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1.
Medicine (Baltimore) ; 103(18): e38010, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701318

RESUMO

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.


Assuntos
Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Neoplasias , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 9 , Humanos , Neoplasias/genética , Neoplasias/epidemiologia , Hidroximetilglutaril-CoA Redutases/genética , Feminino , Inibidores de PCSK9 , Hipolipemiantes/uso terapêutico , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
3.
Pharmacoepidemiol Drug Saf ; 33(6): e5817, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38783416

RESUMO

PURPOSE: It has been suggested that statins may exert thermo-protective effects that can reduce mortality on hot days. We aimed to examine the relationship between statin adherence and mortality in days with high temperature. METHODS: Utilizing data from a prior historical new-user cohort study, we analyzed a cohort of 229 918 individuals within a state-mandated health provider in Israel who initiated statin therapy between 1998 and 2006. Adherence to statins was assessed through the mean proportion of days covered (PDC) with statins during the follow-up period. The study's primary outcome was all-cause mortality during hot days. RESULTS: During the study follow-up period, a total of 13 165 individuals (5.7%) died. In a multivariable model, a 10% increase in PDC with statins was associated with an HR of (0.85; 95% CI: 0.72-1.00) for deaths (n = 16) in extremely hot days (≥39°C). This association was numerically stronger compared to HR = 0.94 (0.93-0.94) in cooler days and displayed a significant difference between sexes. In males, the fully-adjusted HR for a 10% increase in PDC with statins was 0.66 (0.45-0.95), while in women, it was 0.98 (0.78-1.23). In contrast, no such effect modification was observed for death in cooler days. CONCLUSIONS: These findings align with earlier research, supporting the notion that adherence with statin treatment may be associated with a reduced risk of death during extremely hot days, particularly among men.


Assuntos
Temperatura Alta , Inibidores de Hidroximetilglutaril-CoA Redutases , Adesão à Medicação , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Feminino , Israel/epidemiologia , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Idoso , Temperatura Alta/efeitos adversos , Estudos de Coortes , Mortalidade/tendências , Seguimentos , Adulto , Fatores Sexuais
4.
BMJ Ment Health ; 27(1)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772637

RESUMO

BACKGROUND: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established. OBJECTIVES: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders. METHODS: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18-100 years with first-episode depression, registered with English primary care practices over January 1998-August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs. FINDINGS: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2-12months 0.66-0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2-6months 0.90-0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified. CONCLUSIONS: We found no evidence that statin use among people with depression increases mortality or other adverse events. CLINICAL IMPLICATIONS: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Atenção Primária à Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Estudos de Coortes , Adolescente , Idoso de 80 Anos ou mais , Adulto Jovem , Inglaterra/epidemiologia , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/mortalidade , Transtorno Depressivo/epidemiologia , Depressão/tratamento farmacológico , Depressão/epidemiologia
5.
BMC Geriatr ; 24(1): 444, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773394

RESUMO

BACKGROUND: Randomized clinical trials have shown that, under optimal conditions, statins reduce the risk of cardiovascular events in older adults. Given the prevalence and consequences of suboptimal adherence to statin among older adults, it is essential to document strategies designed to increase statin adherence in this population. The objective of this systematic review is to describe and summarize the effectiveness of interventions to improve statin adherence in older adults (≥ 65 years old). METHODS: This review followed PRISMA guidelines. Studies were identified from PubMed, PsycINFO, Embase, CINAHL and Web of Science. Study selection was conducted independently by four reviewers working in pairs. Included studies reported data on interventions designed to increase adherence to statin therapy in older adults and were original trials or observational studies. Interventions were pragmatically regrouped into 8 different categories going from patient to administrative level. Two reviewers extracted study data and assessed study quality independently. Given the heterogeneity between the included studies, a narrative critique and summary was conducted. RESULTS: Twelve out of the 2889 identified articles were included in the review. Our review showed that simplifying patients' drug regimen, administrative improvements and large-scale pharmacy-led automated telephone interventions show positive effects on patient adherence to statin therapy, with odds ratios between > 1.0 and 3.0, while education-based strategies and intensified patient care showed mixed results. CONCLUSIONS: Current evidence suggests that some interventions can increase statin adherence in older adults, which could help in the reduction of the risk of a cardiovascular event in this population.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Adesão à Medicação , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/tratamento farmacológico
6.
Curr Probl Cardiol ; 49(7): 102637, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735347

RESUMO

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Hyperlipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C) is one of the major risk factors for CVD. Major landmark cardiovascular outcome clinical trials demonstrated that LDL-C lowering medications reduce cardiovascular events, and the lower the LDL-C the better the outcome. This article discusses the evolution of LDL-C lowering medications starting from bile acid sequestrants (BAS), statin therapy, bempedoic acid, the proprotein convertase subtilisin kexin 9 (PCSK9) synthesis inhibitor, novel small interfering RNA-based therapy (inclisiran) to the most recent oral PCSK9 inhibitors (MK-0616) which is currently under phase 3 clinical trial studies.


Assuntos
Doenças Cardiovasculares , LDL-Colesterol , Humanos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol/sangue , Anticolesterolemiantes/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de PCSK9 , Ácidos Dicarboxílicos , Ácidos Graxos , RNA Interferente Pequeno
7.
Prim Health Care Res Dev ; 25: e29, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38751186

RESUMO

AIMS: This study serves as an exemplar to demonstrate the scalability of a research approach using survival analysis applied to general practice electronic health record data from multiple sites. Collection of these data, the subsequent analysis, and the preparation of practice-specific reports were performed using a bespoke distributed data collection and analysis software tool. BACKGROUND: Statins are a very commonly prescribed medication, yet there is a paucity of evidence for their benefits in older patients. We examine the relationship between statin prescriptions for general practice patients over 75 and all-cause mortality. METHODS: We carried out a retrospective cohort study using survival analysis applied to data extracted from the electronic health records of five Australian general practices. FINDINGS: The data from 8025 patients were analysed. The median duration of follow-up was 6.48 years. Overall, 52 015 patient-years of data were examined, and the outcome of death from any cause was measured in 1657 patients (21%), with the remainder being censored. Adjusted all-cause mortality was similar for participants not prescribed statins versus those who were (HR 1.05, 95% CI 0.92-1.20, P = 0.46), except for patients with diabetes for whom all-cause mortality was increased (HR = 1.29, 95% CI: 1.00-1.68, P = 0.05). In contrast, adjusted all-cause mortality was significantly lower for patients deprescribed statins compared to those who were prescribed statins (HR 0.81, 95% CI 0.70-0.93, P < 0.001), including among females (HR = 0.75, 95% CI: 0.61-0.91, P < 0.001) and participants treated for secondary prevention (HR = 0.72, 95% CI: 0.60-0.86, P < 0.001). This study demonstrated the scalability of a research approach using survival analysis applied to general practice electronic health record data from multiple sites. We found no evidence of increased mortality due to statin-deprescribing decisions in primary care.


Assuntos
Medicina Geral , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Feminino , Masculino , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Austrália , Medicina Geral/estatística & dados numéricos , Análise de Sobrevida , Registros Eletrônicos de Saúde/estatística & dados numéricos , Causas de Morte
8.
Respir Res ; 25(1): 207, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750572

RESUMO

BACKGROUND: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities. METHODS: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up. RESULTS: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year. CONCLUSION: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.


Assuntos
Doenças Cardiovasculares , Comorbidade , Inibidores de Hidroximetilglutaril-CoA Redutases , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Feminino , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Estudos de Coortes , Estudos Longitudinais , Progressão da Doença , Alemanha/epidemiologia , Seguimentos
9.
Medicine (Baltimore) ; 103(19): e38122, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728464

RESUMO

BACKGROUND: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. METHODS: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. RESULTS: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. CONCLUSIONS: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.


Assuntos
Atorvastatina , Remodelação Óssea , Inibidores de Hidroximetilglutaril-CoA Redutases , Pós-Menopausa , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/uso terapêutico , Rosuvastatina Cálcica/administração & dosagem , Feminino , Atorvastatina/uso terapêutico , Atorvastatina/farmacologia , Pessoa de Meia-Idade , Remodelação Óssea/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Biomarcadores/sangue , Colágeno Tipo I/sangue , Osteoporose Pós-Menopausa/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Dislipidemias/sangue
10.
J Am Board Fam Med ; 37(2): 316-320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38740491

RESUMO

BACKGROUND: Creating useful clinical quality measure (CQM) reports in a busy primary care practice is known to depend on the capability of the electronic health record (EHR). Two other domains may also contribute: supportive leadership to prioritize the work and commit the necessary resources, and individuals with the necessary health information technology (IT) skills to do so. Here we describe the results of an assessment of the above 3 domains and their associations with successful CQM reporting during an initiative to improve smaller primary care practices' cardiovascular disease CQMs. METHODS: The study took place within an AHRQ EvidenceNOW initiative of external support for smaller practices across Washington, Oregon and Idaho. Practice facilitators who provided this support completed an assessment of the 3 domains previously described for each of their assigned practices. Practices submitted 3 CQMs to the study team: appropriate aspirin prescribing, use of statins when indicated, blood pressure control, and tobacco screening/cessation. RESULTS: Practices with advanced EHR reporting capability were more likely to report 2 or more CQMs. Only one-third of practices were "advanced" in this domain, and this domain had the highest proportion of practices (39.1%) assessed as "basic." The presence of advanced leadership or advanced skills did not appreciably increase the proportion of practices that reported 2 or more CQMs. CONCLUSIONS: Our findings support previous reports of limited EHR reporting capabilities within smaller practices but extend these findings by demonstrating that practices with advanced capabilities in this domain are more likely to produce CQM reports.


Assuntos
Registros Eletrônicos de Saúde , Atenção Primária à Saúde , Humanos , Atenção Primária à Saúde/normas , Atenção Primária à Saúde/organização & administração , Registros Eletrônicos de Saúde/estatística & dados numéricos , Registros Eletrônicos de Saúde/normas , Oregon , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/diagnóstico , Washington , Qualidade da Assistência à Saúde , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idaho , Aspirina/administração & dosagem , Indicadores de Qualidade em Assistência à Saúde , Melhoria de Qualidade , Abandono do Hábito de Fumar/métodos , Liderança
11.
BMC Cardiovasc Disord ; 24(1): 245, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730371

RESUMO

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.


Assuntos
Fidelidade a Diretrizes , Inibidores de Hidroximetilglutaril-CoA Redutases , Análise de Séries Temporais Interrompida , Guias de Prática Clínica como Assunto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estados Unidos , Fatores de Tempo , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Fidelidade a Diretrizes/normas , Biomarcadores/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/mortalidade , Dislipidemias/epidemiologia , Atorvastatina/uso terapêutico , Atorvastatina/efeitos adversos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Bases de Dados Factuais , Padrões de Prática Médica/normas , Colesterol/sangue , Adesão à Medicação , Medicamentos Genéricos/uso terapêutico , Medicamentos Genéricos/efeitos adversos , Medição de Risco
12.
Int J Mol Sci ; 25(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38732177

RESUMO

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.


Assuntos
Insuficiência Cardíaca , Inibidores de Hidroximetilglutaril-CoA Redutases , Volume Sistólico , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Ensaios Clínicos como Assunto
14.
Ther Adv Cardiovasc Dis ; 18: 17539447241249650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708947

RESUMO

Currently, cardiovascular risk stratification to guide preventive therapy relies on clinical scores based on cardiovascular risk factors. However, the discriminative power of these scores is relatively modest. The use of coronary artery calcium score (CACS) and coronary CT angiography (CCTA) has surfaced as methods for enhancing the estimation of risk and potentially providing insights for personalized treatment in individual patients. CACS improves overall cardiovascular risk prediction and may be used to improve the yield of statin therapy in primary prevention, and possibly identify patients with a favorable risk/benefit relationship for antiplatelet therapies. CCTA holds promise to guide anti-atherosclerotic therapies and to monitor individual response to these treatments by assessing individual plaque features, quantifying total plaque volume and composition, and assessing peri-coronary adipose tissue. In this review, we aim to summarize current evidence regarding the use of CACS and CCTA for guiding lipid-lowering and antiplatelet therapy and discuss the possibility of using plaque burden and plaque phenotyping to monitor response to anti-atherosclerotic therapies.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Placa Aterosclerótica , Valor Preditivo dos Testes , Calcificação Vascular , Humanos , Calcificação Vascular/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Medição de Risco , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco de Doenças Cardíacas , Resultado do Tratamento , Tomada de Decisão Clínica , Seleção de Pacientes
15.
Cancer Epidemiol ; 90: 102573, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692143

RESUMO

BACKGROUND: Statins are a group of lipid-lowering drugs with pleiotropic effects that include, but are not limited to the inhibition of cholesterol synthesis resulting in a wide range of anti-inflammatory, anti-tumor, immunomodulatory, and anti-thrombotic properties. This study aimed to determine the impact of the prior to- or after- breast surgery usage of statins on the tumor prognosis in breast cancer (BC) patients. METHODS: A cohort of patients diagnosed with early invasive ductal BC (n=301) at the Hospital Italiano de Buenos Aires, Argentina, with a minimum follow-up period of 10 years after the surgical procedure were included and stratified according to the time of use of statins and type of statin used. Then, local relapse-free survival (RFS), metastasis-free survival (MFS), bone metastasis-free survival (BMFS), visceral metastasis-free (VMFS), mixed metastasis (bone and visceral)-free survival (mix-MFS) and overall survival (OS) were analyzed. RESULTS: Statins usage after breast surgery was related with lesser metastatic occurrence (p=0.017), lower number of metastatic foci (p=0.034) and fewer dead events (p=0.041), as well as longer MFS (p=0.013) and OS (p=0.027). When stratified by the nature of statins (hydrophilic or lipophilic), only the relatively hydrophilic statin rosuvastatin (ROSU) had an impact on the increase of MFS and OS (p=0.018 and p=0.030, respectively). CONCLUSION: Post-surgery statins usage was associated with increased MFS and OS, with increased benefits of ROSU over simvastatin (SIM) or atorvastatin (ATOR). These results set the rationale for additional studies addressing the use of statins, and particularly, rosuvastatin, to improve the outcome of BC patients.


Assuntos
Neoplasias da Mama , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pessoa de Meia-Idade , Idoso , Prognóstico , Argentina/epidemiologia , Mastectomia , Seguimentos , Adulto , Estudos Retrospectivos , Carcinoma Ductal de Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/mortalidade , Taxa de Sobrevida
16.
BMC Cancer ; 24(1): 602, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760735

RESUMO

BACKGROUND: Melanoma proliferation is partly attributed to dysregulated lipid metabolism. The effectiveness of lipid-lowering drugs in combating cutaneous melanoma (CM) is a subject of ongoing debate in both in vitro and clinical studies. METHOD: This study aims to evaluate the causal relationship between various lipid-lowering drug targets, namely 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, targeted by statins), Proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by alirocumab and evolocumab), and Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and the outcomes of cutaneous melanoma. To mimic the effects of lipid-lowering drugs, we utilized two genetic tools: analysis of polymorphisms affecting the expression levels of drug target genes, and genetic variations linked to low-density lipoprotein cholesterol levels and drug target genes. These variations were sourced from genome-wide association studies (GWAS). We applied Summary-data-based Mendelian Randomization (SMR) and Inverse Variance Weighted Mendelian Randomization (IVW-MR) to gauge the effectiveness of these drugs. RESULTS: Our findings, with SMR results showing an odds ratio (OR) of 1.44 (95% CI: 1.08-1.92; P = 0.011) and IVW-MR results indicating an OR of 1.56 (95% CI: 1.10-2.23; P = 0.013), demonstrate a positive correlation between PCSK9 expression and increased risk of CM. However, no such correlations were observed in other analyses. CONCLUSION: The study concludes that PCSK9 plays a significant role in the development of CM, and its inhibition is linked to a reduced risk of the disease.


Assuntos
Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Melanoma , Análise da Randomização Mendeliana , Pró-Proteína Convertase 9 , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/tratamento farmacológico , Pró-Proteína Convertase 9/genética , Hidroximetilglutaril-CoA Redutases/genética , Melanoma Maligno Cutâneo , Anticorpos Monoclonais Humanizados/uso terapêutico , Polimorfismo de Nucleotídeo Único , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ezetimiba/uso terapêutico , Hipolipemiantes/uso terapêutico , Hipolipemiantes/farmacologia
17.
Int J Mol Sci ; 25(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38791422

RESUMO

The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.


Assuntos
Síndrome Coronariana Aguda , Atorvastatina , Citocromo P-450 CYP2C19 , Humanos , Citocromo P-450 CYP2C19/genética , Atorvastatina/uso terapêutico , Feminino , Masculino , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Pessoa de Meia-Idade , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Alelos
18.
Sci Rep ; 14(1): 12094, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802400

RESUMO

Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30-1.84, P = 6.87 × 10-7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.


Assuntos
Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Transtornos de Enxaqueca , Polimorfismo de Nucleotídeo Único , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Locos de Características Quantitativas , Predisposição Genética para Doença
20.
Front Endocrinol (Lausanne) ; 15: 1381746, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726340

RESUMO

Background: A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Data and methods: Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Results: Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Conclusion: Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.


Assuntos
Nefropatias Diabéticas , Inibidores de Hidroximetilglutaril-CoA Redutases , Inquéritos Nutricionais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto , Idoso , Incidência , Fatores de Risco
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