Changes In Lipoproteins Research Articles

Effects of a social support family caregiver training program on changing blood pressure and lipid levels among elderly at risk of hypertension in a northern Thai community.

Hypertension is becoming increasingly prevalent among the elderly. Family caregivers play an important role in caring for elderly people and empowering them to care for themselves. This study's goal was to see how social support training for family caregivers affected changes in hypertension, total cholesterol, and high-density lipoprotein (HDL), and how such support led to the prevention of hypertension behaviors among the elderly in rural areas. This was a quasi-experimental study with 268 elderly people at risk of hypertension and their caregivers. Sixty seven pairs of elderly people and their caregivers were assigned to the intervention and control groups. Baseline data were collected in November 2020. The intervention group received the Social Support Family Caregiver Training Program (SSFCTP), while the control group received a regular program from the local health authority. The activity lasted 12 weeks, with home visits and telephone check-ups along the way, and data collection took place after the program ended. The final data were collected three months after the end of the intervention. An analysis of repeated measures ANOVA showed the overall effect of the SSFCTP on knowledge, self-efficacy, health care behaviors, and blood pressure among elderly people during three different time periods (p<0.05). Furthermore, the intervention program had a time-dependent effect on knowledge, blood pressure, and total cholesterol levels (p<0.05). In terms of caregiver outcomes, there was an overall difference among the degrees of knowledge, self-efficacy, and behaviors toward health care displayed by elderly hypertensive patients during the three different time periods (p<0.05). The average knowledge and self-efficacy of the participants improved after the intervention. As a result, better self-care behaviors and lower blood pressure and total cholesterol levels were observed among the elderly participants after the intervention. The programs emphasized the importance of caregivers' roles in providing social support, boosting confidence, and encouraging participation in caring, monitoring, and assisting the elderly in controlling blood pressure and other health issues.

Association of Lipoprotein(a)-Associated Mortality and the Estimated Glomerular Filtration Rate Level in Patients Undergoing Coronary Angiography: A 51,500 Cohort Study.

Background: High lipoprotein(a) is associated with poor prognosis in patients at high risk for cardiovascular disease. Renal function based on the estimated glomerular filtration rate (eGFR) is a potential risk factor for the change of lipoprotein(a). However, the regulatory effect of eGFR stratification on lipoprotein(a)-associated mortality has not been adequately addressed.Methods: 51,500 patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) were included from the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936). These patients were grouped according to lipoprotein(a) quartiles (Q1–Q4) stratified by eGFR categories (<60 and ≥60 mL/min/1.73m2). Cox regression models were used to estimate hazard ratios (HR) for mortality across combined eGFR and lipoprotein(a) categories.Results: The mean age of the study population was 62.3 ± 10.6 years, 31.3% were female (n = 16,112). During a median follow-up of 5.0 years (interquartile range: 3.0–7.6 years), 13.0% (n = 6,695) of patients died. Compared with lipoprotein(a) Q1, lipoprotein(a) Q2–Q4 was associated with 10% increased adjusted risk of death in all patients (HR: 1.10 [95% CI: 1.03–1.17]), and was strongly associated with about 23% increased adjusted risk of death in patients with eGFR <60 mL/min/1.73m2 (HR: 1.23 [95% CI: 1.08–1.39]), while such association was not significant in patients with eGFR ≥60 mL/min/1.73m2 (HR: 1.05 [95% CI: 0.97–1.13]). P for interaction between lipoprotein(a) (Q1 vs. Q2–Q4) and eGFR (≥60 vs. eGFR <60 mL/min/1.73m2) on all-cause mortality was 0.019.Conclusions: Elevated lipoprotein(a) was associated with increased risk of all-cause mortality and such an association was modified by the baseline eGFR in CAG patients. More attention should be paid to the patients with reduced eGFR and elevated lipoprotein(a), and the appropriate lipoprotein(a) intervention is required.

Abstract 9768: Relationship of Atherogenic Lipoproteins with Insulin Resistance and Carotid Intimal Thickness in Youth at Risk for Cardiovascular Disease

Introduction: Youth with obesity and abnormal glucose tolerance (AGT) have an atherogenic lipoprotein (Lp) profile (small dense HDL and small LDL) and an increased risk for atherosclerotic disease, but the relative contributions of hyperglycemia and insulin resistance to the development of subclinical atherosclerosis in youth are not well defined. Hypothesis: Atherogenic Lp concentrations (ApoB, small LDLp, small HDLp) are associated with lower insulin sensitivity (Si) and greater carotid intimal thickness (cIMT), irrespective of glycemic status. Methods: In 155 youth with obesity (14.5±1.4y (mean±SD), 50% female; 42 lean (LC: BMI 25-85%ile), 44 insulin sensitive (OIS, fasting insulin ≤20μM/mL, BMI≥95%ile), 35 insulin resistant (OIR; fasting insulin&gt;20μM/mL, BMI≥95%ile) and 34 with AGT (23 prediabetes, 11 type 2 diabetes) we compared a standard lipid panel and Lp size and number. Linear regressions were used to test the associations between lipids/ NMR-derived Lp with Si index derived from a minimal model during an intravenous glucose test. cIMT was determined by ultrasonography. In a subset of 56 youth (21 LC, 19 OIS, 10 OIR, and 7 AGT) we explored the change in Si with the change in Lp and cIMT after 2 years. Results: OIR and AGT had higher triglycerides and lower HDL compared to LC, P &lt;0.01. Total cholesterol, LDL, and cIMT were comparable among all youth. ApoB, total triglyceride-rich Lp, LDLp and small LDLp) were similar in OIS, OIR, and AbGT and higher compared to LC. Among adolescents with obesity, Si was inversely associated with ApoB (β=-0.016), total LDLp (β=-0.91), small HDLp (β=-0.11) and cIMT (β= -2.99), all P &lt;0.001. There was no effect modification by obesity group. LnSi was associated with total HDL (β=1.30), large HDLp (β= 0.23) and small HDLp (β=-0.11), all P &lt;0.01) with steeper associations between AGT vs OIR and AGT vs OIS. After 2 years, the change in insulin sensitivity was not associated with changes in lipoproteins or cIMT. Conclusions: Among youth with obesity, insulin resistance was associated with atherogenic lipoproteins and cIMT, regardless of glucose tolerance status. Alterations in HDL particle number and size were distinct early manifestations that were observed in youth with AGT compared to their peers.

Abstract 9971: Longitudinal Lipoprotein(a) Concentrations and Cardiovascular Risk: A Prospective Cohort Study

Introduction: When indicated, current guidelines recommend a single measurement of lipoprotein(a) for cardiovascular risk assessment. However, temporal variability in lipoprotein(a) concentration is not well understood, and it is unclear if repeat testing may help refine risk prediction of coronary artery disease (CAD). Hypothesis: We examined the longitudinal stability of lipoprotein(a) measurements and tested whether instability in lipoprotein(a) molar concentration was associated with incident CAD. Methods: We assessed the correlation between baseline and first follow-up measurements of lipoprotein(a) in the UK Biobank (molar concentration n=16,017) and Mass General Brigham cohorts (molar concentration n=271; mass n=1,748; cholesterol n=1,237). The association between change in lipoprotein(a) molar concentration and incident CAD was assessed among 15,432 UK Biobank participants using Cox proportional-hazards models. Results: Baseline and follow-up lipoprotein(a) molar concentration were significantly correlated in the UK Biobank over a median 4.42 years (IQR: 1.24 years) and Mass General Brigham cohorts over a median 0.94 years (IQR: 0.60 years) (Spearman correlations: 0.96 and 0.92, respectively; p-values &lt;0.0001). Similar results were observed for lipoprotein(a) mass and cholesterol. Follow-up lipoprotein(a) molar concentration was significantly associated with risk of incident CAD (HR [95% CI] per 120 nmol/L: 1.31 [1.14-1.51], p-value=0.0002). However, delta lipoprotein(a) was not significantly associated with incident CAD independent of follow-up lipoprotein(a) (p-value=0.98). Conclusions: These findings suggest that, in the absence of therapies substantially altering lipoprotein(a) measures, longitudinal assessments of lipoprotein(a) are likely unnecessary for CAD risk assessment in the context of primary prevention.

Abstract 10469: Cardiometabolic Risk Factors as Causal Mediators of the Relationship Between High Body Mass Index and Chronic Kidney Disease: A Two-Step Mendelian Randomization Study and Mediation Analyses

Introduction: Observational studies suggest that obesity is a risk factor of chronic kidney disease (CKD). It is unclear whether this reflects a direct causal effect of obesity or an effect mediated by obesity-related metabolic changes. Hypotheses: We hypothesised that 1) obesity is a causal risk factor of CKD defined as eGFR &lt;60mL/min/1.73m 2 and 2) this causal effect is mediated through changes in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols, triglycerides, glucose, blood pressure and C-reactive protein (CRP) levels. Methods: To assess causality and investigate mediation, we used a combination of observational, two-step Mendelian randomization, and mediation analyses on individual-level data from two cohorts of the Danish general population (N=117,213). Results: Observationally, higher BMI was associated with a lower eGFR (change in eGFR; -0.81, confidence interval [CI]: -0.89- -0.73)) and a higher risk of CKD (odds ratio [OR]:1.19; 95% CI: 1.16-1.22) per 5kg/m 2 higher BMI (p for trend for both &lt;2.9 x10 -40 ). Mendelian randomization analyses supported a causal effect of higher BMI on lower eGFR (change in eGFR -17.3 mL/min/1.73m 2 (95%CI: -19.3- -15.3), and risk of CKD (risk ratio [RR]6.99 (95%CI: 1.63-30.1) per 5kg/m 2 higher BMI. Measured BMI and the BMI allele score used in Mendelian randomization analyses were associated with changes in levels of LDL and HDL cholesterols, triglycerides, glucose, blood pressure, and CRP. Observational and Mendelian randomization analyses showed evidence to support a causal effect of changes in levels of systolic and diastolic blood pressure, LDL cholesterol and CRP with lower eGFR and higher risk of CKD. Of the excess risk of CKD coming from high BMI, elevated systolic and diastolic blood pressure mediated 18%(95%CI:14-22) and 9% (7-11), respectively. 9% (95%CI: 8-12) was mediated by elevated LDL cholesterol and 29% (95%CI: 23-35) by elevated CRP. Conclusion: Triangulating evidence from observational and Mendelian randomization analyses provided evidence to support a causal role of obesity on the risk of CKD and that this causal effect may be partly mediated by elevated systolic and diastolic blood pressure, CRP and LDL cholesterol levels.

Changes of lipoprotein(a) levels with endogenous steroid hormones.

BackgroundLipoprotein(a) [Lp(a)] is an LDL‐like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a).MethodsLipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family‐based, multicentre, population‐based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24‐h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available.ResultsThe participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90th percentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty‐three per cent of Lp(a) variability was explained respectively by: age (2%, p < .001), LDL‐C (1%, p = .001), and two SNPs (39%, p value<2⋅10−16). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α‐OH‐DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%–1% of Lp(a) variability, but none of them reached significance in multivariable models.ConclusionsIn this contemporary population‐based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

Dielectric Properties of Phosphatidylcholine Membranes and the Effect of Sugars.

Simple carbohydrates are associated with the enhanced risk of cardiovascular disease and adverse changes in lipoproteins in the organism. Conversely, sugars are known to exert a stabilizing effect on biological membranes, and this effect is widely exploited in medicine and industry for cryopreservation of tissues and materials. In view of elucidating molecular mechanisms involved in the interaction of mono- and disaccharides with biomimetic lipid systems, we study the alteration of dielectric properties, the degree of hydration, and the rotational order parameter and dipole potential of lipid bilayers in the presence of sugars. Frequency-dependent deformation of cell-size unilamellar lipid vesicles in alternating electric fields and fast Fourier transform electrochemical impedance spectroscopy are applied to measure the specific capacitance of phosphatidylcholine lipid bilayers in sucrose, glucose and fructose aqueous solutions. Alteration of membrane specific capacitance is reported in sucrose solutions, while preservation of membrane dielectric properties is established in the presence of glucose and fructose. We address the effect of sugars on the hydration and the rotational order parameter for 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC) and 1-stearoyl-2-oleoyl-sn-glycero-3- phosphocholine (SOPC). An increased degree of lipid packing is reported in sucrose solutions. The obtained results provide evidence that some small carbohydrates are able to change membrane dielectric properties, structure, and order related to membrane homeostasis. The reported data are also relevant to future developments based on the response of lipid bilayers to external physical stimuli such as electric fields and temperature changes.

Myrmecodia platytyrea Methanol Tuber Extract Ameliorates Hyperglycemia In STZ-Induced Diabetic Sprague-Dawley Male Rats

Type 2 diabetes mellitus (T2DM) is one of the main non-communicable chronic diseases that has many complications that compromise the quality of life. Hence, the need to find alternatives to replace the current therapy or as an adjuvant. Tubers of Myrmecodia platytytrea (Rubiaceae) has been used traditionally as an alternative therapy for the management of cancer and other inflammatory-related disorders. The aim of this study was to investigate the potency of M. platytytrea methanolic tuber extract (MPMTE) as an antihyperglycemic agent, in vivo. :The streptozotocin (STZ)-induced diabetic rats were treated orally with MPMTE (100, 200 and 400 mg/kg) and metformin (positive control, 100 mg/kg) daily for 14 days. Blood glucose level and other biochemistry analysis were conducted including histological examination on liver, kidney and pancreas. The STZ-induced diabetic rats treated with MPMTE (200 and 400 mg/kg) had significant decreased (p&lt;0.05) in fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein (LDL) with no significant changes in high-density lipoprotein (HDL) compared to STZ-induced untreated diabetic rats. Liver, kidney and pancreas were devoid of any damage caused by STZ. MPMTE had strong antihyperglycaemic activity and was protective against any STZ-induced organ damage. Thus, MPMTE can be further developed into an adjuvant therapy for diabetic patients.

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

BackgroundPrevious studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients.MethodsA systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL.ResultsSix studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL.ConclusionsFor HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.

Insulin Resistance Is Associated with Right Ventricular Dysfunction.

Rationale: The effect of insulin resistance on left ventricular function is well documented; however, less is known regarding its effect on the right ventricle (RV). Objectives: To evaluate the association between insulin resistance and RV function by echocardiography in a cohort of adults without baseline cardiovascular disease. Methods: We performed a retrospective cohort study in the MESA (Multi-Ethnic Study of Atherosclerosis). Linear regression was used to examine the association between overall insulin resistance measured by the mean triglyceride (TG) to high-density lipoprotein (HDL) cholesterol ratio (TG:HDL) and change in TG:HDL over time for each participant with echocardiographic RV function. Logistic regression was used to calculate the odds ratios (ORs) of RV systolic and diastolic dysfunction. Results: Among 3,032 participants, higher mean TG:HDL was associated with lower (worse) absolute RV longitudinal strain (β, -0.38; 95% confidence interval [CI], -0.64 to -0.13; P < 0.01), tricuspid annular plane systolic excursion (β, -0.05; 95% CI, -0.07 to -0.04; P < 0.001), and higher odds of abnormal RV strain (OR, 1.26; 95% CI, 1.08 to 1.47; P < 0.01) and abnormal tricuspid annular plane systolic excursion (OR, 1.31; 95% CI, 1.14 to 1.51; P < 0.001). TG:HDL was also associated with lower ratio of tricuspid early to late ventricular filling velocities (E/A) (β, -0.03; 95% CI, -0.04 to -0.01; P < 0.01), higher ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity (E/e') (β, 0.15; 95% CI, 0.07 to 0.23; P < 0.001), and higher odds of graded RV diastolic dysfunction (OR, 1.19; 95% CI, 1.03 to 1.39; P < 0.05). These associations remained following multivariable adjustment. Conclusions: Insulin resistance was associated with decreased RV systolic and diastolic function after adjusting for alternative causes of RV dysfunction, suggesting that insulin-resistant individuals are at risk for early RV dysfunction, even in the absence of cardiovascular disease.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Effects of Fixed-dose Combination of Low-intensity Rosuvastatin and Ezetimibe Versus Moderate-intensity Rosuvastatin Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia: A Randomized, Double-blind, Multicenter, Phase III Study

We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy. This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p<0.0001), R2.5 group (-32.6±15.1%, p<0.0001), and R5 group (-38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups. Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349.

Quantitative Magnetic Resonance Imaging Assessment of the Relationships Between Fat Fraction and R2* Inside Carotid Plaques, and Circulating Lipoproteins.

Lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) are morphological features of high-risk atherosclerotic plaques. However, their relationship to circulating lipoproteins is unclear. To study associations between changes in lipoproteins vs. changes in LRNC (represented by fat fraction [FF]) and IPH (represented by R2*). Prospective. Fifty-two patients with carotid plaques, 33 males (63.5%), mean age 72 (±5). Four-point fast gradient Dixon magnetic resonance imaging (MRI) was used to quantify FF and R2* (to measure IPH) inside plaques and in vessel wall. Turbo-spin echo was used for T1 weighted sequences to guide manual segmentation. Carotid MRI and serum lipid levels were assessed at baseline and at 1-year follow-up. For patients, lipid-lowering therapy was customized to reduce low-density lipoprotein (LDL) levels below 1.8 mmol/L. Segmentation was performed with one set of regions of interest for the plaque and one for the vessel wall at the location of the plaque. Thereby MRI data for FF, R2*, and volumes in plaque- and vessel-wall segmentations could be obtained from baseline and follow-up, as well as changes over the study year. Pearson correlation coefficient for correlations. Paired samples t-test for changes over time. Significance at P < 0.05, 95% confidence interval. LDL decreased significantly (2.19-1.88 mmol/L, Z - 2.9), without correlation to changes in plaque composition, nor to the significant reduction in vessel-wall volume (-106.3 mm3 ). Plaque composition remained unchanged, FF +8.5% (P=0.366) and R2* +3.5% (P=0.304). Compared to plaque segmentations, R2* was significantly lower in the vessel-wall segmentations both at baseline (-9.3%) and at follow-up (-9.1%). The absence of correlations between changes in lipoproteins and changes in plaque composition indicates more complex relationships between these parameters than previously anticipated. The significant differences in both R2* and volume dynamics comparing plaque segmentations and vessel-wall segmentations suggest differences in their pathobiology of atherosclerosis. 1 TECHNICAL EFFICACY: Stage 4.

Antioxidant and Hypolipidemic Effects of Ipomoea batatas L and Pandanus conoideus Lam Combination on Rats Fed with High Cholesterol Diet

BACKGROUND: Chronic hypercholesterolemia is an important predisposing factor of cardiovascular diseases. The underlying process is commonly associated with oxidative stress. AIM: This study aimed to evaluate the effects of Ipomoea batatas (IB) L tablet and Pandanus conoideus (PC) Lam extract against oxidative stress and lipid profile in rats. METHODS: This study used a pre- and post-test control group design. Wistar male rats were randomized into four groups consisting of seven rats each. The groups were control group, PC Lam extract 0.4 cc/rat/day (PC group), IB L tablet 200 mg/rat/day (IB group), and PC 0.2 cc+IB 200 mg/rat/day (PC+IB group). All groups were received high cholesterol diet for 4 weeks. The blood samples at baseline and the end of this study were used for the lipid profile, superoxide dismutase (SOD), and malondialdehyde (MDA) examination. The result was then analyzed with an Analysis of Variance test. RESULTS: There were significant differences in changes of total cholesterol, Low-density lipoprotein, triglycerides, high-density lipoprotein, MDA, and SOD in the treatment group (PC, IB, PC+IB) compared to the control (p &lt; 0.001). The decrease of MDA and increase of SOD were mainly found in the PC+IB group compared to the PC group and IB group (p &lt; 0.05). The changes in lipid profiles were mainly found in the PC+IB group and PC group compared to the IB group (p &lt; 0.05). CONCLUSION: Administration of PC and IB combination is an effective hypolipidemic agent. This combination has superior antioxidant activity compared to the single-agent (PC or IB) and control.

Effects of Exenatide on Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes.

ObjectiveTo explore the effect of the glucagon-like peptide-1 receptor agonist exenatide on coagulation function and platelet aggregation in patients with type 2 diabetes mellitus (T2DM).MethodsThirty patients with newly diagnosed T2DM were enrolled as the case group, and 30 healthy people with matching age and sex were selected as the control group. Patients in the case group received exenatide treatment for 8 weeks. The general clinical data and biochemical indicators of all subjects were collected; and their peripheral blood platelet count, coagulation index, nitric oxide (NO), platelet membrane glycoprotein (CD62p), platelet activation complex-1 (PAC-1) and platelet aggregation induced by collagen, epinephrine (EPI), arachidonic acid (AA), and adenosine diphosphate (ADP) were detected.ResultsThe fibrinogen, CD62p, PAC-1, and platelet aggregation rates of the case group (pretreatment) are higher than those in the control group (EPI 77.90±6.31 vs 60.15±5.37, ADP 52.89±9.36 vs 47.90±6.16, and AA 76.09±3.14 vs.55.18±3.55); and the NO level is lower in the case group than in the control group (p<0.05, respectively). After 8 weeks of exenatide treatment in the case group, the CD62p, PAC-1, and platelet aggregation rates were lower than before the treatment (EPI: 61.96±8.94 vs 77.90±6.31 and AA: 50.98±6.73 vs 76.09±3.14); and the NO level was higher than before the treatment (p<0.05, respectively). Pearson correlation analysis showed that the changes in platelet aggregation rates (Δ EPI and ΔAA) of the patients in the case group after 8 weeks of exenatide treatment were positively correlated with the changes in body mass index, waist circumference, weight, blood lipids, fasting plasma glucose, haemoglobin A1c, fibrinogen, CD62p, and PAC-1 and negatively correlated with the changes in high-density lipoprotein and NO (p<0.05). Multiple linear regression analysis showed that the changes in NO, CD62p and PAC-1 were independent risk factors affecting the changes in platelet aggregation rates.ConclusionThe GLP-1R agonist exenatide can inhibit the activation state of platelets in patients with T2DM and inhibit thrombosis, which is beneficial to reduce the risk of cardiovascular events.

Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, open-label, active-controlled study (DOLOMITES).

BackgroundRoxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated for treatment of anaemia of chronic kidney disease (CKD).MethodsThis randomized, open-label, active-controlled Phase 3 study compared roxadustat versus darbepoetin alfa (DA) in non-dialysis-dependent (NDD) CKD patients with anaemia for ≤104 weeks. Doses were titrated to correct and maintain haemoglobin (Hb) within 10.0–12.0 g/dL. The primary endpoint was Hb response in the full analysis set, defined as Hb ≥11.0 g/dL and Hb change from baseline (BL; CFB) ≥1.0 g/dL in patients with BL Hb >8.0 g/dL or CFB ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL during the first 24 weeks of treatment without rescue therapy (non-inferiority margin, −15%). Key secondary endpoints included change in low-density lipoprotein (LDL), time to first intravenous (IV) iron use, change in mean arterial pressure (MAP) and time to hypertension occurrence. Adverse events were assessed.ResultsOf 616 randomized patients (roxadustat, 323; DA, 293), 424 completed treatment (roxadustat, 215; DA, 209). Hb response with roxadustat was non-inferior to DA (roxadustat: 256/286, 89.5% versus DA: 213/273, 78.0%, difference 11.51%, 95% confidence interval 5.66–17.36%). Roxadustat maintained Hb for up to 2 years. Roxadustat was non-inferior to DA for change in MAP and time to occurrence of hypertension and superior for change in LDL and time to first IV iron use. Safety profiles were comparable between groups. Findings suggest that there was no difference between groups regarding the composite endpoints major adverse cardiovascular events (MACEs) and MACE+ [MACE: 0.81 (0.52–1.25), P = 0.339; MACE+: 0.90 (0.61–1.32), P = 0.583].ConclusionsRoxadustat is a viable option to treat anaemia in NDD CKD patients maintaining Hb levels for up to 104 weeks.

Изменение концентрации сфинголипидов в плазме крови на фоне гиполипидемической терапии у пациентов с ранним атеросклерозом

Lipid-lowering drugs affect standard lipoproteins. However, we have no knowledge of changes in other plasma lipids upon treatment. The study was aimed to assess the dynamic changes in cholesterol, high- and low-density lipoproteins (HDL and LDL), triglycerides, and sphingolipids against the background of lipidlowering therapy in patients with premature coronary artery disease, atherosclerosis and hypercholesterolemia. A total of 18 patients were enrolled (the average age was 53 ± 6.7 years): in group 1, six patients received starting statin doses; group 2 included six patients, who failed to achieve LDL target levels against the background of treatment with starting statin doses, and received escalated statin doses; seven patients in group 3 failed to achieve LDL target levels against the background of treatment with maximum tolerated doses of statins and ezetimibe, and received alirocumab. Sphingolipid levels were assessed by mass spectrometry. In group 1, the decreased levels of ceramide Cer 14:1 (p = 0.046) and sphingomyelins SM 22:1, SM 22:0, SM 24:0 (p = 0.028) were observed. There were no significant changes in the levels of total cholesterol, LDL-C, HDL-C, and triglycerides. In group 2, the significantly decreased levels of total cholesterol (p = 0.028), LDL (p = 0.043), sphingomyelins SM 18:1, SM 24:1 and SM 26:1, and ceramide Cer 16:1 (p = 0.028) were observed. The level of Cer 22:1 significantly increased (p = 0.028). In group 3, total cholesterol decreased by 36.2%, and LDL-C (p = 0.018) decreased by 60.1% compared to baseline (ΔLDL-C = –2.67 ± 3.12); the elevated levels of ceramide Cer 22:1 (p = 0.028) were observed. It has been shown, that decreased sphingomyelin levels are associated with statin therapy and correlate with decreased levels of LDL-C. No significant dynamic changes in ceramides and ceramide risk against the background of statin therapy were observed, however, PCSK9 inhibitor added to therapy reduced the Cer 16:0/24:0 ratio.

Comparison of The Two Lipoprotein Apheresis Methods in The Treatment of Familial Hypercholesterolemia

Objective: Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder that causes a significant increase in low-density lipoprotein (LDL) cholesterol levels and leads to early coronary heart disease and cardiac mortality. Although this disease has a heterozygous (HeFH) and homozygous (HoFH) form, the incidence of HeFH is reported to be 1: 500, while HoFH is reported to be 1: 1 000 000. This disease is often caused by LDL receptor (most common), apolipoprotein B (Apo B), Proprotein Convertase Subtilisin/Kexin 9 (PCSK9), and LDL receptor adaptor protein (LDLRAP) gene mutations. Patients with FH do not respond well to lipid-lowering therapies such as a statin, and so lipoprotein apheresis is the treatment of choice. Material and Methods: We compared the results of lipoprotein apheresis in a 20-year-old female patient diagnosed with HoFH with two different methods [double-filtration plasmapheresis (DFPP) and dextran sulfate column (DSC) methods]. 40 lipoprotein apheresis procedures including 20 sessions of DFPP and 20 sessions of DSC were evaluated. Results: When the two methods were compared the changes in high-density lipoprotein, white blood cells, platelets, potassium, calcium, prothrombin time (INR) and activated partial thromboplastin time values were statistically significant. Conclusions: In conclusion, our study suggests that it would be more appropriate to choose the apheresis method according to the clinical and laboratory findings of the patient since it shows that two different methods have different effects on serum electrolyte values, hemostasis criteria and leukocyte and platelet counts.

Abstract P020: Triglyceride-lowering Lipoprotein Lipase Gene Variants And Improvements In Lipids And Lipoprotein Subspecies Defined By Apolipoprotein C-iii: Pounds Lost Trial

Introduction: Triglyceride-lowering variants in the lipoprotein lipase ( LPL ) gene have been associated with a lower risk of coronary heart disease. Lipoproteins are heterogeneous, and lipoprotein subspecies containing apolipoprotein C-III (ApoCIII) have adverse effects on cardiovascular disease (CVD) risk. Hypothesis: We examined associations of triglyceride-lowering LPL gene variants with long-term improvement in lipids and lipoprotein subspecies with ApoCIII in patients with obesity. We also investigated whether the LPL gene variants were significantly related to the improvement of the 10-year CVD risk estimated using the Framingham risk score in the participants of a weight-loss dietary intervention trial. Methods: This study included 382 overweight and obese adults of white European ancestry in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. We evaluated changes in lipids (triglycerides and cholesterol) and lipoproteins (such as very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) subfractions defined by the presence or absence of ApoCIII from baseline to 2 years after the intervention. A genetic risk score of LPL (LPL-GRS) was calculated by summing triglyceride-lowering alleles of five independent single nucleotide polymorphisms (SNPs). We calculated the Framingham risk score and estimated changes in the 10-year CVD risk after the intervention. Results: At baseline, higher scores of triglyceride-lowering LPL-GRS were significantly associated with higher levels of HDL cholesterol (p= 0.0065) and lower levels of triglycerides (p= 0.017). Higher LPL-GRS was also associated with more decreases in total triglycerides (p= 0.028) and triglycerides in VLDL with ApoCIII (p=0.018) at 2 years. The LPL-GRS was also predictive of 2-year improvements in other atherogenic lipoprotein subtypes, such as cholesterol in VLDL with ApoCIII (p= 0.037) and cholesterol in LDL with ApoCIII (p= 0.027) after the intervention. Further, the LPL-GRS was significantly associated with a 2-year reduction of the estimated CVD risk, regardless of the initial risk status (p=0.034). Conclusion: The triglyceride-lowering LPL-GRS was significantly predictive of improvements in unfavorable lipid profiles, including lipoprotein subtypes containing ApoCIII after consuming a weight-loss diet in patients with obesity. The reduction of the estimated CVD risk after the dietary intervention was predicted by the LPL-GRS at the pre-intervention.

Acquired hypolipoproteinemia and hemophagocytic lymphohistiocytosis: A previously unexplored association?

e19041 Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that is the result of macrophage hyperactivation, leading to disordered cellular phagocytosis that is highly fatal if left untreated. The precise precipitating factor that leads to HLH is presently unknown. Secondary HLH is more common in adults and has numerous causes, including several autoimmune diseases, rheumatological disorders, cancers, and infections. These predisposing conditions are similar in that they are characterized by increased rates of cellular replication and often accompanied by significant oxidative stress. Lipoprotein changes in HLH have not been previously described. Methods: Between August 2018 and June 2020, three cases of secondary HLH were discovered to have profound hypolipoproteinemia with severely reduced total cholesterol, undetectable LDL-C, and extremely depressed HDL-C levels. As a result, a retrospective review of the University of Michigan HLH registry was performed, identifying cases of HLH where full lipid panels were performed as part of their diagnosis and/or treatment between 2012 and 2020. 18 total patients were identified with a confirmed diagnosis of HLH and who had a full lipid panel performed as a part of their diagnostic evaluation. Results: 100% of patients were found to have HDL-C less than 30 mg/dL, consistent with severe HDL-C deficiency, and 84% had HDL-C less than 20 mg/dL. Similarly, 74% of patients were found to have LDL-C &lt; 100 mg/dL, 47% with LDL-C &lt; 50 mg/dL, and 33% had undetectable LDL-C levels. Median total cholesterol was 124 mg/dL, median LDL-C was 35 mg/dL, and median HDL-C was 7 mg/dL. Notably, these reductions were not explained by the observed variability in hypertriglyceridemia, and marked hypertriglyceridemia &gt; 500 mg/dL was not seen in 88% of patients, with a median triglyceride value of 279. Interestingly, one patient displayed an opposite phenotype with extreme hyperlipidemia, with total cholesterol of 727 mg/dL and LDL-C of 658 md/dL. Conclusions: Severe derangements in circulating lipoproteins appear to be a common finding within sHLH.These findings have not been previously described within the context of the disease. Herein, we provide a framework for hypothesizing why HLH may potentially occur in the setting of hypolipidemia. Furthermore, we provide an additional hypothesis that serves to justify why these changes may occur in an evolutionary context.