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1.
Gene ; 849: 146919, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36179965

RESUMO

PIWI-interacting RNAs (piRNAs) are single-stranded, 23-36 nucleotide long RNAs that regulate gene expression in the germline but are also detected in some cancers. However, there are no reports yet on piRNA expression in tongue squamous cell carcinoma (TSCC), the most common oral cancer (80-90% percent of all oral cancers). We performed small RNA and whole transcriptome sequencing in H357 tongue cancer and HOK cells (GEO database accession numbers: GSE196674 and GSE196688). We also examined nine published sets of gene expression array data of TSCC tissues from the GEO database to decode piRNAs and their putative targets that may be involved in tumorigenesis. We identified a pool of 16,058 and 25,677 piRNAs in H357 and HOK, respectively, among which 406 are differentially expressed. We also found that 2094 protein-coding genes are differentially expressed in either TSCC tissues or cell lines. We performed target predictions for these piRNAs, pathway and disease function (DF) analyses, as well as qRT-PCR validation of piRNA-target pairs. These experiments revealed one up-regulated (FDFT1) and four down-regulated (OGA, BDH1, TAT, HYAL4) target genes that are enriched in 11 canonical pathways (CPs), with postulated roles in the initiation and progression of TSCC. Downregulation of piR-33422 is predicted to upregulate the FDFT1 gene, which encodes a mevalonate/cholesterol-pathway related farnesyl-diphosphate farnesyltransferase. The FDFT1 appears to be involved in the largest number of oncogenesis-related processes and is interacting with statins, which is a classical cancer drug. This study provides the first evidence of the piRNome of TSCC, which could be investigated further to decode piRNA-mediated gene regulations in malignancy and potential drug targets, such as FDFT1.


Assuntos
Carcinoma de Células Escamosas , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias da Língua , Humanos , RNA Interferente Pequeno/genética , Neoplasias da Língua/genética , Carcinoma de Células Escamosas/genética , Ácido Mevalônico , Farnesil-Difosfato Farnesiltransferase , Nucleotídeos , Língua/química
2.
J Affect Disord ; 320: 421-427, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206879

RESUMO

BACKGROUND: Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows. METHODS: We identified patients aged 40-75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data Analysis & Reporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk. RESULTS: We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09-1.74) for suicide attempt, 1.29 (95 % CI, 1.15-1.45) for depression, 1.35 (95 % CI, 1.19-1.53) for anxiety, and 1.45 (95 % CI, 1.21-1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91-365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription. LIMITATIONS: CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods. CONCLUSIONS: Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Tentativa de Suicídio/prevenção & controle , Depressão/tratamento farmacológico , Depressão/epidemiologia , Convulsões/epidemiologia , Ansiedade/tratamento farmacológico , Ansiedade/epidemiologia
3.
Eur J Prev Cardiol ; 28(18): 2001-2009, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33624058

RESUMO

AIM: The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS: Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION: This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Colesterol , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Infarto do Miocárdio/prevenção & controle
4.
Biomed Res Int ; 2022: 1589660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330458

RESUMO

Background: Pulmonary alveolar proteinosis (PAP) is a rare disorder which is characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy has been reported to be a novel therapy for PAP with hypercholesterolemia. We aimed to evaluate the safety and efficacy of oral statin therapy for PAP without hypercholesterolemia. Methods: In a prospective real-world observational study, 47 PAP patients without hypercholesterolemia were screened. Oral statin was initiated as therapy for these PAP patients with 12 months of follow-up. Results: Forty PAP patients completed the study. 26 (65%) of 40 PAP patients responded to statin therapy according to the study criteria. Partial pressure of arterial oxygen (PaO2) and percentage of diffusion capacity predicted (DLCO%) significantly increased while disease severity score (DSS) and radiographic abnormalities decreased after 12 months of statin therapy (all p < 0.05). The factors associated with response were higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody and baseline total cholesterol/high-density lipoprotein cholesterol (TC/HDL) (p = 0.015 and p = 0.035, respectively). The area under the receiver operating characteristic curve (AUROC) of dose of atorvastatin for predicting the response to statin therapy for PAP was 0.859 (95% CI: 0.738-0.979, p < 0.001). The cutoff dose of atorvastatin was 67.5 mg daily with their corresponding specificity (64.3%) and sensitivity (96.2%). No severe side effects were observed during the study. Conclusions: In PAP patients without hypercholesterolemia, statin therapy resulted in improvements in arterial blood gas (ABG) measurement, pulmonary function, and radiographic assessment.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Proteinose Alveolar Pulmonar , Humanos , Proteinose Alveolar Pulmonar/tratamento farmacológico , Proteinose Alveolar Pulmonar/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Estudos Prospectivos , Atorvastatina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Macrófagos Alveolares/metabolismo , HDL-Colesterol/metabolismo
5.
Allergol Immunopathol (Madr) ; 50(6): 76-83, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36335449

RESUMO

OBJECTIVE: The aim of this study is to summarize studies on statins used to treat multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) and its underlying mechanisms. METHODS: We searched some representing databases. Some studies were included if the effects of statins were tested on MS and EAE. The methodological quality was evaluated by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist. RESULTS: Studies have confirmed that statins have immunomodulatory, neuroprotective and anti-inflammatory effects, and can be used in combination with immunomodulators of different mechanisms to treat MS and EAE. Statins have been shown to improve the following symptoms MS, reduce the number of attacks and the number of lesions, through immunomodulatory, neuroprotective and anti-inflammatory effects, and has a good safety profile. CONCLUSIONS: In short, statins represent an attractive new measure for treating MS. Some studies indicate that in addition to immunomodulatory effects, statins may have neuroprotective and neuro-repairing effects. The combination of statins with other immunosuppressive drugs has also produced encouraging results. This can be broadly prospects prospected to treat MS and EAE. It is hoped that in the near future, a combination of statins with less adverse reactions and high efficacy combined with other immunomodulators will bring exact results to patients with MS.


Assuntos
Encefalomielite Autoimune Experimental , Inibidores de Hidroximetilglutaril-CoA Redutases , Esclerose Múltipla , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Esclerose Múltipla/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fatores Imunológicos/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico
6.
Oxid Med Cell Longev ; 2022: 7692215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338344

RESUMO

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.


Assuntos
Epilepsia , Inibidores de Hidroximetilglutaril-CoA Redutases , Acidente Vascular Cerebral , Humanos , Idoso , Incidência , Qualidade de Vida , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco
7.
Open Heart ; 9(2)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36318599

RESUMO

OBJECTIVE: Postoperative atrial fibrillation (POAF) is a common complication affecting approximately one-third of patients after cardiac surgery and valvular interventions. This umbrella review systematically appraises the epidemiological credibility of published meta-analyses of both observational and randomised controlled trials (RCT) to assess the risk and protective factors of POAF. METHODS: Three databases were searched up to June 2021. According to established criteria, evidence of association was rated as convincing, highly suggestive, suggestive, weak or not significant concerning observational studies and as high, moderate, low or very low regarding RCTs. RESULTS: We identified 47 studies (reporting 61 associations), 13 referring to observational studies and 34 to RCTs. Only the transfemoral transcatheter aortic valve replacement (TAVR) approach was associated with the prevention of POAF and was supported by convincing evidence from meta-analyses of observational data. Two other associations provided highly suggestive evidence, including preoperative hypertension and neutrophil/lymphocyte ratio. Three associations between protective factors and POAF presented a high level of evidence in meta-analyses, including RCTs. These associations included atrial and biatrial pacing and performing a posterior pericardiotomy. Nineteen associations were supported by moderate evidence, including use of drugs such as amiodarone, b-blockers, glucocorticoids and statins and the performance of TAVR compared with surgical aortic valve replacement. CONCLUSIONS: Our study provides evidence confirming the protective role of amiodarone, b-blockers, atrial pacing and posterior pericardiotomy against POAF as well as highlights the risk of untreated hypertension. Further research is needed to assess the potential role of statins, glucocorticoids and colchicine in the prevention of POAF. PROSPERO REGISTRATION NUMBER: CRD42021268268.


Assuntos
Fibrilação Atrial , Substituição da Valva Aórtica Transcateter , Humanos , Amiodarona , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Metanálise como Assunto , Fatores de Proteção , Substituição da Valva Aórtica Transcateter/efeitos adversos
8.
Sci Rep ; 12(1): 18435, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319655

RESUMO

High-sensitivity C-reactive protein (hs-CRP) is a key inflammatory factor in atherosclerotic cardiovascular diseases. In Chinese patients with coronary heart disease (CHD), the changes in hs-CRP levels after a daily meal and the effect of statins on those were never explored. A total of 300 inpatients with CHD were included in this study. Hs-CRP levels were measured in the fasting and non-fasting states at 2 h and 4 h after a daily breakfast. All inpatients were divided into two groups according to fasting hs-CRP ≤ 3 mg/L or not. Group with fasting hs-CRP ≤ 3 mg/L had a significantly higher percentage of patients with statins using ≥ 1 month (m) before admission than that with fasting hs-CRP > 3 mg/L (51.4% vs. 23.9%, P < 0.05). Hs-CRP levels increased significantly in the non-fasting state in two groups (P < 0.05). About 32% of patients with non-fasting hs-CRP > 3 mg/L came from those with fasting hs-CRP ≤ 3 mg/L. In conclusion, hs-CRP levels increased significantly in CHD patients after a daily meal. It suggested that the non-fasting hs-CRP level could be a better parameter to evaluate the inflammation state of CHD patients rather than fasting hs-CRP level.


Assuntos
Doença das Coronárias , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Proteína C-Reativa/metabolismo , Jejum , China
9.
Sci Rep ; 12(1): 19383, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371594

RESUMO

We explored the association between cholesterol levels and dementia risk according to the presence of diabetes and statin use. In this population-based longitudinal cohort study, the Korean National Health Insurance Service datasets (2002-2017) were used. Among individuals aged ≥ 40 years who underwent health examinations in 2009 (N = 6,883,494), the hazard of dementia was evaluated according to cholesterol levels. During a median 8.33 years, 263,185 dementia cases were detected. In statin non-users with or without diabetes, the hazards of all-cause dementia were highest for those in the lowest quartile or quintile of low-density lipoprotein-cholesterol (LDL-C) level, showing an inverted J-shaped relationship. Among statin users with or without diabetes, an advance in LDL-C group was associated with an increase in hazards of all-cause dementia. In statin users with diabetes, even very low LDL-C level was not associated with an increased risk of all-cause dementia. Although there was a seemingly paradoxical association between low LDL-C level and dementia risk in statin non-users, the trend was not observed in statin users and is not likely to be clinically relevant. Rather, an advance in LDL-C levels was associated with an increase in the hazard of all-cause dementia in statin users, regardless of the presence of diabetes.


Assuntos
Demência , Diabetes Mellitus , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , LDL-Colesterol , Estudos de Coortes , Estudos Longitudinais , Diabetes Mellitus/epidemiologia , Demência/epidemiologia , Demência/etiologia , Fatores de Risco
10.
BMC Med ; 20(1): 441, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36372869

RESUMO

BACKGROUND: Aggressive lipid lowering by high-dose statin treatment has been established for the secondary prevention of coronary artery disease (CAD). Regarding the low-density lipoprotein cholesterol (LDL-C) level, however, the "The lower is the better" concept has been controversial to date. We hypothesized that there is an optimal LDL-C level, i.e., a "threshold" value, below which the incidence of cardiovascular events is no longer reduced. We undertook a subanalysis of the REAL-CAD study to explore whether such an optimal target LDL-C level exists by a novel analysis procedure to verify the existence of a monotonic relationship. METHODS: For a total of 11,105 patients with CAD enrolled in the REAL-CAD study, the LDL-C level at 6 months after randomization and 5-year cardiovascular outcomes were assessed. We set the "threshold" value of the LDL-C level under which the hazards were assumed to be constant, by including an artificial covariate max (0, LDL-C - threshold) in the Cox model. The analysis was repeated with different LDL-C thresholds (every 10 mg/dl from 40 to 100 mg/dl) and the model fit was assessed by log-likelihood. RESULTS: For primary outcomes such as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization, the model fit assessed by log-likelihood was best when a threshold LDL-C value of 70 mg/dl was assumed. And in the model with a threshold LDL-C ≥ 70 mg/dl, the hazard ratio was 1.07 (95% confidence interval 1.01-1.13) as the LDL-C increased by 10 mg/dl. Therefore, the risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dl, but when the level was further reduced, the risk was independent of LDL-C. CONCLUSIONS: Our analysis model suggests that a "threshold" value of LDL-C might exist for the secondary prevention of cardiovascular events in Japanese patients with CAD, and this threshold might be 70 mg/dl for primary composite outcomes. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . Unique identifier: NCT01042730.


Assuntos
Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Humanos , LDL-Colesterol , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/epidemiologia , Modelos de Riscos Proporcionais , Resultado do Tratamento
11.
Cochrane Database Syst Rev ; 11: CD013521, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36373961

RESUMO

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol deficiency and accumulation of various precursor molecules, mainly 7-dehydrocholesterol and 8-dehydrocholesterol. There is currently no cure for SLOS, with cholesterol supplementation being primarily a biochemical therapy of limited evidence. However, several anecdotal reports and preclinical studies have highlighted statins as a potential therapy for SLOS. OBJECTIVES: To evaluate the effects of statins, either alone or in combination with other non-statin therapies (e.g. cholesterol, bile acid, or vitamin co-supplementation), compared to cholesterol supplementation alone or in combination with other non-statin therapies (e.g. bile acid or vitamin supplementation) on several important outcomes including overall survival, neurobehavioral features, and adverse effects in individuals with SLOS. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and three trials registers on 15 February 2022, together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs with parallel or cross-over designs, and non-randomized studies of interventions (NRSIs) including non-randomized trials, cohort studies, and controlled before-and-after studies, were eligible for inclusion in this review if they met our prespecified inclusion criteria, i.e. involved human participants with biochemically or genetically diagnosed SLOS receiving statin therapy or cholesterol supplementation, or both. DATA COLLECTION AND ANALYSIS: Two authors screened titles and abstracts and subsequently full-texts for all potentially-relevant references. Both authors independently extracted relevant data from included studies and assessed the risks of bias. We analyzed the data extracted from the included NRSIs and cohort studies separately from the data extracted from the single included RCT. We used a random-effects model to account for the inherent heterogeneity and methodological variation between these different study designs. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included six studies (61 participants with SLOS); one RCT (N = 18), three prospective NRSIs (N = 20), and two retrospective NRSIs (N = 22). Five studies included only children, and two limited their participant inclusion by disease severity. Overall, there were nearly twice as many males as females. All six studies compared add-on statin therapy to cholesterol supplementation alone. However, the dosages, formulations, and durations of treatment were highly variable across studies. We judged the RCT as having a high risk of bias due to missing data and selective reporting. All included NRSIs had a serious or critical overall risk of bias assessed by the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I). None of the included studies evaluated survival or reported quality of life (QoL). Only the included RCT formally assessed changes in the neurobehavioral manifestations of SLOS, and we are uncertain whether statin therapy improves this outcome (very low-certainty evidence). We are also uncertain whether the adverse events reported in the RCT were statin-related (very low-certainty evidence). In contrast, the adverse events reported in the NRSIs seem to be possibly due to statin therapy (risk ratio 13.00, 95% confidence interval 1.85 to 91.49; P = 0.01; low-certainty evidence), with only one of the NRSIs retrospectively mentioning changes in the irritability of two of their participants. We are uncertain whether statins affect growth based on the RCT or NRSI results (very low-certainty evidence). The RCT showed that statins may make little or no difference to plasma biomarker levels (low-certainty evidence), while we are uncertain of their effects on such parameters in the NRSIs (very low-certainty evidence). AUTHORS' CONCLUSIONS: Currently, there is no evidence on the potential effects of statin therapy in people with SLOS regarding survival or QoL, and very limited evidence on the effects on neurobehavioral manifestations. Likewise, current evidence is insufficient and of very low certainty regarding the effects of statins on growth parameters in children with SLOS and plasma or cerebrospinal fluid (CSF) levels of various disease biomarkers. Despite these limitations, current evidence seemingly suggests that statins may increase the risk of adverse reactions in individuals with SLOS receiving statins compared to those who are not. Given the insufficient evidence on potential benefits of statins in individuals with SLOS, and their potential for causing adverse reactions, anyone considering this therapy should take these findings into consideration. Future studies should address the highlighted gaps in evidence on the use of statins in individuals with SLOS by collecting prospective data on survival and performing serial standardized assessments of neurobehavioral features, QoL, anthropometric measures, and plasma and CSF biomarker levels after statin introduction. Future studies should also attempt to use consistent dosages, formulations and durations of cholesterol and statin therapy.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome de Smith-Lemli-Opitz , Criança , Feminino , Humanos , Masculino , Ácidos e Sais Biliares , Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Síndrome de Smith-Lemli-Opitz/tratamento farmacológico , Vitaminas , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Cross-Over
12.
Tijdschr Gerontol Geriatr ; 53(3)2022 May 30.
Artigo em Holandês | MEDLINE | ID: mdl-36408752

RESUMO

We describe a case of a geriatric patient with repeated hepatotoxicity after (re)start of atorvastatin. We also noticed an increased effect, a fast decline of LDL-cholesterol, after intake of atorvastatin. The intake of rosuvastatin or low dose lovastatin was not associated with hepatotoxicity. Multiple hypotheses were investigated and applied on the case. Genetic testing of statin transporters and CYP-enzymes and medication interactions could not explain the hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Idoso , Atorvastatina/efeitos adversos , Rosuvastatina Cálcica/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , LDL-Colesterol , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico
13.
Open Heart ; 9(2)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36396295

RESUMO

OBJECTIVES: To describe medical management in aortic dissection (AD) and to analyse the possible associations between antihypertensive, antithrombotic, anticoagulant and statin agents, respectively, and long-term survival. METHODS: From Swedish medical registers, all patients diagnosed with AD in 2006-2015 were identified. Filled prescriptions prior to admission and within 1 year from discharge in patients discharged and alive at 30 days were registered. Associations between pharmacological treatment and long-term survival were analysed using Cox proportional hazards models. RESULTS: Of 3951 patients hospitalised with acute AD, 3046 (77%) were discharged and alive at 30 days. In hospitalised patients, mean age was 66 years (SD 13), and 36% (n=1098) were women. Within 1 year from discharge, 96% (n=2939) had at least one antihypertensive drug. Beta blocker was the most commonly used drug type (90%, n=2741). Statin treatment (47%, n=1418) was associated with higher long-term survival; HR 0.74 (95% CI 0.63 to 0.87, p<0.001). The positive association between statins and long-term survival remained, in subgroup analysis, in medically managed patients (HR 0.72 (95% CI 0.60 to 0.86, p<0.001)), but not in patients undergoing surgical repair (HR 0.82 (95% CI 0.58 to 1.14, p=0.230)). Beta blockers were associated with favourable long-term survival in surgically managed patients (HR 0.58 (95% CI 0.35 to 0.97, p=0.038)) but not in medically managed patients (HR 0.93 (95% CI 0.72 to 1.12, p=0.057)). Neither antiplatelet therapy nor anticoagulants were associated with long-term survival. CONCLUSIONS: Statin treatment was associated with favourable long-term outcome in medically managed AD patients, whereas treatment with beta blocker was associated with higher survival only in surgically managed AD patients. Statin use as well as optimal antihypertensive therapy in the chronic stage of the disease need to be further analysed, preferably in randomised controlled trials.


Assuntos
Aneurisma Dissecante , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Feminino , Idoso , Masculino , Anti-Hipertensivos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Resultado do Tratamento , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/tratamento farmacológico , Modelos de Riscos Proporcionais , Antagonistas Adrenérgicos beta/efeitos adversos
14.
Vnitr Lek ; 68(7): 458-460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36402572

RESUMO

The development of lipid modifying drugs was expanding during the past 30 years. Statins stay to be the first choice drugs in dyslipidemia treatment. Inhibitors of proprotein convertase subtilisin- kexin type 9 (PCSK9) enzyme in combination with statin and/or ezetimibe represent very effective therapy and better atherosclerotic cardiovascular disease (ASCVD) prevention. Antisense therapy based on oligonucleotides belongs to the new technology drugs. This therapy inhibits translation of some proteins important for the production of atherogenic lipid particles. Inclisiran is a small interfering RNA that suppresses translation of PCSK9 in the liver cells. It is applied subcutaneously twice a year and it represents a big chance for the improvement of ASCVD treatment and prevention.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Hipolipemiantes/uso terapêutico , Pró-Proteína Convertase 9/genética , RNA Interferente Pequeno/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aterosclerose/tratamento farmacológico , Lipídeos
15.
Biomed Res Int ; 2022: 4842699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317110

RESUMO

Background: Persistent inflammation has been recognized as an important comorbid condition in patients with chronic kidney disease (CKD) and is associated with many complications, mortality, and progression of CKD. Previous studies have not drawn a clear conclusion about the anti-inflammatory effects of statins in CKD. This meta-analysis is aimed at assessing the anti-inflammatory effects of statins therapy in patients with CKD. Methods: A comprehensive literature search was conducted in these databases (Medline, Embase, Cochrane library, and clinical trials) to identify the randomized controlled trials that assess the anti-inflammatory effects of statins. Subgroup, sensitivity, and trim-and-fill analysis were conducted to determine the robustness of pooled results of the primary outcome. Results: 25 eligible studies with 7921 participants were included in this meta-analysis. The present study showed that statins therapy was associated with a decreased C-reactive protein (CRP) (-2.06 mg/L; 95% CI: -2.85 to -1.27, p < 0.01). Subgroup, sensitivity, and trim-and-fill analysis showed that the pooled results of CPR were stable. Conclusion: This meta-analysis demonstrates that statins supplementation has anti-inflammatory effects in patients with CKD. Statins exert an anti-inflammatory effect that is clinically important in improving complications, reducing mortality, and slowing progression in CKD. We believe that the benefits of statins to CKD are partly due to their anti-inflammatory effects. However, stains usually are prescribed in the CKD patients with dyslipidemia, whether statins can reduce inflammation in CKD patients with normal serum lipid needed to explore in the future. Therefore, we suggest that randomized clinical trials need to assess the effect of statins in CKD patients with normal serum lipid. Whether statins can be prescribed for aiming to inhibit inflammation in CKD also needed further study. Trial Registration. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42022310334.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Insuficiência Renal Crônica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Lipídeos
17.
Cells ; 11(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36359845

RESUMO

(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestations, COVID-19 recovered patients, and healthy controls. We performed ex vivo flow cytometry analysis to study γδ T cell frequency, phenotype, and exhaustion status. PBMCs were treated with Atorvastatin followed by non-specific and specific stimulation, to evaluate the expression of pro-inflammatory cytokines; (3) Results: COVID-19 patients had a lower frequency of circulating Vδ2+ T lymphocytes but showed a pronounced pro-inflammatory profile, which was inhibited by in vitro treatment with statins; (4) Conclusions: the in vitro capacity of statins to inhibit Vδ2+ T lymphocytes in COVID-19 patients highlights a new potential biological function of these drugs and supports their therapeutical use in these patients.


Assuntos
COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Leucócitos Mononucleares/metabolismo , COVID-19/tratamento farmacológico
18.
Artigo em Inglês | MEDLINE | ID: mdl-36360652

RESUMO

Statin therapy can effectively reduce recurrent transient ischemic attack (TIA) risk. However, studies have reported that statin use is associated with incidence of diabetes mellitus (DM). Whether statin therapy remains associated with higher DM risk in patients with TIA remains unknown. This study investigated whether statin treatment influences incident DM risk in patients with TIA. We conducted a retrospective cohort study using the Longitudinal Health Insurance Database 2000. Participants who were newly diagnosed with TIA (ICD-9-CM code 435) from 1 January 1997 to 31 December 2011 were recruited. The Kaplan-Meier method and Cox proportional risk model of time-dependent covariance were used. We enrolled 8342 patients with newly diagnosed TIA from 1 January 1997 to 31 December 2011. Of these, 1255 patients were classified as statin users and 7087 as nonusers. During the 14-year follow-up, the incidence of newly diagnosed DM was 0.545-fold lower in the statins group compared with nonusers (95% confidence interval [CI] = 0.457-0.650). According to cumulative defined daily doses (cDDDs), the adjusted hazard ratios for DM were 0.689, 0.594, and 0.463 when patients were treated with statins at cDDDs = 28-89, 90-180, and >180, respectively. In patients with TIA, statin use is associated with a lower incident DM risk compared with the nonuse of statins.


Assuntos
Diabetes Mellitus , Inibidores de Hidroximetilglutaril-CoA Redutases , Ataque Isquêmico Transitório , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/tratamento farmacológico , Estudos Retrospectivos , Incidência , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/induzido quimicamente , Fatores de Risco
20.
J Cardiopulm Rehabil Prev ; 42(6): 397-403, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36342682

RESUMO

PURPOSE: The objective of this report was to review the application of the pooled cohort equations in primary prevention and the assessment of cardiovascular health. REVIEW METHODS: Literature review was conducted using the PubMed database. In addition, the 2018 Multi-Society Guidelines on Management of Blood Cholesterol and the 2019 American College of Cardiology/American Heart Association Guidelines on the Primary Prevention of Cardiovascular Disease were reviewed. SUMMARY: Primary prevention refers to individuals with no history of atherosclerotic cardiovascular disease, severe hypercholesterolemia, or diabetes. For these adults, aged 40-75 yr, who have a low-density lipoprotein-cholesterol of ≥70 mg/dL and <190 mg/dL, the pooled cohort equations should be used to provide a quantitative assessment of 10-yr atherosclerotic cardiovascular disease risk. From here, individuals are grouped as low risk (<5%), borderline risk (5 to <7.5%), intermediate risk (7.5 to <20%), or high risk (≥20%). Statin therapy should be strongly advised in those with an atherosclerotic cardiovascular disease risk of ≥20%, while statin therapy can be considered in those with a risk between 5% and <20%, especially if risk enhancing factors are present. If uncertainty still exists regarding treatment, a coronary artery calcium score can help further refine risk. All individuals, regardless of atherosclerotic cardiovascular disease risk, should have a cardiovascular health assessment using Life's Essential 8, which includes diet, physical activity, nicotine exposure, body mass index, blood glucose, blood lipids, blood pressure, and sleep.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Adulto , Estados Unidos , Humanos , Doenças Cardiovasculares/prevenção & controle , Aterosclerose/prevenção & controle , Fatores de Risco , Prevenção Primária , Colesterol , Medição de Risco
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