Decrease In Low-density Lipoprotein Cholesterol Levels Research Articles

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

MANAGING LIPID LEVELS IN THE LIFE-LONG REHABILITATION OF PATIENTS WITH CORONARY ARTERY DISEASE

Cardiac rehabilitation includes secondary prevention of cardiovascular events. Since the level of LDL cholesterol, which is an important risk factor for cardiovascular events, had been shown to be insufficiently controlled in persons included in the third phase of cardiac rehabilitation in the Coronary Club of Ljubljana, we aimed to explore if an additional educational program would improve the control of blood lipids and self-management ability in these subjects. Members of the Coronary Club of Ljubljana were invited to join a ten-month structured program for the management of cardiovascular risk factors with an emphasis on lipid control. Participation in the program activities was optional. A total of 146 subjects were enrolled. During the study, a slight decrease was seen in the following parameters: total cholesterol, HDL cholesterol, triglycerides and glycated haemoglobin (p&lt;0.05). In the whole group of participants, the median LDL cholesterol level decreased from 2.5 mmol/L (interquartile range [IQR], 1.8-3.4) to 2.2 mmol/L (IQR, 1.7-3.5), but the difference was not statistically significant (p=0.081), while in the participants who attended individual consultations or workshops, a significant decrease in LDL cholesterol levels was observed. At the beginning of the study, very high-risk patients had higher activation, indicated with higher median baseline Patient Activation Measure (PAM) score, than high-risk patients (60.6 versus 55.6). During the study, the median PAM score increased in high-risk patients (from 55.6 to 60.6), but not in very high-risk patients. Thus, an additional educational program can improve lipid control and patient activation in subjects included in the third phase of cardiac rehabilitation.

Case Report: Effect of Ajwa Date Consumption on LDL Levels in Perimenopausal Women

During perimenopause, there can be a decrease in estrogen production, which indicates the end of a woman’s reproductive years. The production of the hormone estrogen that continues to decrease will cause hypercholesterolemia. Decrease in LDL cholesterol levels can be increased by giving antioxidant properties, which are rich in vitamin C and contain flavanoids and phenolics that function as antioxidants. The method used in this study is Literature Review with Design Narrative Review. The result from the literature it was found the effect of giving ajwa dates (Phoenix Dactylifera L) before and after administration showed a change, namely a decrease in LDL levels after giving ajwa dates. This is because ajwa dates contain flavanoids, phenolics, and plant sterols that function as antioxidant that can prevent the formation of lipid peroxidation. The conclusion based on the results of the literature review, it can be concluded that giving ajwa dates to perimenopause women decreased LDL levels where ajwa dates have antioxidant functions to prevent lipid peroxidation to reduce LDL. The suggestion from the study is necessary to conduct further research on the effect of consumption of ajwa dates on LDL levels in perimenopause women using experimental methods of pretest and posttest design.

Long-term comparison of renal and metabolic outcomes after sodium–glucose co-transporter 2 inhibitor or glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes

BackgroundRenal outcomes in patients with type 2 diabetes following treatment with sodium–glucose co-transporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP1RAs) have not been directly compared. This study compared the impact of SGLT2i and GLP1RA therapy on renal function and metabolic parameters.MethodsPatients with type 2 diabetes who initiated SGLT2i or GLP1RA therapy in a tertiary hospital between January 2009 and August 2023 were included to assess composite renal outcomes, such as a 40% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease, renal death, or new-onset macroalbuminuria. Alterations in blood pressure, glucose regulation parameters, lipid profile, and anthropometric parameters, including body fat and muscle masses, were examined over 4-years.ResultsA total of 2,112 patients were enrolled using a one-to-three propensity-score matching approach (528 patients for GLP1RAs, 1,584 patients for SGLT2i). SGLT2i treatment was favoured over GLP1RA treatment, though not significantly, for composite renal outcomes (hazard ratio [HR], 0.63; p = 0.097). SGLT2i therapy preserved renal function effectively than GLP1RAs (decrease in eGFR, ≥ 40%; HR, 0.46; p = 0.023), with improving albuminuria regression (HR, 1.72; p = 0.036). SGLT2i therapy decreased blood pressure and body weight to a greater extent. However, more patients attained HbA1c levels < 7.0% with GLP1RAs than with SGLT2is (40.6% vs 31.4%; p < 0.001). GLP1RA therapy enhanced β-cell function and decreased LDL-cholesterol levels below baseline values.ConclusionsSGLT2is were superior for preserving renal function and reducing body weight, whereas GLP1RAs were better for managing glucose dysregulation and dyslipidaemia.

The Efficacy of Tafolecimab in Chinese Patients with Hypercholesterolemia: A Systematic Review and Meta-analysis.

Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels. A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I2 index. The risk of bias was assessed using Cochrane's RoB2 tool. This review has been registered with PROSPERO (CRD42023471020). A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = - 63.78, 95% CI - 65.88 to - 61.68, pvalue < 0.00001, I2 = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, pvalue < 0.00001, I2 = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, pvalue < 0.00001, I2 = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB2 tool. Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations. PROSPERO identifier number CRD42023471020.

Effect and safety of PCSK9 inhibitor in-hospital use on blood lipid level in the ACS patients: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): none Aims To evaluate the effect and safety of in-hospital use of the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor on blood lipid levels in the acute coronary syndrome (ACS) patients. Methods We searched the PubMed, MEDLINE, Web of Science, Ovid and Cochrane Library electronic databases through July 2023 to identify randomized controlled trials (RCTs) and cohort studies using PCSK9 inhibitors during ACS hospitalization. Then we compared the PCSK9 inhibitor group with a placebo or a blank control group with the same background of lipid-lowering therapy. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias for the included studies. A software was used to analyze the changes in overall lipids from baseline and the adverse event rates. Results A total of 15 studies enrolling 3891 patients with ACS were eligible, including 10 RCTs (n = 1406) and 5 cohort studies (n = 2485). Treatment with PCSK9 inhibitors showed a greater reduction in low-density lipoprotein cholesterol (LDLC) (SMD=1.46, 95% CI: 1.16-1.76, P&amp;lt;0.01). The cumulative meta-analysis of follow-up time showed that the degree of LDLC reduction stabilized after 12 weeks (SMD=1.42 at 12 weeks, 95% CI: 1.06-1.79, P&amp;lt;0.01), and thus, PCSK9 inhibitors dramatically decreased LDLC levels in comparison to controls at both ≤12 weeks and 12–72 weeks. The LDLC levels with PCSK9 inhibitors that reached the recommended standards of AHA/ACC (≤1.8mmol/l) and ESC (≤1.4mmol/l) were 95% and 80% respectively, which were significantly higher than those of the control group (58% and 22%). PCSK9 inhibitors can also reduce the total cholesterol, triglycerides, apolipoprotein B, and lipoprotein (a), while increasing the high-density lipoprotein cholesterol, but they have no statistical significance in reducing apolipoprotein A1. Compared with placebo or blank control, the addition of PCSK9 inhibitor did not increase the occurrence of adverse events (RR =-0.01,95% CI:-0.19-0.18, P = 0.95) and serious adverse events (RR =-0.03, 95% CI:-0.48-0.43, P=0.91). Conclusion In-hospital use of PCSK9 inhibitors can significantly improve the blood lipid levels of ACS patients and increase the target LDLC attainment rate, with satisfactory safety and good tolerance.

Effects of a Six-Week Aerobic Exercise Training Program on Lipid Profiles in Sedentary Women

This study investigated how a six-week training program involving aerobic exercise affected the lipid profile of women who were sedentary. Using the pre-test post-test model, 36 sedentary female volunteers aged 18-29 years participated in the study. After the participants had fasted overnight, healthcare professionals took blood samples from them both before and after the training program in a clinical setting. Measurements were taken of triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol. The data obtained was subjected to a paired-samples test using the SPSS 22.0 statistical program to compare the values before and after training. Effect sizes (Cohen's d) were used to clarify the levels of comparison. Statistically significant differences were seen in blood lipid levels (triglycerides, HDL, LDL, and total cholesterol) between pre- and post-training assessments (p &amp;lt; 0.05). This study found that a six-week aerobic exercise program significantly increased HDL cholesterol levels by 15.8% (from 46.66 mg/dL to 54.05 mg/dL, p = 0.000) and decreased LDL cholesterol levels by 15.7% (from 96.72 mg/dL to 81.52 mg/dL, p = 0.000) in sedentary women. The study adds to the growing body of evidence suggesting that aerobic exercise programs, such as spinning, can significantly improve lipid profiles in sedentary women, potentially reducing their risk of cardiovascular disease. Future research should incorporate control groups to strengthen these findings.

Effectiveness of inclisiran lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Moscow healthcare

Aim. To evaluate the effectiveness of PCSK9-targeted therapy (inclisiran, alirocumab, and evolocumab) in patients with atherosclerotic cardiovascular disease (ASCVD) and who did not achieve the target low-density lipoprotein cholesterol (LDL-C) level on basic therapy (statins in maximum tolerated doses and/or ezetimibe).Material and methods. This observational study included 50 patients receiving the inclisiran and 30 patients of the control group with ASCVD treated with PCSK9 inhibitors (alirocumab, n=1; evolocumab, n=29). In all participants, we assessed medical history data and initially performed electrocardiography, echocardiography, Doppler ultrasound of extracranial and lower limb arteries, and laboratory tests (complete blood count, biochemical and lipid profile). Three Moscow public health facilities took part in the study.Results. Data on achievement of primary and secondary endpoints by the 12th month are presented. The study groups were comparable in basic clinical characteristics. In inclisiran group, a significant decrease in LDL-C level was found from 2,53±0,7 mmol/l initially to 1,29±0,5 mmol/l (by 49%), p=0,0002; the target LDL-C &lt;1,4 mmol/l was achieved by 73,9% of the subjects. Alirocumab/ evolocumab showed significant lipid-lowering effect with a LDL-C decrease from 2,4±0,9 mmol/l to 1,32±0,7 mmol/l (by 45%), p&lt;0,0001.Conclusion. The final results are consistent with the intermediate data and indicate not only the possibility of early achievement of target LDL-C levels in PCSK9targeted combination therapy, but their maintenance with a favorable tolerability and safety profile.

Acoustic Delivery of Plasma Low-Density Lipoprotein into Liver via ApoB100-Targeted Microbubbles Inhibits Atherosclerotic Plaque Growth.

Atherosclerosis is the main risk factor for cardiovascular disease, which accounts for the majority of mortality worldwide. A significantly increased plasma level of low-density lipoprotein cholesterol (LDL-C), surrounded by a monolayer of phospholipids, free cholesterol, and one apolipoprotein B-100 (ApoB-100) in the blood, plays the most significant role in driving the development of atherosclerosis. Commercially available cholesterol-lowering drugs are not sufficient for preventing recurrent cardiovascular events. Developing alternative strategies to decrease the plasma cholesterol levels is desirable. Herein, we develop an approach for reducing LDL-C levels using gas-filled microbubbles (MBs) that were coated with anti-ApoB100 antibodies. These targeted MBApoB100 could selectively capture LDL particles in the bloodstream through forming LDL-MBApoB100 complexes and transport them to the liver for degradation. Further immunofluorescence staining and lipidomic analyses showed that these LDL-MBApoB100 complexes may be taken up by Kupffer cells and delivered to liver cells and bile acids, greatly inhibiting atherosclerotic plaque growth. More importantly, ultrasound irradiation of these LDL-MBApoB100 complexes that accumulated in the liver may induce acoustic cavitation effects, significantly enhancing the delivery of LDL into liver cells and accelerating their degradation. Our study provides a strategy for decreasing LDL-C levels and inhibiting the progression of atherosclerosis.

Substitution of dietary monounsaturated fatty acids from olive oil for saturated fatty acids from lard increases low-density lipoprotein apolipoprotein B-100 fractional catabolic rate in subjects with dyslipidemia associated with insulin resistance: a randomized controlled trial

BackgroundThe substitution of monounsaturated acids (MUFAs) for saturated fatty acids (SFAs) is recommended for cardiovascular disease prevention but its impact on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains largely unknown. ObjectivesThis study aimed to evaluate the impact of substituting MUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo)B-containing lipoproteins and on the plasma lipidomic profile in adults with IR-induced dyslipidemia. MethodsMales and females with dyslipidemia associated with IR (n = 18) were recruited for this crossover double-blind randomized controlled trial. Subjects consumed, in random order, a diet rich in SFAs (SFAs: 13.4%E; MUFAs: 14.4%E) and a diet rich in MUFAs (SFAs: 7.1%E; MUFAs: 20.7%E) in fully controlled feeding conditions for periods of 4 wk each, separated by a 4-wk washout. At the end of each diet, fasting plasma samples were taken together with measurements of the in vivo kinetics of apoB-containing lipoproteins. ResultsSubstituting MUFAs for SFAs had no impact on triglyceride-rich lipoprotein apoB-48 fractional catabolic rate (FCR) (Δ = –8.9%, P = 0.4) and production rate (Δ = 0.0%, P = 0.9), although it decreased very low-density lipoprotein apoB-100 pool size (PS) (Δ = −22.5%; P = 0.01). This substitution also reduced low-density lipoprotein cholesterol (LDL-C) (Δ = −7.0%; P = 0.01), non–high-density lipoprotein cholesterol (Δ = −2.5%; P = 0.04), and LDL apoB-100 PS (Δ = −6.0%; P = 0.05). These differences were partially attributed to an increase in LDL apoB-100 FCR (Δ = +1.6%; P = 0.05). The MUFA diet showed reduced sphingolipid concentrations and elevated glycerophospholipid levels compared with the SFA diet. ConclusionsThis study demonstrated that substituting dietary MUFAs for SFAs decreases LDL-C levels and LDL PS by increasing LDL apoB-100 FCR and results in an overall improved plasma lipidomic profile in individuals with IR-induced lipidemia. Trial registrationThis trial was registered as clinicaltrials.gov as NCT03872349.

Genetic aspects of decreased low-density lipoprotein cholesterol values

Aim. To study genetic causes of decreased low-density lipoprotein cholesterol (LDL-C) in Russian patients.Material and methods. The study included the following Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) participants: individuals with LDL-C&lt;5th percentile, taking into account sex and age (n=52), who underwent targeted sequencing of protein-coding regions of 6 genes (APOB, PCSK9, MTTP, ANGPTL3, SAR1B, APOC3) and determination of the genetic risk score (GRS) for hypercholesterolemia; and a representative sample of the Ivanovo region population (ESSEIvanovo, n=1667), for which only GRS was determined. Genetic testing was performed using next generation sequencing.Results. In 10 (19,2%) of 52 participants with decreased LDL-C levels, the following rare variants potentially associated with hypocholesterolemia were identified: 8 — leading to a premature termination codon in the APOB gene, 1 — leading to a premature termination codon in the APOC3 gene and 1 missense variant in the PCSK9 gene. Of the 10 identified variants, 6 are described by us for the first time. GRS in the LDL-C group (0,27±0,25) was significantly lower than in the ESSE-Ivanovo population sample (0,43±0,27) (p=4,7×10-06).Conclusion. Genetic reasons explain decreased LDL-C levels (&lt;5th percentile) in 32,7% of patients, of which only monogenic variants were identified in 13,5%, a combination of monogenic and polygenic hypocholesterolemia — in 5,7%, and polygenic hypocholesterolemia — in 13,5%.

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.

EFEKTIVITAS PEMBERIAN JELLY PORANG (Amorphophallus Muelleri) KOMBINASI JAMBU BIJI (Psidium Guajava) TERHADAP KADAR KOLESTEROL LDL PADA PASIEN HIPERKOLESTEROLEMIA

Hypercholesterolemia sufferers tend to be experienced at the age of 45-59 years and over 60 years. Hypercholesterolemia is caused by several factors, namely lifestyle, diet and physical activity. Guava and Porang tubers are one alternative to lower LDL cholesterol levels. Combination guava porang jelly is a snack made from porang flour and guava which is high in fiber and vitamin C. This study is an experimental quasy research. The subjects of the study amounted to 20 people consisting of 10 treatment groups and 10 control groups. The data collected were the intake of fat, fiber and vitamin C obtained by the method of recall of food consumption 1x24 hours before and during the intervention 4 times. Examination of LDL cholesterol levels using the CHOD-PAP method. Data were tested with the Mann-Whitney test to look at the effect of treatment on LDL cholesterol levels between the control group and the intervention group. The treatment group of LDL cholesterol levels before and during the study also decreased by 19,5 mg/dl while the control group by 7,7 mg/dl. There was no significant difference in LDL cholesterol levels after the intervention. However, there was a decrease in LDL cholesterol levels decreased by 19,5 mg/dl in the treatment group and 7,7 mg/dl in the control group.

Chronic PCSK9 inhibitor therapy leads to sustained improvements in endothelial function, arterial stiffness, and microvascular function.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients at very high cardiovascular risk. Recent short-term studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor (PCSK9i) therapy on endothelial function and arterial stiffness, whereas it is unknown if this effect persists and what the effect is on microcirculation. To investigate the effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect. In this prospective trial, 32 patients at very high cardiovascular risk and indication for PCSK9i therapy were included. Measurements were performed at baseline and after 6 months of PCSK9i treatment. Endothelial function was assessed as flow-mediated dilation (FMD). Arterial stiffness was measured as pulse wave velocity (PWV) and aortic augmentation index (AIx). Peripheral tissue oxygenation (StO2) as a marker of microvascular function was assessed at the distal extremities using near-infrared spectroscopy camera. Six months of PCSK9i therapy decreased LDL-C levels from 141 ± 54 to 60 ± 30 mg/dl (-56 ± 21 %, p < 0.001), FMD significantly increased from 5.4 ± 1.7 % to 6.4 ± 1.9 % (+19 ± 10 %, p < 0.001), PWV decreased in male patients significantly from 8.9 ± 2.1 to 7.9 ± 1.5 m/s (-12 ± 9 %, p = 0.025). AIx decreased from 27.1 ± 10.4 % to 23.0 ± 9.7 % (-16 ± 14 %, p < 0.001), StO2 significantly increased from 67 ± 12 % to 71 ± 11 % (+7 ± 6 %, p = 0.012). Brachial and aortic blood pressure showed no significant changes after six months. There was no correlation between LDL-C reduction and changes in vascular parameters. Chronic PCSK9i therapy is associated with sustained improvements in endothelial function, arterial stiffness, and microvascular function independent from lipid lowering.

#2768 DIFFERENT EFFECTS OF HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITORS ON SERUM LIPIDS LEVELS IN HEMODIALYSIS PATIENTS

Abstract Background The activity of hypoxia-inducible factor (HIF), an oxygen-sensitive transcription factor involved in erythropoiesis, is regulated by HIF-prolyl hydroxylases. With reduced oxygen tension, the activity of these enzymes is suppressed, resulting in increased erythropoiesis. Chen et al. reported that the decrease in that total cholesterol (TC) was greater with roxadustat than with epoetin alfa, as was the decrease in low density lipoprotein-cholesterol (LDL-C) in patients undergoing dialysis [1]. Csiky et al. reported roxadustat was superior to erythropoiesis-stimulating agent (ESA) in decreasing LDL-C levels from baseline in patients on dialysis [2]. Roxadustat is an oral HIF-prolyl hydroxylase inhibitor (HIF-PHI) developed for dialysis-dependent chronic kidney disease (CKD) anemia. While the impact of HIF-PHI on mean hemoglobin (Hb) change in patients on hemodialysis (HD) has been investigated [1], its effects on serum lipid levels have yet to be explored. Clarifying such effects is particularly important because HD patients usually have lower plasma high-density lipoprotein-cholesterol (HDL-C) levels than healthy individuals. Low HDL-C levels are associated with an increased risk of death in HD patients. The effects of HIF-PHIs on dyslipidemia in patients on HD are unclear. This study aimed to investigate the effects of HIF-PHIs on serum lipid levels in HD patients. Methods We investigated the effect of HIF-PHIs in three groups by measuring the levels Hb, serum TC, LDL-C, HDL-C, triglycerides (TG), iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), ferritin. Study 1: We evaluated the efficacy of roxadustat in 13 patients (1 female and 12 males) with HD-dependent CKD anemia and dyslipidemia over 24 weeks. Study 2: We evaluated the efficacy of daprodustat in 9 patients (2 females and 7 males) with HD-dependent CKD anemia and dyslipidemia over 24 weeks. Study 3: We evaluated the efficacy of enarodustat in 15 patients (3 females and 12 males) with HD-dependent CKD anemia and dyslipidemia over 12 weeks. Results Study 1: The mean age and mean HD vintage were 77.7 and 6.6 years, respectively. After roxadustat treatment, the mean Hb values (from 10.4 to 10.7 g/dL) did not significantly change. There were no significant changes in mean serum iron, TG, ferritin. However, the following parameters showed a significant decrease: mean TC (from 138.4 to 106.6 mg/dL, p = 0.0002), LDL-C (77.7 to 53.8 mg/dL, p = 0.0002), HDL-C (from 43.3 to 35.9 mg/dL, p = 0.0005), and TSAT (from 32.6 to 31.2%, p = 0.0479). There was a significant increases in the mean TIBC (from 220.5 to 265.1 μg/dL, p = 0.0002). Study 2: The mean age and mean HD vintage were 74.6 and 3.2 years, respectively. After daprodustat treatment, the mean Hb values did not significantly change. There were no significant changes in the mean TC, LDL-C, TG, TSAT, ferritin. However, the mean HDL-C levels showed a statistically significant decrease (from 50.4 to 45.3 mg/dL, p = 0.0117). Furthermore, there were significant increases in the serum iron level (from 72.5 to 89.1 μg/dL, p = 0.0078) and the mean TIBC level (from 229.7 to 272.8 μg/dL, p = 0.0039). Study 3: The mean age and mean HD vintage were 69.3 and 8.9 years, respectively. After enarodustat treatment, the mean Hb values did not significantly change. There were no significant changes in the mean TC, LDL-C, HDL-C, TG, TSAT, ferritin, iron. There was a significant increase in the mean TIBC (from 230.0 to 259.4 μg/dL, p = 0.0151). Conclusions We found that HIF-PHIs had different effects on serum lipids levels in HD patients. Roxadustat treatment improved iron metabolism stabilized Hb levels, and significantly decreased LDL-C levels. Daprodustat and enarodustat treatment improved iron metabolism, maintained stable Hb levels.

Safety and Effectiveness of Evolocumab During Acute and Sub-acute Phases of Acute Coronary Syndrome (ACS): A Systematic Review and Meta-analysis.

Coronary artery disease (CAD), manifested mainly as acute coronary syndrome (ACS), continues to be a major cause of mortality globally and a significant contributing factor to the global disease burden. Elevation of low-density lipoprotein cholesterol levels attributed to proprotein convertase subtilisin/Kexin type-9 (PCSK9) during and following ACS puts patients at high risk of subsequent adverse events. Evolocumab is a PCSK9 inhibitor that is associated with a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels through PCSK9 inhibition in comparison to traditional statin therapy. We conducted a systematic review and meta-analysis of literature addressing the efficacy and safety of evolocumab compared to other lipid-lowering therapies or placebo. An extensive internet-based literature search using pre-determined key phrases supported by medical sub-headings and Boolean operators was performed in October 2022 to identify literature pertinent to the research topic. The search was primarily based on the National Library of Medicine (PubMed and Clinical Trials), MEDLINE, Cochrane, and the Science direct literature databases. Subsequently, the researchers devised PICOs-based screening criteria which had to be met by each identified study for inclusion in the review and meta-analysis. Two independent reviewers conducted data stratification and quality assessment of identified studies. Statistical analysis of the primary and secondary outcomes was conducted on the Cochrane REVMAN 5.4 statistical softwarefor randomized trials. Two thousand five hundred and seventy-six potential studies were identified for inclusion in the systematic review. Data stratification, screening, and quality assessment of these studies based on the eligibility criteria led to the exclusion of two thousand five hundred and sixty-seven studies as they did not meet the standards set. Nine randomized controlled trials progressed to numerical analysis for validity and reliability. Eight studies were included in the meta-analysis. Meta-analytical results showed a significant decrease in LDL-C changes from initiation of evolocumab therapy to 8 weeks following ACS compared to placebo. Similar results were derived in the sub-acute phase of ACS [SMD -1.95 (95% CI -2.29, -1.62)].The meta-analysis revealed no statistically significant relationship between the risk of adverse effects, serious adverse effects, and major adverse cardiovascular events (MACE) from treatment using evolocumab in comparison to placebo [(relative risk, RR 1.04 (95% CI 0.99, 1.08) (Z = 1.53; p=0.12)]. Early evolocumab therapy initiation was associated with a significant decrease in LDL-C levels and was not associated with an increased risk of adverse effects in comparison to placebo.

Serum lipid levels in chronic spontaneous urticaria – An analytical cross-sectional study from a tertiary care center

Objectives: The primary objective was to compare serum lipid levels in patients with chronic spontaneous urticaria (CSU) and normal subjects. The secondary objective was to study the clinical profile of patients with CSU. Materials and Methods: This was a hospital-based analytical cross-sectional study comparing the serum lipid levels in 45 patients with CSU with that of age- and gender-matched normal subjects who attended a tertiary care center during a period of 1 year (January 2020 to December 2020). A structured questionnaire was used to record history and examination findings. Lipid levels were estimated by collecting blood samples after 12 hours of fasting. The data were analyzed by independent sample t-test to compare the mean values between the different groups and Chi-square test for comparing proportion. P ≤ 0.05 was considered statistically significant. Results: Most of the study participants belonged to the age group of 21–30 years (mean 29.3 years, standard deviation 8.4 years). The male-to-female ratio was 1: 2.2. The majority of the patients in this study (27, 60%) were either overweight or obese. There was a statistically significant elevation in mean serum triglyceride level (TG) in CSU patients in comparison to normal controls (P = 0.008). Patients with a disease duration of more than 6 months had a significantly higher levels of non-high-density lipoprotein-cholesterol (non-HDL-C) (P = 0.026) and remnant cholesterol (P = 0.038), and significantly lower levels of mean low-density lipoproteincholesterol (LDL-C) (P = 0.027) and mean LDL/HDL (P = 0.026) in comparison to patients with a disease duration of 6 months or less. Limitations: Small sample size and the cross sectional design were the main limitations. Conclusion: Patients with CSU showed significantly higher levels of serum TG in comparison to controls. Patients with a disease duration of more than 6 months showed a significant increase in mean remnant cholesterol and non-HDL-C levels, and a significant decrease in LDL-C levels and LDL-C/HDL-C, when compared to those with a disease duration of 6 months or less.

Estimating the changing disease burden attributable to raised low-density lipoprotein cholesterol in South Africa for 2000, 2006 and 2012.

Low-density lipoprotein cholesterol (LDL-C) is the most important contributor to atherosclerosis, a causal factor for ischaemic heart disease (IHD) and ischaemic stroke. Although raised LDL-C is a key contributor to cardiovascular disease (CVD), the exact attributable disease risk in South Africa (SA) is unknown. The the first SA comparative risk assessment (SACRA1) study assessed the attributable burden of raised total cholesterol, and not specifically LDL-C. To estimate the national mean serum LDL-C by age, year and sex and to quantify the burden of disease attributable to LDL-C in SA for 2000, 2006 and 2012. The comparative risk assessment (CRA) method was used. Estimates of the national mean of LDL-C, representing the 3 different years, were derived from 14 small observational studies using a meta-regression model. A theoretical minimum risk exposure level (TMREL) of 0.7 - 1.3 mmol/L was used. LDL-C estimates together with the relative risks from the Global Burden of Disease Study 2017 were used to calculate a potential impact fraction (PIF). This was applied to IHD and ischaemic stroke estimates sourced from the Second National Burden of Disease Study. Attributable deaths, years of life lost, years lived with disability and disability-adjusted life years (DALYs) were calculated. Uncertainty analysis was performed using Monte Carlo simulation. LDL-C declined from 2.74 mmol/L in 2000 to 2.58 mmol/L in 2012 for males, while in females it declined from 3.05 mmol/L in 2000 to 2.91 mmol/L in 2012. The PIFs for LDL-C showed a slight decline over time, owing to the slight decrease in LDL-C levels. Attributable DALYs increased between 2000 (n=286 712) and 2006 (n=315 125), but decreased thereafter in 2012 (n=270 829). Attributable age-standardised death rates declined between 2000 and 2012 in both sexes: in males from 98 per 100 000 members of the population in 2000 to 78 per 100 000 in 2012, and in females from 81 per 100 000 in 2000 to 58 per 100 000 in 2012. Mean LDL-C levels were close to 3 mmol/L, which is the recommended level at which cholesterol-lowering treatment should be initiated for people at low and moderate risk for cardiovascular outcomes. The decreasing trend in the age-standardised attributable burden due to LDL-C is encouraging, but it can be lowered further with the introduction of additional population-based CVD prevention strategies. This study highlights the fact that high LDL-C concentration in relation to the TMREL in SA is responsible for a large proportion of the emerging CVD, and should be targeted by health planners to reduce disease burden.

Secondary prevention in diabetic and nondiabetic coronary heart disease patients: Insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys

BackgroundPatients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012–13; and EA-V, 2016–17) in Germany.MethodsThe EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V).Results384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%).ConclusionBetween 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.

Reduction of C-reactive protein, low-density lipoprotein cholesterol, and its relationship with cardiovascular events of different lipid-lowering therapies: A systematic review and meta-analysis of randomized controlled trials.

Background:To evaluate the reductions of C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDL-C) in different lipid-lowering drugs, and to assess the relationships between the reductions of CRP, LDL-C, and cardiovascular (CV) events.Methods:We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to September 1, 2021. Randomized controlled trials (RCTs) comparing statins, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs), or ezetimibe against placebo with a treatment duration of at least 4 weeks and data on the effects of cholesterol-lowering interventions on LDL-C and CRP were included in this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated.Results:Compared with placebo treatment, statins and ezetimibe treatments resulted in a significant decrease in LDL-C level (statins: WMD −47.94 mg/dL, 95% CI −51.21 to −44.67 mg/dL; ezetimibe: WMD −22.84 mg/dL, 95% CI −26.76 to −18.92 mg/dL) and CRP level (statins: WMD −0.67 mg/L, 95% CI −0.90 to −0.45 mg/dL; ezetimibe: −0.64 mg/L, 95% CI −1.07 to −0.21 mg/dL). Compared with placebo treatment, treatment with PCSK9-mAbs resulted in significant decrease in LDL-C level (WMD −54.24 mg/dL, 95% CI −59.77 to −48.70 mg/dL), while the concentration of CRP did not decrease significantly. Meta-regression analysis showed no significant association between change in CRP level and change in LDL-C level. Subgroup comparisons suggested that treatment with PCSK9-mAbs showed a greater reduction in LDL-C level when compared with the statins group and ezetimibe group, while the risks of CV death, myocardial infarction (MI), and stroke showed no significant differences.Conclusion:Based on the current study, our results suggested that statins, ezetimibe, and PCSK9-mAbs are effective in reducing LDL-C levels. Treatment with statins and ezetimibe also demonstrated a significant effect on CRP. The traditional lipid-lowering strategy including statin and ezetimibe showed similar benefit on CV outcomes compared with the PCSK9-mAbs treatment.