Low Lipoprotein Research Articles

Genetic proxies for PCSK9 inhibition associate with lipoprotein(a): Effects on coronary artery disease and ischemic stroke

Background and aimsPost hoc analyses of clinical trials show that PCSK9 inhibitors might lower lipoprotein(a), but whether this effect contributes to reductions in cardiovascular risk remains unknown. We aimed to assess whether genetically proxied PCSK9 inhibition influences lipoprotein(a) (Lp(a)), and whether any such effect could mediate its effects on coronary artery disease (CAD) and ischemic stroke (IS). MethodsTo explore associations between the genetic proxies for PCSK9 inhibitors and Lp(a) levels, we used UK Biobank data (310,020 individuals). We identified 10 variants in the PCSK9 gene associated with lower PCSK9 and LDL-C levels as proxies for PCSK9 inhibition. We explored the effects of genetically proxied PCSK9 inhibition on Lp(a) levels, as well as on odds of CAD (60,801 cases, 184,305 controls) and IS (60,341 cases, 454,450 controls) in two-sample Mendelian randomization analyses. In mediation analyses, we assessed the effects of genetically proxied PCSK9 inhibition on CAD and IS mediated through reductions in Lp(a) levels. ResultsGenetically proxied PCSK9 inhibition (1-SD decrement in PCSK9 concentration; corresponding to 20.6 mg/dl decrement in LDL-C levels) was associated with a 4% decrease in log-Lp(a) levels (beta: −0.038, 95%CI: −0.053 to −0.023). We estimated a 0.8% reduction in the odds for CAD (OR: 0.992, 95%CI: 0.989–0.995) and a 0.5% reduction in the odds for atherosclerotic IS (OR: 0.995, 95%CI: 0.992–0.998) due to reductions in Lp(a) levels through genetically proxied PCSK9 inhibition, corresponding to 3.8% and 3.2% of the total effects, respectively. ConclusionsGenetic proxies for PCSK9 inhibition are associated with lower Lp(a) levels. However, Lp(a) lowering explains only a small proportion of the total effects of genetic proxies for PCSK9 inhibitors on risk of CAD and IS.

Isolation and analysis of tumor‑derived extracellular vesicles from head and neck squamous cell carcinoma plasma by galectin‑based glycan recognition particles.

Extracellular vesicles (EVs) have recently come into the spotlight as potential cancer biomarkers. Isolation of pure EVs is complex, so wider use requires reliable and time-efficient isolation methods. In the present study, galectin-based magnetic glycan recognition particles, EXÖBead® were investigated for their practicality as a novel EV isolation technique, exemplified here for squamous cell carcinoma of the head and neck. Analysis of the isolation method showed a high concentration of pure EVs with detection of specific EV markers such as CD9, CD63, CD81 and TSG101. No apolipoprotein A1 was shown in the isolates, indicating low contamination of this isolation technique compared with size exclusion chromatography. In addition, common leukocyte antigen (CD45), three HNSCC [epithelial cell adhesion molecule (EpCAM), pan-cytokeratin and programmed death-ligand 1 (PD-L1)] and PanEV markers (premixed CD9, CD63 and CD81 anti-bodies) were measured by bead-based flow cytometry (BFC). BFC revealed that CD45Neg PanEV+, EpCAM+ PanEV+ and PD-L1+ PanEV+ were significantly higher in tumor patients compared with healthy control plasma. CD45Neg PanEV+ and CD45+ PanEV+ carrying two or three HNSCC biomarkers were also significantly higher in tumor patients compared with healthy controls (BFC). Comparison of the functional immunosuppression effect of eluted tumor patient plasma EVs from EXÖBead® and commercial polyethylene glycol isolation showed a significant tumor-dependent increase in concentration of EVs. A peripheral blood mononuclear cell activation assay also showed that the T-cell functionality of tumor patient plasma EVs isolated with EXÖBead® was preserved in vitro. In conclusion, isolation using galectin-based magnetic glycan recognition particles is a novel method for isolating plasma EVs with low lipoprotein contamination. Bead-based flow cytometry provided an easy way to understand EV subpopulations. EXÖBead® therefore showed great potential as a new isolation tool with high throughput capacity that could potentially be used in a clinical setting.

New Horizons: Revival of Lipoprotein (a) as a Risk Factor for Cardiovascular Disease.

The status of lipoprotein (a) [Lp(a)] as a cardiovascular risk factor has been resurrected by advances in genetics. Mendelian randomization studies show a causal link of Lp(a) with coronary artery disease (CAD), peripheral artery disease (PAD), and calcific aortic valve stenosis (CAVS). The genetics of Lp(a) is complex and extends beyond the kringle-IV type 2, as it is also dependent on ancestry. The plasma concentration of Lp(a) is determined by the hepatic production of apolipoprotein(a) [apo(a)] component of Lp(a), supporting the use of nucleic acids that inhibit the messenger RNA (mRNA) gene transcript for apo(a). Analytical barriers to measurement of Lp(a) are being addressed using isoform independent assays and a traceable standard. The association of Lp(a) and atherosclerotic cardiovascular disease is higher for myocardial infarction than PAD and CAVS. Increased risk of type 2 diabetes mellitus associated with low Lp(a) levels is perplexing and requires further investigation. The greatest advancement in Lp(a)-lowering therapies is based on using RNA therapeutics that are now being investigated in clinical trials. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition lowers Lp(a) modestly, but whether cardiovascular benefit is independent of low-density lipoprotein lowering remains unclear. Opportunistic and selective testing for Lp(a) is supported by moderate evidence, with the case for universal screening premature. Modification of behavioral and clinical risk factors may be targeted to mitigate Lp(a)-mediated risk of cardiovascular disease. Clinical practice guidelines have been developed to address gaps in care of high Lp(a), but full implementation awaits the findings of clinical outcome trials using RNA-directed therapies currently underway.

Lipoprotein(a) during COVID-19 hospitalization: Thrombosis, inflammation, and mortality

Background and aimsHigh levels of lipoprotein(a) could worsen the outcome of COVID-19 due to prothrombotic and proinflammatory properties of lipoprotein(a). We tested the hypotheses that during COVID-19 hospitalization i) increased thrombotic activity and inflammation are associated with lipoprotein(a) levels, and ii) lipoprotein(a) levels are associated with rate of hospital death and discharge. MethodsWe studied 211 patients admitted to Copenhagen University Hospital in 2020 with COVID-19, that is, prior to any vaccination. Thrombotic activity was marked by elevated D-dimer while inflammation was marked by elevated interleukin-6, C-reactive protein, and procalcitonin. Patients were followed until death (N = 36) or discharge (N = 175). ResultsA 2-fold higher D-dimer was associated with 14% (95%CI: 8.1–20%) higher lipoprotein(a). Conversely, 2-fold higher interleukin-6, C-reactive protein, and procalcitonin were associated with respectively 4.3% (0.62–7.8%), 5.7% (0.15–5.2%), and 8.7% (5.2–12%) lower lipoprotein(a).For hospital death, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 1.26 (95%CI:0.91–1.73). Corresponding hazard ratios per 2-fold higher biomarker were 0.93 (0.75–1.16) for D-dimer, 1.42 (1.17–1.73) for interleukin-6, 1.44 (0.95–2.17) for C-reactive protein, and 1.44 (1.20–1.73) for procalcitonin. For hospital discharge, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 0.91 (95%CI:0.79–1.06). Corresponding hazard ratios per 2-fold higher biomarker were 0.86 (0.75–0.98) for D-dimer, 0.84 (0.76–0.92) for interleukin-6, 0.80 (0.71–0.90) for C-reactive protein, and 0.76 (0.67–0.88) for procalcitonin. ConclusionsIn COVID-19 patients, thrombotic activity marked by elevated D-dimer was associated with higher lipoprotein(a) while elevated inflammatory biomarkers of interleukin-6, C-reactive protein, and procalcitonin were associated with lower lipoprotein(a); however, elevated lipoprotein(a) was not associated with rate of hospital death or discharge.

Structural studies on LDL from patients with high and low lipoprotein (a)

Structural studies on LDL from patients with high and low lipoprotein (a)

Lipoprotein (a) in familial hypercholesterolaemia.

The role of lipoprotein (a) in atherogenesis has been the subject of argument for many years. Evidence that it is raised in familial hypercholesterolaemia has been disputed not least because a mechanism related to low density lipoprotein (LDL) receptor mediated catabolism has been lacking. Whether lipoprotein (a) increases the already raised atherosclerotic cardiovascular disease (ASCVD) risk in familial hypercholesterolaemia is also more dubious than is often stated. We review the evidence in an attempt to provide greater clarity. Lipoprotein (a) levels are raised as a consequence of inheriting familial hypercholesterolaemia. The mechanism for this is likely to involve increased hepatic production, probably mediated by PCSK9 augmented by apolipoprotein E. The extent to which raised lipoprotein (a) contributes to the increased ASCVD risk in familial hypercholesterolaemia remains controversial.Unlike, for example, statins which are effective across the whole spectrum of LDL concentrations, drugs in development to specifically lower lipoprotein (a) are likely to be most effective in people with the highest levels of lipoprotein (a). People with familial hypercholesterolaemia may therefore be in the vanguard of those in whom theses agents should be exhibited. Inheritance of familial hypercholesterolaemia undoubtedly increases the likelihood that lipoprotein (a) will be raised. However, in familial hypercholesterolaemia when ASCVD incidence is already greatly increased due to high LDL cholesterol, whether lipoprotein (a) contributes further to this risk cogently needs to be tested with drugs designed to specifically lower lipoprotein (a).

LncRNA KCNQ1OT1 Participates in Ox-LDL-Induced Proliferation/Apoptosis Imbalance in Vascular Smooth Muscle Cells by Regulating the MiR-196a-5p/FOXO1 Axis

Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxidation low lipoprotein stimulation.Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The functions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed.Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative regulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipoprotein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum samples from individuals with carotid atherosclerosis.Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.

The prevalence of smoking among the population of residents of Primorsky krai (according to the regional stage of the ESSAY-RF in Primorsky Krai)

Objective: to analyze the prevalence of smoking in the population of conditionally healthy residents of Primorsky Krai included in the regional stage of the ESSAY–RF study and establish its relationship with traditional cardiovascular risk factors.Materials and methods: the work uses the database of the study «Epidemiology of cardiovascular diseases in various regions of the Russian Federation» (ESSAY-RF) in Primorsky Krai. In the study population, age, gender, smoking fact, pack/years index (PYI), body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP) levels, heart rate (HR), lipid spectrum (total cholesterol (TC), low lipoproteins (LDL) and high-density lipoproteins (HDL), non-high-density lipoproteins (non-HDL), triglycerides (TG)), uric acid level (UA) were analyzed. Statistical data processing was carried out using the StatTech v. 2.7.1 program (developed by Stattech LLC, Russia).Results: predictors of the development of chronic non-communicable diseases (CNCD) in groups of smokers (n=327) and non-smokers (n=1160) were studied. In the general group of smokers, an increase in the level of UA was found. When dividing the group of smokers into subgroups depending on the intensity of smoking (I-A with a low-medium degree of nicotine dependence at PYI<10, and I-B with a high degree of nicotine dependence at PYI>10), higher values of SBP, DBP, HR, TG, UA and lower values of HDL between groups I-B and non-smokers. The conducted correlation analysis showed the presence of a direct relationship between the intensity of smoking and the indicators of SBP, DBP, HR, TG and the reverse — with the level of HDL. The use of the method of paired linear regression with the condition of an increase in PYI by 1 in intensely smoking individuals showed a slight effect on the growth of SBP, DBP, UA, TG and HDL. Obviously, a high degree of nicotine dependence per se is a factor closely associated with an increase in the level of SBP, DBP, HR, UA, TG content and a decrease in HDL. With its even greater increase, the change in the predictors of CNCD occurs less noticeably and may be influenced by other positions, indicating the need for complete cessation of smoking at the stage of the presence of risk factors.Conclusion: taking into account the established relationships, it is necessary to strengthen preventive-oriented measures and motivating the population to completely give up smoking, and it is also necessary to monitor the main and additional significant predictors in the framework of outpatient follow-up.

Probiotics Interact With Lipids Metabolism and Affect Gut Health.

Probiotics have attracted much attention due to their ability to modulate host intestinal microbe, participate in nutrient metabolism or immunomodulatory. Both inflammatory bowel disease (IBD) and bowel cancer are digestive system disease, which have become a global public health problem due to their unclear etiology, difficult to cure, and repeated attacks. Disturbed gut microbiota and abnormal lipid metabolism would increase the risk of intestinal inflammation. However, the link between lipid metabolism, probiotics, and IBD is unclear. In this review, we found that different lipids and their derivatives have different effects on IBD and gut microbes. ω-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid, eicosapentaenoic acid, and their derivatives resolvin E1, resolvin D can inhibit oxidative stress and reactive oxygen species activate NFκB and MAPk pathway. While ω-6 PUFAs linoleic acid and arachidonic acid can be derived into leukotrienes and prostaglandins, which will aggravate IBD. Cholesterol can be converted into bile acids to promote lipid absorption and affect microbial survival and colonization. At the same time, it is affected by microbial bile salt hydrolase to regulate blood lipids. Low denstiy lipoprotein (LDL) is easily converted into oxidized LDL, thereby promoting inflammation, while high denstiy lipoprotein (HDL) has the opposite effect. Probiotics compete with intestinal microorganisms for nutrients or ecological sites and thus affect the structure of intestinal microbiota. Moreover, microbial short chain fatty acids, bile salt hydrolase, superoxide dismutase, glutathione, etc. can affect lipid metabolism and IBD. In conclusion, probiotics are directly or indirectly involved in lipids metabolism and their impact on IBD, which provides the possibility to explore the role of probiotics in improving gut health.

Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk.

Statins lower low-density lipoprotein cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced low-density lipoprotein reduction increases risk of intracerebral haemorrhage has been debated for almost two decades. Here, we explored whether genetically predicted on-statin low-density lipoprotein response is associated with intracerebral haemorrhage risk using Mendelian randomization. Using genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms of on-statin low-density lipoprotein response and tested it in the population-based UK Biobank. We extracted statin drug and dose information from primary care data on a subset of 225 195 UK Biobank participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal low-density lipoprotein measurements with generalized mixed models and explored associations with incident intracerebral haemorrhage using Cox regression analysis. Statins were prescribed at least once to 75 973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean low-density lipoprotein decreased by 3.45 mg/dl per year [95% confidence interval (CI): (-3.47, -3.42)] over follow-up. A higher genetic score of statin response [1 standard deviation (SD) increment] was associated with significant additional reductions in low-density lipoprotein levels [-0.05 mg/dl per year, (-0.07, -0.02)], showed concordant lipidomic effects on other lipid traits as statin use and was associated with a lower risk for incident myocardial infarction [hazard ratio per SD increment 0.98 95% CI (0.96, 0.99)] and peripheral artery disease [hazard ratio per SD increment 0.93 95% CI (0.87, 0.99)]. Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher intracerebral haemorrhage risk in a model adjusting for statin dose [hazard ratio per SD increment 1.16, 95% CI (1.05, 1.28)]. On the contrary, there was no association with intracerebral haemorrhage risk among statin non-users (P = 0.89). These results provide further support for the hypothesis that statin-induced low-density lipoprotein reduction may be causally associated with intracerebral haemorrhage risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacological low-density lipoprotein lowering in the pathogenesis of intracerebral haemorrhage.

Role of Lipoproteins in the Pathophysiology of Breast Cancer.

Breast cancer is one of the most common malignancies in women and the leading cause of cancer mortality. Hypercholesterolemia and obesity are potential risk factors for the incidence of breast cancer, and their detection can enhance cancer prevention. In this paper, we discuss the current state of investigations on the importance of lipoproteins, such as low denisity lipoproteins (LDL) and high density lipoproteins (HDL), and cholesterol transporters in the progression of breast cancer, and the therapeutic strategies to reduce breast cancer mortality. Although some research has been unsuccessful at uncovering links between the roles of lipoproteins and breast cancer risk, major scientific trials have found a straight link between LDL levels and incidence of breast cancer, and an inverse link was found between HDL and breast cancer development. Cholesterol and its transporters were shown to have significant importance in the development of breast cancer in studies on breast cancer cell lines and experimental mice models. Instead of cholesterol, 27-hydroxycholesterol, which is a cholesterol metabolite, is thought to promote propagation and metastasis of estrogen receptor-positive breast cancer cell lines. Alteration of lipoproteins via oxidation and HDL glycation are thought to activate many pathways associated with inflammation, thereby promoting cellular proliferation and migration, leading to metastasis while suppressing apoptosis. Medications that lower cholesterol levels and apolipoprotein A-I mimics have appeared to be possible therapeutic agents for preventing excessive cholesterol’s role in promoting the development of breast cancer.

Effect of oral administration and topical gel application of thymol and low-level laser therapy on oxidative stress, inflammatory biomarkers and dermatitis in patients with type 2 diabetes mellitus

Background:Unmanaged diabetes mellitus, as a chronic metabolic disease, has dangerous consequences. The consequences of diabetes can be delayed and controlled by using antioxidants and anti-inflammatory substances in the food compounds.Objective: One of the main objectives of this study was to evaluate thymol administration and low-level laser therapy on the change of inflammatory and, oxidative indicators, and lipid profiles in patients with type 2 diabetes. Another aim was to study the effect of thymol oil extract on dermatitis.Methods:Thirty volunteers with type 2 diabetes and thirty healthy volunteers as controls were selected. Blood samples were taken from all subjects before the study. The diabetic group was divided into four groups: untreated, treated with low-level laser, treated with thymol (25 mg/kg/30 days) and treated with thymol and laser. Glucose, advanced glycation end products, malondialdehyde, oxidized low level laser, reactive oxygen species, peroxide hydrogen, total cholesterol, triglyceride, and inflammatory cytokines such as tumor necrosis factor alpha, interleukin-1 beta and interleukin-1 alpha were measured and compared between diabetic and control groups and within diabetic groups. Thymol gel oil extract (0.5%) was studied in reduction of dermatitis in the feet of the diabetic group.Results:Thymol administration, along with low-level laser therapy, reduced levels of cytokines except for interleukin-1 alpha, total cholesterol, triglycerides, advanced glycation end products, hydrogen peroxide, malondialdehyde, and oxidized low density level lipoprotein (P value < 0.05). The effect of 0.5% thymol oil as a gel on the reduction of dermatitis was not significant.Conclusion:Thymol administration and thymol gel as well as low-level laser therapy, as adjunctive methods, through the reduction of free radicals and oxidative stress can be useful in controlling and reducing the diabetes complications.Keywords: Diabetes mellitus, Thymol, Topical gel, Low-level laser therapy, Dermatitis

Statin intolerance and statin-associated muscular pain

Statine gehören zu den bestuntersuchten Medikamenten. Aufgrund der umfangreichen Evidenz in Bezug auf Wirksamkeit und Sicherheit gehören sie zur Basis der lipidsenkenden Therapie. Während die Verträglichkeit von Statinen in den großen verblindeten Studien auf Placeboniveau liegt, stellt die sogenannte Statinintoleranz (SI) im klinischen Alltag ein häufiges und komplexes Problem dar. Am häufigsten werden statinassoziierte muskuläre Schmerzen (SAMS) berichtet. SI ist in vielen Fällen mit einer unzureichenden Senkung des LDL(„low-density lipoprotein“)-Cholesterins (LDL-C) assoziiert und erhöht damit das kardiovaskuläre Risiko. Die Diagnose von SAMS basiert auf dem Ausschluss möglicher alternativer Ursachen für Muskelsymptome und dem Ausschluss von Noceboeffekten durch eine diagnostische Strategie des Absetzens der Statinbehandlung, der Beobachtung und Bewertung der Symptome, gefolgt von einer erneuten Verabreichung eines anderen, zunächst niedrig dosierten Statins mit nachfolgender Dosissteigerung. Ein Großteil der Patienten mit SI und SAMS kann durch dieses Vorgehen Statine dauerhaft und ohne Beschwerden einnehmen. Bei unzureichender LDL-C-Senkung kommen frühzeitig Kombinationstherapien zum Einsatz. Es ist eine wichtige Aufgabe der verschreibenden Ärzte und aller an der Behandlung Beteiligten, durch eine geeignete Kommunikation die Einnahmetreue von Statinen zu erhöhen. Zahlreiche Fragen zu SI sind noch offen und werden u. a. in einem laufenden Register adressiert.

Update on PCSK9 inhibition

Lowering of low-density lipoprotein (LDL) cholesterol represents one of the most effective interventions in cardiovascular prevention. Besides the oral treatment with statins, ezetimibe and bempedoic acid, subcutaneously administered inhibitors of proprotein convertase subtilisin-kexin type9 (PCSK9) have been established as further cornerstones of lipid-lowering treatment. The antibodies evolocumab and alirocumab are administered subcutaneously every 2-4 weeks and lower LDL cholesterol by around 60%, independent of pre-treatment with very good tolerability. Both drugs successfully reduced cardiovascular endpoints in large outcome trials. Anovel principle of PCSK9 inhibition is RNA interference, which is exploited by the novel compound inclisiran. Inclisiran is adouble-stranded modified RNA molecule, which neutralizes the mRNA of PCSK9 and thus inhibits PCSK9 protein synthesis intracellularly. Inclisiran only needs to be administered every 6months. The cardiovascular outcome trial ORION‑4 is currently ongoing. In Germany, prescription of PCSK9 inhibitors is regulated by the decision of the Federal Joint Committee. Novel strategies to inhibit PCSK9 function are under development and include orally available drugs and animal experiment concepts on gene editing, which are in different states of evaluation.

Comparison of plasma separation using centrifugation or filtration for MONET lipoprotein apheresis in patients with cardiovascular disease and severe dyslipidemia.

Homozygous or severe heterozygous familial hypercholesterolemia and elevated lipoprotein(a) levels may be treated with membrane filtration. The MONET system (Fresenius Medical Care, Bad Homburg, Germany) involves plasma separation by centrifugation or filtration. Whether the method of plasma separation affects lipoprotein lowering and treatment safety was investigated in a single-center retrospective study. The centrifugation-based plasma separation achieved a higher plasma flow and shorter time to treat 1L of plasma (46.2 ± 8.6min), than the filtration-based system (71.5 ± 40.0min; p=0.001). The mean reduction of LDL-cholesterol was 69% and 67% with centrifugation and filtration and was 75% for lipoprotein(a) with both plasma separation methods. A reduction of IgM by more than 60%, of albumin and total protein by approximately 20% and low frequency of side effects was observed. The efficacy of lowering atherogenic lipoproteins was comparable with both plasma separation methods. Centrifugation was more time-efficient compared to filtration.

Serum Levels of Cholesterol and Lipoproteins in Patients With Symptomatic Paravalvular Leaks

Paravalvular leak (PVL) is a complication of valve replacement surgery which may lead to serious clinical consequences including hemolytic anemia. This study aimed to retrospectively evaluate the effect of successful intervention on serum lipid parameters in patients with PVL. A total of 106 patients (mean age: 57.2 ± 13.6 years, male: 67) who underwent surgical or transcatheter closure for symptomatic PVL were enrolled in this study. During the follow-up period, hemolysis and lipid parameters were evaluated at each clinical visit. This is the first study describing the effects of PVL on lipid metabolism after surgical or transcatheter closure. In the study, 18 patients (17%) had aortic PVL, 84 patients (79%) had mitral PVL, and 4 patients (3.8%) had both aortic and mitral PVL. A total of 59 patients underwent transcatheter closure and 47 patients were treated surgically. Technical success of the procedures was 83%. After successful PVL closure, hemoglobin and haptoglobin levels increased significantly (9.5 ± 1.3 vs 11.9 ± 2.1 g/dl, p <0.001 and 16.6 ± 7.9 vs 34.1 ± 19.9 mg, p <0.001, respectively). A significant increase in total cholesterol (158.9 ± 42.7 vs 209.3 ± 58.7 mg/dl, p <0.001), low-density lipoprotein cholesterol (99.1 ± 33.8 vs 133.9 ± 45.7 mg/dl, p <0.001), and high-density lipoprotein cholesterol (39.8 ± 12.4 vs 44.8 ± 11.7 mg/dl, p <0.001) levels was observed after successful PVL closure. In conclusion, symptomatic patients with PVL had hypocholesterolemia, reflected by low serum lipoprotein levels. After successful PVL closure, an increase in serum lipoprotein levels was observed. The recovery in levels of lipoproteins could be used as a marker of successful PVL closure, and absence of recovery of lipoprotein levels may indicate incomplete closure.

Analysis of C reactive protein and other inflammatory markers in the cardiovascular risk prediction in women

Objective: To evaluate the role of C Reactive Protein and other inflammatory markers in cardiovascular risk prediction. Study Design: A prospective case-control study. Place and Duration: At Cardiology Department of Nishtar Medical University &amp; Hospital Multan from 5th Oct 2020 to 5th Oct 2021. Methodology: A total of 150 postmenopausal women were studied and divided into CVD patients (n=50) and control patients (n=100). The analyzed markers of inflammation included Interleukin-6, high-sensitivity C-reactive Protein, Soluble ICAM-1 (slCAM-1), and Amyloid-A. The Homocysteine, Lipid Profile, and Low and High-density lipoprotein levels were also evaluated. Cardiovascular events considered in our study were death after coronary artery disease, non-fatal heart attack or stroke, or requiring coronary-revascularization methods. Results: In univariate analysis, it was observed that high-sensitivity C-reactive protein levels were the strongest risk predictor of cardiovascular diseases. Amyloid-A, High-density lipoprotein, Cholesterol, Low-density lipoprotein cholesterol, Soluble lCAM-1, Interleukin-6, Apolipoprotein B-100, Homocysteine, total cholesterol, and the ratio of total cholesterol to high-density lipoprotein cholesterol also contributed to predicting cardiovascular diseases. High-sensitivity C-reactive protein (95% Cl: 1.4(1.0-2.0)) and Amyloid-A (95% Cl: 0.9(0.7-1.5)) were also strong risk predictors in women. On the other hand, in multivariate analyses, only High-sensitivity C-reactive protein and the ratio of total cholesterol to high-density lipoprotein cholesterol were independent risk predictors. Conclusion: As high-sensitivity CRP is an independent cardiovascular risk predictor, adding it to lipid screening may be a good procedure for identifying women at risk of cardiovascular diseases. Keywords: High sensitivity C-reactive protein, Cardiovascular events, Amyloid-A, Lipids, Inflammatory markers

Value of Genetic Testing for Lipoprotein(a) Variants

Value of Genetic Testing for Lipoprotein(a) Variants

Biomembrane-mimetic hemoperfusion adsorbent for efficient removal of low-density lipoprotein from hyperlipemia blood.

Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Low and High-Density Lipoprotein Cholesterol and 10-Year Mortality in Community-Dwelling Older Adults: The Shanghai Aging Study

BackgroundThe relationship between serum cholesterol and mortality remains disputed. This study aimed to examine the association of low and high-density lipoprotein cholesterol (LDL-C and HDL-C) with all-cause mortality among community-dwelling older adults in the Shanghai Aging Study.MethodsWe followed 3,239 participants free of lipid-lowering agents for a median of 10 years. Levels of LDL-C and HDL-C were measured at baseline using fasting blood samples. Survival status was confirmed by the local mortality surveillance system. The associations between the levels of LDL-C, HDL-C, and all-cause mortality were assessed by Cox proportional hazards models.ResultsThe increment of LDL-C concentration was related to a lower risk of mortality (p for trend < 0.05). Using the highest quintile of LDL-C (≥4.10 mmol/L) as a reference, the lowest quintile of LDL-C (<2.61 mmol/L) was associated with the highest risk of mortality, after adjusting for confounders (HR 1.67; 95% CI 1.26–2.21), exclusion of death within the first 2 years of follow-up (HR 1.57; 95% CI 1.17–2.11), and exclusion of functionally impaired participants (HR 1.46; 95% CI 1.07–2.00). A U-shape relationship was found between HDL-C level and the mortality risk. Using the third quintile of HDL-C (1.21–1.39 mmol/L) as a reference, HR (95% CI) was 1.46 (1.09–1.95) for the lowest quintile (<1.09 mmol/L) and 1.45 (1.07–1.96) for the highest quintile (≥1.61 mmol/L) of HDL-C, after adjusting for confounders; and 1.57 (1.15–2.15) for the lowest quintile and 1.45 (1.04–2.01) for the highest quintile of HDL-C, after exclusion of death within the first 2 years of follow-up; and 1.55 (1.11–2.16) for the lowest quintile and 1.42 (1.00–2.02) for the highest quintile of HDL-C, after exclusion of functionally impaired participants.ConclusionsWe found an inverse association of LDL-C and a U-shape relationship of HDL-C with long-term all-cause mortality in a cohort with community-dwelling older Chinese adults. Levels of LDL-C and HDL-C are suggested to be managed properly in late life.