Decrease In Low-density Lipoprotein Cholesterol Research Articles

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety

BackgroundLipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT.MethodsWe retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles.ResultsOf 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94–4.22] for mRS ≤ 3 and 0.47[0.27–0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time.ConclusionEarly use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.

Impact of Lipoprotein(a) Levels on Cardiovascular Risk Estimation.

A new cardiovascular risk (CVR) calculator that incorporates Lipoprotein(a) [Lp(a)] levels has recently been designed. To estimate CVR using the new score and to identify the reduction in low-density lipoprotein cholesterol (LDL-C) or systolic blood pressure (SBP) necessary to balance the risk attributable to Lp(a). CVR throughout life and at 10 years was estimated with the new score in patients in primary prevention, both considering and not considering the value of Lp(a). When the estimated risk considering Lp(a) levels exceeded the baseline risk, the reduction in LDL-C levels or SBP necessary to balance the risk attributable to Lp(a) was calculated. In total, 671 patients (mean age 54.2 years, 47.2% women) were included. Globally, 22.7% of the population had high Lp(a) values (>50 mg/dL or >125 nmol/L). When calculating CVR throughout life and considering the Lp(a) value, the global risk increased in 66.7% of cases (median 19.3%). Similar results were observed when we assessed the 10-year risk. The risk associated with Lp(a) could be completely compensated by decreasing LDL-C (average 21 mg/dL) or SBP (average 6.3 mmHg) in 79.2% and 74.7% of cases, respectively. When calculating the CVR with the new score, two-thirds and one-third of the population were bidirectionally recategorized as 'up' or 'down,' respectively. The decrease in LDL-C or SBP mitigated the increased risk caused by Lp(a) levels across a substantial proportion of patients.

Decreased LDL cholesterol exposure following ANGPTL3 inhibition reduces coronary plaque development in Homozygous Familial Hypercholesterolemia

Decreased LDL cholesterol exposure following ANGPTL3 inhibition reduces coronary plaque development in Homozygous Familial Hypercholesterolemia

The maintenance of long-term weight loss after semaglutide withdrawal in obese women with PCOS treated with metformin: a 2-year observational study.

Withdrawal of semaglutide is frequently followed by weight regain due to compensatory biological changes that prevent the maintenance of long-term weight loss. There are some studies implying that metformin might attenuate weight regain. The weight trajectory after discontinuation of short-term semaglutide treatment in obese women with PCOS who continued metformin treatment has not yet been evaluated. We explored changes in body weight, cardiometabolic and endocrine parameters in obese women with PCOS who continued treatment with metformin 2 years after discontinuation of short-term intervention with semaglutide. 25 women with PCOS and obesity, aged 33.7 ± 5.3 years (mean ± SD), were treated with once-weekly subcutaneous semaglutide 1.0 mg as an adjunct to metformin 2000 mg/day and lifestyle intervention for 16 weeks. At week 16, semaglutide was discontinued. Treatment with metformin 2000 mg/day and promotion of lifestyle intervention were continued during the 2-year follow-up period. Weight change, cardiometabolic, and endocrine parameters were assessed 2 years after semaglutide discontinuation. During semaglutide treatment phase, weight decreased from 101 (90-106.8) kg to 92 (83.3-100.8) kg. Two years after semaglutide withdrawal, weight was 95 (77-104) kg. The net weight loss 2 years after discontinuation of semaglutide remained significant when compared to baseline (p=0.003). At the end of the study, 21 out of 25 subjects had lower body weight compared to baseline. Improvements in cardiometabolic parameters including decrease in total and LDL cholesterol, fasting glucose, and glucose after OGTT that had been seen during semaglutide-treatment phase reverted towards baseline two years after semaglutide cessation. Free testosterone levels significantly decreased during semaglutide treatment from 6.16 (4.07-9.71) to 4.12 (2.98-6.93) nmol/l, (p= 0.012) and did not significantly deteriorate after semaglutide discontinuation. Two years after semaglutide withdrawal, women with PCOS who continued with metformin regained about one-third of the semaglutide-induced weight loss. At the end of the follow up, 84% of women had a lower body weight than at baseline.

Metabolic and inflammatory parameters in relation to baseline characterization and treatment outcome in patients with prolactinoma: insights from a retrospective cohort study at a single tertiary center.

Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory profiles in PRL patients, aiming to identify potential prognostic markers. The study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage. The PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels. This study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices. However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients.

Effect of sodium-glucose cotransporter 2 inhibitors on serum low-density lipoprotein cholesterol in Japanese patients with type 2 diabetes mellitus.

We aimed to evaluate factors that influence changes in blood low-density lipoprotein cholesterol (LDL-C) levels after treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors in Japanese patients with type 2 diabetes. We retrospectively analyzed clinical data of outpatients newly initiated on SGLT2 inhibitors (n = 176) and other oral antidiabetic drugs (n = 227). The patients were classified into four subgroups according to statin administration and baseline LDL-C levels (<120 or ≥120 mg/dL). Clinical characteristics were compared among the subgroups. Multivariate analysis was carried out to identify factors contributing to changes in LDL-C. The median follow-up period was 13.0 weeks (range 11.9-14.1 weeks, min 8 weeks, maximum 16 weeks) in the SGLT2i group, and 12.0 weeks (range 10.0-14.0 weeks, min 8 weeks, maximum 16 weeks) in the control group. Both groups showed a significant decrease in LDL-C (SGLT2i group -3.8 ± 24.7 mg/dL, control group -3.4 ± 15.0 mg/dL). Multivariate regression analyses showed that in both groups, the change in LDL-C depended on statin use and baseline LDL-C levels. Stratified analyses showed that LDL-C level was significantly decreased in statin users with baseline LDL-C ≥120 mg/dL (from 148.9 ± 33.5 to 109.3 ± 17.9 mg/dL, P = 0.002), and significantly increased in statin non-users with baseline LDL-C <120 mg/dL (from 96.3 ± 27.3 to 104.7 ± 24.8 mg/dL, P = 0.002). These changes were more characteristic for SGLT2 inhibitors than for other oral antidiabetic drugs (P for interaction = 0.010 and <0.001, respectively). LDL-C levels and statin medication at baseline influence changes in LDL-C after SGLT2 inhibitors treatment in Japanese patients with type 2 diabetes.

Is there a role for earlier use of combination therapy?

As the global population ages and cardiovascular risk factors rise, we can expect a continued increase in atherosclerotic disease. Low-density lipoprotein cholesterol (LDL-C) reduction is a cornerstone of cardiovascular risk reduction with strong, causal evidence indicating that the greatest benefit is derived from early and large decreases in LDL-C. Despite the adoption of statins as the backbone of lipid-therapy regimens, numerous studies and registry analyses reveal our collective inability to achieve LDL-C goals in high-risk patients. Combination therapy with ezetimibe has been shown to result in statistically significant decreases in LDL-C level, atheroma volume, and cardiovascular adverse event rates. A major barrier to implementing an upfront combination therapy approach is the perceived side effects from therapeutic agents although multiple studies show that a therapeutic patient-physician relationship could overcome this issue. Novel agents such as PCSK-9 inhibitors, bempedoic acid, and inclisiran have the potential to achieve similar outcomes although additional research is needed regarding the cost effectiveness of these approaches. Despite these hurdles, there is a role for the newer agents early in the disease course of high-risk patients such as those with markedly elevated LDL-C >190 mg/dL and FH.The implementation of upfront combination therapy, especially in high-risk patients, will decrease clinical inertia while allowing for earlier consideration of newer, effective agents to decrease cardiovascular burden.

Nutritional and Antioxidative Benefits of Dietary Macroalgae Supplementation in Weaned Piglets.

This study explores the effects of dietary brown macroalgae (Ascophyllum nodosum) inclusion on digestibility and blood biochemical indices and redox markers in piglets fed diets with varying levels (0%, 0.6% and 1%) of macroalgae from 18 to 64 days of age. Macroalgae significantly influenced lipid profiles, reducing total cholesterol levels (quadratic contrast p = 0.001) and demonstrating an increase in high-density lipoprotein cholesterol levels, particularly with 1% macroalgae inclusion (linear contrast p < 0.001), with a decrease in low-density lipoprotein cholesterol in both macroalgae-supplemented groups (linear contrast p = 0.001). Additionally, macroalgae had a positive impact on the activities of antioxidative enzymes (ferric-reducing ability of plasma, superoxide dismutase, reduced glutathione) and reduced lipid peroxidation products (lipid hydroperoxide, malondialdehyde) in the blood, liver tissue, and intestinal epithelium of the ileum, suggesting enhanced antioxidative defense mechanisms. These changes were dose-dependent; in blood plasma, they exhibited both a linear and quadratic response, while in the tissues, the response was primarily linear. Additionally, an increase in the digestibility of crude fat in macroalgae-supplemented groups was observed (linear contrast p < 0.001), highlighting their potential role in improving nutrient absorption and digestion. The study findings emphasize the health benefits of natural, seaweed-based additives in diets, particularly in managing oxidative stress and improving lipid profiles, and highlight the potential of macroalgae as a natural dietary supplement to improve antioxidant systems and lipid metabolism in piglets.

The use of statins and inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK 9) in patients with dyslipidemia

Scientific relevance. According to the WHO data, cardiovascular diseases rank first as the cause of human death. In 2022, 18,601,923 people died from cardiovascular diseases, which amounted to 33 % of the total mortality in the world. Malignant neoplasms rank second with 9,958,133 deaths, representing 17.6 % of total mortality. Among cardiovascular diseases, ischemic heart disease (IHD), the pathogenesis of which is associated with impaired cholesterol and lipoprotein metabolism, is leading. The use of statin drugs is recommended as a first-line lipid-lowering therapy. As an alternative to HMG-CoA reductase inhibitors (statins), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9) were discovered in 2003, however, they are less popular due to insuf ficient data on these drugs and their costliness. Purpose of the work: to study the safety of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with dyslipidemia and compare the advantages and disadvantages in relation to the ef fects of HMG-CoA reductase (statins). Discussion: The analysis of literature data has shown that the most frequent manifestations of intolerance to statins are muscle symptoms. The main mechanisms of statin-associated complications are mediated by inhibition of HMG-CoA reductase, as well as by the effect of drugs on cellular and subcellular processes, skeletal muscles and genetic features of patients. PCSK9 inhibitors have a fundamentally different mechanism of action — they bind and inactivate PCSK9, which leads to a decrease of low-density lipoprotein cholesterol in the blood level. A small number of undesirable reactions have been identified for drugs of this group, the most important of which is immunogenicity. However, even if patients have antibodies to PCSK9 inhibitor, the efficacy of the drug in reducing the level of low-density lipoproteins remains high.Conclusion. In medical studies, PCSK9 inhibitors have been shown to perform better compared to HMG-CoA reductase inhibitors; meanwhile, patients continue to use statins as lipid-lowering medications.

Auxological and metabolic effects of long-term treatment with recombinant growth hormone in children born small for gestational age: a retrospective study.

Children born small for gestational age (SGA) not showing catch-up during the first two years of life reportedly show an impaired growth rate and adult height, as well as a worse metabolic outcome, mainly in terms of glycemic and lipid profile, compared to general population. In SGA children with short stature, treatment with recombinant growth hormone (GH) is currently recommended until adolescence; therefore, it may last long-term. The aim of the current study was to evaluate the auxological and metabolic effects and the safety of long-term recombinant GH treatment in SGA children. The study included 15 SGA children (5 F, 10 M; mean age: 6.78 yrs) treated with GH for at least 48 months. Growth and metabolic parameters, including glycemic and lipid profile, transaminases, and urycemia, were collected every six months. Compared to baseline, SGA children showed a significant improvement in height, weight, and growth rate after four yaers of treatment with GH (p ≤ 0.002), being already evident after six months of treatment (p < 0.001). Noteworthy, patients showed a constant, significant improvement in height throughout the treatment, as it was significantly higher at each follow-up compared to the previous one, until 42 months of treatment, except at 30 months of treatment (p < 0.001 T6VST12; p < 0.01 T12VST18, T18VST24; p < 0.05 T30VST36, T36VST42). Considering metabolic parameters, compared to baseline, a recurring increase in glycemia (p ≤ 0.028 vs T30, T36, and T48) and decrease in AST (p ≤ 0.035 vs T36, T42, and T48) and an occasional decrease in LDL cholesterol (p ≤ 0.04 vs T24 and T42) and triglycerides (p = 0.008 vs T18) and increase in urycemia (p = 0.034 vs T42). Considering safety profile, treatment was well tolerated, as the most frequently reported adverse event was poor compliance (20%); no hyperglycemia, hypercholesterolemia or hyperstransaminasemia occurred throughout the treatment, CONCLUSIONS: Long-term GH treatment showed to be effective in improving height and growth rate in SGA children, with a positive impact of metabolic profile and a safety profile, although glycemia should be carefully monitored over time.

Impacts of ainuovirine-based and efavirenz-based antiretroviral therapies on the lipid profile of HIV/AIDS patients in southern China: a real-world study.

The newly approved third-generation oral anti-HIV-1 drug, ainuovirine (ANV), was used in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in our study, and its effects on the lipid profile of antiretroviral-experienced HIV/AIDS patients are unclear. This study aimed to examine the effects of antiretroviral agents on the lipid profile in patients with HIV/AIDS. We conducted a real-world prospective study involving treatment-naive and treatment-experienced adult participants living with HIV-1 infection provided with ANV- or efavirenz (EFV)-based regimens. The primary endpoint was the proportion of participants with an HIV-1 RNA level of <50 copies/mL at week 24 of treatment. Secondary endpoints included the change from baseline in CD4+ T-cell count and lipid profile. A total of 60 treatment-naive and 47 treatment-experienced participants received an ANV-based regimen, while 88 treatment-naive and 47 treatment-experienced participants receiving an EFV-based regimen were, respectively, matched as controls. At week 24 following treatment, the proportion of participants with an HIV-1 RNA level of <50 copies/mL and the mean changes of CD4+ T-cell counts from baseline were significantly higher in naive-ANV group than those in naive-EFV group (p < 0.01). Compared with the EFV group, both naive and experienced ANV groups exhibited a favorable lipid profile, including constant changes in total cholesterol and triglycerides, a significant decrease in LDL-cholesterol (p < 0.0001), and a dramatic increase in HDL-cholesterol (p < 0.001). The efficacy of ANV was non-inferior to EFV when combined with two NRTIs. Patients receiving ANV-based regimens had a decreased prevalence of dyslipidemia.

The Effect of Exercise During Ketogenic Diet on Hepatokines and Blood Lipid Profile in Overweight or Obese Men

Background and Aims Liver heptokines are important factors in obesity-related diseases. Both exercise and diet are essential interventions for obesity control. This study aims to compare the effectiveness of six weeks of aerobic and resistance exercises and ketogenic diet on fibroblast growth factor 21 (FGF21) selenoprotein P. levels and blood lipid profile in overweight or obese men. Methods This is a quasi-experimental study with a pretest-posttest design. Participants were 36 overweight or obese male college students with a body mass index above 25 kg/m2 , who were selected using a convenience sampling method, and were randomly divided into three groups including aerobic exercise + ketogenic diet (n=12), resistance exercise + ketogenic diet (n=12), and ketogenic diet (n=12). Aerobic exercise consisted of moderate-intensity running for six weeks at three sessions per week. Resistance training consisted of circuit training for six weeks at three sessions per week. The ketogenic diet included the restriction of carbohydrate intake to ≤10% of total daily energy intake. Fasting blood samples were collected in pre-test and post-test phases. Serum levels of FGF21 and selenoprotein P. were measured by the ELISA method, and blood lipid profile including total cholesterol, HDL, and LDL were measured by enzyme assay method. Two-way mixed analysis of variance (ANOVA) was used for statistical analysis. Bonferroni post hoc test was used for between-group comparison and paired t-test was used for within-group comparison. Results The interaction effect of time and group was no significant for FGF21 (P˃0.05), but the main effect of time was significant (P=0.001). All three groups showed a significant increase in FGF21 in the posttest phase compared to the pretest phase (P≤0.05). The selenoprotein P. serum level was not significantly different between groups or between two evaluation times (P˃0.05). The interaction effect of time and group was not significant for lipid profile (P˃0.05). The within-group comparison indicated a significant decrease in LDL and total cholesterol and an increase in HDL in all groups (P≤0.05). Conclusion It seems that both aerobic and resistance exercises during a ketogenic diet can increase FGF21 and improve lipid profile in overweight or obese men. There is no significant difference between the two methods. They have no superiority over the ketogenic diet alone in affecting heptokines and lipid profile.

Review on PCSK9: A Pertinent Therapeutic Target in Cardiovascular Disease

A Proprotein convertase subtilisin/kexin type-9 is considered a zymogen, extensively found in the liver. PCSK9 is found in circulation in the plasma, where it attaches to low-density lipoprotein (LDL) receptors on the cell surface, is internalized, and subsequently directs the receptors to be degraded by lysosomes. Investigations of naturally or organically found PCSK9 gene variations, which generated high levels of plasma LDL cholesterol deviations and varied atherosclerosis proportion factors, released floods of pharmaceutical along with biological and live sciences research into the world. Significant advances in our understanding of the physiological control of PCSK9 led quickly to the development of biological inhibitors of PCSK9 that are now available for purchase. These inhibitors decreased LDL cholesterol levels with other improved cardiovascular outcomes. The current manuscript will show the rapid development of PCSK9, beginning with its discovery as a novel gene and progressing through its use as a therapeutic target, followed by its testing on animals and humans and, eventually, its use in outcome trials and clinical applications.

Effect of chronic apple consumption (Malus domestica Borkh.) on the lipid profile of adults with dyslipidemia: a systematic review

Aim: Cardiovascular disease (CVD) are among the main causes of death worldwide and dyslipidemias account for one of the risk factors for these diseases. Habitual apple consumption appears to be inversely associated with reduced cardiovascular risk. Then, this systematic review aims to investigate the effect of chronic apple consumption on the lipid profile of adults with dyslipidemia. Methods: A systematic search was performed in electronic databases, including PubMed, Embase, Web of Science and Scopus, without restriction of year of publication. Inclusion criteria were randomized clinical trials in humans that investigated the effect of chronic consumption of whole fresh or dried apple, for a period longer than two weeks of intervention on the lipid profile. Results: Based on the methodology used and following the pre-established search strategies, 4,468 articles were found. After applying the inclusion and exclusion criteria, five articles were selected for qualitative evaluation, covering 522 adult participants of both sexes. Three randomized controlled trials included in this review demonstrated that there was a decrease in plasma total cholesterol (TC), triglyceride and low-density lipoprotein cholesterol (LDL-c) concentrations, in addition to an increase in high-density lipoprotein cholesterol (HDL-c) concentration. Two other studies found different results. Low risk of bias was identified in three studies. Conclusions: The analysis of the studies indicates that the consumption of fresh and/or dried apples with the peel has a beneficial effect on the lipid profile of adults, with a decrease in TC and LDL-c. These effects may be related to polyphenols and soluble fibers, among other functional compounds present in this fruit.

Observational study of inclisiran effectiveness in Moscow healthcare

Aim. To evaluate the effectiveness of PCSK9 inhibitors (alirocumab, inclisiran and evolocumab) in patients with atherosclerotic cardiovascular disease (ASCVD) and failure to achieve the target low-density lipoprotein cholesterol (LDL-C) level for the period from November 21, 2022 to December 31, 2023.Material and methods. For the observational study, 50 patients were included in the inclisiran therapy group and 30 patients in the control group (patients with ASCVD receiving PCSK9 inhibitors (alirocumab, n=1; evolocumab, n=29)). All study participants had their anamnestic data analyzed, and initially underwent electrocardiography, echocardiography, extracranial and lower limb Doppler ultrasound, and laboratory tests (complete blood count, biochemical blood tests, lipid profile). Three medical organizations of the Moscow State Healthcare System participate in the study.Results. Interim data are presented to evaluate the effectiveness of PCSK9 targeted therapy in patients with ASCVD, obtained 3 months from the study start. The comparison groups were comparable in main clinical characteristics. When analyzing the lipid-lowering effect of inclisiran in the examined patients with ASCVD, LDL-C level significantly decreased from 2,53±0,10 mmol/l to 110±0,08 mmol/l (by 56,5%), p&lt;0,0001, while the target LDL-C level &lt;1,4 mmol/l was achieved by 77,5% of the subjects. Analysis of the lipid-lowering effect of alirocumab/evolocumab showed a significant LDL-C decrease from 2,48±0,16 mmol/l to 1,07±0,11 mmol/l (by 56,8%), p&lt;0,0001.Conclusion. The use of PCSK9 targeted therapy (alirocumab or inclisiran or evolocumab) in patients with ASCVD in Moscow make it possible to achieve target LDL-C levels, which are indicated in clinical guidelines, by 3 months.

Comparative efficacy and safety of probiotics, prebiotics, and synbiotics for type 2 diabetes management: A systematic review and network meta-analysis

AimsTo compare the effects of probiotics, prebiotics, and synbiotics for type 2 diabetes (T2D) management. MethodsWe searched PubMed, Scopus, CENTRAL, and grey literature sources to December 2022 for randomized trials of the impacts of probiotics, prebiotics, or synbiotics in patients with T2D. We performed network meta-analyses with a Bayesian framework to calculate mean difference [MD] and 95 % credible interval [CrI] and rated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results68 randomised trials were included. All results are presented in comparison to the placebo. Supplementation with probiotics (MD: -0.25 %, 95%CrI: -0.42, -0.08; GRADE = moderate) and synbiotics (MD: -0.31 %, 95%CrI: -0.61, -0.04; GRADE = very low) resulted in a trivial/unimportant decrease in glycated hemoglobin. Supplementation with probiotics (MD: -0.69 mmol/L, 95%CrI: -0.98, -0.40; GRADE = very low) and synbiotics (MD: -0.82 mmol/L, 95%CrI: -1.22, -0.43; GRADE = very low) resulted in a trivial/unimportant decrease in fasting plasma glucose. Supplementation with probiotics resulted in a small but important decrease in low-density lipoprotein cholesterol (MD: -0.19 mmol/L; 95%CrI: -0.34, -0.05; GRADE = very low). Supplementations had moderate effects on serum triglyceride (GRADE = low). ConclusionsExisting evidence is uncertain and does not support supplementation with probiotics, prebiotics, and synbiotics for T2D management.

Effects of proprotein convertase subtilisin-kexin type 9 inhibitors on inflammatory and hemostatic parameters in post myocardial infarction patients

Despite progress in treatment, elevated levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) (Lp(a)), represent a significant part of the residual risk. Both are associated with inflammation and the coagulation fibrinolytic system. The purpose of our research was to evaluate the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on lipid parameters and indicators of inflammation, coagulation and fibrinolysis. We included 100 post myocardial infarction (MI) patients with insufficiently controlled LDL-C values despite the maximum dose of statin, and highly elevated Lp(a). Patients received alirocumab or evolocumab (150 mg sc or 140 mg sc every two weeks, respectively), or placebo for 6 months.In patients receiving PCSK9i, a significant decrease in total cholesterol (TC), LDL-C, triglycerides (TG) and Lp(a), and an increase in high density lipoprotein cholesterol (p < 0.001 for all) was found. Before treatment, the concentrations of TC, LDL-C and TG correlated with the concentrations of thrombin activatable fibrinolysis inhibitor (r = 0.41, p < 0.001; r = 0.353, p < 0.001; r = 0.311, p = 0.003, respectively), and plasminogen activator inhibitor-1 (r = 0.302, p = 0.007; r = 0.218, p = 0.049; r = 0.278; p = 0.013, respectively). The concentrations of TC and LDL-C correlated with overall fibrinolytic potential (r = −0.220, p = 0.034; r = −0.207, p = 0.047, respectively). The concentration of TG was related to the concentration of interleukin 6 (r = 0.290, p = 0.004) and interleukin 8 (r = 0.332, p = 0.001). No correlations between Lp(a) and inflammatory or hemostatic variables were found. No associations were found after treatment. Our results show that inflammatory cytokines and fibrinolytic parameters are related to LDL-C and not Lp(a) in post-MI patients before and with neither of them following PCSK9i treatment.The trial registration number: NCT04613167, Date of registration: November 3, 2020.

Age and the Residual Risk of Cardiovascular Disease following Low Density Lipoprotein-Cholesterol Exposure.

We believe that there is sufficient evidence from basic science, longitudinal cohort studies and randomised controlled trials which validates the low-density lipoprotein cholesterol (LDL-C) or lipid hypothesis. It is important that we can communicate details of the cardiovascular disease (CVD) risk reduction that the average patient could expect depending on the scale of LDL-C decrease following lipid lowering therapy. It is also essential that residual risk (ResR) of CVD be highlighted. To achieve this aim by using existing trial evidence, we developed mathematical models initially for relative risk reduction (RRR) and absolute risk (AR) reduction and then showed that despite optimising LDL-C levels, a considerable degree of ResR remains that is dependent on AR. Age is significantly associated with AR (odds ratio: 1.02, 95% confidence intervals: 1.01-1.04) as was previously demonstrated by analysing the Whickham study cohort using a logistic regression model (age remaining significant even when all the other significant risk factors such as sex, smoking, systolic blood pressure, diabetes and family history were included in the regression model). A discussion of a paper by Ference et al. provided detailed evidence of the relationship between age and AR, based on lifetime LDL-C exposure. Finally, we discussed non-traditional CVD risk factors that may contribute to ResR based on randomised controlled trials investigating drugs improving inflammation, thrombosis, metabolic and endothelial status.

Особливості ліпідного та вуглеводного обмінів у пацієнтів з гастроезофагеальною рефлюксною хворобою на тлі цукрового діабету 2-го типу залежно від наявності ожиріння

Особливості ліпідного та вуглеводного обмінів у пацієнтів з гастроезофагеальною рефлюксною хворобою на тлі цукрового діабету 2-го типу залежно від наявності ожиріння

Biochemical Blood Plasma Changes of Awassi Sheep Using Different Levels of Olive Pulp

16 male Awassi lambs were used, four months age weaning was diagnosed bythe teeth, it was placed in the animal field and left to acclimate for 14 days, then the actual experiment was introduced for a period of three months. The lambs were reared in four standard barns with a stage containing feeders and water troughs, it was divided from the inside by iron partitions into three sections. Four lambs, each treated under hygienic conditions, were placed in each section, underwent a treatment and vaccination program that supported to ensure her safety and that she was free from diseases. The animals were divided into four groups were T1: was fed on a diet devoid of olive pulp (control group). And fed on a diet containing 5, 10 and 15% olive pulp were T2, T3 and T4 respectively. fed on a diet containing 15% olive pulp. The results indicated that all olive pulp treatments led to a significant decrease in LDL cholesterol, triglycerides, glucose, uric acid, ALP and ALT, with a significant increase in HDL, total protein, albumin, globulin, phosphorus and calcium compared to the control treatment. The addition of 15% olive pulp in the diets of Awassi lambs gave the best results compared to a concentration of 5 and 10% olive pulp.