Search results for: statin

Authors: Fakhr Eddin Alnaal, Angela Dahdal, Duaa Aladib, Sabeen Ibrahim, Ibrahim Ghoraibi, Bissan Ahmed

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Dementia is one of the diseases which had several stages and Alzheimer’s term was selected in respect for the first doctor Alzheimer who defined the first symptoms of this diseases in a woman whom was well treated by him. The fact that this is a type of a silent disease on which you have a long-term process of neurological degradation and suddenly gives symptoms which are most often irreversible, on clinical level likely we can consider it as a malignancy, one in terms of that it is sudden shocking irreversible and on the level of behavior and some mortality beside the lack of early detection tools for diagnosis. Therefore, the goal of our project is to test the concept of the ability of Statin in prevention of such disease and we investigated that both on experimental level and most importantly on clinical one, the clinical part was performed in a recognized house of aged people who had accidently a high cholesterol and were for years given Statin to treat that elevation, however after the symptoms of Alzheimer’s appeared and when diagnosed, they were well treated and rapidly recovered compared to Alzheimer’s patients in the same house who did not receive Statin had a mild improvement in their symptoms after the therapy, on the other hand we confirmed such observation by a well-organized experimental work.

Keywords: Alzheimer's, dementia, silent disease, statin

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Authors: Yusra Pintaningrum, Ilma Fahira Basyir, Sony Hilal Wicaksono, Vito A. Damay

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Background: Coronary artery calcium (CAC) scores play an important role in improving prognostic accuracy and can be selectively used to guide the allocation of statin therapy for atherosclerotic cardiovascular disease outcomes and potentially associated with the occurrence of MACE (Major Adverse Cardiovascular Event) and MI (Myocardial Infarction). Objective: This systematic review and meta-analysis aim to analyze the findings of a study about CAC Score and statin treatment effect on MI and MACE risk. Methods: Search for published scientific articles using the PRISMA (Preferred Reporting, Items for Systematic Reviews and Meta-Analysis) method conducted on PubMed, Cochrane Library, and Medline databases published in the last 20 years on “coronary artery calcium” AND “statin” AND “cardiovascular disease” Further systematic review and meta-analysis using RevMan version 5.4 were performed based on the included published scientific articles. Results: Based on 11 studies included with a total of 1055 participants, we performed a meta-analysis and found that individuals with CAC score > 0 increased risk ratio of MI 8.48 (RR = 9.48: 95% CI: 6.22 – 14.45) times and MACE 2.48 (RR = 3.48: 95% CI: 2.98 – 4.05) times higher than CAC score 0 individual. Statin compared against non-statin treatment showed a statistically insignificant overall effect on the risk of MI (P = 0.81) and MACE (P = 0.89) in an individual with elevated CAC score 1 – 100 (P = 0.65) and > 100 (P = 0.11). Conclusions: This study found that an elevated CAC scores individual has a higher risk of MI and MACE than a non-elevated CAC score individual. There is no significant effect of statin compared against non-statin treatment to reduce MI and MACE in elevated CAC score individuals of 1 – 100 or > 100.

Keywords: coronary artery calcium, statin, cardiovascular disease, myocardial infarction, MACE

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Authors: Eva Kirzner

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Based on outcome studies published over the past two decades, in 2018, the ACC/AHA published new guidelines for the management of hypercholesterolemia that incorporate the use of coronary artery calcium (CAC) scanning as a decision tool for ascertaining which patients may benefit from statin therapy. This use is based on the recognition that the absence of calcium on CAC scanning (i.e., a CAC score of zero) usually signifies the absence of significant atherosclerotic deposits in the coronary arteries. Specifically, in patients with a high risk for atherosclerotic cardiovascular disease (ASCVD), initiation of statin therapy is generally recommended to decrease ASCVD risk. However, among patients with intermediate ASCVD risk, the need for statin therapy is less certain. However, there is a need for new outcome studies that provide evidence that the management of hypercholesterolemia based on these new ACC/AHA recommendations is safe for patients. Based on a Pub-Med and Google Scholar literature search, four relevant population-based or patient-based cohort studies that studied the relationship between CAC scanning, risk assessment or mortality, and statin therapy that were published between 2017 and 2021 were identified (see references). In each of these studies, patients were assessed for their baseline risk for atherosclerotic cardiovascular disease (ASCVD) using the Pooled Cohorts Equation (PCE), an ACC/AHA calculator for determining patient risk based on assessment of patient age, gender, ethnicity, and coronary artery disease risk factors. The combined findings of these four studies provided concordant evidence that a zero CAC score defines patients who remain at low clinical risk despite the non-use of statin therapy. Thus, these new studies confirm the use of CAC scanning as a safe tool for reducing the potential overuse of statin therapy among patients with zero CAC scores. Incorporating these new data suggest the following best practice: (1) ascertain ASCVD risk according to the PCE in all patients; (2) following an initial attempt trial to lower ASCVD risk with optimal diet among patients with elevated ASCVD risk, initiate statin therapy for patients who have a high ASCVD risk score; (3) if the ASCVD score is intermediate, refer patients for CAC scanning; and (4) and if the CAC score is zero among the intermediate risk ASCVD patients, statin therapy can be safely withheld despite the presence of an elevated serum cholesterol level.

Keywords: cholesterol, cardiovascular disease, statin therapy, coronary calcium

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Authors: Ibrahim Mohammed

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Background: Diabetes mellitus is a chronic disease that can cause devastating secondary complications, reducing the quality and length of life as well as increasing medical costs for the patient and society. The guidelines recommend both clinical and preventive strategies for diabetes management and are regularly updated. The aim of the study is to assess the level of adherence of physicians to American Diabetes Association Guidelines. Method: Observational multicenter retrospective study will be conducted among different hospitals in the central region. Patient data will be collected from the records of the last three years (2017- 2020). Records will be selected randomly after a complete randomized design. The study focuses on the management of type 2 according to ADA not changed in the last three updating; those standards; all patients should be taking Metformin 1500 to 2000 mg/day as recommended dose and should be received a high dose of statin if the high risk to ASCVD or moderate statin if not at risk, patients with hypertension and diabetes should taking ACE or ARBS. Result: The study aimed to evaluate the commitment of physicians in the central region to the ADA. Out of the 153 selected patients, only 17 % were able to control their diabetes with an average A1c below 7. ADA stated that to reach the minimum benefit of using Metformin, the daily dose should be between 1500 and 2000 mg. Results showed that 110 patients were on Metformin, where 68% of them were on the recommended dose. ADA recommended the intake of high statin for diabetic patients with ASCVD risk, while diabetic patients without ASCVD risk should be on a moderate statin. Results showed that 61.5% of patients with ASCVD risk were at high statin while only 36% of patients without ASCVD risk were at moderate statin. Results showed that 89 patients have hypertension, and 80% of them are getting ACE/ARBs as recommended by the ADA. Recommendation: It is necessary to implement periodic training courses for some physicians to enhance and update their knowledge.

Keywords: American Diabetic Association, diabetes mellitus, atherosclerotic cardiovascular disease, ACE inhibitors

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Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

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Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Abeer Kharshid, Nor Azizah Aziz, Tarek M. Elsayed

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Medication safety is always an issue. In 2015, the National Pharmaceutical Control Bureau released a statement requesting all statins manufacturers in Malaysia to include the risk of diabetes information in the drug information leaflet in response to United States Food and Drug Administration (U.S. FDA) report. However, the data regarding this warning label in Malaysia is limited, so there is still some uncertainty whether such risk can also be observed in the Malaysian population or not. The study aims to determine the effect of statins on HbA1c% in type 2 diabetic outpatients in endocrine clinics at Hospital Pulau Pinang between June 2015 and May 2016 in Malaysia. In a prospective cohort study, records of 400 type 2 diabetic patients (control group 104 patients not using statin and treatment group 296 patients using statin) were reviewed to identify demographic criteria and lab tests. The prevalence of glycemic control (Glycated hemoglobin, HbA1C ≤ 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, according to American Diabetes Association guidelines 2015. The results were presented as descriptive statistics. From 296 patients with Type 2 diabetes using statins cohort with a mean age of 57.52 ± 12.2 years, only 81 (27.4%) cases had controlled glycemia, and 215 (72.6%) had uncontrolled glycemia, CI: 95% (6.3–11.1). While the control group 104 diabetic patients had a mean age 46.1 ± 18 years and distributed among 59 (56.7%) patients with controlled diabetes and 45 (43.3%) cases, had uncontrolled glycemia, CI: 95% (5.2–10.3). The relative risk (RR) of uncontrolled glycemia in diabetic patients used statins was 1.68, and the excessive relative risk (ERR) was 68%. The absolute risk (AR) was 29.3%, and the number needed to harm (NNH) was 4. Diabetic patients using statins have more risk of uncontrolled glycemia than the patients with Type 2 diabetes non-using statins.

Keywords: diabetes mellitus, HbA1c, Malaysia, outpatients, statin, type 2, uncontrolled glycemia

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Authors: Nurul Izzah Ibrahim, Isa Naina Mohamed, Norazlina Mohamed, Ahmad Nazrun Shuid

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Osteoporosis disease delays fracture healing. Statins have shown potential for osteoporosis and to promote fracture healing. The effects of statin can be further potentiated by combining it with a carrier known as poly-(DL-lactide), which would provide persistent release of statin to the fracture site. This study was designed to investigate the effects of direct injection of poly-(DL-lactide)-incorporated lovastatin on fracture healing of postmenopausal osteoporosis rat model. Twenty-four Sprague-Dawley female rats were divided into 3 groups: sham-operated (SO), ovariectomized-control rats (OVxC) and poly-(DL-lactide)-incorporated lovastatin (OVx+Lov) groups. The OVx+Lov group was given a single injection of 750 µg/kg lovastatin particles incorporated with poly-(DL-lactide). After 4 weeks, the fractured tibiae were dissected out for biomechanical assessments of the callus. The OVx+Lov group showed significantly better callus strength than the OVxC group (p<0.05). In conclusion, a single injection of lovastatin-incorporated poly-(DL-lactide) was able to promote better fracture healing of osteoporotic bone.

Keywords: statins, fracture healing, osteoporosis, poly-(DL-lactide)

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Authors: Abhijit Trailokya

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Background: Cardiovascular diseases (CVD’s) are the major cause of morbidity and mortality in both developed and developing countries. Many clinical trials have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, reduces the incidence of coronary and cerebrovascular events across a broad spectrum of patients at risk. Guidelines for the management of patients at risk have been established in Europe and North America. The guidelines have advocated progressively lower LDL-C targets and more aggressive use of statin therapy. In Indian patients, comprehensive data on dyslipidemia management and its treatment outcomes are inadequate. There is lack of information on existing treatment patterns, the patient’s profile being treated, and factors that determine treatment success or failure in achieving desired goals. Purpose: The present study was planned to determine the lipid control status in high-risk dyslipidemic patients treated with lipid-lowering therapy in India. Methods: This cross-sectional, non-interventional, single visit program was conducted across 483 sites in India where male and female patients with high-risk dyslipidemia aged 18 to 65 years who had visited for a routine health check-up to their respective physician at hospital or a healthcare center. Percentage of high-risk dyslipidemic patients achieving adequate LDL-C level (< 70 mg/dL) on lipid-lowering therapy and the association of lipid parameters with patient characteristics, comorbid conditions, and lipid lowering drugs were analysed. Results: 3089 patients were enrolled in the study; of which 64% were males. LDL-C data was available for 95.2% of the patients; only 7.7% of these patients achieved LDL-C levels < 70 mg/dL on lipid-lowering therapy, which may be due to inability to follow therapeutic plans, poor compliance, or inadequate counselling by physician. The physician’s lack of awareness about recent treatment guidelines also might contribute to patients’ poor adherence, not explaining adequately the benefit and risks of a medication, not giving consideration to the patient’s life style and the cost of medication. Statin was the most commonly used anti-dyslipidemic drug across population. The higher proportion of patients had the comorbid condition of CVD and diabetes mellitus across all dyslipidemic patients. Conclusion: As per the European Society of Cardiology guidelines the ideal LDL-C levels in high risk dyslipidemic patients should be less than 70%. In the present study, 7.7% of the patients achieved LDL-C levels < 70 mg/dL on lipid lowering therapy which is very less. Most of high risk dyslipidemic patients in India are on suboptimal dosage of statin. So more aggressive and high dosage statin therapy may be required to achieve target LDLC levels in high risk Indian dyslipidemic patients.

Keywords: cardiovascular disease, diabetes mellitus, dyslipidemia, LDL-C, lipid lowering drug, statins

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Ahmed A. Khamis, Abeer Kharshid, Nor Azizah Aziz

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The effect of statins dose intensity (SDI) on glycemic control in patients with existing diabetes is unclear. Also, there are many contradictory findings were reported in the literature; thus, it is limiting the possibility to draw conclusions. This project was designed to compare the effect of SDI on glycated hemoglobin (HbA1c%) control in outpatients with Type 2 diabetes in the endocrine clinic at Hospital Pulau Pinang, Malaysia, between July 2015 and August 2016. A prospective cohort study was conducted, where records of 345 patients with Type 2 diabetes (Moderate-SDI group 289 patients and high-SDI cohort 56 patients) were reviewed to identify demographics and laboratory tests. The target of glycemic control (HbA1c < 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, and the results were presented as descriptive statistics. From 289 moderate-SDI cohorts with a mean age of 57.3 ± 12.4 years, only 86 (29.8%) cases were shown to have controlled glycemia, while there were 203 (70.2%) cases with uncontrolled glycemia with confidence interval (CI) of 95% (6.2–10.8). On the other hand, the high-SDI group of 56 patients with Type 2 diabetes with a mean age 57.7±12.4 years is distributed among 11 (19.6%) patients with controlled diabetes, and 45 (80.4%) of them had uncontrolled glycemia, CI: 95% (7.1–11.9). The study has demonstrated that the relative risk (RR) of uncontrolled glycemia in patients with Type 2 diabetes that used high-SDI is 1.15, and the excessive relative risk (ERR) is 15%. The absolute risk (AR) is 10.2%, and the number needed to harm (NNH) is 10. Outpatients with Type 2 diabetes who use high-SDI of statin have a higher risk of uncontrolled glycemia than outpatients who had been treated with a moderate-SDI.

Keywords: cohort study, diabetes control, dose intensity, HbA1c, Malaysia, statin, type 2 diabetes mellitus, uncontrolled glycemia

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Background: Endothelial Progenitor Cells (EPCs) are depleted and contribute to increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Statins exert a protective effect in CAD partly by promoting EPC mobilization. This vasculoprotective effect of statin has not yet been investigated in RA. We aimed to investigate the effect of rosuvastatin on EPCs in RA. Methods: 50 RA patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=25) and placebo (n=25) as an adjunct to existing stable antirheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures included DAS28, CRP and ESR were measured at baseline and after treatment. Lipids and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) were estimated at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. At baseline, EPCs inversely correlated with DAS28 and TNF-α in both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin but did not show significant change with placebo. Rosuvastatin exerted positive effect on lipid spectrum: lowering total cholesterol, LDL, non HDL and elevation of HDL as compared with placebo. At 6 months, DAS28, ESR, CRP, TNF-α and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and DAS28, CRP, TNF-α, and IL-6 after treatment with rosuvastatin. Conclusion: First study to show that rosuvastatin improves inflammation and EPC biology in RA possibly through its anti-inflammatory and lipid lowering effect. This beneficial effect of rosuvastatin may provide a novel strategy to prevent cardiovascular events in RA.

Keywords: RA, Endothelial Progenitor Cells, rosuvastatin, cytokines

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

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Authors: Agung A. Ginanjar, Lilitasari, Indra Prasetya, Rizal R. Hanif, Yusrina Rismandini, Atina Hussaana, Nurita P. Sari

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Hyperlipidemia is an increase of lipids and cholesterol in the blood that causes the formation of atherosklerosis. The recent pharmacological therapy nowadays is statin. Many Indonesian people use of medicinal plants. There are several medical plants that people always use to cure hyperlipidemia such as bulbs onion sabrang, areca nuts, and seed of fenugreek. Most people often use a combination therapy of conventional medicine and herbs to achieve the desired therapeutic effect of combination therapy. The use of combination therapy might cause the interaction of pharmacodynamic from those medicines so that it influences the pharmacological effect of one of medicine. The aim of this study is to know the interaction of simvastatin and a cholesterol-lowering herb seen in rats pharmacodynamic simvastatin phase. This research used post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. The ANOVA test is used when the data is obtained homogeneous but if it is found that the data are not homogeneous then kruskal-wallis test is used. Normal (63.196 mg/dl), negative (70.604 mg/dl), positive (62.512 mg/dl), areca nuts (56.564 mg/dl), fenugreek seed (47.538 ,g/dl), onion sabrang (62.312 mg/dl). The results prove that the combination of herbs and simvastatin did not have a significant difference (P>0,05). The conclusion of this study is that the combination of simvastatin and a cholesterol-lowering herb can cause some pharmacodynamic interactions such as a synergistic effect, antagonist, and a powerful additive, so that combination therapy is not more effective than single simvastatin therapy. The use of the combination therapy is not given in the same time. It would be better if there are some period of time when the combination therapy is applied.

Keywords: onion bulb sabrang, areca nuts, seed of fenugreek, interaction medicine, hyperlipidemia

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Authors: Anne R. Fernandez, Mohammad Akmal Adnan, Tanes Prasat, Indu Bala Jaganath, Brian Kirby, Kamalan Jeevaratnam

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Introduction: Plants from the Phyllantus genus have been used indigenously for the treatment of a variety of ailments for generations. A cocktail of phytonutrients prepared from a plant of the genus Phyllanthus has demonstrated the potential to alleviate ailments which include cardiovascular disorders. In this study, we investigated the cholesterol modulating properties of a highly purified proprietary extract of a Phyllanthus species in hypercholesteraemic mice. Methods: Hypercholesteraemia was induced in ICR mice by ad-libitum feeding of high fat diet daily for six weeks. The mice were then divided into 3 groups and force fed with 10mg/kg of atorvastatin, 200mg/kg of the proprietary Phyllanthus extract and water respectively. Blood samples were taken at the end of fourth week of treatment by a tail prick. At the end of the eighth week of treatment, mice were sacrificed and serum levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides were measured. Results: The mean cholesterol levels in the mice fed with high fat diet were 44% (p < 0.05) higher than the mice on normal diet thus validating the model developed. The plasma HDL was significantly elevated in mice treated with the formulation (p ˂ 0.05) in comparison to the statin-treated and control mice. The total cholesterol levels in the mice treated with the proprietary extract were reduced significantly (p < 0.05) at the end of 4 weeks of treatment in comparison to the mice treated with atorvastatin. By the end of 8 weeks of treatment, there was no significant difference in the cholesterol levels of the mice in all groups. Conclusion: These results demonstrate that this proprietary extract from Phyllanthus species has the beneficial effect of reducing total cholesterol level more rapidly than atorvastatin and increasing HDL levels. Since an increase in the HDL cholesterol can reduce the risk of heart disease, this proprietary extract is a useful and safe therapeutic option compared to atorvastatin.

Keywords: high-density lipoprotein, hypercholesteraemic mice model, ICR mice, Phyllanthus spp.

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Authors: Hernán A. Perez, Luis J. Armando, Néstor H. García

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Background and aims Cardiovascular disease rates are very high in patients with renal failure (CRF), but the underlying mechanisms are incompletely understood. Traditional cardiovascular risk factors do not explain the increased risk, and observational studies have observed paradoxical or absent associations between classical risk factors and mortality in dialysis patients. A large randomized controlled trial, the 4D Study, the AURORA and the ALERT study found that statin therapy in CRF do not reduce cardiovascular events. These results may be the results of ‘accelerated atherosclerosis’ observed on these patients. The objective of this study was to investigate if carotid total plaque area (TPA), a measure of carotid plaque burden growth is increased at progressively lower creatinine clearance in patients with CRF. We studied a cohort of patients with CRF not on dialysis, reasoning that risk factor associations might be more easily discerned before end stage renal disease. Methods: The Blossom DMO Argentina ethics committee approved the study and informed consent from each participant was obtained. We performed a cohort study in 412 patients with Stage 1, 2 and 3 CRF. Clinical and laboratory data were obtained. TPA was determined using bilateral carotid ultrasonography. Modification of Diet in Renal Disease estimation formula was used to determine renal function. ANOVA was used when appropriate. Results: Stage 1 CRF group (n= 16, 43±2yo) had a blood pressure of 123±2/78±2 mmHg, BMI 30±1, LDL col 145±10 mg/dl, HbA1c 5.8±0.4% and had the lowest TPA 25.8±6.9 mm2. Stage 2 CRF (n=231, 50±1 yo) had a blood pressure of 132±1/81±1 mmHg, LDL col 125±2 mg/dl, HbA1c 6±0.1% and TPA 48±10mm2 ( p< 0.05 vs CRF stage 1) while Stage 3 CRF (n=165, 59±1 yo) had a blood pressure of 134±1/81±1, LDL col 125±3 mg/dl, HbA1c 6±0.1% and TPA 71±6mm2 (p < 0.05 vs CRF stage 1 and 2). Conclusion: Our data indicate that TPA increases along the renal function deterioration, and it is not related with the LDL cholesterol and triglycerides levels. We suggest that mechanisms other than the classics are responsible for the observed excess of cardiovascular disease in CKD patients and finally, determination of total plaque area should be used to measure effects of antiatherosclerotic therapy.

Keywords: hypertension, chronic renal failure, atherosclerosis, cholesterol

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Authors: Nurjannatul Naim Kamaruddin, Tengku Sifziuzl Tengku Muhammad, Aina Farahiyah Abdul Manan, Habsah Mohamad

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Atherosclerosis which leads to cardiovascular diseases such as myocardial infarction, unstable angina (ischemic heart pain), sudden cardiac death and stroke is the principal cause of death worldwide. It has been a very critical issue as current common drug treatment, statin therapy has left bad side effects like rhabdomyolysis, atrial fibrillation, liver disease, abdominal and chest pain. Interestingly, the discoveries of proprotein convertase subtilisin-kexin type 9 have paved a new way in the treatment of atherosclerosis. This serine protease is believed to involve in the regulation of LDL- uptake by LDL-receptor. Therefore, this study was conducted to evaluate the potential of Acanthaster plancii fractions to reduce the transcriptional activity of the PCSK9 promoter. In this study, the marine organism which is Acanthaster plancii has been used as the source for marine compounds in inhibiting PCSK9. The cytotoxicity activity of ten fractions from the methanol extracts of Acanthaster plancii was investigated on HepG2 cell lines using MTS assay and dual glo luciferase assay was carried out later to analyses the effects of the samples in reducing the transcriptional activity of the PCSK9 promoter. Both assays used fractions with five different concentrations, 3.13µg/mL, 6.25µg/mL, 12.5µg/mL, 25µg/mL, and 50µg/mL. MTS assay indicated that the fractions are non-cytotoxic towards HepG2 cell lines as their IC50 value is greater than 30µg/mL. Whilst, for the dual glo luciferase assay, among all the fractions, Enhance Fraction 2 (EF2) showed the best potential in reducing the transcriptional activity of the PCSK9 promoter. The results indicated that this EF2 gave the lowest PCSK9 promoter expression at low concentration which is 0.2 fold change at 6.25µg/mL. This finding suggested that further analysis should be done to validate the potential of Acanthaster plancii as the source of anti-atherosclerotic agent.

Keywords: Acanthaster plancii, atherosclerosis, luciferase assay, PCSK9

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Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

Procedia PDF Downloads 69

Authors: Xi Chen, King-Yip Cheng

Abstract:

Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

Procedia PDF Downloads 36