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Suprapti, Herni. "Pharmacogenomics Statins: Biomarkers for Clinical Prediction." Jurnal Ilmiah Kedokteran Wijaya Kusuma 7, no. 1 (March 30, 2018): 1. http://dx.doi.org/10.30742/jikw.v7i1.61.
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Statins are the most widely prescribed drug for hyperlipidemic therapy and for the prevention of Cardiovascular disease. But although statins are very effective for the prevention of atherosclerosis, there are still patients with CVD. In this case, it is thought to be the influence of genetic factors. There is a static gene link to statin dose required for therapy, but there are still no relevant pharmacogenomic tests for statin therapy guidelines. This article describes basic pharmacogenomic terminology, genes (CETP, HMGCR, SLCO1B1, ABCB1, and CYP3A4 / 5), and progression of statin pharmacogenomic biomarkers for predicted therapeutic outcomes.
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Turkoski, Beatrice B. "One Statin, Two Statins, Three Statins, More." Orthopaedic Nursing 30, no. 1 (2011): 62–65. http://dx.doi.org/10.1097/nor.0b013e318205752a.
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&NA;. "One Statin, Two Statins, Three Statins, More." Orthopaedic Nursing 30, no. 1 (2011): 66–67. http://dx.doi.org/10.1097/nor.0b013e3182099340.
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Ma, Wei-li, Yu Yun Shao, Chih-Hung Hsu, Kun-Huei Yeh, Ho-Min Chen, Yi-Chun Yeh, Chiu-Lin Lai, Zhong-Zhe Lin, Ann-Lii Cheng, and Mei-Shu Lai. "Regular statin users and colorectal cancer (CRC) prognosis." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3554. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3554.
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3554 Background: Statins are frequently used for the control of hyperlipidemia. Statins have multiple anti-cancer properties and may be associated with lower CRC risks among their users. This study tries to go a step further and explores whether statin use affects the prognosis of curatively resected CRC. Methods: We established a population cohort with patients (age ≥ 40 y) who were diagnosed as having stage I or II CRC from 2004 to 2008 and received curative surgery from the database of Taiwan Cancer Registry. Data of medication prescription and co-morbidities were retrieved from the database of National Health Insurance, Taiwan. Regular statin use was defined as taking statins for > 180 days within the observation period from one year before the cancer diagnosis to one year afterward. The database of National Death Registry was used for survival outcomes. Another similar cohort consisting of patients with hepatocellular carcinoma (HCC) was used for comparison. Results: In total, 10762 patients with CRC were enrolled; 891 (8%) patients were regular stain users, 812 (8%) patients took statins but were not regular users, and 9059 (84%) patients never used statins. Regular statin users, compared to never users, were more likely to be female (p < 0.001), older (p < 0.001), have stage I disease (p < 0.001) and co-morbidities such as diabetes, coronary artery disease, and renal disease. Adjuvant therapy was less frequently administered in regular statin users. In univariate analysis, cancer-specific survival (CSS) of regular stating users was significantly longer than that of never users (5-y CSS, 87% vs. 84%, p = 0.022), but overall survival (OS) was not significantly different (5-y OS, 80% vs. 77%, p = 0.156). In multivariate analysis adjusting for age, gender, stage, adjuvant therapy, co-morbidities, and the use of aspirin, regular stating use was an independent predictor both for better CSS (hazard ratio [HR] 0.72, p < 0.001) and for better OS (HR 0.71, p< 0.001). In contrast, no associations were found between statin use and CSS or OS in the HCC comparison cohort. Conclusions: Regular statin use was associated with better prognosis in CRC patients who received curative therapy. (This study was supported by grants DOH-101-TD-B-111-001 and DOH-102-TD-B-111-001).
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Son, Kyung-Bok, and SeungJin Bae. "Patterns of statin utilisation for new users and market dynamics in South Korea: a 13-year retrospective cohort study." BMJ Open 9, no. 3 (March 2019): e026603. http://dx.doi.org/10.1136/bmjopen-2018-026603.
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ObjectiveThis study analysed utilisation of statins for new statin users and assessed market dynamics of statins in South Korea.DesignThis study is a retrospective cohort study.SettingThe yearly claims data for statins were retrieved from the National Health Insurance Service-National Sample Cohort.Main outcome measureWe are interested in new statin users during 2003–2015 in Korea. Information on prescribed statins, including intensity of statins and entry of new and follow-on statins in the market, and healthcare institutions that prescribed the statins were also collected. In time series analysis, we estimated the effect of introduction of generics in the market, specifically for newly prescribed statin users.ResultsThis 13-year longitudinal study of a sample cohort provided by the National Health Insurance Service found that the incidence of new statin user increase from 838.1/100 000 persons in 2003 to 1626.9/100 000 persons in 2015. Most new users were initiated on a monotherapy that was prescribed at primary healthcare institutions. However, the statin market for new users were quite dynamic in Korea. First, the most commonly prescribed statin changed several times during the study period. Second, the use of moderate-intensity statins increased from 57% in 2003 to 92% in 2015. In line with this result, we could not observe substantial differences in prescription of statins in groups having selected diseases history. Lastly, we found market invasion or switch of statins among new statin users, specifically at primary healthcare institutions.ConclusionSimilar to other countries, the incidence of new statin users has been increased in Korea. However, the statin market in Korea is quite dynamic compared with other countries. Interestingly, discounted price of originals after the introduction of generics immediately expand markets or substitute the market particularly in primary healthcare institutions in Korea.
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Abdullah, Kazeen, and Anand Rohatgi. "Statins: Practical Considerations – A Review." European Cardiology Review 9, no. 2 (2014): 71. http://dx.doi.org/10.15420/ecr.2014.9.2.71.
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Statins are currently the most efficacious and widely prescribed lipid-lowering medications. The 2013 ACC/AHA cholesterol guidelines provide a dramatic shift in treatment approach with a focus on fixed-dose statins matched to individual risk scores. Statin intolerance is not uncommon and can be challenging to diagnose and manage; however, several therapeutic strategies have been successful in achieving statin tolerance. Statin use is also associated with liver enzyme elevations and increased risk of incident diabetes, but studies show these individuals benefit from statins. Several guidelines exist and statin use is expected to increase with the new cholesterol guidelines bringing along new challenges for prescribers. This review article will provide practical considerations for statin use and management of statin intolerance.
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Bubnova, Marina G. "Adverse effects of statin therapy: real evidence." CardioSomatics 10, no. 1 (March 15, 2019): 51–61. http://dx.doi.org/10.26442/22217185.2019.1.190264.
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Aim. To provide a current view on the tolerability and safety of statin therapy. Materials and methods. The data of 73 scientific sources from Russian and foreign literature published within 1996-2018 are considered. Results. It is generally accepted that statins are first-line therapeutic agents for hypercholesterolemia and combined hyperlipidemia. Today there in growing evidence that lowering of low-density lipoprotein cholesterol levels prevents atherosclerotic diseases and reduces a risk of cardiovascular and overall mortality. Main issues of current statin therapy include a use of inadequate dosage for atherosclerotic diseases prevention, low treatment compliance and drug intolerance. In recent years the issue of statin intolerance has become of great importance. Criteria were proposed for determining an inability to tolerate statins, some experts suggest replacing definition of “statin intolerance” with the term “statin-associated side-effects”. Most discussed adverse effects due to statins include muscle-related symptoms (myalgia/myopathy), hepatotoxicity (hepatic hyperenzymemia) new-onset diabetes, dementia and cognitive impairment. Mechanisms of development of these adverse effects are still unclear. Certain factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were established. Some factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were identified. Occurrence of statin-associated side-effects depends on statin dose, a patient's age, gender, comorbidity and concomitant therapy. Many adverse effects of statins are drug class effect. At the same time each of statins has specific features of its structure, metabolism, drug interactions and pharmacokinetics. Pitavastatin belongs to the last generation of statins and it has distinct pharmacological features and neutral diabetogenic effects, etc. Risk of adverse effects due to statins is often exaggerated while benefit from the use of statins for preventing atherosclerotic diseases outweighs potential risks. Real occurrence of some adverse effects due to statin therapy requires additional evidence. Conclusion. Overall, statins have a good tolerability profile and are approved for use in the vast majority of patients who required lipid-lowering therapy.
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Khanna, Roopali, and Dandu Himanshu. "Statin Intolerance: Diagnosis and Management." Indian Journal of Cardiovascular Disease in Women WINCARS 02, no. 03 (September 2017): 014–20. http://dx.doi.org/10.1055/s-0037-1607193.
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AbstractStatins are the main cornerstone in the treatment of coronary artery disease. Statins not only reduce the cardiovascular events but also significantly reduce the all-cause mortality. Due to adverse effects of statins, 20 to 30% of patients discontinue statins without consulting the physician. Most common adverse effects reported are muscle symptoms. Studies have shown that the majority of these patients can tolerate statin upon rechallenge. Alternative statin dosing, alternate-day statin, or twice-weekly statin dosing are different strategies to be given before changing to nonstatin lipid-lowering therapy. The newer nonstatin lipid-lowering drugs (ezetimibe, PCSK9 inhibitors) can be added if the low-density lipoprotein (LDL) target level can be achieved despite the maximally tolerated statin dose. This article reviews the etiology, clinical symptoms, and management of statin intolerance.
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DeWitt, Cassandra M., Robert B. Ponce, Hayley Bry, Soma Wali, Erica Sedlander, and Joseph A. Ladapo. "Patient-Reported Reasons for Not Using Primary Prevention Statin Therapy." Journal of Clinical Medicine 9, no. 10 (October 18, 2020): 3337. http://dx.doi.org/10.3390/jcm9103337.
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Almost half of patients who meet American College of Cardiology/American Heart Association (ACC/AHA) criteria for statin therapy are untreated. We aimed to evaluate patient-reported reasons for not using guideline-recommended statin therapy in a public healthcare system. Achieving this goal is key to addressing gaps in care and reducing preventable cardiovascular morbidity. We surveyed patients who met 2013 ACC/AHA guidelines for statin therapy but were not using statins. The survey probed domains of patient knowledge regarding cardiovascular health and benefits of statins, barriers to use, physician trust, and interest in cardiovascular care. Among 71 patients eligible for guideline-recommended statin therapy but not currently taking statins, 49 (69%) had a high school education or lower, 41 (58%) reported that they were unaware they should be prescribed a statin and 49 (69%) were unaware of the benefits of statins. Almost all patients, 70 (99%), reported caring about their cardiovascular health, 61 (86%) reported that they had a high level of trust in their physician, and 51 (72%) reported a willingness to follow their physician’s advice. Despite interest in cardiovascular health, awareness of benefits of statin therapy was low and knowledge of recommended statin therapy was low. Increasing patients’ awareness of their eligibility through systematic testing and linkage to statin therapy, along with education, may increase statin use among patients recommended for therapy.
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McBride, Cameron L., Julia M. Akeroyd, David J. Ramsey, Vijay Nambi, Khurram Nasir, Erin D. Michos, Ruth L. Bush, et al. "Statin prescription rates and their facility-level variation in patients with peripheral artery disease and ischemic cerebrovascular disease: Insights from the Department of Veterans Affairs." Vascular Medicine 23, no. 3 (March 30, 2018): 232–40. http://dx.doi.org/10.1177/1358863x18758914.
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The 2013 American College of Cardiology/American Heart Association cholesterol guideline recommends moderate to high-intensity statin therapy in patients with peripheral artery disease (PAD) and ischemic cerebrovascular disease (ICVD). We examined frequency and facility-level variation in any statin prescription and in guideline-concordant statin prescriptions in patients with PAD and ICVD receiving primary care in 130 facilities across the Veterans Affairs (VA) health care system between October 2013 and September 2014. Guideline-concordant statin intensity was defined as the prescription of high-intensity statins in patients with PAD or ICVD ≤75 years and at least moderate-intensity statins in those >75 years. We calculated median rate ratios (MRR) after adjusting for patient demographic factors to assess the magnitude of facility-level variation in statin prescribing patterns independent of patient characteristics. Among 194,151 PAD patients, 153,438 patients (79.0%) were prescribed any statin and 79,435 (40.9%) were prescribed a guideline-concordant intensity of statin. PAD patients without ischemic heart disease were prescribed any statin and a guideline-concordant intensity of statin therapy less frequently (69.1% and 28.9%, respectively). Among 339,771 ICVD patients, 265,491 (78.1%) were prescribed any statin and 136,430 (40.2%) were prescribed a guideline-concordant intensity of statin. ICVD patients without ischemic heart disease were prescribed any statin and a guideline-concordant intensity of statin less frequently (70.9% and 30.5%, respectively). MRRs for both PAD and ICVD patients demonstrated a 20% and 28% variation among two facilities in treating two identical patients with statin therapy and guideline-concordant intensity of statin therapy, respectively. The prescription of statins, especially guideline-recommended intensity of statin therapy, is suboptimal in PAD and ICVD patients, with significant facility-level variation not explained by patient-level factors.
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Khokhar, Bilal, Linda Simoni-Wastila, Julia F. Slejko, Eleanor Perfetto, Min Zhan, and Gordon S. Smith. "Patterns of Statin Use in Older Medicare Beneficiaries With Traumatic Brain Injury." Journal of Pharmacy Technology 33, no. 4 (May 23, 2017): 156–66. http://dx.doi.org/10.1177/8755122517710671.
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Background: In addition to lowering lipids, statins also may be beneficial for older adults sustaining a traumatic brain injury (TBI), as statin use prior to and following trauma may decrease mortality following injury. However, despite statins’ potential to reduce mortality, there is limited research regarding statin use among older adults. Objective: To characterize and investigate factors associated with statin use among older adults with TBI. Methods: A retrospective drug utilization study was used to characterize statin use among Medicare beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 and with continuous Medicare Parts A, B, and D coverage 6 months prior and 12 months following TBI. Logistic regression was used to investigate the factors associated with statin use. The exposure of interest was statin use prior to and following TBI. Results: Of the 75 698 beneficiaries included in the study, 37 874 (~50%) of beneficiaries used a statin at least once during the study period. The most common statin used was simvastatin, while fluvastatin was the least used statin. Statin users were more likely to have cardiovascular diseases when compared to nonusers. Hyperlipidemia was a major factor associated with statin use and had the greatest impact on statin use compared to nonuse (odds ratio = 9.54; 95% confidence interval = 9.07, 10.03). Conclusions: This national sample of older adults with TBI suggests that statins are commonly used. Future studies must next examine the impact of statin use on mortality and secondary injury in order to shape pharmacological therapy guidelines following TBI.
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Hilton-Jones, David. "Statin-related myopathies." Practical Neurology 18, no. 2 (March 1, 2018): 97–105. http://dx.doi.org/10.1136/practneurol-2017-001738.
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Statins are the Marmite (‘You either love it or hate it!’) of the drug world, both in terms of therapeutic benefit and risk of side effects. Proponents think that they are potential life-savers, opponents that their main benefit is lining the pockets of pharma. Some consider side effects to be a major issue, outweighing any therapeutic benefit, others that they are rare and essentially innocuous. Statin-induced myalgia is relatively common but often mild and for most people does not limit treatment. In others, reducing the dose or changing the preparation may help. In all, withdrawal of the statin leads to resolution. Statin-induced rhabdomyolysis, most often precipitated by drug–drug interaction, affects only a tiny proportion of statin users, but because of the widespread prescribing of statins is an important clinical problem. Statin-induced immune-mediated necrotising myopathy represents a novel disease mechanism and clinically mimics forms of myositis. Resolution often requires immunosuppressant drug treatment, as well as statin withdrawal.
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Aggarwal, Monica, Shivani Juneja, Muskan Goyal, and Tariq Khurana. "A cross sectional observational study to find the difference in occurrence of muscle related adverse effects of statins among geriatric and non-geriatric patients." International Journal of Basic & Clinical Pharmacology 7, no. 9 (August 23, 2018): 1817. http://dx.doi.org/10.18203/2319-2003.ijbcp20183496.
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Background: Statins are effectively used for the treatment of dyslipidemias in geriatric patients. The geriatric patients are more vulnerable to experience consequences of drug intensification leading to the manifestation of adverse effects, such as muscle related adverse effects (MRAE) with statins use. The main objective was to find the difference in the occurrence of MRAE of statins among geriatric and non-geriatric users.Methods: This was a cross-sectional, observational comparative study in which MRAE associated with statins and relevant patient information was noted. Creatine phosphokinase (CPK) levels which are considered as a marker for statin induced muscle damage were obtained for all patients. The different parameters were compared among geriatric and non-geriatric statin users.Results: Sixty one patients, 28 geriatric (≥60 years) and 33 non-geriatric (<60 years) statin users were enrolled in this study. Ten (38%) geriatric statin users as compared to 6 (20%) non-geriatric statin users were found to have MRAE (P = 0.207). No significant difference in the occurrence of MRAE among geriatric and non-geriatric statin users was found.Conclusions: The results obtained from the present study suggest that statins are relatively safe, even in older people. There was no evidence to suggest an increased risk of MRAE in geriatric patients receiving statin therapy as compared to non- geriatric patients.
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Sung, Fung-Chang, Yi-Ting Yeh, Chih-Hsin Muo, Chih-Cheng Hsu, Wen-Chen Tsai, and Yueh-Han Hsu. "Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study." Cancers 14, no. 3 (February 6, 2022): 825. http://dx.doi.org/10.3390/cancers14030825.
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Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999–2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.
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D, Balaraju, Vikram S. Patil, and Satvic CM. "Statin Intolerance: Update." Journal of Cardiovascular Medicine and Surgery 5, no. 3 (2019): 137–42. http://dx.doi.org/10.21088/jcms.2454.7123.5319.5.
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Kim, So Young, Dae Myoung Yoo, Chanyang Min, and Hyo Geun Choi. "Association between Statin Use and Meniere’s Disease: Results from a National Health Screening Cohort." International Journal of Environmental Research and Public Health 18, no. 16 (August 17, 2021): 8692. http://dx.doi.org/10.3390/ijerph18168692.
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The protective effects of statins against inner ear diseases have been suggested. This study investigated the relationship between previous statin use and the occurrence of Meniere’s disease (MD). Participants ≥40 years old in the Korean National Health Insurance Service-Health Screening Cohort 2002–2015 were enrolled. A total of 7734 MD participants were matched with 38,670 comparison participants. The dates of statin prescriptions for the 2 years before the onset of MD were examined. A conditional logistic regression analysis was performed to estimate the odds ratios (ORs) of statin use for MD. Regarding the different types of statins, lipophilic statins, but not hydrophilic statins, were associated with lower odds of MD in the <65 year-old group (adjusted OR = 0.81, 95% CI = 0.68–0.97, p = 0.023). Prior statin use did not show association with MD in the adult population. Regarding the different types of statins, lipophilic statin use was related to a lower rate of MD in a middle-aged population.
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Kim, Joungyoun, Na-Young You, Jae-Woo Lee, Yesul Kim, Yong-Whan Kim, and Hee-Taik Kang. "Inverse Association Between Statin Use and Overall Cancer Incidence in Individuals With Hypercholesterolemia, Based on the Korean Health Insurance Service Between 2002 and 2015." Asia Pacific Journal of Public Health 31, no. 2 (February 27, 2019): 136–46. http://dx.doi.org/10.1177/1010539519830235.
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The Korean National Health Insurance Service provided the Health Screening Cohort Database. To investigate the cumulative effect of statins on cancer development, we defined statin users as those who used statins during 2002 to 2003 at baseline. Statin users were divided into high and low users. Statin nonusers were defined as individuals who had never used statins during the entire period of 2002 to 2015, despite having hypercholesterolemia. In total, 17 737 statin users and 13 412 statin nonusers were included in the final analyses. The median follow-up duration was 12.6 years. Compared with nonusers, the hazard ratios (95% confidential intervals) for any cancer incidence of low users and high users were 1.047 (0.941-1.164) and 0.663 (0.589-0.747) in men and 1.057 (0.938-1.190) and 0.592 (0.517-0.678) in women, respectively, after fully adjusting for possible confounding factors. An inverse association between statin use and any cancer incidence in individuals with hypercholesterolemia was observed.
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Elkomos, Mary, Raha Jahromi, and Michael S. Kelly. "Pharmacist-Led Programs to Increase Statin Prescribing: A Narrative Review of the Literature." Pharmacy 10, no. 1 (January 7, 2022): 13. http://dx.doi.org/10.3390/pharmacy10010013.
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Statins are lipid-lowing medications shown to reduce cardiovascular events and are recommended for specific patient populations at elevated risk of atherosclerotic cardiovascular disease (ASCVD). Despite the demonstrated efficacy of statins for reducing ASCVD risk, and guidance on which populations should receive statin therapy, a substantial portion of eligible patients are not prescribed statin therapy. Pharmacists have attempted to increase the number of eligible patients receiving appropriate statin therapy through a variety of interventions and across several clinical settings. In this article, we highlight multiple studies evaluating the effectiveness of pharmacist-led interventions to improve statin use. A total of seven studies were selected for this narrative review, demonstrating the effectiveness and barriers of different statin-initiation programs delivered by pharmacists to increase statin use in eligible patients. Among the interventions assessed, a combination of provider communicating and statin prescribing through collaborative drug therapy management (CDTM) appear to the be the most useful at increasing statin use. Pharmacists can significantly improve statin use rates among eligible patients through multiple intervention types and across different clinical settings. Further studies should evaluate continued statin adherence and clinical outcomes among patients served by pharmacists.
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Pawar, Ajinkya M., Kerry L. LaPlante, Tristan T. Timbrook, and Aisling R. Caffrey. "Optimal duration for continuation of statin therapy in bacteremic patients." Therapeutic Advances in Infectious Disease 5, no. 5 (May 17, 2018): 83–90. http://dx.doi.org/10.1177/2049936118775926.
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Background: Evidence suggests statins may improve survival in patients with bloodstream infections. However, there is no consensus on optimal timing and duration of exposure. Objectives: To quantify statin therapy duration associated with decreased mortality in bacteremic statin users. Methods: We conducted a case-control study using OptumClinformatics™ with matched Premier hospital data (1 October 2009–31 March 2013). Cases who died during the hospitalization were matched 1:1 to survivors on disease risk scores (DRSs). Post-admission statin therapy duration was evaluated in patients with at least 90 days of pre-admission continuous statin use. Classification and regression tree (CART) analysis was conducted to identify the optimal duration of statin continuation which provided the lowest inpatient mortality. Logistic regression was used to calculate the odds of mortality. Results: We included 58 DRS matched pairs of cases and controls: 47 patients (41%) continued statin therapy during the hospital admission, 15 (32%) cases and 32 (68%) controls. The CART analysis partitioned the continuation of statin therapy at ⩾2 days, representing lower mortality for patients who continued statins for 2 days or more and higher mortality for patients who did not continue or remained on statins for only 1 day. Inpatient mortality was 76% lower among those with at least 2 days of continued statin use (odds ratio 0.24, 95% confidence interval 0.11–0.55). Conclusion: Among matched cases and controls with at least 90 days of baseline statin use prior to the admission, the continuation of statins for at least 2 days after admission demonstrated a survival benefit among bacteremic patients.
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Soldán, M. Mateo Paz, Sean J. Pittock, Stephen D. Weigand, Barbara P. Yawn, and Moses Rodriguez. "Statin therapy and multiple sclerosis disability in a population-based cohort." Multiple Sclerosis Journal 18, no. 3 (September 9, 2011): 358–63. http://dx.doi.org/10.1177/1352458511421920.
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Background: Axonal damage and inflammatory demyelination both occur in multiple sclerosis (MS). Some studies suggest that statins, through pleiotropic effects, reduce inflammatory episodes and protect neurons. However, other studies suggest statins have disparate impacts on these pathologic processes. Objective: The objective of this study was to assess disability progression in MS patients receiving statin therapy. Methods: We performed a retrospective medical record review of an established population-based MS prevalence cohort in Olmsted County, Minnesota, comparing disability progression between patients receiving statins and controls. Results: Duration of statin use ranged from 1.9 to 20.3 years with a mean and standard deviation of 6.8 ± 4 years. Years between assessments ranged from 0.6 to 8.2 (75% of patients having intervals >6.4 years). The median (interquartile range) absolute change of disability among the statin group was 0 (0 to +1), compared with +0.5 (0, +1) in the no-statin group. Distributions were not significantly different ( p = 0.39). The mean (standard deviation) absolute change of disability scores among the statin group was +0.69 (+1.49), not significantly different from +0.61 (+1.31) in the no-statin group. Likewise, annualized disability scores did not differ significantly ( p = 0.23). Eighteen (40%) patients worsened by 1.0 or more on Expanded Disability Status Scale (EDSS) in the statin group and 36 (40%) in the no-statin group ( p = 0.85, chi-squared test). Conclusions: In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.
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Shalaby, Sherif Y., and Elan D. Louis. "Statin Use and Its Association with Essential Tremor and Parkinson's Disease." Neuroepidemiology 47, no. 1 (2016): 11–17. http://dx.doi.org/10.1159/000446655.
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Background: Statins have potent anti-inflammatory and immunomodulating effects, and may have neuroprotective properties in patients with Parkinson's disease (PD). There are no studies about the use of statins in the related tremor disorder, essential tremor (ET). We determined whether statin use differed in ET cases vs. controls and PD cases vs. controls. Methods: One hundred and thirty nine ET cases, 108 PD cases, and 124 controls participated in a research study of the epidemiology of movement disorders. They were frequency matched based on age and gender. Statin use was assessed by self-report. Results: In adjusted logistic regression analyses, statin use (current or ever) was inversely associated with PD (ORs 0.56-0.63), with marginal values (p values = 0.07-0.187). In similar adjusted models, ET was not associated with statin use (p values = 0.45-0.50). However, ET was inversely associated with longer-term statin use (adjusted OR 0.27, p values = 0.04-0.048). Conclusions: We observed a marginally significant inverse association between PD and statin use. Although in primary analyses we found no evidence that statin use was protective in ET, there was an inverse association in analyses that assessed longer term use of statins. Further observational studies are warranted.
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Dominguez, H., T. K. Schramm, M. L. Norgaard, S. Z. Abildstrøm, L. Kober, C. Jørgensen, T. J. Guterbaum, H. E. Poulsen, C. Torp-Pedersen, and G. H. Gislason. "Initiation and Persistence to Statin Treatment in Patients with Diabetes Receiving Glucose-Lowering Medications 1997- 2006." Open Cardiovascular Medicine Journal 3, no. 1 (November 12, 2009): 152–59. http://dx.doi.org/10.2174/1874192400903010152.
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Aims: Since 2001 guidelines recommend statin treatment in most patients with diabetes. We investigated secular changes in initiation and persistence to statin treatment during a 10-year period in a nationwide cohort of patients initiating glucose-lowering medication (GLM). Methods: All Danish citizens 30 years and older who claimed prescriptions of GLM between 1997 and 2006 were identified from nationwide registers of drug dispensing from pharmacies and hospitalizations, and followed until 2006. Statin treatment was registered if a prescription was claimed during the period. By logistic regression we analyzed factors related to initiation and persistence to statin treatment. Results: In total 128,106 patients were included. In 1997 only 7% of the patients receiving GLM claimed statins within the first year after GLM initiation. Despite increasing statin prescriptions the following years, only 62% were using statins at the end of follow up. The chance of ever receiving statins was lowest if not initiated within 180-days following the first purchase of GLM (OR 0.75, 95% CI 0.74-0.76). A previous myocardial infarction was associated with increased statin treatment (OR 4.51; 95% CI 4.31 - 4.71), while low income was associated with lower use of statins (OR 0.68; 95%CI 0.66-0.72). Between 75-85 % of the patients who initiated statins treatment were persistent to treatment by 2007. Conclusions: In spite of increasing use of statins in diabetes patients over time, many patients remain untreated. Early initiation of statin treatment in diabetic patients and focus on patients with low socioeconomic status is needed to give long-term benefits.
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Kang, Jenny H., Quynh-Nhu Nguyen, Juleann Mutka, and Quang A. Le. "Rechallenging Statin Therapy in Veterans With Statin-Induced Myopathy Post Vitamin D Replenishment." Journal of Pharmacy Practice 30, no. 5 (October 24, 2016): 521–27. http://dx.doi.org/10.1177/0897190016674407.
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Background: Statins are the primary class of medications used to lower cholesterol and reduce risks for coronary heart disease. However, statin muscular adverse effects are one of the main reasons for statin nonadherence and a barrier to cardiovascular risk reduction. Objectives: The primary objective of our study was to examine the effect of replenishing vitamin D on statin-induced myopathy in veteran patients who failed to maintain statin therapy in a pharmacist-run ambulatory care setting. Secondary objectives were to examine changes in patients’ vitamin D levels, fasting lipid profiles, and achievement of lipid goals after reinitiation of statin therapy. Methods: This was a retrospective cohort study of veteran patients conducted at a pharmacist-managed cholesterol-optimization clinic. Patients with low-serum vitamin D, history of statin-induced myopathy, and who received vitamin D replenishment prior to rechallenging statin therapy between December 1, 2008, and April 1, 2015, were identified. The primary outcome was the percentage of patients who maintained their statin therapy at 12 months after statin reinitiation. Results: Twenty-seven patients met the study criteria. All patients were able to maintain their statin therapy without myalgia after vitamin D supplementation. Eleven patients (40.7%) tolerated their previously failed statins. The most frequently restarted statins were atorvastatin, pravastatin, and rosuvastatin. A 22% to 30% increase in the number of patients who achieved cholesterol goals based on the national lipid guidelines was observed at 12-month follow-up. Conclusion: Replenishing low vitamin D in patients with statin-induced myopathy appears to be an effective strategy in improving medication adherence and subsequently preventing cardiovascular and mortality events.
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Yoon, Harrison, Suhong Luo, Kristen Marie Sanfilippo, Travis Linneman, Alison Whitmer, and Martin W. Schoen. "Statin type and survival of patients with metastatic castrate-resistant prostate cancer receiving abiraterone and enzalutamide: A nationwide retrospective cohort study." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 50. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.050.
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50 Background: Studies have suggested that statin use is associated with prostate cancer mortality. However, uncertainties exist in how the solubility profile of statins impact cancer outcomes. Lipophilic statins have greater accessibility in extrahepatic tissues, which may lead to stronger inhibitory effects on cancer cells, whereas hydrophilic statins exhibit greater hepato-selectivity and therefore less likely to cause drug interactions and adverse events. Abiraterone (ABI) and enzalutamide (ENZ) are antiandrogen agents used in metastatic castrate-resistant prostate cancer (mCRPC). In this study, we sought to examine whether statin usage and lipophilicity of statins is associated with survival benefits in mCRPC patients receiving ABI or ENZ. Methods: We conducted a nationwide retrospective cohort study of the Veteran Affairs population. Patients with mCRPC who received statin therapy one year prior to initiation of either ABI or ENZ between 9/10/2014 and 6/3/2017 were included and followed until April 2020. Statins were categorized as lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin, pitavastatin) and hydrophilic (rosuvastatin and pravastatin). A cox proportional hazards model was used to estimate adjusted hazards ratio (aHR) with 95% confidence interval (CI) of overall survival after controlling for known prognostic factors including age, Charlson-Romano Comorbidity Index, use of bone-modifying agents, Body-Mass Index, and prostate specific antigen levels. Results: A total of 4919 patients (mean age 75.0 years) were included in our cohort. Of those, 969 patients (19.7%) received lipophilic statins and 452 patients (9.2%) received hydrophilic statins. After adjusting for known factors, statin use was not associated with improved overall survival (aHR 0.93; 95% CI 0.87 – 1.00). Similarly, the use of lipophilic statins (aHR 0.98; 95% CI 0.90 – 1.06) or hydrophilic statins (aHR 0.90; 95% CI 0.80 – 1.01) were not associated with improved overall survival in mCRPC. Conclusions: Our study found no differences in overall survival between mCRPC patients with statin use compared to those without statins. When analyzing statin lipophilicity, we saw a higher trend towards survival in the hydrophilic statin group compared to the lipophilic statin group, which contradicts the direct anticancer benefits of lipophilic statins, but neither group reached statistical significance. Further studies analyzing statin usage and types with specific outcome measures such as cardiovascular events, duration of antiandrogen therapy, and adverse events related to ABI or ENZ will support in optimal therapy choices for mCRPC.
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Reilly, Eimear O., Cormac Everard, and Lisa Cogan. "321 Review of Statin Therapy in Frail Older Patients over 75 Years Old Residing in Long Term Care." Age and Ageing 48, Supplement_3 (September 2019): iii17—iii65. http://dx.doi.org/10.1093/ageing/afz103.207.
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Abstract Background Statins are frequently prescribed in older patients for prevention of cardiovascular disease and treatment of hypercholesterolemia. However, there is little evidence to indicate that statins have any benefit in older patients with life expectancy less than 10 years and of those patients in long term care whose average life expectancy is approximately 3-5 years. In addition, statins are associated with significant adverse side effects and contribute to the burden of polypharmacy in older patients. Methods Patients residing in a long term care facility were reviewed and data was collected from their medical notes and medication records in order to; (1) Quantify the proportion of patients on statin therapy (2) Review the indication for statin therapy (3) Investigate the inappropriate prescribing of statins in nursing home patients. Results 55 patients were included in the study. Of the 55 patients, 7 [12.7%] patients were on a statin. Average age of patients on a statin was 77.8 years[SD 9.4]. Of the 7 patients, 2 were on a statin for primary prevention and 5 patients were on for secondary prevention. Average cholesterol in primary prevention group was 3.3mmol/L, average LDL was 1.3 mmol/L. Of the 7 patients on statin for secondary prevention, indications included ischaemic stroke[n= 4] and ischaemic heart disease [n=3]. Average Total cholesterol in secondary prevention group was 3.8 mmol/L and average LDL was 1.91 mmol/L. The average Rockwood Clinical Frailty Scale Score of the patients on statin therapy was 7. Conclusion Firstly, this study highlights the incidence of inappropriate prescribing of statins for primary prevention in frail older patients in long term care. It also raises the question surrounding the indication of statin therapy in secondary prevention where cholesterol level are within target range highlighting the need for further studies examining the benefit of statins in frail older patients in LTC.
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Chen, Ching-Jen, Dale Ding, Natasha Ironside, Thomas J. Buell, Lori J. Elder, Amy Warren, Amy P. Adams, et al. "Statins for neuroprotection in spontaneous intracerebral hemorrhage." Neurology 93, no. 24 (November 11, 2019): 1056–66. http://dx.doi.org/10.1212/wnl.0000000000008627.
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Statins, a common drug class for treatment of dyslipidemia, may be neuroprotective for spontaneous intracerebral hemorrhage (ICH) by targeting secondary brain injury pathways in the surrounding brain parenchyma. Statin-mediated neuroprotection may stem from downregulation of mevalonate and its derivatives, targeting key cell signaling pathways that control proliferation, adhesion, migration, cytokine production, and reactive oxygen species generation. Preclinical studies have consistently demonstrated the neuroprotective and recovery enhancement effects of statins, including improved neurologic function, reduced cerebral edema, increased angiogenesis and neurogenesis, accelerated hematoma clearance, and decreased inflammatory cell infiltration. Retrospective clinical studies have reported reduced perihematomal edema, lower mortality rates, and improved functional outcomes in patients who were taking statins before ICH. Several clinical studies have also observed lower mortality rates and improved functional outcomes in patients who were continued or initiated on statins after ICH. Subgroup analysis of a previous randomized trial has raised concerns of a potentially elevated risk of recurrent ICH in patients with previous hemorrhagic stroke who are administered statins. However, most statin trials failed to show an association between statin use and increased hemorrhagic stroke risk. Variable statin dosing, statin use in the pre-ICH setting, and selection biases have limited rigorous investigation of the effects of statins on post-ICH outcomes. Future prospective trials are needed to investigate the association between statin use and outcomes in ICH.
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Bosco, Giosiana, Francesco Di Giacomo Barbagallo, Salvatore Spampinato, Lorena Lanzafame, Antonino Di Pino, Salvatore Piro, Francesco Purrello, and Roberto Scicali. "Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice." Journal of Clinical Medicine 12, no. 6 (March 22, 2023): 2444. http://dx.doi.org/10.3390/jcm12062444.
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Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.
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Finnikin, Samuel, Ronan Ryan, and Tom Marshall. "Statin initiations and QRISK2 scoring in UK general practice: a THIN database study." British Journal of General Practice 67, no. 665 (October 23, 2017): e881-e887. http://dx.doi.org/10.3399/bjgp17x693485.
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BackgroundStatin prescribing should be based on cardiovascular disease (CVD) risk, but evidence suggests overtreatment of low-risk groups and undertreatment of high-risk groups.AimTo investigate the relationship between CVD risk scoring in primary care and initiation of statins for the primary prevention of CVD, and the effect of changes to the National Institute for Health and Care Excellence (NICE) guidance in 2014.Design and settingHistorical cohort study using UK electronic primary care records.MethodA cohort was created of statin-naïve patients without CVD between 1 January 2000 and 31 December 2015. CVD risk scores (calculated using QRISK2 available from 2012) and statin initiations were identified. Rates of CVD risk score recording were calculated and relationships between CVD risk category (low-, intermediate-, and high-risk: <10%, 10–19.9%, and ≥20% 10-year CVD risk) and statin initiation were analysed.ResultsA total of 1.4 million patients were identified from 248 practices. Of these, 151 788 had a recorded CVD risk score since 2012 (10.67%) and 217 860 were initiated on a statin (15.31%). Among patients initiated on a statin after 2012, 27.1% had a documented QRISK2 score: 2.7% of low-risk, 13.8% of intermediate-risk, and 35.0% of high-risk patients were initiated on statins. Statin initiation rates halved from a peak in 2006. After the 2014 NICE guidelines, statin initiation rates declined in high-risk patients but increased in intermediate-risk patients.ConclusionMost patients initiated on statins had no QRISK2 score recorded. Most patients at high risk of CVD were not initiated on statins. One in six statin initiations were to low-risk patients indicating significant overtreatment. Initiations of statins in intermediate-risk patients rose after NICE guidelines were updated in 2014.
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Cheng, Kelvin KW, Diane MA Swallow, Katherine A. Grosset, and Donald G. Grosset. "Statin usage, vascular diagnosis and vascular risk factors in Parkinson’s disease." Scottish Medical Journal 62, no. 3 (August 2017): 104–9. http://dx.doi.org/10.1177/0036933017727432.
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Background and aims Vascular disease is a common comorbidity in Parkinson’s disease patients. Statins are potentially neuroprotective for Parkinson’s disease through non-vascular mechanisms. We investigated prevailing statin use in a Parkinson’s disease cohort. Methods and results Data on diagnostic indication for statins, anti-Parkinson therapy, vascular risk factors, and statin prescription, were obtained from electronic medical record review for consecutive Parkinson’s disease patients. The ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network system was used to calculate future cardiovascular risk and identify those warranting statin use. Of 441 patients included, 59.9% were male, with a mean age of 68.9 years (standard deviation 10.3). One hundred and seventy-four (39.5%) patients had at least one diagnostic indication for statin use, of whom 136 (78.2%) were prescribed a statin. In the 267 (60.5%) cases without a diagnostic indication, 54 (20.2%) were excluded owing to age limitations defined in ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network. Of the remaining 213, 62 (29.1%) had an ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network score in the recommended range for statin therapy, of whom 15 (24.1%) were prescribed statins. Conclusion There is suboptimal implementation of statin therapy in Parkinson’s disease patients. Given the possible neuroprotective effects of statins in Parkinson’s disease in addition to reducing cardiovascular risk, reasons for suboptimal implementation warrant further investigation.
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Sanfilippo, Kristen M., Jesse Keller, Suhong Luo, Brian F. Gage, Gerald Moskowitz, and Kenneth R. Carson. "Statin Therapy Improves Multiple Myeloma (MM) Specific Surviva." Blood 126, no. 23 (December 3, 2015): 879. http://dx.doi.org/10.1182/blood.v126.23.879.879.
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Abstract Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for treatment of dyslipidemia and prevention of coronary heart disease. Recently, a multicenter clinical trial found discontinuation of statin therapy in patients with estimated survival of < 1 year had no significant impact on mortality or cardiovascular outcomes [Kutner JAMA Int Med 2015]. In this trial, approximately 50% of patients had cancer as their primary diagnosis. However, statin use has been associated with improved cancer-specific survival in several malignancies. Preclinical evidence suggests that this effect may be independent of the lipid lowering properties. In addition, in the case of MM, statins influence similar pathways as the bisphosphonates. To understand the putative benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of MM patients. Methods: We identified patients diagnosed with MM in the Veterans Administration Cancer Registry from September 1, 1999 to December 31, 2009 and followed them through October 2014. We excluded patients who did not receive MM directed therapy within 6 months of diagnosis or who died within 6 months of diagnosis. We defined statin use as the presence of any prescription for a statin on or after the date of MM diagnosis. To standardize statin utilization, we calculated the defined daily dose (DDD), which allows normalization of dose and potency amongst differing statins. The DDD is the assumed average maintenance dose per day for a drug used for its main indication. To reduce immortal time bias, we assessed statin use as a time varying covariate. Cox proportional hazards regression modeling assessed the association between statin use, overall mortality, and cause-specific mortality, while controlling for known MM prognostic factors. Propensity score analyses balanced baseline differences between statin users and non-users. Results: The cohort included a total of 3,069 patients, of whom 1,334 received statin therapy. Statin use was associated with a significant decrease in all-cause mortality (adjusted HR (aHR) 0.81, 95% CI: 0.73-0.90). Stratifying statin use by DDD, MM patients receiving <365 days of statins had a 14% reduction in all-cause mortality (aHR 0.86, 95%: CI 0.76-0.97), while patients receiving ≥365 days of statin therapy had a 24% reduction in mortality (aHR 0.76; 95% CI: 0.66-0.87). When looking at MM-specific mortality, statin use was associated with a 19% reduction in death from MM (aHR 0.81, 95% CI: 0.71-0.93). Stratifying statin use by DDD, we found that patients receiving <365 days of statin use had a 15% reduction in MM-specific mortality (aHR 0.85, 95%: CI 0.72-0.99), while patients receiving ≥365 days of statin therapy had a 25% reduction in mortality (aHR 0.75; 95% CI: 0.62-0.91). At baseline, statin users were more likely to be older, obese, Caucasian, and have more medical comorbidities (diabetes, chronic kidney disease, ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and dyslipidemia). These differences were well balanced in the propensity score analysis, in which statin use remained significantly associated with a reduction in mortality (aHR 0.60; 95% CI: 0.52-0.70). Conclusion: In this cohort of patients with MM, statin therapy was significantly associated with a reduction in both all-cause and MM-specific mortality. These findings argue against discontinuing statin therapy in patients with MM, including those with a prognosis of < 1 year. Disclosures Sanfilippo: Amgen: Speakers Bureau.
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Katsargyris, Athanasios, Chris Klonaris, Sotirios Tsiodras, Elias Bastounis, Athanasios Giannopoulos, and Stamatios Theocharis. "Statin treatment is associated with reduced toll-like receptor 4 immunohistochemical expression on carotid atherosclerotic plaques: a novel effect of statins." Vascular 19, no. 6 (September 8, 2011): 320–26. http://dx.doi.org/10.1258/vasc.2011.oa0306.
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Toll-like receptor 4 (TLR4) has been recently implicated in inflammatory pathways involved in carotid plaque destabilization. Given that statins have plaque stabilization and inflammation reduction effects, we investigated whether TLR4 expression on carotid atherosclerotic plaques correlates with statin intake. Carotid atherosclerotic plaques were obtained on 140 patients (preoperative statin intake, n = 70). TLR4 immunohistochemical expression was investigated in endothelial cells (ECs), macrophages (MACs) and smooth muscle cells (SMCs) of carotid atheroma. TLR4 positivity, over-expression and intensity of immunostaining were compared in statin versus no-statin users. The results of this study showed that statin users had a significantly lower expression of TLR4 in ECs ( P = 0.02, 0.001, 0.006 for TLR4 positivity, increased intensity and over-expression, respectively). Similarly, TLR4 positivity was less pronounced in carotid plaque MACs of statin users ( P = 0.03). No carotid specimen with increased EC TLR4 intensity or over-expression was observed among statin users. The prevalence of any cerebrovascular accident was 61.4% in the ‘no statin’ versus 18.6% in the ‘statin’ group (odds ratio for statin use: 0.14, 95% CI: 0.07–0.31, P < 0.001). In conclusion, statin treatment is associated with attenuated TLR4 expression on human carotid atherosclerotic plaques and a reduced risk of carotid-related cerebrovascular events. TLR4 may potentially mediate statins' plaque stabilization effects. Further investigation is necessary.
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Rosenson, Robert S. "Statin non-adherence: clinical consequences and proposed solutions." F1000Research 5 (April 21, 2016): 714. http://dx.doi.org/10.12688/f1000research.8215.1.
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Large controlled clinical trials have demonstrated reductions with statin therapy in cardiovascular events in patients presenting with acute coronary syndromes and stable coronary heart disease and individuals at high risk of a cardiovascular event. In trials of acute coronary syndromes and stable coronary heart disease, high-intensity statin therapy is more effective in the prevention of recurrent cardiovascular events than low-intensity statin therapy. Thus, evidence-based guidelines recommend in-hospital initiation of high-intensity statin therapy for all acute coronary syndrome patients. Clinical trials report high adherence to and low discontinuation of high-intensity statin therapy; however, in clinical practice, high-intensity statins are prescribed to far fewer patients, who often discontinue their statin after the first refill. A coordinated effort among the patient, provider, pharmacist, health system, and insurer is necessary to improve utilization and persistence of prescribed medications. The major cause for statin discontinuations reported by patients is perceived adverse events. Evaluation of potential adverse events requires validated tools to distinguish between statin-associated adverse events versus non-specific complaints. Treatment options for statin-intolerant patients include the use of a different statin, often at a lower dose or frequency. In order to lower LDL cholesterol, lower doses of statins may be combined with ezetimibe or bile acid sequestrants. Newer treatment options for patients with statin-associated muscle symptoms may include proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors.
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Sprügel, Maximilian I., Joji B. Kuramatsu, Bastian Volbers, Justina I. Saam, Jochen A. Sembill, Stefan T. Gerner, Stefanie Balk, et al. "Impact of Statins on Hematoma, Edema, Seizures, Vascular Events, and Functional Recovery After Intracerebral Hemorrhage." Stroke 52, no. 3 (March 2021): 975–84. http://dx.doi.org/10.1161/strokeaha.120.029345.
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Background and Purpose: The impact of statins on hematoma characteristics, perihemorrhagic edema (PHE), cardiovascular events, seizures, and functional recovery in patients with intracerebral hemorrhage (ICH) is insufficiently studied. Methods: Patients with ICH of the prospective UKER-ICH (Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage) study (URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03183167) were analyzed by multivariable regression modeling and propensity score matching, and PHE volumes were volumetrically assessed. Outcomes comprised hematoma characteristics, the impact of continuation, discontinuation, and initiation of statins on peak PHE extent, and the influence of statin treatment on the occurrence of seizures, cardiovascular adverse events, and functional recovery after ICH. Results: A total of 1275 patients with ICH with information on statin treatment were analyzed. Statin treatment on hospital admission (21.7%) was associated with higher rates of lobar versus nonlobar ICH (odds ratio, 1.57 [1.03–2.40]; P =0.038). Initiation of statins after ICH was associated with increased peak PHE (β=0.12, SE=0.06, P =0.008), whereas continuation versus discontinuation of prior statin treatment was not significantly associated with edema formation ( P >0.10). There were no significant differences in the incidence of remote symptomatic seizures according to statin exposure during follow-up (statins: 11.5% versus no statins: 7.8%, subdistribution hazard ratio: 1.15 [0.80–1.66]; P =0.512). Patients on statins revealed less cardiovascular adverse events and more frequently functional recovery after 12 months (functional recovery: 57.7% versus 45.0%, odds ratio 1.67 [1.09–2.56]; P =0.019). Conclusions: Among statin users, lobar ICH occurs more frequently as compared with nonstatin users. While continuation of prior statin treatment appears to be safe regarding PHE formation, the initiation of statins during the first days after ICH may increase PHE extent. However, statins should be initiated thereafter (eg, at hospital discharge) to prevent cardiovascular events and potentially improve functional recovery.
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Peltomaa, Antti I., Kirsi Talala, Kimmo Taari, Teuvo L. J. Tammela, Anssi Auvinen, and Teemu J. Murtola. "Inverse Association between Statin Use and Cancer Mortality Relates to Cholesterol Level." Cancers 14, no. 12 (June 14, 2022): 2920. http://dx.doi.org/10.3390/cancers14122920.
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Statins have been associated with a decreased cancer mortality. However, cholesterol level as such may modify the risk of cancer death. To clarify the complex interplay between statins, cholesterol level, and cancer mortality, we conducted a comprehensive analysis to separate the effects of cholesterol level and statin medication on cancer mortality. Our study population consisted of 16,924 men participating in the Finnish Randomized Study of Screening for Prostate Cancer with at least one cholesterol measurement during follow-up (1996–2017). Cox proportional regression was used to estimate hazard ratios. In total, 1699 cancer deaths were observed during the median follow-up of 19 years. When statins’ association with the risk of cancer death was estimated without adjustment for cholesterol level, statin use was associated with a lowered cancer mortality (HR 0.87; 95% CI 0.79–0.97) compared to non-users. However, with further adjustment for total cholesterol level, statin use was no longer associated with a lower cancer mortality (HR 1.08; 95% CI 0.97–1.20). Upon stratified analysis, statin use was associated with a decreased cancer mortality only if the total cholesterol level decreased after the initiation of statin use (HR 0.66; 95% CI 0.58–0.76). The inverse association between statin use and cancer mortality is limited to men with a reduction in total cholesterol level after the commencement of statins, i.e., statin use is associated with a lowered cancer mortality only if the total cholesterol level decreases. This suggests that the effect of statin use on cancer mortality relates to the decreased total cholesterol level.
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Ananthakumar, Anandita, Yiling Liu, Cristina E. Fernandez, George A. Truskey, and Deepak Voora. "Modeling statin myopathy in a human skeletal muscle microphysiological system." PLOS ONE 15, no. 11 (November 25, 2020): e0242422. http://dx.doi.org/10.1371/journal.pone.0242422.
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Statins are used to lower cholesterol and prevent cardiovascular disease. Musculoskeletal side effects known as statin associated musculoskeletal symptoms (SAMS), are reported in up to 10% of statin users, necessitating statin therapy interruption and increasing cardiovascular disease risk. We tested the hypothesis that, when exposed to statins ex vivo, engineered human skeletal myobundles derived from individuals with (n = 10) or without (n = 14) SAMS and elevated creatine-kinase levels exhibit statin-dependent muscle defects. Myoblasts were derived from muscle biopsies of individuals (median age range of 62–64) with hyperlipidemia with (n = 10) or without (n = 14) SAMS. Myobundles formed from myoblasts were cultured with growth media for 4 days, low amino acid differentiation media for 4 days, then dosed with 0 and 5μM of statins for 5 days. Tetanus forces were subsequently measured. To model the change of tetanus forces among clinical covariates, a mixed effect model with fixed effects being donor type, statin concentration, statin type and their two way interactions (donor type*statin concentration and donor type* statin type) and the random effect being subject ID was applied. The results indicate that statin exposure significantly contributed to decrease in force (P<0.001) and the variability in data (R2C [R square conditional] = 0.62). We found no significant differences in force between myobundles from patients with/without SAMS, many of whom had chronic diseases. Immunofluorescence quantification revealed a positive correlation between the number of straited muscle fibers and tetanus force (R2 = 0.81,P = 0.015) and negative correlation between number of fragmented muscle fibers and tetanus force (R2 = 0.482,P = 0.051) with no differences between donors with or without SAMS. There is also a correlation between statin exposure and presence of striated fibers (R2 = 0.833, P = 0.047). In patient-derived myobundles, statin exposure results in myotoxicity disrupting SAA organization and reducing force. We were unable to identify differences in ex vivo statin myotoxicity in this system. The results suggest that it is unlikely that there is inherent susceptibility to or persistent effects of statin myopathy using patient-derived myobundles.
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Tsimikas, Sotirios, Philip L. S. M. Gordts, Chelsea Nora, Calvin Yeang, and Joseph L. Witztum. "Statin therapy increases lipoprotein(a) levels." European Heart Journal 41, no. 24 (May 20, 2019): 2275–84. http://dx.doi.org/10.1093/eurheartj/ehz310.
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Abstract Aims Lipoprotein(a) [Lp(a)] is elevated in 20–30% of people. This study aimed to assess the effect of statins on Lp(a) levels. Methods and results This subject-level meta-analysis includes 5256 patients (1371 on placebo and 3885 on statin) from six randomized trials, three statin-vs.-placebo trials, and three statin-vs.-statin trials, with pre- and on-treatment (4–104 weeks) Lp(a) levels. Statins included atorvastatin 10 mg/day and 80 mg/day, pravastatin 40 mg/day, rosuvastatin 40 mg/day, and pitavastatin 2 mg/day. Lipoprotein(a) levels were measured with the same validated assay. The primary analysis of Lp(a) is based on the log-transformed data. In the statin-vs.-placebo pooled analysis, the ratio of geometric means [95% confidence interval (CI)] for statin to placebo is 1.11 (1.07–1.14) (P < 0.0001), with ratio >1 indicating a higher increase in Lp(a) from baseline in statin vs. placebo. The mean percent change from baseline ranged from 8.5% to 19.6% in the statin groups and −0.4% to −2.3% in the placebo groups. In the statin-vs.-statin pooled analysis, the ratio of geometric means (95% CI) for atorvastatin to pravastatin is 1.09 (1.05–1.14) (P < 0.0001). The mean percent change from baseline ranged from 11.6% to 20.4% in the pravastatin group and 18.7% to 24.2% in the atorvastatin group. Incubation of HepG2 hepatocytes with atorvastatin showed an increase in expression of LPA mRNA and apolipoprotein(a) protein. Conclusion This meta-analysis reveals that statins significantly increase plasma Lp(a) levels. Elevations of Lp(a) post-statin therapy should be studied for effects on residual cardiovascular risk.
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Schmidt, Jean, Tanaz A. Kermani, Francesco Muratore, Cynthia S. Crowson, Eric L. Matteson, and Kenneth J. Warrington. "Statin Use in Giant Cell Arteritis: A Retrospective Study." Journal of Rheumatology 40, no. 6 (April 1, 2013): 910–15. http://dx.doi.org/10.3899/jrheum.121150.
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Objective.(1) To examine the association between statin use and giant cell arteritis (GCA); (2) to compare the clinical features and disease course of GCA among statin users and nonusers.Methods.For this retrospective study, we reviewed the medical records of all patients with biopsy-positive GCA diagnosed between 1998 and 2008. Using a case-control design, we compared the frequency of statin use in GCA patients to non-GCA population-based subjects who were randomly selected and individually matched by sex, age, and calendar year to the GCA cases. Statin use at diagnosis or index date and during followup was abstracted. In subjects with GCA, clinical information at diagnosis and followup was collected.Results.We included 594 patients, 297 with GCA (73% female), mean age at diagnosis 75 years. The rate of statin exposure at index date was 18.1% for GCA patients versus 33.3% for controls (p < 0.001). Patients using statins were less likely to develop GCA compared with patients not using statins (OR 0.31, 95% CI 0.15–0.6, p < 0.001), even after adjustment for cardiovascular risk factors. Among patients with GCA, the presenting clinical features and acute-phase reactants were similar in patients receiving statins compared to those not on statin therapy. These 2 groups were also similar with regard to relapse rate, prednisone tapering, and overall survival.Conclusion.Patients using statins may be less likely to develop GCA compared to patients who are not using statins. Statin use does not appear to modify the clinical presentation or the course of the disease.
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Mansi, Ishak A., Christopher R. Frei, Ethan A. Halm, and Eric M. Mortensen. "Association of statins with diabetes mellitus and diabetic complications: role of confounders during follow-up." Journal of Investigative Medicine 65, no. 1 (August 29, 2016): 32–42. http://dx.doi.org/10.1136/jim-2016-000218.
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Studies have associated statin use with increased risk of diabetes and diabetic complications. These studies often ensure comparability of statin users and non-users at baseline; however, most studies neglect to consider confounders that occur during follow-up. Failure to consider these confounders, such as new medications or procedures, may result in identification of a spurious association between statins and outcomes. The objective of this study was to examine the association of statins with diabetes mellitus and diabetic complications; and to examine potential confounders during the follow-up period that might affect this relationship. We conducted a retrospective cohort study using Tricare data (from October 1, 2003 to March 31, 2012). We propensity score-matched statin users and non-users on 115 baseline characteristics before starting statins; these characteristics would be potentially associated with the use of statins or the outcomes of interest. Outcomes included the risk of diabetes mellitus and diabetic complications. Out of 60,455 patients (10,910 statin users and 49,545 non-users), we propensity score-matched 6728 statin users to 6728 non-users. Statin users had higher ORs for diabetes (OR 1.34, 95% CI 1.24 to 1.44) and diabetes with complications (OR 1.28, 95% CI 1.16 to 1.42). Adjustment for potential confounders that occurred during the follow-up period did not explain or diminish the association between statins and adverse outcomes. Statin users in comparison to similar non-users were more commonly diagnosed with diabetes and diabetic complications, even after adjustment for potential confounders that occurred during the follow-up period.
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Hanbali, A. S., E. Urbaez Duran, D. Wang, M. Jankowski, A. Syed, S. Farhan, and R. Chapman. "The use of statins and the effect on survival in patients with small cell lung cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 17121. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.17121.
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17121 Background: Hypercholesterolemia is one of the most common morbidities in United States. Statins have been proven as effective cholesterol-lowering agents and have been widely used in this country. They have been reported reducing the incidence and risk of various cancer types. However, the impact of using statins on the survival of patients with diagnosed small cell lung cancer is unknown. Methods: A retrospective study involved a cohort of 282 patients with diagnosed small cell lung cancer. Patients were identified from the Tumor Registry at Henry Ford Health System between January 1995 and December 2002. Electronic medical records of these patients were reviewed. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 282 patients, there were 73 patients with hypercholesterolemia, 37 of them were statin users at the time of their small cell lung cancer diagnosis. Average age was 65 (range 34–87) years for non statin users and 69 (range 52–85) years for statin users. Median survival of 282 subjects was 7.37 months. After stratifying for statin use, the median survival of statin users was 8.66 months while the median survival of non statin users was 7.17 months (p = 0.29). Conclusion: Though slightly prolonged median survival in statin-users was observed, no survival benefit is demonstrated from this patient population. Factors that may have contributed to this result will be further discussed. With the trend of an increase in median survival among statin users, whenever possible, continuation of statins as co-morbidity management may still benefit patients with small cell lung cancer, during their receiving standard anti-tumor therapies. No significant financial relationships to disclose.
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You, Hyo-Sun, Nayoung You, Jae-Woo Lee, Hyoung-Ji Lim, Joungyoun Kim, and Hee-Taik Kang. "Inverse Association between Statin Use and Stomach Cancer Incidence in Individuals with Hypercholesterolemia, from the 2002–2015 NHIS-HEALS Data." International Journal of Environmental Research and Public Health 17, no. 3 (February 7, 2020): 1054. http://dx.doi.org/10.3390/ijerph17031054.
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Purpose: To investigate the association between statin use and stomach cancer incidence in individuals with hypercholesterolemia. Materials and methods: To examine the cumulative effect of statins, we defined a statin user as one who used statins during 2002–2003 at baseline. Statin users were further classified into high and low users according to the medication possession rate. Statin non-users consisted of participants who had never used statins during the entire period of 2002–2015, despite having hypercholesterolemia (total cholesterol level ≥250 mg/dL at baseline). Ultimately, 17,737 statin users and 13,412 statin non-users were used in the analysis. We performed survival analyses, considering the diagnosis of stomach cancer as an event of interest. Results: Median follow-up duration was 12.9 years. The cumulative incidence rates of stomach cancer were lowest in high users (1.90% in men and 0.98% in women). Compared to non-users, hazard ratios (95% confidential intervals) for stomach cancer of low users and high users were 0.953 (0.755–1.203) and 0.526 (0.399–0.693) in men and 0.629 (0.457–0.865) and 0.370 (0.256–0.535) in women, respectively, after adjusting for possible confounders. Conclusions: We observed an inverse association between statin use and stomach cancer incidence in participants with hypercholesterolemia.
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Rabaeus, Mikael, Paul V. Nguyen, and Michel de Lorgeril. "Recent flaws in Evidence Based Medicine: statin effects in primary prevention and consequences of suspending the treatment." Journal of Controversies in Biomedical Research 3, no. 1 (April 17, 2017): 1–10. http://dx.doi.org/10.15586/jcbmr.2017.18.
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Statin therapy is presented as a protection against ischemic heart disease (IHD) complications. As IHD is often a fatal disease, statins are thereby supposed to decrease cardiovascular mortality and increase life expectancy. However, these benefits are increasingly challenged in the medical community, the controversy being particularly intense when discussing the effects of statins in primary prevention and the consequences of statin discontinuation. Both primary prevention and treatment discontinuation have been recently used by investigators linked to the pharmaceutical industry to justify and boost prescription and consumption of statins and other cholesterol-lowering medications. We herein review some recent commercial data related to primary prevention with rosuvastatin and statin discontinuation and their respective effects on IHD and overall mortality rate. We conclude that (1) despite the recent hype raised by HOPE-3, the cholesterol-lowering rosuvastatin is likely not beneficial in intermediate-risk individuals without cardiovascular disease (primary prevention). This trial may even represent a typical example of how evidence-based medicine has been flawed in commercial studies. (2) Statin discontinuation does not lead to increased IHD and overall mortality, at least in the months following interruption of treatment. On the contrary, one might even conclude that statin discontinuation could save lives. One possible explanation of this apparently paradoxical finding is that statin discontinuers, in the same time they stop statin therapy, likely try to adopt a healthy lifestyle. Further studies are needed to confirm the real effects of statin discontinuation in various clinical conditions. In the meantime, it is not evidence based to claim that statin discontinuation increases mortality or saves lives.
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Park, Sun-Kyoung, Ji-Hye Lee, Ho-Sik Hwang, Hyun-Seung Kim, Kyung-Do Han, and Kyung-Sun Na. "Association of Meibomian Gland Dysfunction with Oral Statin Use." Journal of Clinical Medicine 11, no. 15 (August 8, 2022): 4632. http://dx.doi.org/10.3390/jcm11154632.
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This retrospective cross-sectional study aimed to determine the association of oral statin use, dry eye disease (DED), and meibomian gland dysfunction (MGD). A total of 93 subjects were included and divided into two groups: statin users (n = 45) and nonstatin users (n = 47). Significant differences were observed in the total cholesterol (p = 0.013), low-density lipoprotein (LDL) (p = 0.005), and meiboscore (p = 0.000) levels between the two groups. For stratified analysis, the statin group was divided into subgroups according to the type or dose of statin and total duration of statin use. However, there were no differences in clinical features between the subgroups. In multiple regression analysis, meiboscore was significantly associated with age (slope = 0.05, p = 0.00) and statin use (slope = −1.19, p = 0.00), with an R2 of 0.44. Thus, older adults and participants who do not use statin appeared to have higher scores. In conclusion, although the mechanism is unclear, statins may exert a protective effect on the meibomian gland. Further lipidomic studies are required to determine the pharmacological effects of statins on the meibomian gland and other meibum components.
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Lee, Sang-Eun, Ji Min Sung, Daniele Andreini, Matthew J. Budoff, Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, et al. "Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) study." European Heart Journal - Cardiovascular Imaging 20, no. 11 (February 20, 2019): 1307–14. http://dx.doi.org/10.1093/ehjci/jez022.
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Abstract Aims Coronary artery calcium score (CACS) is a strong predictor of major adverse cardiac events (MACE). Conversely, statins, which markedly reduce MACE risk, increase CACS. We explored whether CACS progression represents compositional plaque volume (PV) progression differently according to statin use. Methods and results From a prospective multinational registry of consecutive patients (n = 2252) who underwent serial coronary computed tomography angiography (CCTA) at a ≥ 2-year interval, 654 patients (61 ± 10 years, 56% men, inter-scan interval 3.9 ± 1.5 years) with information regarding the use of statins and having a serial CACS were included. Patients were divided into non-statin (n = 246) and statin-taking (n = 408) groups. Coronary PVs (total, calcified, and non-calcified; sum of fibrous, fibro-fatty, and lipid-rich) were quantitatively analysed, and CACS was measured from both CCTAs. Multivariate linear regression models were constructed for both statin-taking and non-statin group to assess the association between compositional PV change and change in CACS. In multivariate linear regression analysis, in the non-statin group, CACS increase was positively associated with both non-calcified (β = 0.369, P = 0.004) and calcified PV increase (β = 1.579, P < 0.001). However, in the statin-taking group, CACS increase was positively associated with calcified PV change (β = 0.756, P < 0.001) but was negatively associated with non-calcified PV change (β = −0.194, P = 0.026). Conclusion In the non-statin group, CACS progression indicates the progression of both non-calcified and calcified PV progression. However, under the effect of statins, CACS progression indicates only calcified PV progression, but not non-calcified PV progression. Thus, the result of serial CACS should be differently interpreted according to the use of statins.
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Mohammad, S., H. Nguyen, M. Nguyen, M. Abdel-Rasoul, V. Nguyen, C. D. Nguyen, K. T. Nguyen, L. Li, and J. P. Kitzmiller. "Pleiotropic Effects of Statins: Untapped Potential for Statin Pharmacotherapy." Current Vascular Pharmacology 17, no. 3 (February 26, 2019): 239–61. http://dx.doi.org/10.2174/1570161116666180723120608.
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Background: Statins are effective for primary and secondary prevention of atherosclerotic cardiovascular disease. They also have systemic anti-inflammatory and immunomodulating properties suggesting potential utility for improving clinical outcomes for a wide range of diseases. The literature provides data suggesting benefit in patients with comorbidities associated with contrast-induced nephropathy (CIN), chronic obstructive pulmonary disease (COPD), pneumonia, head injury, neurological disease (e.g. Alzheimer’s and Parkinson’s disease), prostate cancer, nuclear cataract and spinal cord injury. This systematic review evaluates the current evidence supporting the potential benefit of statins outside their customary role of attenuating cardiovascular risk reduction. </P><P> Methods: The electronic databases MEDLINE, EMBASE, and clinicaltrials.gov were searched for studies published January 2000 - March 2018 reporting comorbidity reduction associated with statin use. </P><P> Results: Fifty-eight publications that satisfied our selection criteria (based on the PRISM guidance for systematic reviews) were selected and included case-control, cohort, cross-sectional and observational studies as well as systematic reviews and meta-analyses. Ten studies addressed statin use and incidence of CIN after coronary imaging; 8 addressed statin use in patients with COPD; 14 addressed statin use and comorbidity reduction associated with head injury and/or a neurological disease disorder; 5 addressed the association between statin use and nuclear cataract; 9 addressed the association between statin use and prostate/colorectal cancer; 9 studies addressed the role of statin use in treating infections; and 3 addressed the association between statin use and spinal cord injury related survival rate. </P><P> Conclusion: Overall, the literature supports beneficial pleiotropic effects of statin use in contrastinduced nephropathy, head injury, Alzheimer’s and Parkinson’s disease, nuclear cataract, prostate cancer, infection management, and spinal cord injury. Further investigation is warranted, and randomized clinical trials are needed to confirm the clinical utility suggested by the reported studies included in this meta-analysis.
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Henriksbo, Brandyn D., Akhilesh K. Tamrakar, Jobanjit S. Phulka, Nicole G. Barra, and Jonathan D. Schertzer. "Statins activate the NLRP3 inflammasome and impair insulin signaling via p38 and mTOR." American Journal of Physiology-Endocrinology and Metabolism 319, no. 1 (July 1, 2020): E110—E116. http://dx.doi.org/10.1152/ajpendo.00125.2020.
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Statins lower cholesterol and risk of cardiovascular disease. Statins can increase blood glucose and risk of new-onset diabetes. It is unclear why statins can have opposing effects on lipids versus glucose. Statins have cholesterol-independent pleiotropic effects that influence both insulin and glucose control. Statin lowering of isoprenoids required for protein prenylation promotes pancreatic β-cell dysfunction and adipose tissue insulin resistance. Protein prenylation influences immune function and statin-mediated adipose tissue insulin resistance involves the NLR family pyrin domain-containing 3 (NLRP3) inflammasome and IL-1β. However, the intracellular cues that statins engage to activate the NLRP3 inflammasome and those responsible for IL-1β-mediated insulin resistance in adipose tissue have not been identified. We hypothesized that stress kinases or components of the insulin signaling pathway mediated statin-induced insulin resistance. We tested the associations of p38, ERK, JNK, phosphatase, and tensin homolog (PTEN), and mTOR in statin-exposed adipose tissue from WT and IL-1β−/− mice. We found that statins increased phosphorylation of p38 in WT and IL-1β−/− mice. Statin activation of p38 upstream of IL-1β led to priming of this NLRP3 inflammasome effector in macrophages. We found that mTORC1 inhibition with low doses of rapamycin (2 or 20 nM) lowered macrophage priming of IL-1β mRNA and secretion of IL-1β caused by multiple statins. Rapamycin (20 nM) or the rapalog everolimus (20 nM) prevented atorvastatin-induced lowering of insulin-mediated phosphorylation of Akt in mouse adipose tissue. These results position p38 and mTOR as mediators of statin-induced insulin resistance in adipose tissue and highlight rapalogs as candidates to mitigate the insulin resistance and glycemic side effects of statins.
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Kwon, Mi Jung, Ho Suk Kang, Joo-Hee Kim, Ji Hee Kim, Se Hoon Kim, Nan Young Kim, Eun Sook Nam, Kyueng-Whan Min, and Hyo Geun Choi. "Association between Statin Use and Gastric Cancer: A Nested Case-Control Study Using a National Health Screening Cohort in Korea." Pharmaceuticals 14, no. 12 (December 8, 2021): 1283. http://dx.doi.org/10.3390/ph14121283.
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Concerns about the hazards of statins on the development and mortality of stomach cancers remain controversial. Here, we investigated the likelihood of incident gastric cancers and related mortality depending on statin exposure, statin type, and the duration of use. This nested case–control-designed study was composed of 8798 patients who were diagnosed with gastric cancer and matched with 35,192 controls at a 1:4 ratio based on propensity scores of age, sex, residential area, and income from the Korean National Health Insurance Service—Health Screening Cohort database (2002–2015). Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior use of statins (any statin, hydrophilic statins vs. lipophilic statins) with incident gastric cancer and its mortality depending on the medication duration (<180 days, 180–545 days, and >545 days) after adjusting for multiple covariates. After adjustment, the use of any statin, hydrophilic statins, or lipophilic statins showed significant associations with lower odds for incident stomach cancer when used for a short-term period (180–545 days) (OR = 0.88, 95% CI = 0.81–0.86, p = 0.002; OR = 0.78, 95% CI = 0.66–0.92, p = 0.004; and OR = 0.91, 95% CI = 0.84–0.99, p = 0.039, respectively) compared to the control group. Hydrophilic statin use for 180–545 days was associated with 53% lower overall mortality (OR = 0.47; 95% CI = 0.29–0.77). In subgroup analyses, beneficial effects on both cancer development and mortality persisted in patients ≥65 years old, patients with normal blood pressure, and patients with high fasting glucose levels. There were no such associations with long-term statin use (>545 days). Thus, the current nationwide cohort study suggests that prior short-term statin use may have anti-gastric cancer benefits in elderly patients with hyperglycemia.
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Yi, Sang-Wook, Se Hwa Kim, Ki Jun Han, Jee-Jeon Yi, and Heechoul Ohrr. "Higher cholesterol levels, not statin use, are associated with a lower risk of hepatocellular carcinoma." British Journal of Cancer 122, no. 5 (December 20, 2019): 630–33. http://dx.doi.org/10.1038/s41416-019-0691-3.
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AbstractWe aimed to examine whether statin users have a lower risk of hepatocellular carcinoma (HCC) after careful consideration of prevalent statin use and cholesterol levels. During a mean prospective follow-up of 8.4 years in 400,318 Koreans, 1686 individuals were diagnosed with HCC. When prevalent users were included, HCC risk was reduced by >50% in statin users, regardless of adjustment for total cholesterol (TC). When prevalent users were excluded, new users who initiated statins within 6 months after baseline had a 40% lower risk of HCC (hazard ratio [HR] = 0.59) in a TC-unadjusted analysis. However, this relationship disappeared (HR = 1.16, 95% CI = 0.80–1.69) after adjusting for TC levels measured within 6 months before statin initiation. TC levels had strong inverse associations with HCC in each model. High cholesterol levels at statin initiation, not statin use, were associated with reduced risk of HCC. Our study suggests no protective effect of statins against HCC.
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Donmez-Altuntas, Hamiyet, Fahri Bayram, Ayse N. Coskun-Demirkalp, Osman Baspınar, Derya Kocer, and Peter P. Toth. "Therapeutic effects of statins on chromosomal DNA damage of dyslipidemic patients." Experimental Biology and Medicine 244, no. 13 (August 19, 2019): 1089–95. http://dx.doi.org/10.1177/1535370219871895.
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Statins are a group of cholesterol lowering drugs and frequently used in the therapy of dyslipidemia. Our knowledge of the impact of statin therapy on DNA damage is as yet rudimentary. In this study, we aimed to assess the possible (1) genotoxic, cytostatic, and cytotoxic effects of statins in peripheral blood lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay, and (2) oxidative DNA damage by measuring plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in response to statin therapy. Thirty patients with dyslipidemia who had no chronic diseases and did not use any medicines that interfere lipid values and twenty control subjects were included in the study. Statin therapy was initiated at risk-stratified doses. Blood samples were taken before and after treatment with statins and from control subjects, and CBMN-cyt assay parameters and 8-OHdG levels were evaluated. The chromosomal DNA damage (micronuclei and nucleoplasmic bridges [NPBs]), cytostasis (nuclear division index [NDI]), and cytotoxicity (apoptotic and necrotic cell frequencies) were decreased in patients with dyslipidemia after statin treatment. No significant differences were found for 8-OHdG levels between patients with dyslipidemia before or after statin therapy. The total cholesterol and low-density lipoprotein-cholesterol levels showed positive correlations with NPB frequency in patients with dyslipidemia prior to statin treatment. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before and after treatment with statins. The observed reductions of chromosomal DNA damage and NDI values with statin treatment could represent an important and under-appreciated pleiotropic effect of these agents. Impact statement In literature, it is possible to find some in vitro cytokinesis-block micronucleus (CBMN) assay studies about human lymphocytes and statins. But, there are no data on CBMN-cytome (CBMN-cyt) assay parameters related to statin therapy in patients with dyslipidemia. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before treatment and after treatment with statins (5–10 mg/day rosuvastatin or 10–20 mg/day atorvastatin). In this study we show that statin therapy decreased chromosomal DNA damage (micronuclei and nucleoplasmic bridges) and nuclear division index (NDI) values in patients with dyslipidemia by possible molecular reasons independent of oxidative DNA damage. In addition, the decrease of chromosomal DNA damage and NDI values with statin treatment could be indicated by the association between statin use and reduced risk of cancer.
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Al-Karaghouli, Mustafa, Sonia Fuentes, Tracy Davyduke, Mang Ma, and Juan G. Abraldes. "Impact of statin treatment on non-invasive tests based predictions of fibrosis in a referral pathway for NAFLD." BMJ Open Gastroenterology 9, no. 1 (January 2022): e000798. http://dx.doi.org/10.1136/bmjgast-2021-000798.
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ObjectiveIn non-alcoholic fatty liver disease (NAFLD), fibrosis determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NAFLD Fibrosis Score (NFS) and Hepamet, have been proposed as a tool to triage NAFLD patients in primary care (PC). These NITs include AST±ALT in their calculations. Many patients with NAFLD take statins, which can affect AST/ALT, but it is unknown if statin affects NITs fibrosis prediction.MethodsWe included 856 patients referred through a standardised pathway from PC with a final diagnosis of NAFLD. 832 had reliable vibration controlled transient elastography (VCTE) measurements. We assessed the effects of statins on the association between NITs and VCTE at different fibrosis thresholds.Results129 out of 832 patients were taking a statin and 138 additional patients had indication for a statin. For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for body mass index, diabetes and age almost completely abrogated these differences, suggesting that these were related to patient’s profile rather to a specific effect of statins. Negative predictive values (NPVs) of FIB-4 <1.3 for VCTE >8, 10, 12 and 16 were, respectively, 89, 94, 96% and 100% in patients on a statin and 92, 95, 98% and 99% in patients not on a statin. Statins had similar impact on Hepamet predictions but did not modify NFS predictions.ConclusionIn patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value, but this had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3).
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Dyadyk, A. I., T. E. Kugler, S. R. Zborowskyy, and Yu V. Suliman. "Statin-associated muscle symptoms: epidemiology, risk factors, mechanisms and treatment." Kardiologiia 59, no. 5S (June 20, 2019): 4–12. http://dx.doi.org/10.18087/cardio.2522.
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Statins are widely prescribed and the risk of adverse drug reactions of lipid-lowering therapy is actively discussed, including muscle symptoms. This review synthesizes the knowledge about the clinical aspects of statin-associated muscle symptoms, which is important for the practitioner. Potential mechanisms of their development, risk factors, clinical manifestations, treatment and prevention are described. Timely detection the side effects of statins makes it possible to diagnose and eliminate, which is crucial for conducting lipid-lowering therapy for patients with atherosclerotic cardiovascular diseases. Management of statin-associated muscle symptoms requires altering (reduced dosages, use of another statin or alternative lipid-lowering drugs) or discontinuing the statin treatment.