Low-density Lipoprotein Cholesterol Particles Research Articles

Sex differences in the correlation between lipids related to cardiovascular risk factors and small dense LDL particles in patients with type 2 diabetes.

Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2. The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence. An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001). The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk.

Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study

BackgroundDefining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. MethodsA community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. ResultsSpearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. ConclusionBased on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.

AN AYURVEDIC METHODOLOGY FOR MANAGING DIABETIC DYSLIPIDEMIA - A CASE REPORT

Diabetic dyslipidemia is characterized by elevated plasma triglyceride levels, decreased HDL cholesterol levels, and an increase in small dense LDL-cholesterol particles. These lipid alterations in diabetes are linked to heightened free fatty acid flux due to insulin resistance. With the availability of various lipid-lowering medications and supplements, patients now have more options to reach target lipid levels. Lipid-lowering therapies in modern medicine, such as statins and fibrates, are generally well-tolerated with minimal side effects. However, these treatments often necessitate lifelong usage, which can impose significant financial strain, particularly in developing countries like India.In Ayurveda, dyslipidemia is understood as the manifestation of an imbalance in the Medovahasrotas.Dyslipidemia manifests as the consequent output of Medovahasrotodushti. A 31-year-old male patient presented with complaints of pain in calf muscles and weight gain. Upon investigation, his total cholesterol level was found to be elevated at 211 mg/dl, and triglycerides were elevated to 683.80 mg/dl. Giloykwath along with arjunkwath, Madhunashinivati extra power, Tablet lipidom, and Tablet Madhugrit were administered for the shaman therapy. Upon completion of the treatment, significant improvements were observed in the patients complaints. Additionally, a significant improvement was noted in the Lipid Profile.

Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology: A Prospective Cohort Study.

Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China. This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time. Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00-6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15-9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014). Higher sdLDL-C was associated with an increased risk of incident carotid plaques, especially carotid plaques with vulnerable morphology, even in participants with normal LDL-C. This suggests the potential of sdLDL-C as a therapeutic target for stroke prevention. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017197.

#207 : Mendelian Randomization Study Reveals a Casual Effect of Blood Lipids and Apolipoprotein on Uterine Fibroids

Background and Aims: Despite an early insight into the risk factors of uterine fibroids (UFs), there is still controversy about the roles of blood lipids and apolipoprotein on UFs. Therefore, to provide more reliable evidence, we investigated the causal effect of blood lipids and apolipoprotein on the risk of UFs through Mendelian randomization (MR). Method: We utilized the large genome-wide association studies of blood lipids and apolipoprotein as instruments and integrated them in the inverse-variance-weighted (IVW) model in two-sample MR to investigate their causal relationship in large sample sizes. To eliminate potential pleiotropy, we listed a conclusive table of genes related to confounding factors, such as body mass index, waist circumference, blood pressure, glucose, hypertension, the metabolic syndrome and smoking and removed the repeated SNPs in the exposure data.To adjust for multiple comparisons, the statistical significance of the MR effect estimates was evaluated in a false discovery rate correlation of less than 5%. Neither pleiotropy nor heterogeneity was reported in all MR sensitivity analysis, including IVW, MR-Egger, simple median, weighted median, weighted mode and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods. Results: Total triglycerides, very low-density lipoprotein (VLDL) cholesterol, including large, medium and small VLDL particles and free cholesterol in large VLDL cholesterol showed positive association with UFs. Meanwhile, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1, free cholesterol in small and medium VLDL and total cholesterol are not statistically related to the development of UFs. Conclusion: Exposure to various aberrant blood lipids increases the risk of UFs, providing genetic evidence for the vital role of aberrant lipid levels in the pathogenesis of UFs. Meanwhile, our results provided genetic insights suggesting intervention in blood lipids might be a prospective strategy in the early prevention and treatment of UFs.

Probucol will become a new model for treating cerebral infarction with a high risk of hemorrhage: A narrative review.

Lipid-lowering agents are relevant in stroke prevention. Probucol (PU) is an antioxidative and lipid-lowering drug that has been used to treat atherosclerotic cardiovascular diseases and xanthomas. The drug penetrates the core of low-density lipoprotein cholesterol (LDL-C) particles, enhancing the activity of plasma cholesterol l ester transfer protein (CETP) and strengthening the liver scavenger receptor type I, resulting in reducing LDL-C; by increasing the activity of paraoxonase 1, upregulating the antioxidant function of high-density lipoprotein (HDL), and it decreases the serum HDL-cholesterol (HDL-C) level. This drug has been retired from the Western markets for lowering HDL-C levels and Q-interval prolongation. The latter side effect has been rarely reported and may be transient. Recent clinical evidence supports the effectiveness of PU in preventing cardiovascular events and in reducing mortality, irrespective of the reduction of HDL-C. Based on basic research and clinical studies, it appears that PU might be a valuable alternative when statins are ineffective or contraindicated, in patients at high risk of recurrence of cerebral ischemia and hemorrhage.

SYNERGISTIC EFFECT OF FRUITS EXTRACTS OF Balanites aeqyptiaca AND Adansonia digitata ON LIPIDERMIC PARAMETERS OF DIABETICS ALBINO RAT

Lipidemia is a significant risk factor for cardiovascular disease, particularly in people with diabetes mellitus. High plasma triglyceride concentration, low HDL cholesterol concentration, and elevated concentration of tiny dense LDL cholesterol particles are some of its distinguishing features. Fruits from Balanites aeqyptiaca and Adansonia digitata have the ability to decrease blood pressure. Therefore, the purpose of this study is to examine the combined effects of the two fruits on the lipidemia of alloxan-induced albino rats. Utilizing the glucose dehydrogenase method, glucometer accu-check was used for the evaluation of blood glucose levels. Investigations were also conducted on alloxan-induced diabetic albino rats to measure total cholesterol, triglycerides, high density lipoprotein (HDL), and low density lipoprotein (LDL). According to the results, B. aegyptiaca and A. digitata fruit extracts significantly reduced the lipid profiles of the treated groups when used at concentrations of 80:20, 160:40, and 240:60 mg/Kg body weight, respectively. While the lipid profiles were significantly reduced in groups that received treatment at dosages of 100, 200, and 300 mg/kg body weight. However, the groups treated with the highest doses of the extracts demonstrated the most significant effects on the levels of triglycerides (47mg/dl), HDL (79mg/dl), and LDL (40mg/dl). The fruits have shown cumulative effects on their potential to lower the lipid profile of diabetic rats, validating their folkloric usage in the management of cardiovascular illnesses.

Indications for omega-3 fatty acid supplementation in prevention of cardiovascular disease: From fish to pharmaceuticals.

To explore the evidence for omega-3 fatty acid (O3FA) supplementation in primary and secondary prevention of cardiovascular disease (CVD). PubMed, Cochrane reviews, and Google Scholar were searched for meta-analyses and reviews related to O3FAs and CVD. Salient, recent randomized controlled trials referenced in these reviews were retrieved. Current lipid guidelines were reviewed. Most O3FAs are derived from marine or aquatic microalgae, which are consumed by fish. The essential fatty acids eicosapentaenoic acid and docosahexaenoic acid are mainly sourced from fish, with a small fraction coming from plants. Omega-3 fatty acids modestly lower triglyceride levels, but the major impact on CVD is through a variety of other mechanisms related to cell membrane function, antioxidant properties, and reduction of atherogenic small low-density lipoprotein cholesterol particles. Guidelines continue to recommend eating 2 servings of fish per week. There is little evidence of benefit of O3FAs in primary prevention of CVD. Given that 40% of Canadians have insufficient levels and that these low levels may be associated with other chronic diseases over time, supplementation with O3FAs could be considered, particularly in those with hypertriglyceridemia, in those who eat no fish, or for vegetarians or vegans. Doses up to 1 g daily are considered safe. For secondary prevention after statin optimization, if triglyceride levels are between 1.5 and 5.6 mmol/L, guidelines recommend with level 1A evidence taking 2 g of icosapent ethyl twice a day. This is also recommended in primary prevention for patients with diabetes and hypertriglyceridemia and additional CVD risk factors. As fish stocks dwindle over time, preserving fisheries for developing countries and obtaining O3FA from microalgal or genetically modified plant sources may become important. All guidelines recommend at least 2 servings of oily fish per week, although benefit from O3FAs is mostly seen in secondary prevention. Fish oil and combination preparations of eicosapentaenoic acid and docosahexaenoic acid have failed to show benefit at any dose at any level of prevention in patients who are appropriately prescribed statins. High-dose eicosapentaenoic acid shows substantial benefit in selected patients taking statins who have high triglyceride levels.

7-OR: Evaluation of Saroglitazar’s Effects on Small Dense LDL and Non-HDL Cholesterol Particles in Diabetic Dyslipidemia Patients

The dual PPAR α/γ agonist Saroglitazar is used to treat diabetic dyslipidemia (DD) that cannot be managed with statins. Due to its association with high triglycerides (TG), high small dense LDL (sdLDL), and low HDL-C, DD is extremely atherogenic. The efficacy and safety of saroglitazar have been assessed in this prospective multi-centric research in patients with type 2 diabetes and triglycerides (TG) 200 mg/dL following stable statin medication for at least 3 months and a steady lifestyle. A total of 104 patients (78% of whom were men) were enrolled, with a mean age of 59.1 ± 11.4 years. Saroglitazar 4 mg was administered to each subject once daily for 24 weeks. Using a paired t-test, the effects of saroglitazar were assessed after 24 weeks. 73 patients' six-month follow-up data are available. Non-HDL-C and sdLDL levels both significantly decreased at 24 weeks, with non-HDL-C dropping from 138 ± 51 mg/dL to 113 ± 44 mg/dL and from 31.7 ± 11.8 mg/dL to 26.0 ± 11.9 mg/dL, respectively. The values of HDL-C, TG, HbA1c and total cholesterol among the secondary end goals also considerably improved after 24 weeks (Table). No significant adverse event was reported during the investigation. This is the initial investigation on how saroglitazar affects sdLDL in DD patients. According to the findings, saroglitazar effectively lowers non-HDL-C and sdLDL particles while being safe and well tolerated. Disclosure J.Dinkar: None. R.Ranjan: None. A.Chandra: None.

Discordance between LDL cholesterol and apolypoprotein B. Which to prefer to guide treatment?

Abstract Funding Acknowledgements Type of funding sources: None. Current cardiovascular risk guidelines recommend target values of low-density lipoprotein cholesterol (LDLc) &amp;lt; 55 mg/dL and apolipoprotein B (apoB) &amp;lt; 65 mg/dL. However, they don’t clarify what the attitude should be when one of the two targets is not achieved. Our objective was to establish the prevalence of LDLc and ApoB discordance in a secondary prevention population in our cardiac rehabilitation unit and describe the size of LDLc particles in this cohort of patients. We conducted a retrospective observational study including patients with previous ischemic heart disease with lipid-lowering treatment in secondary prevention followed up in our cardiac rehabilitation unit between February 2022 and September 2022. We present a series of 100 patients with a mean age of 60.5 years (S.D. 9.7), 79% male, with high prevalence of cardiovascular risk factors (59% hypertension, 26% diabetes mellitus, 52% smokers). All patients received lipid-lowering therapies, with statins alone or in combination with Ezetimibe. 30 patients (30%) had LDLc &amp;gt; 55 mg/dL and ApoB &amp;lt; 65 mg/dL, 37 (37%) reached target LDL and ApoB levels (LDLc &amp;lt; 55 mg/dL and ApoB &amp;lt; 65 mg/dL), and 33 (33%) did not reach any of the target levels (LDLc &amp;gt; 55mg/dL and ApoB &amp;gt; 65 mg/dL). No patient had LDLc &amp;lt; 55mg/dL and ApoB &amp;gt; 65mg/dL. Among patients with ApoB target level achieved and LDLc &amp;gt; 55mg/dL, the mean LDLc/ApoB ratio was 1.1 (S.D. 0.1). The mean ratios stratified by LDLc level are represented in Figure 1 and specified in Table 1. The conclusion of our study is that in clinical practice we find a group of patients with discrepancy between LDLc and ApoB levels that is not represented in the main studies of cardiovascular outcomes. Therefore, we do not know what therapeutic approach we should take. It is known that these relatively high LDLc values when apoB is in range correspond to larger and less dense particles, and therefore less atherogenic, and it has been suggested that ApoB levels better reflect residual risk than LDLc in statin-treated patients. At this point, the question that arises is: should we take these patients to an LDL &amp;lt; 55mg/dL or is their lipid risk controlled?

Different clinical phenotypes of a pair of siblings with familial hypercholesterolemia: a case report and literature review

BackgroundFamilial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background.Case presentationWe treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister.ConclusionsPatients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

ORF7a Palsies Macrophage to Worsen Diabetes by SMB/BPI/ABC Domains and PARP/Cap/Cyclin Enzyme System

Background: Such factors as diabetes and obesity can dramatically worsen COVID-19 symptoms. In addition, macrophage accumulation in adipose tissue is related to obesity. Therefore, macrophages play a significant role in raising COVID-19 susceptibility and severity in diabetes and obese patients. Methods: In this study, the functional impact of SARS-CoV-2 ORF7a on macrophages was analyzed using a domain-searching bioinformatics technique. Ca2+ binding domain, kinase and phosphatase, SMB/SRCR, LBP/BPI/CETP, ABC, TIR,PARP, Flavivirus Cap enzyme, Cyclin, and other domains have been identified in SARS-CoV-2 ORF7a. ORF7a binds to oxidized low-density lipoprotein cholesterol particles by the macrophage receptor-like domains such as SMB/SRCR and enters macrophages via macropinocytosis. Then, ORF7a prevents 18 S rRNA maturation and adds flavivirus cap 0/1/2 to mRNA to interfere with transcription and translation via PARP, Flavivirus Cap enzyme, and other associated domains. Results: ORF7a activates and promotes G2/M phase transition via cyclin-related enzymatic activity domains. Conclusion: The destructive activity of ORF7a hijacks the nitric oxide release pathway of macrophages and promotes macrophage death, enabling the virus to elude the innate immune system and aggravate diabetes-related problems in patients.

Improving Cardiovascular Risk Assessment to Optimize Therapy

Background: Quantifying ten-year cardiovascular risk can be challenging. Different online risk calculators provide different risk estimates and online risk calculators use only one point in time. However, risk factors occur over the lifetime of the individual. Purpose: This manuscript provides three solutions to improving ten-year cardiovascular risk assessment in individuals at intermediate risk. Methods: Measuring Lipoprotein(a)—Lp(a) is recommended for assessing cardiovascular risk in all individuals who are in the intermediate risk category by standard online risk calculators. Lp(a) is primarily determined by genetic inheritance. It has the undesirable properties of being proatherosclerotic, proinflammatory, and prothrombotic. Measuring apolipoprotein B (apo B) provides a good index of the number of atherosclerotic particles present. Studies have demonstrated that small, dense LDL cholesterol particles are more atherogenic than larger, less dense LDL cholesterol particles. Measuring high sensitivity C-reactive protein (hsCRP) provides a good estimation of the degree of inflammation in the vascular system. Inflammation is a critical component of heart attacks and strokes. It is increased in diabetes and obesity. Treatment to reduce inflammation results in a reduction of cardiovascular events, independent of lipid values. Results: The above three risk factors should be measured in all patients with an intermediate risk score. Routine assays are readily available at a reasonable cost. They are independent risk factors for cardiovascular disease. Their recommendation is based on the pathophysiology of atherosclerotic cardiovascular disease. Successful therapy will result in the decrease of each of these risk factors. Conclusion: The recommended approach will improve the assessment of cardiovascular risk and guide the physician and patient to the correct treatment recommendations.

ODP395 Relationship of serum total insulin-like growth factor-binding protein-3 with triglyceride to high-density lipoprotein cholesterol ratio and glucose tolerance in Korean children and adolescents

Abstract Objectives We investigated the relationships between serum IGF-I/ IGFBP-3 levels and degrees of triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio in Korean children and adolescents who underwentoral glucose tolerance test. Methods children and adolescents without known diabetes were checked an oral glucose tolerance test and collected the clinical and laboratory data. Serum IGF-I and total IGFBP-3 levels, TG/HDL ratio, total cholesterol, low-density lipoprotein cholesterol (LDL),AST, ALT, C-peptide levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, and glycated hemoglobin (HbA1c) levels were measured. Results Serum TG/HDL ratio and IGF-I/ total IGFBP-3 levels were significantly higher in individuals with type 2 diabetes (DM) than in those with normal glucose tolerance (NGT) (P&amp;lt;0. 05). TG/HDL ratio was not related with age and IGF-I levels and it was correlated with serum IGFBP-3 levels, HbA1c, C-peptide, HOMA-IR, and body mass index. However, these relationships were altered in patients with insulin resistance state, especially in those with DM. In the DM group, TG/HDL ratio and total IGFBP-3 levels were positively correlated stronger than no-DM groups. In addition,TG/HDL ratio and total IGFBP-3 levels were positively correlated with total cholesterol and LDL levels but not with age. Conclusions TG/HDL ratio, the marker of small dense LDL particles, is related with IGFBP-3, especially in patients with type 2 diabetes. The IGF-I-IGFBP-3 axis, especially IGFBP-3, may play roles in the pathogenesis and metabolic control of lipid metabolism. Presentation: No date and time listed

Effects of pemafibrate on lipid metabolism in patients with type 2 diabetes and hypertriglyceridemia: A multi-center prospective observational study, the PARM-T2D study

AimsPemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, was shown to ameliorate lipid abnormalities in a phase III clinical trial of patients with type 2 diabetes mellitus (T2DM). However, its efficacy has not been demonstrated in real-world clinical practice in patients with T2DM. MethodsWe performed a multi-center prospective observational study of the use of pemafibrate in patients with T2DM and hypertriglyceridemia versus conventional therapy, with or without a fibrate. The primary outcomes were the changes from baseline in fasting serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations at week 52. ResultsWe recruited 650 patients, and data from 504 (252 per group) were analyzed after propensity score matching. In the pemafibrate group, both TG and HDL-C showed significant improvements (p < 0.001), and several indices reflecting TG-rich lipoproteins, low-density lipoprotein-cholesterol particle size, and liver enzyme elevations were significantly ameliorated compared with the control group, but there was no difference in glycemic control markers. One of the key secondary endpoints showed that switching from conventional fibrates to pemafibrate improved eGFR but increased uric acid concentration. ConclusionsIn patients with T2DM, pemafibrate has superior effects on lipid profile as well as liver and renal dysfunction to conventional fibrates.

N-3 fatty acid supplementation mediates lipid profile, including small dense LDL, when combined with statins: a randomized double blind placebo controlled trial

BackgroundEpidemiological and clinical evidence suggests that high-dose intake of omega 3 fatty acids (n-3 FA) have a favorable role in altering serum triglycerides (TG) and non-high density lipoprotein cholesterol (non-HDL-C) when combined with statins in hyperlipidemic patients. Their efficacy in altering low-density lipoprotein cholesterol (LDL-C) particle size is yet to be established.AimThis study evaluated the effects of supplementing 4 g/day Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on serum blood lipids, including small, dense LDL-C particle concentration, in hyperlipidemic patients receiving stable statin therapy.MethodsIn this randomized, placebo-controlled, double-blind parallel group study, 44 patients on statin therapy for > 8 weeks with non-HDL-C concentrations above 130 mg/dL were randomized into two groups. For 8 weeks, together with their prescribed statin, the intervention group received 4 g/day EPA + DHA (3000 mg EPA + 1000 mg DHA in ethyl ester form) and the placebo group received 4 g/day olive oil (OO). Measurements of serum non-HDL-C, TG, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C (including large - LDL I; intermediate - LDL II; and small - LDL III subclasses), very-low-density lipoprotein cholesterol (VLDL-C) concentration, were taken at baseline and post-intervention. Dietary intake was assessed with a weighed intake, 3-day food diary at week 4. Primary outcome measures were percent change in LDL III, non-HDL-C and LDL particle number.ResultsAt the end of treatment, the median percent change in serum LDL III concentration was significantly greater in the n-3 FA group plus atorvastatin compared to placebo (− 67.5% vs − 0%, respectively; P < 0.001). Supplementation with n-3 FA plus atorvastatin led to significant reductions in serum non-HDL-C (− 9.5% vs 4.7%, P < 0.01), TG (− 21.5% vs 6.2%, P < 0.001) and VLDL-C (− 36.9% vs 4.0%, P < 0.001) and TC (− 6.6% vs 2.1%, P < 0.001). Between the groups, no significant difference in percent change in the serum concentration of LDL-C, HDL-C, as well as in the LDL I and LDL II subclasses was observed.ConclusionIn this group of hyperlipidemic patients on a stable statin prescription, OM3 plus atorvastatin improved small dense LDL concentrations, non-HDL-C, VLDL-C and TG to a greater extent than atorvastatin alone. Further studies are warranted in this area.Trial registrationThis trial was retrospectively registered on 23 May 2019 on ClinicalTrials.gov with ID: NCT03961763.

New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins.

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

Pregnancy-Induced Hypertension: The Potential Role of Cholesterol Crystals in the Maternal Decidua

Lead Author's Financial Disclosures Quest Diagnostics. Study Funding None. Background/Synopsis Pregnancy-induced hypertension/preeclampsia are highly concerning complications of pregnancy, known risk factors for cardiovascular disease including endothelial dysfunction, proteinuria, elevated blood pressure, and presence of atherogenic very small LDL cholesterol particles. Cholesterol crystals (CCs) can form at sites of elevated cholesterol deposition including at the maternal uterine decidua in preparation for embryo implantation. However, CCs can injure the endothelial surfaces of arteries leading to vasospasm - with subsequent placental ischemia - important in the development of hypertension/preeclampsia. Objective/Purpose: Since dyslipidemia is associated with pregnancy complications we sought to determine if CCs are present in the post-delivery decidual tissue attached to the placenta in patients who developed a hypertensive disorder during their pregnancy in the Child Health Advances through Research with Mothers (CHARM) study. Methods Maternal decidua was dissected from placental tissues from both normal (n=5) and late gestational age hypertensive disorder in pregnancy cases (n=5). Cases were of similar gestational age, birth weight, and race. Tissues were prepared by avoiding ethanol to preserve CCs and then examined by scanning electron microscopy (SEM). Two sample runs were performed by SEM and tissues were scored in a blinded manner for presence or absence of CCs. Results Presence of CCs was detected in decidual placental specimens in 4/5 pregnancy- induced hypertensive disorder cases and 2/5 from normal gestational age-matched pregnancies. By SEM both needle and rhomboid forms (representing the anhydrous and monohydrate version of CCs) were found (Figure). Conclusions The presence of CCs in the maternal decidua is a critical finding. CCs are known to trigger an inflammatory response and cause arterial vasospasm. Although preliminary, this is an important finding that could be mechanistically critical in the development of hypertensive disorders of pregnancy. Quest Diagnostics.

Proprotein Convertase Subtilisin Kexin 9 (PCSK9) and nonHDL particles rise during normal pregnancy and differ by BMI

Serum lipids, including total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c), increase during pregnancy. Serum Proprotein Convertase Subtilisin Kexin 9 (PCSK9) is a vital regulator in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of liver cells inhibiting clearance of LDL-c. To determine the influence of weeks of pregnancy and obesity on circulating levels of essential lipid lipoproteins and PCSK9 in women with normal, uncomplicated pregnancies and deliveries. We performed a comprehensive lipid and lipoprotein profile during each trimester of pregnancy in 70 mostly Caucasian women with uncomplicated normal pregnancies and deliveries. Based on their first trimester BMI, we placed them into one of three categories: (<25 kg/m2 n=23, 25-30 kg/m2 n=25, or >30 n=22) kg/m2. Cholesterol, triglycerides, LDL cholesterol (LDL-c), non-HDL particles, and lipoprotein(a) were measured by spectrophotometry, ion mobility, and immunoturbidimetric assays. Elisa assay determined PCSK9 (active and total). Homeostatic Model Assessment (HOMA-IR) assessed insulin resistance in the second and third trimesters of pregnancy. Total and active PCSK9, LDL-c, and nonHDL particle concentrations were higher than reported for non-pregnant normal values, increased after the first trimester of pregnancy, and were highest from mid-gestation to the last trimester of pregnancy in the overweight and the obese. PCSK9 levels rise as normal pregnancy progresses. Levels are higher in persons who are obese, even after adjustment for insulin resistance. Defining normal PCSK9 levels during pregnancy must adjust for gestational age and BMI.