Statin Nonusers Research Articles

The long-term usage of statin prevents adverse events in patients with atrial fibrillation

Abstract Background The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Purpose Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF. Methods This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined. Results We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p < 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p < 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p < 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories. Conclusions Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.

Impaired Renal Function With Higher Remnant Cholesterol Related to Risk of Atherosclerotic Cardiovascular Disease: CGPS.

Chronic kidney disease confers a high risk of atherosclerotic cardiovascular disease (ASCVD), partly due to hyperlipidemia. Although statins reduce the risk of ASCVD in chronic kidney disease, residual risk persists. We investigated whether higher remnant cholesterol is associated with an increased risk of ASCVD in statin users and nonusers with impaired renal function. We included 107 925 individuals from CGPS (Copenhagen General Population Study) initiated in 2003 to 2015, of whom 10 427 had impaired renal function (estimated glomerular filtration rate, <60 mL/min per 1.73 m2). Remnant cholesterol was calculated from a standard lipid profile. ASCVD was myocardial infarction, coronary heart disease death, ischemic stroke, coronary artery bypass graft, or percutaneous coronary intervention extracted from Danish nationwide health registries from baseline through 2018; individuals with events before the start of follow-up were excluded from relevant analysis. In individuals with impaired renal function during up to 15 years of follow-up, 597 were diagnosed with myocardial infarction, 618 with ischemic stroke, and 1182 with ASCVD. In these individuals, a 1-mmol/L (39 mg/dL) higher remnant cholesterol level was associated with multivariable-adjusted hazard ratios of 1.21 (95% CI, 1.03-1.43) for myocardial infarction, 1.12 (95% CI, 0.93-1.34) for ischemic stroke, and 1.19 (95% CI, 1.05-1.35) for ASCVD. Corresponding hazard ratios for ASCVD were 1.36 (95% CI, 1.01-1.81) in statin users and 1.16 (95% CI, 1.01-1.33) in nonusers. Of the 1.36-fold excess risk of ASCVD in impaired versus normal renal function, elevated remnant cholesterol and elevated LDL (low-density lipoprotein) cholesterol explained 25% (95% CI, 2.5%-47%) and 0% in statin users and 8.3% (95% CI, 2.4%-14%) and 14% (95% CI, 6.4%-22%) in nonusers, respectively. Our results suggest that higher remnant cholesterol is a good marker of increased risk of ASCVD in individuals with impaired renal function, while higher LDL cholesterol may not be. Patients with chronic kidney disease who have high levels of remnant cholesterol are identifiable through higher non-HDL (high-density lipoprotein) cholesterol or apoB levels.

Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.

To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%). Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.

Relationships between APOE, Type 2 Diabetes, and Cardiovascular Disease in Postmenopausal Women.

The Apolipoprotein E (APOE) ε4 allele, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) are well-established risk factors for dementia. Relationships between APOE and incidence of T2DM and CVD are not fully understood but may shed light on the mechanisms underlying dementia pathogenesis. Postmenopausal women (N=6,795) from the Women's Health Initiative hormone therapy clinical trial with APOE genotyping and no prior diagnosis of T2DM or CVD were included. We examined associations of APOE status (APOE2+ [ε2/ε2, ε2/ε3], APOE3 [ε3/ε3], and APOE4+ [ε4/ε4, ε3/ε4] carriers) with incidence of T2DM, coronary heart disease (CHD), stroke, and total CVD events using Cox regression. CVD outcomes were examined in baseline non-statin users and adjusted for statin initiation over follow-up to account for possible confounding by statins. Among all participants (mean age 66.7±6.5 years, 100% non-Hispanic white), 451 (6.6%) were using statins at baseline. Over the follow-up (mean 14.9 and 16.0 years for T2DM and CVD, respectively), 1,564 participants developed T2DM and 1,578 developed CVD. T2DM incidence did not differ significantly by APOE status (ps≥0.09). Among non-statin users, APOE4+ had higher incidence of total CVD (hazard ratio [95% confidence interval]=1.18 [1.02-1.38], p=0.03) compared to APOE3 carriers, but risks for CHD (1.09 [0.87-1.36], p=0.47) and stroke (1.14 [0.91-1.44], p=0.27) were not significantly elevated when examined individually. CVD outcomes did not differ between APOE2+ and APOE3 carriers (ps≥0.11). T2DM risk did not differ by APOE status among postmenopausal women, but APOE4+ carriers not using statins had an increased risk of total CVD events.

Cardiovascular effectiveness of newer glucose-lowering agents, with and without baseline lipid-lowering therapy in type 2 diabetes: A systematic meta-analysis of cardiovascular outcome trials and real-world evidence

BackgroundWhether the cardiovascular treatment benefits of sodium–glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by baseline use of statins/lipid lowering therapy is unclear. This systematic review and meta-analysis investigated whether baseline statin use (users vs non-users) influences the cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs in patients with type 2 diabetes (T2D). MethodsWe identified relevant cardiovascular outcome trials (CVOTs) and observational cohort studies from MEDLINE, Embase, the Cochrane Library, and bibliographic searches up to March 2024. The analysis pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for outcomes, categorized by baseline statin use status. We also assessed the interactions between these medications and baseline statin use by calculating and pooling the ratio of HRs (RHRs) within each trial. ResultsTwenty-five articles (13 articles comprising 6 unique CVOTs and 12 articles comprising 9 unique cohort studies) were eligible. In CVOTs of SGLT-2is, the HRs (95% CIs) of MACE; composite of CVD death or hospitalisation for heart failure; stroke; and kidney events in statin users were 0.90 (0.82-1.00), 0.78 (0.60-1.02), 1.00 (0.77-1.31), and 0.60 (0.53-0.69), respectively. The corresponding estimates were similar in non-statin users. In CVOTs of GLP-1RAs, the HRs (95% CIs) for MACE in statin and non-statin users were 0.81 (0.73-0.90) and 0.92 (0.77-1.11), respectively. In observational cohort studies, SGLT-2is similarly reduced the risk of several cardiovascular and kidney outcomes in both statin and non-statin users. The estimated RHRs and p-values for interaction indicated that baseline statin use status did not significantly modify the cardio-kidney benefits of SGLT-2is and GLP-1RAs. ConclusionsAggregate analyses of intervention and real-world evidence show that SGLT-2is and GLP-1RAs provide comparable cardio-kidney benefits in patients with T2D, regardless of baseline statin use status.PROSPERO Registration: CRD42024498939

Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry

ObjectiveTo evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).DesignObservational cohort analysis based on a...

COPD Pathogenesis and Alterations in the Oral, Lung, and Gut Microbiomes

Chronic obstructive pulmonary disease (COPD) is a respiratory and systemic disease affecting more than 300 million people globally every year, and it also becomes a substantial economic burden. COPD is commonly comorbid with various underlying diseases such as cancer, cardiovascular diseases, cerebrovascular diseases, diabetes mellitus, osteoporosis, etc. It has been shown that statins can improve a significant decline in pulmonary function among COPD patients due to their pleiomorphic effect. Some systematic reviews also reported that statins reduced the risk of COPD-related events such as cancer and cardiovascular events, eventually resulting in more favorable outcomes than for non-statin user COPD patients. However, the physiological mechanism is still elucidated. Recently, it has been reported that statins influence the gut microbial composition with increased relative abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii and act with pleiomorphic effects such as anti-inflammatory and anti-cancer effects through modulating gut dysbiosis. We described this review to focus on whether statins can be a useful preventive option for COPD.

Statin use associated with a reduced risk of hip fracture in patients with gout

Studies show that statins users are at reduced risk of fracture and improved bone mineral density. However, the clinical effectiveness of statin use in patients with gout has not been investigated. This retrospective cohort study used data from Taiwan's National Health Insurance Research Database, consisting of 3443 patients with gout using statins aged 50 years and above and 6886 gout patients of non-statin users matched by sex, age and propensity score. The Cox proportional hazards regression analysis showed that statin use was associated with a reduced risk of hip fracture (adjusted hazard ratio [aHR] = 0.78, 95 % confidence interval [CI] = 0.64–0.94) after controlling for potential confounding factors. The association was significant in both genders aged 50–64 years, with aHRs of near 0.35, but not in the elderly. In addition, women aged 50–64 years who used statins also exhibited a lower risk of vertebral fracture (aHR = 0.70, 95 % CI = 0.50–0.99), but not men. In conclusion, the stating use in gout patients could reduce fracture risk for younger patients. Further research is warranted to confirm these findings.

Statin use and development and progression of non-alcohol fatty liver disease based on ultrasonography: a cohort study.

Non-alcohol fatty liver disease (NAFLD) has emerged as a public health issue, while no drugs have been specifically approved for treatment. This study aimed to examine the association between statin use and NAFLD occurrence, progression, and regression. A cohort study was designed based on the Kailuan Study and electronic medical records (EMRs) from the Kailuan General Hospital. Participants aged 18 years with statin indication, including statin and non-statin users, were enrolled in 2010-2017. Propensity score-matched cohorts were also used. In the entire cohort, 21 229 non-NAFLD and 22 419 NAFLD patients (including 12 818 mild NAFLD) were included in the final analysis. After a median follow-up of about four years, the incidence of NAFLD occurrence and progression for statin users were lower than those for non-statin users (occurrence: 84.7 vs. 106.5/1000 person-years; progression: 60.7 vs. 75.5/1000 person-years). Compared with non-statin users, the risk of NAFLD occurrence (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.70-0.87) and regression (HR [95%CI], 0.71[0.60-0.84]) was decreased in statin users. The significantly negative association was only observed in those with cumulative statin duration ≥ 2 years (HR [95%CI] for occurrence 0.56 [0.46-0.69] vs. 0.52 [0.30-0.90] for progression) and those with low or moderate ASCVD-risk (HR [95%CI] for occurrence 0.74 [0.66-0.82] vs. 0.68 [0.57-0.80] for progression). No significant correlation was observed between statin use, statin use duration, and NAFLD regression. The PS-matched cohort had similar results. Taking statin may decrease the risk of NAFLD occurrence and progression in the population with statin indication, suggesting the potential role of statin in both primary and secondary prevention strategies for NAFLD, especially among those with low or moderate ASCVD risk.

PCSK9 inhibitors in real life-Cardiometabolic risk management in dyslipidemic patients in Vienna.

Proprotein convertase subtilisin kexin type9 (PCSK9) inhibitors have emerged as important therapeutic options for patients unable to achieve the low-density lipoprotein cholesterol (LDL‑C) target or to tolerate alternative lipid-lowering agents. The aim of this study was to investigate the efficacy of PCSK9 inhibitor treatment in tertiary routine care, by determining the percentage of patients reaching individual LDL‑C target levels 1 year after treatment initiation. Patients routinely started on PCSK9 inhibitors at our lipid clinic between 2017 and 2020 were retrospectively analyzed. Attainment of the LDL‑C target, utilization of follow-ups, cardiovascular events and effects on laboratory parameters were investigated. In this study 347 patients were included, with the majority managed in secondary prevention (94.5%). The LDL‑C target was achieved by 44.9% after ca. 14months, with differences between statin users and non-users (51.0% vs. 22.7%; p < 0.001). The median LDL‑C decreased from 126.00 mg/dL at baseline to 48 mg/dL (-61.6%; -77.00 mg/dL; p < 0.001) after ~2months and to 60 mg/dL (-52.9%; -59.00 mg/dL; p < 0.001) after ~14months. Median lipoprotein(a) levels decreased significantly from 184.0 nmol/L to 165.5 nmol/L (-25.9%; -25.5 nmol/L; p = 0.001) after ~2months, whereas no effects on creatine kinase, amylase and lipase were detectable. Of the patients 15% utilized 4follow-ups. The PCSK9 inhibitor intolerance occurred in 3.5% of patients. With the effect of LDL-lowering remaining constant over 14months, PCSK9 inhibitor treatment showed effective and sustainable LDL‑C lowering in amajority of patients in secondary prevention, bringing them closer to the recommended LDL‑C goal, particularly those under concomitant statin medication. Treatment with PCSK9 inhibitors appears to be well-tolerated, confirming data from clinical trials in real life.

Statin Use and the Progression of Coronary Artery Calcification in CKD: Findings From the KNOW-CKD Study

IntroductionStatin treatment can reduce the risk of cardiovascular disease (CVD). Paradoxically, previous studies have shown that the use of statin is associated with the progression CAC (coronary artery calcification), a well-known predictor of CVD, in individuals with preserved renal function or in patients on dialysis. However, little is known about the association in predialysis CKD (chronic kidney disease) patients. The aim of this study was to characterize the relationship between statin use and progression of CAC in a CKD cohort of Korean adults. MethodsWe analyzed 1,177 participants registered in the KNOW-CKD cohort. Coronary artery calcium score (CACS) was assessed using cardiac computed tomography at baseline and four years after enrollment. CAC progression was defined using the Sevrukov method. Statin users were defined as those who used statins for 50% or more of the follow-up period. ResultsThe median [interquartile range] of CACS was 0 [0-30.33], and 318 (44.2%) participants had CACS above 0 at baseline. There were 447 (38.0%) statin users and 730 (62.0%) statin non-users. After four years, 374 (52.0%) patients demonstrated CAC progression, which was significantly more frequent in statin users than in statin non-users (218 [58.3%] vs. 156 [41.7%], P<0.001). The multivariate-adjusted odds ratio for CAC progression in statin users compared to statin non-users was 1.78 (1.26-2.50). ConclusionStatin use significantly and independently is associated with CAC progression in Korean predialysis CKD patients. Further research is warranted to verify the prognosis of statin-related CAC progression.

A Systematic Review of Existing Data on Statin Use and New-Onset Type 2 Diabetes: The Need for Clear Answers

Background: The relationship between statins use and the development of new-onset type 2 diabetes mellitus (NOT2DM) has been a subject of ongoing debate and investigation. In February 2012, the Food and Drug Administration (FDA) disclosed that statin use could lead to a modest rise in glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), potentially contributing to the development of diabetes. We systematically reviewed the available evidence and summarized the impact of statin use on NOT2DM. Aim: This systematic review aims to examine and provide a comprehensive overview of existing data relating to statin use and their association with the development of new-onset type 2 diabetes (NOT2DM). The primary objectives were to assess and explore: (1) the potential association between statin use and the development of new-onset diabetes; (2) the magnitude, extent, and incidence of new-onset diabetes due to statin use. The secondary objective was to explore the underlying mechanisms. Data Sources: PubMed, Scopus, Science Direct, Wiley, and Google Scholar and databases between January 2012 and February 2021. Data Extraction: The 2 reviewers Musa Basheer Mansour and Sara Elsheikh Ahmedana [MBM and SEA] independently assessed the qualities of the extracted studies and summarized data of the selected studies in tabulated forms for outcomes of interest and performed methodological and quality assessments based on review questions, citations, country of the study, aim, population characteristics, design, setting, sample size, sample technique, data source, measures, analysis, confounder variable and key observations for systematic review. We applied search keywords such as Statins, New-onset diabetes, Diabetes mellitus, Underlying mechanism, and incidents of diabetes. Results: A total of 66 studies were identified through database searches in the initial search, and 7 studies were included in this review. Of the 2,567,888 adult patients, 861,925 were nondiabetic patients on statin use, and 1,705,963 were diabetic on statin or non-statin users. We considered Hazard Ratios (HR), Odds Ratios (OR), and Confidence Intervals (CI) of each study for further analysis. The mean OR for three studies showed that each statin therapy resulted in a 68% increased risk of NOT2DM (OR, 1.683; 95% CI: 1.273-2.237). The significant relationship between statin use and the rising risk of NOT2DM was also confirmed by an average HR of 1.53 (95% CI: 1.2-1.7) for the remaining four studies. Recent and short-term use of statins, as well as time- and dose-dependent connections, were linked to an increased risk of NOT2DM in statin users compared to non-users. These risks were more prominent among older adults, normotensive males, hypertensive females, and individuals with low physical activity. Although no proven mechanisms were found, the possible processes are discussed. Conclusion: The systematic review found a significant level of risk of NOT2DM associated with statin use. The authors argued that the short-term diabetes risk caused by statin treatment was more prevalent among patients exposed to risk factors for diabetes. Although the precise mechanisms behind this association remain unclear, this research provides clinical practice with evidence-based guidelines. Additionally, conducting future research may be appropriate based on the gaps in knowledge identified from the results of this review.

Association of statin use with risk of depression and anxiety: A prospective large cohort study

ObjectivesTo examine associations between regular statin use and the incidence of depression and anxiety. MethodsThis cohort was based on UK Biobank participants without depression/anxiety recruited between 2006 and 2010. The self-reported regular statin use was collected at baseline. Depression and anxiety outcomes were assessed by diagnostic interviews (international classification of diseases codes) and nondiagnostic scales (mental well-being questionnaires). Cox proportional hazards models adjusted for a wide range of confounders were used to estimate associations of statins with incident depression/anxiety. ResultsAmong 363,551 eligible participants, 55,838 reported regular statin use. During a 13-year follow-up, 14,765 cases of depression and 15,494 cases of anxiety were identified. Compared with non-statin users, statin use was associated with reduced risk of depression (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81, 0.94) and anxiety (HR: 0.90, 95% CI: 0.84, 0.97). Effects of statins on depression were consistent in sensitivity analyses and may be less influenced by unmeasured confounders. However, results of online survey data showed that statin use might not be associated with incident anxiety (HR: 0.96, 95% CI: 0.85, 1.09). ConclusionRegular statin use was associated with a lower risk of depression. No clear associations between statin use and anxiety were found.

A Systematic Review of Existing Data on Statin Use and New - Onset Type 2 Diabetes: The Need for Clear Answers

Background: The relationship between statins use and the development of new-onset type 2 diabetes mellitus (NOT2DM) has been a subject of ongoing debate and investigation. In February 2012, the Food and Drug Administration (FDA) disclosed that statin use could lead to a modest rise in glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), potentially contributing to the development of diabetes. We systematically reviewed the available evidence and summarized the impact of statin use on NOT2DM. Aims and Objectives: This systematic review aims to examine and provide a comprehensive overview of existing data relating to statin use and their association with the development of new-onset type 2 diabetes (NOT2DM). The primary objectives were to assess and explore: (1) the potential association between statin use and the development of new-onset diabetes; (2) the magnitude, extent, and incidence of new-onset diabetes due to statin use. The secondary objective was to explore the underlying mechanisms. Data Sources: PubMed, Scopus, Science Direct, Wiley, and Google Scholar and databases between January 2012 and February 2021. Data Extraction: The 2 reviewers Musa Basheer Mansour and Sara Elsheikh Ahmedana [MBM and SEA] independently assessed the qualities of the extracted studies and summarized data of the selected studies in tabulated forms for outcomes of interest and performed methodological and quality assessments based on review questions, citations, country of the study, aim, population characteristics, design, setting, sample size, sample technique, data source, measures, analysis, confounder variable and key observations for systematic review. We applied search keywords such as Statins, New-onset diabetes, Diabetes mellitus, Underlying mechanism, and incidents of diabetes. Results: A total of 66 studies were identified through database searches in the initial search, and 7 studies were included in this review. Of the 2,567,888 adult patients, 861,925 were nondiabetic patients on statin use, and 1,705,963 were diabetic on statin or non-statin users. We considered Hazard Ratios (HR), Odds Ratios (OR), and Confidence Intervals (CI) of each study for further analysis. The mean OR for three studies showed that each statin therapy resulted in a 68% increased risk of NOT2DM (OR, 1.683; 95% CI: 1.273-2.237). The significant relationship between statin use and the rising risk of NOT2DM was also confirmed by an average HR of 1.53 (95% CI: 1.2-1.7) for the remaining four studies. Recent and short-term use of statins, as well as time- and dose-dependent connections, were linked to an increased risk of NOT2DM in statin users compared to non-users. These risks were more prominent among older adults, normotensive males, hypertensive females, and individuals with low physical activity. Although no proven mechanisms were found, the possible processes are discussed. Conclusion: The systematic review found a significant level of risk of NOT2DM associated with statin use. The authors argued that the short-term diabetes risk caused by statin treatment was more prevalent among patients exposed to risk factors for diabetes. Although the precise mechanisms behind this association remain unclear, this research provides clinical practice with evidence-based guidelines. Additionally, conducting future research may be appropriate based on the gaps in knowledge identified from the results of this review.

The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.

Redox-state-regulating enzymes have prognostic value in diabetic endometrial cancer patients: impact of statin use?

The incidence of endometrial cancer is increasing, and oxidative stress has been suggested to play a vital role in its carcinogenesis. Statins have an impact on the cellular redox-state. The aim of this study was to determine the effects of statin use on redox-state regulating enzymes in endometrial cancer in women with type 2 diabetes. This retrospective study consisted of 119 women with type 2 diabetes who were diagnosed with endometrial cancer at Oulu University Hospital in Finland between 2007 and 2014. There were 58 statin users and 61 non-users based on medication use at the time of endometrial cancer diagnosis. The expression of redox-state regulating proteins nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in the tumor samples was assessed immunohistochemically, and manganese superoxide dismutase (MnSOD) levels were measured both immunohistochemically and from serum samples. High MnSOD expression predicted better progression-free survival (PFS) in statin non-users in a univariate analysis (p=0.02). There was no statistical difference in overall survival (OS) or PFS between strong and weak expression of Nrf2 and Keap1. After adjusting for stage and statin use, the results were similar. Statin non-users with strong MnSOD expression had better PFS compared to statin users which proves that statins have impact on redox-state regulating enzymes. However, these findings are preliminary and require further research.

Meniere's Disease and Statins: Is There an Association? A Single Institution Study.

Meniere's disease (MD) is a complex inner ear disease related to endolymphatic hydrops and with multiple other etiologies suggested including autoimmunity and vascular insufficiency. Statins are lipid-lowering medications with additional effects including reduction of oxidative stress and inflammation. We performed a cross-sectional study comparing patients with MD on statins to those not on statins to see if there is any difference in disease activity (major vertigo spells) and hearing stage utilizing linear and logistic regression. Our analysis showed no difference in the average number of major vertigo spells per month (β = .07, P = .9) between statin users and nonusers; however, statin users were found to have lower odds of worse hearing (odds ratio = 0.46, P = .047). Further studies are needed to confirm our results.

Association between obesity and statin use on mortality and hospital encounters in atrial fibrillation

BackgroundObesity increases risk of atrial fibrillation (AF) at least in part due to pro-inflammatory effects, but has been paradoxically associated with improved mortality. Although statins have pleiotropic anti-inflammatory properties, their interaction with obesity and clinical outcomes in AF is unknown. We explored the relationship between BMI, statin use, and all-cause mortality and AF/congestive heart failure (CHF)-related encounters, hypothesizing that statin exposure may be differentially associated with improved outcomes in overweight/obesity. MethodsThis was a single center retrospective cohort study of adults with AF diagnosed between 2011–2018. Patients were grouped by body mass index (BMI) and statin use at time of AF diagnosis. Outcomes included all-cause mortality and ED or inpatient encounters for AF or CHF. Results and ConclusionsA total of 2503 subjects were included (median age 66 years, 43.4 % female, median BMI 29.8 kg/m2, 54.6 % on baseline statin therapy). Increasing BMI was associated with decreased mortality hazard but not associated with AF/CHF encounter risk. Adjusting for statin-BMI interaction, demographics, and cardiovascular comorbidities, overweight non-statin users experienced improved mortality (adjusted hazard ratio [aHR] 0.55, 95 % CI 0.35–0.84) compared to statin users (aHR 0.98, 95 % CI 0.69–1.40; interaction P-value = 0.013). Mortality hazard was consistently lower in obese non-statin users than in statin users, however interaction was insignificant. No significant BMI-statin interactions were observed in AF/CHF encounter risk. In summary, statin use was not differentially associated with improved mortality or hospitalization risk in overweight/obese groups. These findings do not support statins for secondary prevention of adverse outcomes based on overweight/obesity status alone.

Statin use is associated with a lower risk of all-cause death in patients with breast cancer treated with anthracycline containing regimens: a global federated health database analysis

Anthracyclines are associated with enhanced oxidative stress responsible for adverse events in patients with breast cancer. However, no study has investigated the potential anti-inflammatory role of statins in counteracting anthracycline toxicity. In this retrospective study utilizing a federated health network (TriNetX), patients with breast cancer (ICD code C50) treated with anthracyclines were categorized into two groups: statin users (for at least 6 months); and statin non-users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the risk of myocardial infarction, stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). We identified 3,701 statin users (68.8 ± 10.4 years) and 37,185 statin non-users (59.6 ± 12.8 years). After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.82, 95% CI 0.74–0.91) compared to statins non-users. Analyzing the risk for secondary outcomes, only the risk of stroke was significantly increased in statin users (HR 1.27, 95% CI 1.01–1.61), while no associations were found for the other cardiovascular events. The risk of all-cause death in statin users was the lowest during the first year after the anthracycline’s initiation. No significant difference was found between lipophilic and hydrophilic statins. In patients with breast cancer treated with anthracyclines, statin use is associated with a reduced risk of all-cause death. Prospective studies are needed to investigate the potential beneficial effect of statin initiation in cancer patients without other indications.

Effect modification by statin use status on the association between fine particulate matter (PM2.5) and cardiovascular mortality.

Numerous studies have linked fine particulate matter (PM2.5) to increased cardiovascular mortality. Less is known how the PM2.5-cardiovascular mortality association varies by use of cardiovascular medications. This study sought to quantify effect modification by statin use status on the associations between long-term exposure to PM2.5 and mortality from any cardiovascular cause, coronary heart disease (CHD), and stroke. In this nested case-control study, we followed 1.2 million community-dwelling adults aged ≥66 years who lived in Ontario, Canada from 2000 through 2018. Cases were patients who died from the three causes. Each case was individually matched to up to 30 randomly selected controls using incidence density sampling. Conditional logistic regression models were used to estimate odds ratios (ORs) for the associations between PM2.5 and mortality. We evaluated the presence of effect modification considering both multiplicative (ratio of ORs) and additive scales (the relative excess risk due to interaction, RERI). Exposure to PM2.5 increased the risks for cardiovascular, CHD, and stroke mortality. For all three causes of death, compared with statin users, stronger PM2.5-mortality associations were observed among non-users [e.g. for cardiovascular mortality corresponding to each interquartile range increase in PM2.5, OR = 1.042 (95% CI, 1.032-1.053) vs OR = 1.009 (95% CI, 0.996-1.022) in users, ratio of ORs = 1.033 (95% CI, 1.019-1.047), RERI = 0.039 (95% CI, 0.025-0.050)]. Among users, partially adherent users exhibited a higher risk of PM2.5-associated mortality than fully adherent users. The associations of chronic exposure to PM2.5 with cardiovascular and CHD mortality were stronger among statin non-users compared to users.