Statins Research Articles

Does EFSA statement on Monacolin content of nutraceutical combinations impair their lipid lowering effect? The LopiGLIK experience

BackgroundMonacolin-K, the active component of red yeast rice (RYR), reduces cholesterol by inhibiting HMG-CoA reductase. Following safety concerns, the European Food Safety Authority (EFSA) recommended limiting Monacolin-K intake to less than 3 mg/day due to adverse effects at higher doses.Case presentation: A study comparing Armolipid Plus® and LopiGLIK® found LopiGLIK® more effective in lowering LDL cholesterol, possibly due to slightly higher dosages of Berberine and Monacolin-K. Despite reducing Monacolin-K content to 2.99 mg following EFSA guidelines, LopiGLIK® maintained its cholesterol-lowering efficacy.ConclusionsTaken together, our results indicate that other ingredients, such as Morus alba, may contribute to LopiGLIK®’s enhanced effectiveness, challenging the notion that minor differences in Monacolin-K dosage account for the observed efficacy.

Abstract 4132341: Systematic Examination of the AHA PREVENT Equations

Background: The novel AHA Predicting Risk of CVD Events (PREVENT) equations newly incorporate predictors (estimated glomerular filtration rate [eGFR]) and outcomes (heart failure [HF]) relevant to the novel construct of cardiovascular-kidney-metabolic (CKM) syndrome. Aims: We sought to characterize the intrinsic properties of the PREVENT equations by simulating different risk profiles across the age and CKM risk spectrum. Methods: We applied the PREVENT base equations to estimate 10-year predicted risk for total CVD, which includes atherosclerotic CVD and HF. First, we calculated risk estimates for a hypothetical individual varying age from 30-79 years with an average risk factor profile (mean population risk factor levels based on National Health and Nutrition Examination Survey 2011-2020 data without diabetes, not on anti-hypertensive or statin medication, and who does not smoke). Second, we examined at which age a hypothetical individual would exceed the previously defined intermediate risk threshold ≥7.5% established by national guidelines. Lastly, we examined the differences in predicted risk with or without diabetes and/or Stage 3 CKD (defined as eGFR 44.5 mL/min/1.73m 2 ). Results: For hypothetical individuals aged 30-79 years with average risk factor levels, predicted 10-year CVD risk is shown in the figure for females (Panel A) and males (Panel B). The predicted risk would exceed the intermediate risk threshold at age 68 years if female and 63 years if male. If the individual had Stage 3 CKD, the predicted risk would exceed the intermediate risk threshold at 60 if female and 55 years if male. If the individual had diabetes, the predicted risk would exceed the intermediate risk threshold at 59 if female and 52 years if male. If both diabetes and Stage 3 CKD were present, the predicted risk would exceed the intermediate risk threshold at age 42 years if female and 35 years if male. Conclusions: The PREVENT equations enable more granular differentiation of risk among individuals with varying CKM profiles. Understanding risk estimates across the spectrum of age and CKM can support interpretability among clinicians and patients.

Abstract 4112853: Trends in Statin Use for the Secondary Prevention of Atherosclerotic Cardiovascular Disease among U.S. Adults by Age, 1999-2020

Background: Current research focusing on trends in statin medication usage, particularly for different age groups, is limited. This study explored the change trends in statin usage from 1999 to 2020, with a specific focus on different age groups. Methods: Utilizing data from the National Health and Nutrition Examination Survey spanning the period from 1999 to 2020, our study included individuals aged 18 years and older diagnosed with atherosclerotic cardiovascular disease (ASCVD). Results: In the 18-44 years age group, usage changed from 18.34% (95% CI, 0.18 to 36.50) in 1999 to 16.63% (95% CI, 0.36 to 32.91) in 2020 (linear P value = 0.540, quadratic P value = 0.610) (Figure 1). For individuals aged 45-64 years, usage increased from 39.33% (95% CI, 29.62 to 49.05) in 1999 to 54.97% (95% CI, 47.10 to 662.83) in 2020 (linear P value < 0.001, quadratic P value = 0.777) (Figure 1). In the group aged 65 years and older, usage increased from 35.17% (95% CI, 29.57 to 40.77) in 1999 to 60.62% (95% CI, 55.73 to 65.51) in 2010, and further to 68.62% (95% CI, 63.65 to 73.60) in 2020 (quadratic P value < 0.001) (Figure 1). There was an interaction effect between statin usage trends and age (P for interaction <0.001) (Figure 1). Conclusion: Overall, current health policies are effective for the use of statins for the secondary prevention of ASCVD. However, there was almost no improvement in statin usage within the 18-44 years age group. This highlights the need for greater focus on young ASCVD patients. Therefore, additional research is needed on statin use among young people.

Mitigating neuroinflammation in cognitive areas: exploring the impact of HMG-CoA reductase inhibitor.

Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. The animals were treated with simvastatin or vehicle for 4 days before and 10 days after surgery. The treatment preserved the non-associative memory (P < 0.05), recovered expression of Smad-3 in the hippocampus (P < 0.05), and prevented increased expression of calpain-1 (hippocampus: P < 0.0001; PFC: P < 0.05) and GSKβ (hippocampus: P < 0.0001; PFC: P < 0.0001) in the brain structures of the sepsis survivor animals. These animals also showed mitochondrial dysfunction and decreased axon terminals in the RE. Simvastatin seems to restore energy metabolism by improving the electron transfer system (ETS) values in the hippocampus (P < 0.01) and the oxidative phosphorylation/ETS (P/E) ratio in the PFC (P < 0.05), in addition to preventing the reduction of axon terminals in survivor animals. These results suggest a potential neuroprotective effect and the importance of considering HMG-CoA reductase inhibitors as a possible adjuvant therapy in sepsis.

Effect of diabetes mellitus on 3-year outcomes in patients with acute myocardial infarction with nonobstructive coronary arteries.

Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy.

Zero-Dollar Copayment Impact on Adherence Scores for Centers for Medicare and Medicaid Services Star Ratings Generic Medications.

The Centers for Medicare & Medicaid Services (CMS) Star Ratings system pushes Medicare Advantage health plans to achieve ever greater attainments in key metrics, including adherence to hydroxymethylglutaryl-CoA reductase inhibitor (statins), renin-angiotensin system (RAS) antagonist, and noninsulin antihyperglycemic (DM) medications. The purpose of this observational study was to evaluate the impact of expanding a $0 copayment (copay) benefit from mail order-only to mail order plus retail pharmacies on adherence to statin, RAS, and DM medications. Medicare beneficiaries with and without a $0 copay expansion who received ≥ 1 dispensing of a generic, CMS Star Ratings RAS, statin, and/or DM medication during both 2021 and 2022 were included. Outcomes included changes in proportion of days covered (PDC) from 2021 to 2022 and proportions of patients with a PDC ≥ 0.8 in 2022. Overall (N = 65,716), patients had a high ( > 0.930) mean baseline PDC. Patients with $0 copay expansion had a statistically significant greater mean PDC increase for statin (adjusted P = 0.038), reduction for RAS (adjusted P = 0.036), and no difference for DM (adjusted P = 0.696). Patients with a $0 copay expansion had statistically significant higher proportions of beneficiaries with a PDC ≥ 0.8 for statin (adjusted P = 0.003) and RAS (adjusted P = 0.003) but not DM (adjusted P = 0.256). An expanded $0 copay was associated with minor increased generic statin medication adherence. In populations with a high baseline PDC, expanding a $0 copay benefit on generic statin, RAS, and DM medications to dispensing outside of mail order may only contribute slightly to an increase or sustainment of a health plan's CMS Star Ratings.

Multi-Omics Mendelian Randomization Study Investigating the Impact of PCSK9 and HMGCR Inhibition on Type 2 Diabetes Across Five Populations.

The prevalence of type 2 diabetes (T2D) varies among populations of different race/ethnicity. The influence of genetically-proxied lipoprotein cholesterol (LDL-C) lowering through proprotein convertase subtilisin/kexin 9 (PCSK9) and HMG-CoA Reductase (HMGCR) on T2D in non-European populations is not well established.A drug-target Mendelian randomization (MR) approach was used to assess the effects of PCSK9 and HMGCR inhibition on T2D risk and glycemic traits in five populations: East Asian (EAS), South Asian (SAS), Hispanic (HISP), African (AFR), and European (EUR). Our study did not find relationships between genetically-proxied PCSK9 inhibition and T2D risk in EAS (odds ratio [OR]=1.02, [0.95-1.10]), SAS (OR=1.05, [0.97-1.14]), HISP (OR=1.03, [0.94-1.12]), or EUR (OR=1.04, [0.98-1.11]). However, in AFR, primary analyses suggested an increased risk of T2D due to PCSK9 inhibition (OR=1.53, [1.058-2.22], P-value=0.024), although this was not supported in sensitivity analyses. Genetically-proxied HMGCR inhibition was associated with an increased risk of T2D in SAS (OR=1.44, [1.30-1.61], P-value=9.8×10-12), EAS (OR=1.36, [1.22-1.51], P-value=4.2×10-10), and EUR (OR=1.52, [1.21-1.90], P-value=3.3×10-4). These results were consistent across various sensitivity analyses, including colocalization, indicating a robust finding. The findings indicate a neutral impact of long-term PCSK9 inhibition on T2D and glycemic markers in most non-European populations, with a potential increased risk in AFR cohorts. By contrast, HMGCR inhibition increased the risk of T2D in South Asian, East Asian, and European cohorts, underscoring the need to consider diversity in genetic research on metabolic diseases.

Tracking the Risk of Cardiovascular Disease after Almond and Oat Milk Intervene or Statin Medication with a Powerful Reflex SH-SAW POCT Platform.

Cardiovascular disease (CVD) represents the leading cause of death worldwide. For individuals at elevated risk for cardiovascular disease, early detection and monitoring of lipid status is imperative. The majority of lipid measurements conducted in hospital settings employ optical detection, which necessitates the use of relatively large-sized detection machines. It is, therefore, necessary to develop point-of-care testing (POCT) for lipoprotein in order to monitor CVD. To enhance the management and surveillance of CVD, this study sought to develop a POCT approach for apolipoprotein B (ApoB) utilizing a shear horizontal surface acoustic wave (SH-SAW) platform to assess the risk of heart disease. The platform employs a reflective SH-SAW sensor to reduce the sensor size and enhance the phase-shifted signals. In this study, the platform was utilized to monitor the impact of a weekly almond and oat milk or statins intervention on alterations in CVD risk. The SH-SAW ApoB test exhibited a linear range of 0 to 212 mg/dL, and a coefficient correlation (R) of 0.9912. Following a four-week intervention period, both the almond and oat milk intervention (-23.3%, p < 0.05) and statin treatment (-53.1%, p < 0.01) were observed to significantly reduce ApoB levels. These findings suggest that the SH-SAW POCT device may prove a valuable tool for monitoring CVD risk, particularly during routine daily or weekly follow-up visits.

Association between statin use and immune-related adverse events in patients treated with immune checkpoint inhibitors: analysis of the FAERS database.

Understanding the risk relationship between statin use and immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibitors (ICIs) therapy is crucial for optimizing oncological management. This study aimed to investigate whether the use of statins increases the risk of irAEs in patients receiving ICI therapy. This study primarily utilized data from FAERS database. Multivariable logistic regression was the principal method of analysis, and the Benjamini-Hochberg procedure was employed to adjust for multiple hypothesis testing. In a group of 145,214 patients undergoing ICI therapy, 9,339 reported using statin medications. Multivariable analysis indicated an increased risk of irAEs among statin users (OR 1.199, 95% CI: 1.141-1.261; FDR p < 0.001) in comparison to those not using statins. Notably, increased risks were observed particularly in patients diagnosed with lung, pancreatic, and renal cancers. The link between statin usage and increased irAEs risk remained consistent across various ICIs treatments. Statin medication usage is linked to an elevated probability of experiencing irAEs in patients enrolled in ICI therapy. In cancer patients receiving immune checkpoint inhibitors, careful consideration of statin use is essential to avoid potentially increased irAEs risk. These findings provide critical guidance for clinicians in developing treatment strategies that balance therapeutic efficacy and safety in oncological management.

Association of polypharmacy with clinical outcomes and healthcare utilization in older adults with cardiometabolic diseases: a retrospective cohort study.

Limited knowledge exists on the association between polypharmacy among older patients diagnosed with cardiometabolic diseases and the risk of clinical outcomes and healthcare utilization. This study aimed to estimate the impact of polypharmacy on clinical outcomes and healthcare utilization in older adults with cardiometabolic diseases. A retrospective cohort analysis was performed using data from the Beijing Municipal Medical Insurance Database. The study focused on polypharmacy prescribing patterns in community-dwelling adults 65years and older with cardiometabolic diseases. Polypharmacy was defined as the use of five or more medications on the index date. The primary outcome included clinical outcomes, including hospitalizations and emergency department visits. The secondary outcome focuses on hospital utilization, specifically medication costs and length of stay. The study included a cohort of 405,608 patients. Among these, the most frequently used drug classes in the polypharmacy and non-polypharmacy groups were HMG-CoA reductase inhibitors and dihydropyridines, respectively. After adjustment for covariates, polypharmacy was not associated with an increased risk of hospitalization (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.95-1.26, p = 0.23) or ED visits (OR 1.28, 95% CI 0.97-1.68, p = 0.08). Similarly, no significant association was found with an increase in inpatient medication costs ($2,620.5, 95% CI $2387.3-$2894.3, p = 0.97) or length of stay (3.98days, 95% CI 3.68-4.30days, p = 0.79). However, polypharmacy was associated with higher medication costs in outpatient settings ($73.07, 95% CI $72-$74, p < 0.05) and ED visits ($51.2, 95% CI $44.5-$59.1, p < 0.05). Although polypharmacy is associated with increased healthcare costs in outpatient settings and ED visits, it does not significantly increase the risk of hospitalization or ED visits when properly managed.

Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial

Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21–70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of −1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of −0.69 ± 0.75 (fasting) and −0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (−1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.

Causal impact of statins on susceptibility to osteoarthritis: insights from a two-sample Mendelian randomization analysis.

Osteoarthritis is a widely prevalent cause of pain and disability among older adults. It is an incurable condition, and most treatments are aimed at alleviating symptoms. This study aimed to investigate the impact of statins on osteoarthritis by using a two-sample Mendelian randomization approach, using genetic variants associated with statin use as instrumental variables. Information on single nucleotide polymorphisms associated with statin medication was obtained from the FinnGen study, and data on osteoarthritis were sourced from the UK Biobank. The inverse variance weighted method was used as the primary analytical approach for the Mendelian randomization analysis. Sensitivity analyses were conducted to evaluate horizontal pleiotropy and heterogeneity. To examine the genetic relationship between statins and osteoarthritis, linkage disequilibrium score regression-based estimates were used. Mendelian randomization analysis indicated a positive effect of statin use on the treatment of osteoarthritis (odds ratio 0.951, 95% confidence interval 0.914-0.99, p < 0.05). This conclusion was supported by various Mendelian randomization methods. Sensitivity analyses revealed no significant directional pleiotropy or influential single nucleotide polymorphisms that could compromise the overall causal inference. Linkage disequilibrium score regression-based estimates suggested a modest genetic correlation between statin use and osteoarthritis (Rg = 0.098, Se = 0.034, p < 0.05), thus reinforcing the robustness of the Mendelian randomization analysis. Statins reduce the risk of osteoarthritis, aligning with the results of observational studies. Further research is essential to validate these results and explore the underlying mechanisms in detail.

Risk of Osteoporosis Associated with HMG-CoA Reductase Inhibitors in Patients with Dyslipidemia: A Retrospective Cohort Study in Korea

Risk of Osteoporosis Associated with HMG-CoA Reductase Inhibitors in Patients with Dyslipidemia: A Retrospective Cohort Study in Korea

Utilizing Cinnamomum verum (a culinary spice), as a functional food ingredient ameliorating hypercholesterolemia: In-vivo, in-vitro, and in-silico multi-model analysis

Hypercholesterolemia involves elevated levels of total cholesterol (T.C.), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and reduced high-density lipoprotein (HDL), linked to sedentary lifestyles, irregular eating habits, high-fat diets, type 2 diabetes, and various hereditary and environmental factors. It poses significant health risks, including high blood pressure, atherosclerosis, fatty liver, and cardiovascular disease. This study aimed to evaluate the lipid-lowering effects of ethanolic extract of Cinnamon in hypercholesterolemia-induced rats using in-vivo, in-vitro, and in-silico approaches. In the present work, thirty female Albino rats were divided into six groups: Group I (basal diet), Group II (high-fat diet), Group III (statin treatment), and Groups IV-VI (high-fat diet with different doses of cinnamon extract). Serum lipid profiles were measured after four weeks of treatment. In-vitro HMG-CoA reductase inhibition was assessed. In-silico studies, including molecular docking, ADME analysis, toxicity prediction, and molecular dynamics (M.D.) simulations, were conducted. DFT studies with MESP/HOMO/LUMO analysis provided electronic property insights. High-fat diet increased body weight and serum lipid levels in rats. Cinnamon extract significantly reduces body weight and serum LDL, VLDL, and triglycerides while increasing HDL levels. Histopathology showed reduced fat accumulation and normal liver morphology in cinnamon-treated groups. In-vitro analysis revealed significant HMG-CoA reductase inhibition by cinnamon extract. In-silico docking confirmed strong binding affinities of cinnamon compounds to HMG-CoA reductase. ADME analysis and toxicity prediction indicated favorable pharmacokinetics. MD simulations showed stable ligand-protein complexes, and DFT studies highlighted the electronic properties of active compounds. To conclude, the cinnamon ethanolic extract demonstrated effective lipid-lowering properties in hypercholesterolemic rats, supported by in-vitro and in-silico analyses, suggesting its potential as a therapeutic agent for hypercholesterolemia. Further research is needed to explore underlying mechanisms and clinical outcomes.

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study

Purpose Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005–2013. Methods Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA&lt;100% versus CAA = 100% (ref), 2) CAA&lt;80% versus CAA≥80% (ref) and 3) CAA&lt;80% versus 80%≤CAA&lt;100% versus CAA = 100%. Results Poor statin adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA&lt;100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Conclusions Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

Efficient Biosynthesis of Monacolin J through Enzymatic Hydrolysis Using a Recombinant Lovastatin Hydrolase

Simvastatin is a widely used statin medication that is commonly prescribed to lower cholesterol levels and reduce the risk of cardiovascular events. It is marketed under the brand name Zocor and is known for its effectiveness in treating high cholesterol and managing cardiovascular disease. Monacolin J is an important precursor used to synthesize simvastatin and is mainly produced by chemical methods in industry. Here, monacolin J was synthesized through an enzymatic method under optimized reaction conditions. One recombinant Escherichia coli BL21 (DE3) strain containing lovastatin hydrolase (encoded by CDV55_102090) from Aspergillus turcosus was constructed, which effectively transformed 100 g/L of lovastatin to monacolin J within 3.5 h at pH 8.0 and 30 °C, with a conversion rate of &gt;99.8%. Furthermore, the T5010, the temperature at which the residual activity was half of the initial enzymatic activity after 10 min of heat treatment, was &gt;50 °C, indicating the tremendous potential of this bioprocess for synthesizing monacolin J at an industrial scale.

In silico approach for identification of potential tetracyclic triterpenoids from mushroom as HMG-CoA reductase inhibitor

Cardiovascular disease is estimated to be responsible for one-third of all global deaths annually. It occurs mostly due to hyperlipidemia, a condition where excessive cholesterol deposits in blood vessels. A favorable target for treating hyperlipidemia involves the crucial role of inhibition of a specific enzyme known as 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The primary goal of this present study is to identify potential HMG-CoA reductase inhibitors containing tetracyclic triterpene nucleus derived from mushrooms. A library of 86 myco-constituents bearing a tetracyclic triterpene scaffold was prepared and screened to identify potential HMG-CoA reductase inhibitors targeting proteins 1HW8 and 1HW9. For this purpose, molecular docking, ADME prediction, and molecular dynamics (MD) simulation studies were performed on this in-house prepared database. The virtual screening results exhibited M_02(c) as the best hit with promising SP Glide scores compared to standard statin drugs. In order to assess the stability and interactions, a 100 ns MD simulation was performed. Further, M_02(c) was also analysed for MMGBSA binding energy to access and validate the thermodynamic stability of the protein-ligand complex. The results of this study revealed that M_02(c) is a promising hit molecule and may emerge as a potent HMG-CoA reductase inhibitor in preventing and treating hyperlipidemia.

The impact of breast cancer radiation therapy exposure on the prevalence of breast arterial calcification.

Mammographic breast arterial calcification (BAC) is an emerging imaging biomarker of cardiovascular disease (CVD) risk in women. The purpose of this study was to assess if breast radiation therapy (RT) exposure impacts the screening utility of this imaging biomarker. This cross-sectional study included women ages 40-75 years who underwent index screening mammography between January 1, 2011 and December 31, 2012. Chart review was performed to extract data on the breast cancer RT exposure and CVD risk factors. Mammograms were reviewed for the presence of BAC. Multivariate logistic regression was used to examine breast RT exposure and BAC, with adjustment for age, body mass index, smoking status, hypertension, Type 2 diabetes, statin medication use, and antihypertensive medication use. Of the 1155 women included in this analysis, 222 (19.2%) had mammographic evidence of BAC, 122 (10.6%) had a history of RT exposure, and 39 (32%) women with RT exposure had mammographic BAC. Women with breast RT exposure had higher odds of BAC compared to women without (odds ratio: 2.18, 95% CI: 1.43, 3.28; P-value = .0008). However, this association became non-significant after multivariable adjustment, with the maximally adjusted model demonstrating an odds ratio of 1.52 (95% CI: 0.95, 2.40; P-value = .07). Our findings suggest that breast RT exposure does not impact the prevalence of mammographic BAC. Therefore, it does not affect its utility as an imaging biomarker of CVD risk. This is the first observational study addressing the knowledge gap pertaining to the influence of breast RT exposure on BAC.

The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women with In Situ or Early-Stage Invasive Breast Cancer.

Statins, inhibitors of HMG-CoA reductase, have been shown to have potential anti-carcinogenic effects through the inhibition of the mevalonate pathway and their impact on Ras and RhoGTAases. Prior studies have demonstrated a reduction in breast tumor proliferation, as well as increased apoptosis, among women with early-stage breast cancer who received statins between the time of diagnosis and the time of surgery. The aim of this study was to evaluate the impact of short-term oral high-potency statin therapy on the expression of markers of breast tumor proliferation, apoptosis, and cell cycle arrest in a window-of-opportunity trial. This single-arm study enrolled 24 women with stage 0-II invasive breast cancer who were administered daily simvastatin (20 mg) for 2-4 weeks between diagnosis and surgical resection. Pre- and post-treatment tumor samples were analyzed for fold changes in Ki-67, cyclin D1, p27, and cleaved caspase-3 (CC3) expression. Out of 24 enrolled participants, 18 received statin treatment and 17 were evaluable for changes in marker expression. There was no significant change in Ki-67 expression (fold change = 1.4, p = 0.597). There were, however, significant increases in the expression of cyclin D1 (fold change = 2.8, p = 0.0003), p27 cytoplasmic (fold change = 3.2, p = 0.025), and CC3 (fold change = 2.1, p = 0.016). Statin treatment was well tolerated, with two reported grade-1 adverse events. These results align with previous window-of-opportunity studies suggesting a pro-apoptotic role of statins in breast cancer. The increased expression of markers of cell cycle arrest and apoptosis seen in this window-of-opportunity study supports further investigation into the anti-cancer properties of statins in larger-scale clinical trials.