the effluent was also confirmed by ELISA assay. These results suggest that this filtration method is a simple and promising pretreatment for use with the SH-SAW biosensor as a rapid in vitro diagnostic (IVD) method for predicting sd-LDL concentrations. Overall, we propose a very sensitive and specific SH-SAW biosensor with the ApoB antibody in its sensitive region to monitor sd-LDL levels by employing a simple delay-time phase shifted SH-SAW device. In conclusion, based on the demonstration of our study, the SH-SAW biosensor could be a strong candidate for the future measurement of sd-LDL.

MAFLD and Small Dense LDL Cholesterol: A Mechanistic Link.

MAFLD and Small Dense LDL Cholesterol: A Mechanistic Link.

Is there still a place for fenofibrate-statin combination therapy?

Although low-density lipoprotein cholesterol (LDL-C) is the main target for the prevention of atherosclerotic cardiovascular disease (ASCVD), hypertriglyceridaemia (HTG), a common condition characterised by elevated blood triglyceride (TG) levels, contributes to residual cardiovascular risk independently of LDL-C levels. Elevated TG levels are a feature of atherogenic dyslipidaemia, which also includes low HDL-C levels and high levels of atherogenic small, dense LDL, together with accumulation of atherogenic remnant particles. Treatment of HTG includes lifestyle interventions, but these are not always sufficient to significantly reduce TG levels in people at high cardiovascular risk. Current guidelines for the treatment of dyslipidaemias recommend the use of statins as the first choice in people with HTG (TG &gt;200 mg/dL) and high CV risk, and consideration of the use of specific TG-lowering drugs, such as fenofibrate, bezafibrate or icosapent ethyl if HTG persists. Fenofibrate acts by activating the peroxisome proliferator receptor alpha (PPARα), a nuclear receptor that plays an important role in lipid and lipoprotein metabolism, glucose homeostasis and inflammation. Several clinical trials have shown that fibrates may reduce the incidence of major cardiovascular events only in patients with high TG levels and low HDL-C levels, a finding that was also observed with fenofibrate in combination with a statin compared to statin therapy alone. The recent failure of the PROMINENT trial with pemafibrate in combination with a statin highlighted the notion that treatment with fibrates provides a clinical benefit only if they lower apoB levels.