Decrease In Low-density Lipoprotein Cholesterol Research Articles

Gene-Based Targeting for Treatment of Hypercholesterolemia and Prevention of Atherosclerotic Cardiovascular Disease

Familial hypercholesterolemia, characterized by high levels of LDL cholesterol is a monogenic metabolic disorder linked to atherosclerotic cardiovascular disease. Several genetic mutations in genes such as LDLR and PSK9 are thought to cause familial hypercholesterolemia. This ultimately causes dysfunction of the LDLR pathway, increasing circulating LDL levels. Current treatment revolves around decreasing LDL cholesterol levels in the blood. Statins are the current gold standard while sterol absorption inhibitors (ezetimibe) and PCSK9 inhibitors (evolocumab) are either used as primary treatment in individuals with statin intolerance, or supplementary treatment otherwise. However, CRISPR-Cas9 offers an upstream therapeutic intervention, inducing mutations in pathogenic genes (such as LDLR) to upregulate or downregulate gene expression and subsequently reduce LDL cholesterol levels. This technology thus has great potential as a two-fold treatment option, offering an effective solution for familial hypercholesterolemia, while simultaneously diminishing the risk of atherosclerotic cardiovascular disease. A limitation to current research exists in the sole analysis of monogenic factors in genetic screening, thus polygenic, multifactorial analyses are required to assess more holistic treatment plans. Furthermore, there exist current limitations to CRISPR-Cas9 including ethical limitations and social considerations revolving around the perpetuation of social inequities through technology necessitating future research on global health policies.

Recaticimab as Add-On Therapy to Statins for Nonfamilial Hypercholesterolemia: The Randomized, Phase 3 REMAIN-2 Trial

BackgroundCurrently available antiproprotein convertase subtilisin/kexin type 9 monoclonal antibodies can effectively decrease low-density lipoprotein cholesterol (LDL-C) levels, but require frequent dosing. Recaticimab is a novel humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9. In a phase 1b/2 trial, recaticimab as add-on to stable statins showed robust LDL-C reduction with a dosing interval up to every 12 weeks (Q12W) in patients with hypercholesterolemia. ObjectivesREMAIN-2 (REcaticiMab Add-on therapy In patients with Nonfamilial hypercholesterolemia) aimed to assess the efficacy and safety of 48-week treatment with recaticimab as add-on therapy to statins in nonfamilial hypercholesterolemia. MethodsREMAIN-2 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. During the run-in period, patients received stable moderate or high-intensity statin, with or without cholesterol absorption inhibitors (ezetimibe) or fenofibrate, for ≥4 weeks. Patients with an LDL-C of ≥1.8 mmol/L (if with atherosclerotic cardiovascular disease [ASCVD]) or ≥2.6 mmol/L (if without ASCVD) were then randomized (2:2:2:1:1:1) to receive recaticimab 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg Q12W, or matching placebo injections (Q4W, Q8W, or Q12W) for 48 weeks. The primary efficacy endpoint was percentage change from baseline to week 24 in LDL-C level. ResultsA total of 689 randomly assigned patients received treatment (mean age, 55.8 years; male, 64.4%; ASCVD history, 69.5%; concomitant ezetimibe, 11.2%; mean baseline LDL-C, 2.8 mmol/L). Percentage change in LDL-C from baseline to week 24 was significantly more pronounced with recaticimab vs placebo (P < 0.0001), with least-squares mean differences of −62.2% (95% CI: −67.0% to −57.4%), −59.7% (95% CI: −65.0% to −54.4%), and −53.4% (95% CI: −58.7% to −48.2%) for the 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W regimens, respectively. The decreases in LDL-C with recaticimab were maintained through week 48. Secondary lipid variables, including non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) also favored the recaticimab groups. During the treatment period, the incidence of treatment-related adverse events (28.5% vs 26.6%) and serious treatment-related adverse events (0.4% vs 0.4%) was similarly low in both the recaticimab and placebo groups. ConclusionsRecaticimab as add-on to stable statin therapy significantly decreased LDL-C levels at week 24 and sustained the decreases through week 48, providing a novel therapeutic alternative with a dosing interval of up to every 12 weeks in patients with nonfamilial hypercholesterolemia.

Impact of smoking cessation on metabolic parameters and renal function in patients with and without diabetes mellitus

Backgroud and objectivesAs patients with diabetes are at a significantly higher risk of cardiovascular diseases than those without diabetes, it is important to gain a clinical understanding of the differential effects of smoking cessation on several risk factors between patients with and without diabetes. Materials and methodsPatients who participated in a smoking cessation program received an assessment of the outcomes of interest. The outcomes were changes in metabolic parameters and renal function from baseline to 6-month follow-up after the smoking cessation program. ResultA total of 1,954 patients joined the smoking cessation program, and 1,381 patients were in the smoking cessation failure (SCF) group and 573 were in the smoking cessation success (SCS) group. The decrease in HbA1c after smoking cessation was only observed in patients with diabetes. Smoking cessation was also associated with a significant decrease in LDL cholesterol in patients with diabetes. In terms of renal function, smoking cessation was associated with an improvement in eGFR, and the trend was similar in patients with and without diabetes. ConclusionSuccessful smoking cessation was associated with improvement in renal function. Moreover, it was associated with improvements in HbA1c and LDL cholesterol in patients with diabetes, despite significant weight gain.

Evaluating trends and insights in cardiovascular risk among the polish population

Abstract Introduction Cardiovascular diseases (CVD) are the leading cause of death in Poland and worldwide. Lifestyle changes and early diagnosis can reverse this unfavorable trend. In the face of escalating global health challenges, the identification of CVD risk factors becomes paramount, especially within national contexts where demographic shifts and lifestyle changes can significantly impact the health profile of the population. Aim of the study. Determining the prevalence of CVD risk factors in the Polish population and analyzing their changes over time. Material and Methods Data of 705,420 Poles aged 35-55 years who were enrolled in CVD disease prevention programme between 2012 and 2021 were analysed. The prevalence of the following CVD risk factors was determined: nicotinism, hypertension, elevated total cholesterol, elevated LDL, reduced HDL, elevated triglycerides, elevated glucose (indicating pre-diabetes), low physical activity, overweight, obesity, SCORE ≥5%. In addition, we assessed how the mean SCORE, BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL cholesterol, LDL cholesterol, triglycerides, glucose levels and waist circumference changed over time. Results Nicotinism affected 17.98%-24% of women (W) and 27.29%-36% of men (M). Hypertension was in 7.04%-8.58% of W and 17.45%-19.62% of M. Elevated total cholesterol were in 55.69%-63.64% of W and 65.91%-72.68% of M. Elevated LDL were in 44.77%-54.2% of W and 58.26%-65.48% of M. Reduced HDL were in 9.84%-11.52% of W and 14.48%-16.57% of M. Elevated triglyceride were in 13.44%-15.37% of W and in 33.81%-36.29% of M. Elevated glucose indicating a pre-diabetic status were in 10.70%-13.16% of W and in 18.91%-22.76% of M. Low physical activity was in 75.96%-82.2% of W and 73.32%-81.67% of M. Overweight conditions were in 30.37%-31.67% of W and 48.61%-49.45% of M. Obesity affected 14.04%-17.12% of W and 20.67%-24.69% of M. SCORE ≥ 5% was in 0.23%-0.38% of W and in 13.08%-18.72% of M. There was a decrease in the mean SCORE value (-0.08; 95%CI: -0.09 - -0.06) from 2012. An increase over time was noted in mean BMI (-0.01; 95%CI: -0.05 - 0.04). There was a slight decrease followed by a notable increase over time in mean systolic (-0.35; 95%CI: -0.47 - -0.24) and diastolic blood pressure (-0.25; 95%CI: -0.32 - -0.18). There was a decrease in mean total cholesterol (-3.29; 95%CI: -4.27 - -2.31) and mean LDL cholesterol (-3.11 95%CI: -4.22 - -2.01). A notable increase was observed in mean glucose values (0.01; 95%CI: 0-0.01). Over time, there was an increase in mean waist circumference value (-0.19; 95%CI: -0.54-0.16). Conclusions The escalation of CVD risk among the Polish population is illustrated, with a marked increase in obesity, sedentary lifestyles and indicators of metabolic syndrome. These trends highlight the urgent need for targeted public health initiatives and for the implementation of comprehensive strategies to mitigate these risks

Circulating Amyloid beta 1-40 is independently associated with statin treatment and LDL cholesterol reduction: a prospective cohort study

Abstract Background Accumulating evidence suggests that circulating amyloid beta 1-40 (Aβ40), a pro-inflammatory and pro-atherogenic peptide, is associated with atherosclerotic cardiovascular disease (ASCVD), providing incremental prognostic value and risk stratification refinement in primary and secondary prevention settings. Existing evidence supports conflicting off-target effects of statins on plasma Aβ40. We aim to explore the impact of cardiovascular risk reduction through statin therapy on Aβ40 plasma levels in subjects with dyslipidemia and with/without ASCVD. Methods In this prospective study, patients with dyslipidemia who visited for the first time our lipid clinic for risk stratification and treatment plan assessment (n=146) were consecutively recruited. Αβ40 was measured in plasma samples by enzyme-linked immunosorbent assay at baseline and after a mean follow-up of 5.2 and 15 months. Patients in whom statin treatment was initiated or intensified in terms of dose or regimen (n= 68) were compared against patients not treated with statins or with unchanged statin intensity (n = 78). Statin intensity treatment was defined based on the European Society of Cardiology (ESC) guidelines. Results Increased Aβ40 plasma levels at baseline were associated with ASCVD presence, decreased glomerular filtration rate (GFR), and history of heart failure (p&amp;lt;0.05 for all). An increase in Aβ40 circulating levels between baseline and follow-up 1 was observed in patients in whom statin treatment was initiated or intensified (p=0.041). However, in patients not treated with statins or treated with unchanged statin intensity, an increase in Aβ40 circulating levels was observed between follow-up 1 and follow-up 2 (p=0.05, Figure 1A). These changes in Aβ40 were significantly different between the two groups during the short follow-up period (β=0.226, p for interaction =0.025) independently from age and changes in GFR, systolic blood pressure, and LDL-C. Additionally, patients who achieved a reduction in low-density lipoprotein cholesterol (LDL-C) ≥ 50% in follow-up 2 have unchanged Aβ40 levels during the long follow-up period, while an increase in Aβ40 was observed in the rest population (p=0.012, Figure 1B). These changes were significantly different between the two LDL-C groups independently of statin treatment and changes in high sensitive C-reactive protein (hs-CRP) (β= -0.231, p for interaction=0.035). Conclusion In a dyslipidemic population, statin initiation or intensification and LDL-C decrease showed a short-term increase and a long-term return to initial levels, respectively, in circulating Aβ40 levels. From a mechanistic point of view, our findings suggest that statins have an impact on Aβ40, possibly through an LDL-C-dependent and a non-LDL-C-dependent pathway. Further studies are needed to evaluate the utility of circulating Aβ40 as a novel biomarker in ASCVD risk reduction assessment.

The Effects of Bitter Melon (Mormordica charantia) on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Research indicates that bitter melon could be useful in the management of dyslipidemia. Still, there is disagreement concerning the findings. This systematic study was undertaken to clarify the impact of consuming bitter melon on lipid profile. The databases Web of Science, Cochrane Library, PubMed, and Scopus were queried from inception until February 9, 2023. The study assessed triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. The effect sizes were calculated using weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight randomized controlled trials (RCTs) with a total of 423 participants were included. Bitter melon consumption resulted in a significant decrease in plasma concentrations of TC (WMD; -9.71 mg/dL; CI: -17.69 to -1.74, p = 0.01) and TG (WMD; -10.24 mg/dL; CI: -19.92 to -0.56, p = 0.03), while bitter melon did not significantly lower blood LDL-C (WMD; -8.66 mg/dL; CI: -19.83 to 2.50, p = 0.12) and HDL-C concentrations (WMD; 0.54 mg/dL; CI: -2.38 to 3.45, p = 0.71). Subgroup analysis showed a significant decrease in TC and LDL-C and an increase in HDL-C at a dose of ≤ 2000 mg/day and an intervention period of ≤ 8 weeks. Also, the greatest impact of LDL-C and HDL-C was seen in diabetic and prediabetic people. Bitter melon supplementation positively impacts TC and TG levels. The limitations of this study were short-term trials (less than 3 months).

Ursodeoxycholic Acid for Trans Intestinal Cholesterol Excretion Stimulation: A Randomized Placebo Controlled Crossover Study.

The trans intestinal cholesterol excretion (TICE) pathway is a potential therapeutic target to reduce plasma low-density lipoprotein (LDL) cholesterol levels. TICE encompasses the direct excretion of cholesterol by enterocytes into feces. In mice, TICE has been shown to be stimulated by a hydrophilic bile acid pool, resulting in increased fecal neutral sterol loss and reduced plasma cholesterol levels. We investigated whether treatment with a hydrophilic bile acid, ursodeoxycholic acid (UDCA), would increase fecal neutral sterols in humans as a proxy for TICE. We performed a randomized, double-blind, placebo-controlled, cross-over trial in 20 male participants aged >18 years, with plasma LDL cholesterol levels ≥2.6 mmol/L. After a run-in period of ezetimibe 20 mg once daily for 3 weeks, patients were randomized to UDCA 600 mg or placebo orally once daily for 2 weeks. After a 3 week washout, patients underwent the alternate treatment. At baseline, mean (SD) age, body mass index, and plasma LDL cholesterol were 59±11.3 years, 26.4±3.1 kg/m2, and 3.9±0.8 mmol/L, respectively. After UDCA treatment, the plasma bile acid hydrophobicity index was reduced compared with placebo (-118.7% versus +2.3%, P<0.001). The fecal neutral sterols did not change (-5.8% versus +18.8%, P=0.51) and treatment with UDCA increased LDL cholesterol with 0.39 mmol/L (+8.1% versus -3.64%, P=0.002) when compared with placebo. UDCA in combination with ezetimibe increased plasma bile acid hydrophilicity in healthy subjects with LDL cholesterol levels >2.6 mmol/L but did not result in increased fecal neutral sterols or decreased LDL cholesterol. This suggests that TICE is not stimulated by an increase in the hydrophilicity of the bile acid pool in humans.

Effects of Alpha-Tocopherol (Vitamin E) Treatment on Cardiovascular Biomarkers: A Comprehensive Review

This comprehensive review explores that subjoining of alpha-tocopherol (vitamin E) have improved effect on cardiovascular biomarkers in the human subjects, focusing on its potential role in addressing cardiovascular diseases (CVDs), which are major global health challenges exacerbated by risk factors such as dyslipidaemia and hypertension. Systematic analysis of various randomized controlled trials, evaluates alpha-tocopherol's effects on LDL cholesterol, HDL cholesterol, systolic blood pressure, triglycerides, total cholesterol levels etc. The synthesis of current literature consistently indicates that alpha-tocopherol treatment leads to significant reductions in systolic blood pressure compared to control groups. Furthermore, substantial evidence supports alpha-tocopherol's ability to increase HDL-cholesterol levels and decrease LDL-cholesterol concentrations, suggesting beneficial impacts on lipid profiles. The review also discusses alphatocopherol's influence on additional cardiovascular biomarkers such as Troponin I, B-type Natriuretic Peptide (BNP), Nterminal pro-BNP, Troponin T, C-reactive Protein (CRP), Lipoproteins, Creatine Kinase-MB (CK-MB), Myoglobin, and Fibrinogen, highlighting its potential broader effects on cardiovascular health indicators. Overall, this review underscores alpha-tocopherol's potential as an adjunctive therapy for managing cardiovascular risk factors, particularly hypertension and dyslipidemia. The findings suggest that alpha-tocopherol supplementation may induce favourable changes in cardiovascular biomarkers, offering insights into its therapeutic potential and calling for further investigation in clinical settings.

AMPK-Mediated Hypolipidemic Effects of a Salvia miltiorrhiza and Paeonia lactiflora Mixed Extract on High-Fat Diet-Induced Liver Triglyceride Accumulation: An In Vivo and In Vitro Study.

This study investigates the hypolipidemic effects of a mixed extract of Salvia miltiorrhiza and Paeonia lactiflora (USCP119) in HFD-fed hamsters and in vitro cellular models. Over an 8-week period, HFD-fed hamsters were assigned to one of six groups: normal diet, HFD control, HFD with 50 mg/kg USCP119, HFD with 100 mg/kg USCP119, HFD with 50 mg/kg USCP119 twice daily (BID), and HFD with omega-3 fatty acids. Key outcomes assessed included body weight, serum triglycerides (TG), total cholesterol (TC), liver weight, hepatic TG levels, and epididymal fat. In cellular models, the impact of USCP119 on lipid accumulation and adipogenic markers was evaluated. USCP119 treatment at 50 mg/kg BID resulted in the lowest weight gain (15.5%) and the most significant reductions in serum TG and hepatic TG levels compared to the HFD control. The 100 mg/kg dose also led to substantial reductions in serum TG and TC levels and notable decreases in low-density lipoprotein cholesterol. USCP119 at 50 mg/kg once daily reduced TG and TC levels but was less effective than the higher doses. In cellular models, USCP119 was non-toxic up to 400 µg/mL and effectively reduced lipid accumulation, modulated adipogenic markers, and enhanced AMPK signaling, improving lipid metabolism and insulin sensitivity. All USCP119 treatments demonstrated effectiveness in managing hyperlipidemia and related metabolic disorders, with variations in impact depending on the dosage. The ability of USCP119 to reduce fat accumulation, improve lipid profiles, and enhance insulin sensitivity highlights its potential as a valuable dietary supplement for addressing high-fat diet-induced hyperlipidemia and metabolic disturbances.

Long-term metabolic effectiveness and safety of growth hormone replacement therapy in patients with adult growth hormone deficiency: a single-institution study in Japan.

To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD). We conducted a retrospective study. A total of 110 patients with AGHD receiving GHRT were enrolled. Clinical and laboratory data were collected annually from the beginning of the study. Statistical analysis was performed using a linear mixed-effects model. Of all patients, 46.4% were males, 70.9% had adult-onset GHD, and follow-up was up to 196 months, with a median of 68 months. The insulin-like growth factor-1 standard deviation score increased after the start of GHRT and remained constant for more than 11 years. Seventeen patients were followed up for more than 11 years. The body mass index increased. Waist circumference decreased in the short term but increased in the long term. The diastolic blood pressure decreased 1-5 years after the start of GHRT, and the systolic blood pressure increased 11 years after GHRT. Moreover, a long-term decrease in low-density lipoprotein cholesterol, an increase in high-density lipoprotein cholesterol, and a decrease in aspartate aminotransferase and alanine aminotransferase levels were observed. The glycosylated hemoglobin level increased after 3 years. The bone mineral density in the lumbar spine and total hip increased significantly 3 years after the start of GHRT. Finally, the number of adverse events was eight. We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years.

Addition of Bempedoic Acid to Statin-Ezetimibe versus Statin Titration in Patients with High Cardiovascular Risk: A Single-Centre Prospective Study.

Reducing levels of low-density lipoprotein cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk and with LDL-C above 70 mg/dL. They were randomly divided into two groups: the bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group, including patients who doubled the dose of statin. At 12 weeks, the BA group presented a more significant decrease in LDL-C compared to the ST group (-22.9% vs. 7.5% p 0.002). The total cholesterol decreased significantly in the BA group compared to ST (-14.8% vs.-4.7%; p 0.013) No significant between-group changes in HDL and triglycerides occurred. At 12 weeks, the number of patients who reached LDL-C lower than 70 mg/dL was 38 (63%) in the BA group versus 22 (37%) in the ST group (between groups, p 0.034). In the BA group, the LDL-lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of bempedoic acid to statin-ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C levels and increased the number of patients reaching the LDL-C goal.

Discovery and Preclinical Profile of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta (THR-β) Agonist for the Treatment of MASH.

Agonists of thyroid hormone receptor β (THR-β) decreased LDL cholesterol (LDL-C) and triglyceride (TG) levels in human clinical trials for patients with dyslipidemia. The authors present the highly potent and selective compound ALG-055009 (14) as a potential best in class THR-β agonist. The high metabolic stability and good permeability translated well in vivo to afford a long in vivo half-life pharmacokinetic profile with limited liability for DDI, and it overcomes certain drawbacks seen in recent clinical candidates.

Risk of dyslipidaemia in people living with HIV who are taking tenofovir alafenamide: a systematic review and meta-analysis.

Among many antiretroviral drugs, tenofovir alafenamide is used extensively in combination regimens of tenofovir/emtricitabine or tenofovir/emtricitabine/bictegravir. However, concerns have arisen about the potential of tenofovir alafenamide to exacerbate hyperlipidaemia. This meta-analysis evaluates the relationship between tenofovir alafenamide use and lipid-profile alterations in people living with HIV. We searched PubMed, Ovid MEDLINE, EMBASE and the Cochrane Library to identify studies on changes in cholesterol levels (e.g. total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides) in people living with HIV who received treatment with a regimen containing tenofovir alafenamide (data collected 31 March 2023, review completed 30 July 2023). Potential risk factors for worsening lipid profile during treatment with tenofovir alafenamide were also evaluated. Sixty-five studies involving 39,713 people living with HIV were selected. Significant increases in total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides were observed after treatment with tenofovir alafenamide. Specifically, low-density lipoprotein cholesterol (+12.31 mg/dl) and total cholesterol (+18.86 mg/dl) increased markedly from the third month of tenofovir alafenamide use, with significant elevations observed across all time points up to 36 months. Comparatively, tenofovir alafenamide regimens resulted in higher lipid levels than tenofovir disoproxil fumarate regimens at 12 months of use. Notably, discontinuation of the tenofovir alafenamide regimen led to significant decreases in low-density lipoprotein cholesterol (-9.31 mg/dl) and total cholesterol (-8.91 mg/dl). Additionally, tenofovir alafenamide use was associated with increased bodyweight (+1.38 kg; 95% confidence interval: 0.92-1.84), which became more pronounced over time. Meta-regression analysis identified young age, male sex and low body mass index as risk factors for worsening cholesterol levels in individuals treated with tenofovir alafenamide. Tenofovir alafenamide use in people living with HIV is associated with significant alterations in lipid profile.

Impact of rosuvastatin on metabolic syndrome patients with moderate to severe metabolic associated fatty liver disease without overt diabetes: A randomized clinical trial

ObjectiveThis investigation aimed to evaluate the efficacy and safety of rosuvastatin in treating moderate to severe metabolic associated fatty liver disease (MAFLD). MethodsThis prospective, open-label, randomized study included non-diabetic participants with metabolic syndrome and intrahepatocellular lipid (IHCL) levels >10 %, as determined by proton magnetic resonance spectroscopy (1H-MRS). The primary objective was the effect of a 52-week rosuvastatin treatment (10 mg/day) on IHCL content. Secondary objectives included the association between IHCL reduction and lipid metabolism parameters, along with safety indices such as glycemic control and hepatic and renal function. ResultsThirty-two participants completed the study. Rosuvastatin resulted in a significant absolute (△IHCL: 7.61 ± 4.51 vs. 1.54 ± 5.33, p = 0.002) and relative reduction in IHCL (△IHCL%: −42.28 ± 24.90 % vs. −8.91 ± 31.93 %, p = 0.003) compared to the control. Reduction in IHCL correlated significantly with decreases in low-density lipoprotein cholesterol (LDL-C) (r = 0.574, p < 0.01), apolipoprotein B (ApoB) (r = 0.660, p < 0.001), and free fatty acids (FFA) (r = 0.563, p = 0.005). No significant safety differences were observed between groups. ConclusionsRosuvastatin significantly reduced hepatic steatosis in individuals with moderate to severe MAFLD and metabolic syndrome over 52 weeks, while maintaining a favorable safety profile.

Recipe for Heart Health: A Randomized Crossover Trial on Cardiometabolic Effects of Extra Virgin Olive Oil Within a Whole-Food Plant-Based Vegan Diet.

Whole-food, plant-based vegan diets, low in oils, and Mediterranean diets, rich in extra virgin olive oil (EVOO), reduce cardiovascular disease risk factors. Optimal quantity of dietary fat, particularly EVOO, is unclear. In a randomized crossover trial with weekly cooking classes, adults with ≥5% cardiovascular disease risk followed a high (4 tablespoons/day) to low (<1 teaspoon/day) or low to high EVOO whole-food, plant-based diet for 4 weeks each, separated by a 1-week washout. The primary outcome was difference in low-density lipoprotein cholesterol (LDL-C) from baseline. Secondary measures were changes in additional cardiometabolic markers. Linear mixed models assessed changes from baseline between phases, with age, sex, and body weight change as covariates. In 40 participants, fat intake comprised 48% and 32% of energy during high and low EVOO phases, respectively. Both diets resulted in comparable reductions in LDL-C, total cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, glucose, and high-sensitivity C-reactive protein (all P<0.05). With diet-sequence interactions for LDL-C, differences were detected between diets by diet order (mean±SEM high to low: Δ-12.7[5.9] mg/dL, P=0.04 versus low to high: Δ+15.8[6.8] mg/dL, P=0.02). Similarly, low to high order led to increased glucose, total cholesterol, and high-density lipoprotein cholesterol (all P<0.05). Over period 1, LDL-C reductions were -25.5(5.1) post-low versus -16.7(4.2) mg/dL post-high EVOO, P=0.162, which diminished over period 2. Both plant-based diet patterns improved cardiometabolic risk profiles compared with baseline diets, with more pronounced decreases in LDL-C after the low EVOO diet. Addition of EVOO after following a low intake pattern may impede further lipid reductions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04828447.

Changes in the exposure to cardiovascular disease risk factors in an 18 year follow-up study of a cohort of middle age urban residents. The Polish arm of the HAPIEE study.

Cross-sectional studies revealed that risk factor exposure increases with age but after reaching its peak decreases. This decline may be attributed to higher mortality among exposed individuals, lifestyle, or natural physiological changes related to age. Only prospective observations at the individual level provide credible insights of exposure during the transition from middle to old age. This study addresses changes in cardiovascular risk factors among older urban residents in Poland over an 18-year period. The study analyzed data from the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) project, a prospective cohort study investigating cardiovascular disease determinants. The sample included 312 participants (46-69 years). Data on demographic characteristics, blood lipids, blood pressure, body mass index (BMI), fasting glucose, and smoking status were collected at baseline and during re-examination. The analysis yielded a decrease in diastolic blood pressure, total cholesterol, LDL-cholesterol, and non-HDL cholesterol concentrations. However, BMI and fasting glucose levels increased. The decrease in blood pressure was mainly attributed to treatment effects, while the reduction in lipid concentrations was observed regardless of treatment. In addition, smoking prevalence decreased over the course of 18 years. The results of the prospective nearly 20 year observation at the individual level confirm findings from repeated cross-sectional studies on decrease in lipid concentrations, blood pressure and prevalence of smoking in older individuals.

Early Use of PCSK9 Inhibitors in the Prognosis of Patients with Acute Coronary Syndrome by Protecting Vascular Endothelial Function.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has a protective effect on acute coronary syndrome (ACS). However, most studies have shown that this protective effect is based on a decrease in low-density lipoprotein cholesterol, while other mechanisms remain limited. This study aimed to determine whether PCSK9i can improve the prognosis of ACS patients by protecting endothelial function. A total of 113 ACS patients were enrolled and randomly assigned to PCSK9i group (PCSK9i combined with statins) and control group (statins only). Blood lipids and endothelial function indicators were measured and analyzed 6 weeks before and after treatment. The effect of PCSK9i on the expression and secretion of endothelial function indicators in vascular endothelial cells were studied by cell experiments. After 6 weeks of treatment, endothelial function indicators such as nitric oxide (NO), thrombomodulin, intercellular cell adhesion molecule-1, endothelin-1, and flow-mediated vasodilation were significantly improved in PCSK9i group compared with control group. Only the changes of NO and von Willebrand factor were associated with blood lipid levels, whereas the changes of other endothelial function indicators were not significantly associated with blood lipid levels. PCSK9i reduced the incidence of major adverse cardiovascular events in patients with ACS compared to those in the control group. In cell experiments, PCSK9i treatment significantly ameliorated LPS induced endothelial injury in HUVECs. PCSK9i can protect vascular endothelial function partly independently of its lipid-lowering effect and ameliorate the prognosis of patients with ACS within 6 weeks. This mechanism may involve heat shock transcription factor 1/heat shock proteins -related signaling pathways. Early use of PCSK9i in patients with ACS should be strongly considered in clinical practice.

Effect of Crushed Flaxseed Consumption on Cardiovascular Risk Indicators in Menopausal Women.

Flaxseed is known for its numerous health benefits and is often used in the prevention and treatment of civilizational diseases. This study aimed to evaluate the impact of consuming crushed flaxseed on cardiovascular risk in 51 menopausal women. The intervention lasted for 8 weeks, during which participants received a daily dose of 40 g of crushed flaxseed from two varieties with differing lignan contents. Participants were divided into three subgroups based on the variety of flaxseed consumed: (1) high-lignan group (HL), (2) low-lignan group (LL), and (3) control group (no flaxseed consumption). Biochemical blood parameters were measured using a BiOLis 24i Premium automatic analyzer. Body composition was assessed using an InBody 720 device. In the lipid profile, we observed a significant increase in total cholesterol (T-C) and high-density lipoprotein cholesterol (HDL-C) levels, along with a significant decrease in low-density lipoprotein cholesterol (LDL-C) levels in both the HL and LL groups. Triglyceride (TG) levels exhibited no significant change, whereas high-sensitivity C-reactive protein (hs-CRP) levels were significantly reduced in both the HL (p < 0.01) and LL (p < 0.01) groups. Visceral fat area (VFA) and percent body fat (PBF) showed a slight decreasing trend in the HL group, whereas in the LL group, VFA showed a slight increase. Body mass index (BMI) remained stable across all groups. These findings suggest that for the modulation of cardiovascular disease (CVD) risk factors, the daily dosage, duration of consumption, form of intake, and the specific variety of flaxseed (based on lignan content) are crucial factors.

Effect of Omega-3 Fatty Acids Supplementation in Pediatric Patients with Type 1 Diabetes Mellitus

Abstract Background Omega-3 fatty acids (O3FAs) are polyunsaturated fatty acids derived from fish oil. Beneficial effects of O3FA supplementation in a wide range of disease condition have been well studied. However; the role of O3FA in management of type 1 diabetes mellitus (T1DM) remains unclear and controversial. Objectives Therefore, we performed a randomized-controlled trial to assess the effect of oral O3FAssupplementation on glycemic control and lipid profile in pediatric patients with T1DM. Methods This study included 70 children and adolescents with T1DM. Patients were randomly assigned into two groups; intervention group and received oral O3FAs capsules (1 gram daily). The other group did not receive any supplementation and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c and fasting lipids. Results Supplementation with O3FAs was safe and well-tolerated. After 6 months, O3FAs adjuvant therapy for the intervention group resulted in a significant decrease of systolic blood pressure, insulin dose, FBG, HbA1c, triglycerides, total cholesterol and LDL-cholesterol compared with baseline levels and compared with the control group (p &amp;lt; 0.05). On the other hand, T1DM patients without O3FAs adjuvant therapy (control group) had higher blood glucose levels and HbA1c at study end compared with baseline levels (p &amp;lt; 0.001). Conclusions O3FAs as an adjuvant therapy to insulin improved blood glucose levels, glycemic control and dyslipidemia leading to reduction in insulin dose in pediatric patients with T1DM.

Development of rosuvastatin calcium nano-carrier patches by central composite design

Rosuvastatin (RS) is a statin medication used to lower cholesterol levels and reduce the risk of cardiovascular diseases. RS works by inhibiting an enzyme called HMG-CoA reductase, which helps decrease LDL cholesterol and increase HDL cholesterol. The typical dose range for rosuvastatin is 5-40 mg once daily, with the starting dose usually being 10 mg. However, the dosage may vary depending on the patient's cholesterol levels and individual response to the medication. Rosuvastatin has a half-life of approximately 19 hours and undergoes metabolism mainly in the liver. The aim of the study was to develop a transdermal patch containing Rosuvastatin in the form of niosomes (NP). The Rosuvastatin niosomes were prepared using the solvent casting method, and the optimized formulation showed a particle size of 211.6 nm with a polydispersity index (PDI) of 0.197. The zeta potential of the niosomes was found to be -44.7. These results indicate that the developed formulation has a uniform particle size distribution and a stable zeta potential, which are important factors for the effective delivery of Rosuvastatin through a transdermal patch. Invitro diffusion studies of the optimized patch RN-T6 released upto 24 hours with %CDR of 98.98% and the drug diffusion data is fitted into various mathematical models and RN-T6 followed zero order drug release kinetics and the diffusion mechanism was non-fickian diffusion.