Regular Statin Use Research Articles

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.

Statin use in resected, high-risk cutaneous melanoma: A multi-centre retrospective cohort study

BackgroundPre-clinical and clinical studies propose that statins may have chemopreventive effects against cancer, suggesting their possible roles as adjunctive therapies for melanoma. ObjectiveTo investigate the association between regular statin use and disease recurrence in patients with resected Stage I-III melanoma. MethodsWe conducted a retrospective analysis of patients enrolled in the multi-center Melanoma Research Victoria cohort with a histologically confirmed, resected American Joint Committee on Cancer Stage I-III cutaneous melanoma. Patients with uveal melanoma, melanoma of unknown primary site, or mucosal melanoma were excluded. Melanoma recurrence outcomes were compared between statin users and statin non-users, with statin use determined by linkage to the Pharmaceutical Benefits Scheme (Australia) prescription database. Results624 patients with resected Stage I-III melanoma at diagnosis were eligible for the study. 193 patients were classified as statin users and 431 patients as statin non-users. In all, 45 statin users experienced disease recurrence compared to 140 (23.3 vs 32.5%, p = 0.05) statin non-users with similar durations of follow-up (median 2.2 and 2.4 years, respectively). After adjustment, statin users had a lower risk melanoma recurrence than statin non-users (HR 0.66, 95%CI 0.44–0.99, p = 0.04). A lower risk of recurrence was also observed in subset analyzes of statin users on high-dose therapy (HR 0.50, 95%CI 0.25–0.99, p = 0.05) and patients who were adherent to statin therapy (HR 0.60, 95%CI 0.39–0.92, p = 0.02). ConclusionOur study supports the possibility that an association exists between statin use and reduced disease recurrence in resected cutaneous melanoma.

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed. To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population. This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023. Regular statin use. Primary outcomes were liver disease and HCC development as well as liver-associated death. A total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02). This cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

Association between statin use and the risk of gout in patients with hyperlipidemia: A population-based cohort study.

Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia. Methods: In this population-based retrospective cohort study, patients ≥20years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models. Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90-1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84-1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of >720 (aHR, 0.57; 95% CI, 0.47-0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34-0.67 compared with OLLA use) or a therapy duration of >3years (aHR, 0.76; 95% CI, 0.64-0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37-0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses. Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.

Molecular Epidemiology of Acute Myeloid Leukemia (AML): Novel Association of Clinical Epidemiologic Exposures with Unique Mutation Groups on Exome Sequencing of Leukemia DNA in the Mayo Clinic AML Epidemiology Cohort

Background: Clinical epidemiologic risk factors associated with leukemia development are prevalent, and can be identified in over 90% of AML patients. We previously demonstrated an association of clinical exposures with cytogenetic risk group and outcome after therapy, but the molecular impact of such exposures is unclear, and specifically it is not known whether specific epidemiologic exposures are associated with unique genetic lesions. We therefore performed Exome Sequencing in 98 patients from our clinical epidemiology cohort to determine whether there was an association of clinically relevant AML risk factors and exposures with unique deleterious non-synonymous (nonsyn.) mutations.Methods: The Mayo Clinic AML Epidemiology cohort comprises a highly annotated series of n=295 unselected and consecutive patients diagnosed and treated at Mayo Clinic Florida & Arizona [Cancer Epidemiol 39:1084, 2015]. We obtained AML DNA from remnant diagnostic cytogenetic pellets identified in 98 patients in the cohort, and performed Exome Sequencing [ExSeq] using standard techniques. The ~100 million paired-end 100bp reads from each sample were mapped to human genome build hg19 using BWA-MEM 1. The single nucleotide variants (SNVs) and small INDELs in the exome capture regions were identified using Mayo Clinic in-house developed analytic pipeline GenomeGPS 4.0.1 following Broad GATK 2 variant discovery best practices of alignment, realignment and recalibration, haplotype caller, and multi-sample joint genotyping. The variants passed the GATK's Variant Quality Score Recalibration (VQSR) quality control were kept. Since no patient matched normal were sequenced, SNVs and INDELs were filtered using both germline whole exome and whole genome sequencing of ~1200 Mayo Clinic Biobank samples and the public germline variant databases of 1000 genome project, 6500 individuals sequenced in the exome sequencing project (ESP), and HapMap phase 3. The remaining variants were annotated using ANNOVAR 3, and potential functional variants of non-synonymous, truncating, frame-shift, and splice-sites were used in the statistical association analyses. We evaluated the association of unique mutations occurring in 10 or more patients and in TP53, and also gene categories according to algorithm of Lindsley et al (Blood 125:1367, 2015) with relevant clinical and epidemiology exposures identified in our prior analysis. Risk factors and exposures were compared between patients with and without a mutation in different genes of interest using Fisher's exact test.Results: The read quality was excellent, and results from 97 evaluable samples were included in analysis. Results are noted in Table. We found a strong and significant association of prior history of immunosuppressive therapy (IST) or solid organ transplantation (SOT) with RUNX1 mutation (p=0.0001), and of regular Statin use with ASXL1 mutation (p=0.008). Statin use was also associated with mutations in genes involved in DNA methylation (p=0.036) and in Chromatin Modifier genes (p=0.049). We identified a novel inverse association of obesity - the most prevalent AML risk factor - with spliceosome mutation (p=0.010), and of IST/SOT with mutations in Myeloid Transcription Factors (TF, p=0.015) and Activated Signaling pathways [RAS, FLT3, KIT, CBL, NF1] (p=0.026). We confirm the association of secondary AML [sAML] with spliceosome mutation (p=0.018), observed as expected most strongly for Antecedent Hematologic Disorder (p=0.008, not shown). Other borderline associations (p≤0.10) are noted in Table. We did not identify any association of family history [FHx] of hematologic malignancy or of smoking [TOB] with unique mutations, nor did we identify clinical exposures associated with TP53 mutation.Conclusion: For the first time (apart from sAML) we have identified a unique leukemia genotype associated with some common clinical and epidemiologic exposures. Some mutations groups (Cohesin, TP53) were not associated with any clinical exposures, suggesting alternate mechanisms of leukemogenesis. ExSeq was for the first time successfully performed on archived diagnostic cytogenetic cell pellets, we believe a novel source of leukemia DNA. These results will guide a planned prospective study to determine frequency and mechanism of leukemogenesis after exposures, and development of strategies for prediction of leukemia risk and ultimately prevention. [Display omitted] DisclosuresCerhan:Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering .

Regular Statin Use and Incidence of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.

Endoscopic retrograde cholangiopancreatography is widely utilized to diagnose and treat various pancreaticobiliary diseases, but postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) can be a fatal adverse event. Evidence suggests that statins may exhibit suppressive effects on inflammation in the pancreas. We carried out an observational cohort study to examine the protective effect of statins on PEP. We retrospectively identified consecutive patients who underwent endoscopic retrograde cholangiopancreatography at a tertiary care center in Japan between January 2010 and January 2019. The incidences of PEP were compared between regular and nonregular statin users. Using the multivariable logistic regression model, we examined the association of regular statin use with the incidence of PEP controlling for potential risk factors for PEP. We included 2664 patients (328 regular statin users and 2336 nonregular users). The incidence of PEP did not differ by statin use status (P=0.52): 8.8% in regular statin users and 7.9% in nonregular users. The multivariable-adjusted odds ratio for PEP comparing regular statin use with nonregular use was 1.08 (95% confidence interval, 0.67-1.72; P=0.76). When we examined specific statin types (hydrophilic and lipophilic statins), we consistently observed the null association: 6.8% of 132 hydrophilic statin users and 10% of 196 lipophilic statin users (P=0.74 and 0.27, respectively, compared with nonregular users). Regular statin use was not shown to be protective against PEP. A further investigation is warranted before this medication is tested in prospective randomized trials.

Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer

Statin medications, most commonly prescribed to reduce lipid levels and prevent cardiovascular disease, may be associated with longer survival times of patients with cancer. However, the association of statins with outcomes of patients with pancreatic adenocarcinoma is not clear. We analyzed the association of statin use before a diagnosis of pancreatic cancer with survival times of 648 participants in the Nurses' Health Study and Health Professionals Follow-up Study who were diagnosed with pancreatic adenocarcinoma from 2000 through 2013. We estimated hazard ratios (HRs) for overall mortality using Cox proportional hazards models with adjustment for potential confounders. We assessed the temporal association between prediagnosis statin use and cancer survival by 2-year lag periods to account for a possible latency period between statin use and cancer survival. Regular statin use before diagnosis of pancreatic cancer was associated with modestly prolonged survival compared with nonregular use (adjusted HR, 0.82; 95% CI, 0.69-0.97; P= .02). A 1-month longer median survival was observed in regular statin users compared with nonregular users. Regular statin use within the 2 years prior to cancer diagnosis was most strongly associated with longer survival. We observed no statistically significant effect modification by smoking status, body mass index, diabetes, or cancer stage (all Pinteraction > .53). Regular statin use before diagnosis was similarly associated with survival in the Nurses' Health Study (HR, 0.79; 95% CI, 0.64-0.97) and Health Professionals Follow-up Study (HR, 0.86; 95% CI, 0.63-1.15). Regular statin use before diagnosis of pancreatic cancer was associated with modest increases in survival times in 2 large prospective cohort studies.

Abstract P2-13-03: Statin use and breast cancer survival – a Swedish nationwide study

Abstract Background: A sizeable body of evidence shows that statins can cease proliferation of breast cancer and prevent breast cancer recurrence. Given the epidemiological findings from other Scandinavian populations, we hypothesized that statins may have anticancer effects and therefore reduce cancer-related mortality in a Swedish population. This study investigates the association between both pre- and post diagnostic statin use and breast cancer outcome. Methods: A Swedish nation-wide retrospective cohort study of 20,559 Swedish women diagnosed with breast cancer (July 1st, 2005 through 2008). Dispensed statin medication was identified through the Swedish Prescription Registry. Breast cancer-specific death information was obtained from the national cause-of-death registry until December 31st, 2012. Cox regression models yielded hazard ratios (HR) and 95% confidence intervals (CI) regarding associations between statin use and breast cancer-specific and overall mortality. Results: During follow-up, a total of 4,678 patients died, whereof 2,669 were considered breast cancer-specific deaths. Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer-specific death (HR=0.77 (95%CI 0.63-0.95), P=0.014). When evaluating diabetes patients only (N=545), this association was strengthened (HR=0.63 (95%CI 0.40-0.98), P=0.044). Post diagnostic statin use was in similarity associated with lower risk of breast cancer–related death compared to non-use (HR=0.83 (95%CI 0.75-0.93), P=0.001). Conclusion: This study supports the notion that statin use is protective regarding breast cancer-specific mortality in agreement with previous Scandinavian studies, although less so with British studies. These disparities should be investigated further. Citation Format: Borgquist S, Broberg P, Olsson H. Statin use and breast cancer survival – a Swedish nationwide study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-13-03.

Statin use and pancreatic cancer risk in two prospective cohort studies.

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are common lipid-lowering agents and may reduce the risk of several cancer types including pancreatic cancer. However, the association between statin use and pancreatic cancer risk has not been fully evaluated in prospective studies. We studied the association between statin use and incident pancreatic cancer in 113,059 participants from the prospective Nurses' Health Study and Health Professionals Follow-up Study. Statin use was self-reported via study questionnaires and updated biennially. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of pancreatic cancer were estimated using multivariable Cox proportional hazards models with adjustment for potential confounders. In total, 583 participants developed incident pancreatic cancer during 1.4 million person-years of follow-up. No difference was identified in pancreatic cancer risk for regular versus non-regular statin users (multivariable-adjusted HR 0.98; 95% CI 0.82-1.16). There was no significant heterogeneity in the association of statin use with pancreatic cancer risk between the cohorts. Similarly, longer duration of regular statin use was not associated with decreased risk of pancreatic cancer (Ptrend=0.65). The results remained similar when we examined statin use status at baseline or accounting for 4-year latency period. We observed no statistically significant effect modification for the association of statin use with pancreatic cancer risk by body mass index, smoking status, or diabetes mellitus status (all Pinteraction>0.21). Regular statin use was not associated with pancreatic cancer risk in two large prospective cohort studies in the U.S.

Pharmacoepidemiology of statins in Еast region of Kazakhstan

Objective: To determine frequency, structure of antihyperholesterinemic therapy in the east region of Kazakhstan and compliance of the patients. Material and Methods: The pharmacoepidemiological analysis was carried out on the basis of archival documents (medical history, outpatient cards) of 14 treatment and prevention institutions in Semey city of the East Kazakhstan region. A total of 3458 units of primary material were analyzed. The study included medical documentation of people with the diagnosis of ischemic heart disease, arterial hypertension, arterial atherosclerosis of lower limbs and other chronic diseases, as well as clinically healthy individuals with a study of the content of cholesterol in the blood. To determine adherence, the Moriski-Green test is used. Results: It was revealed that the frequency of prescribing antihypercholesterolemic drugs (statins) in the conditions of Semey city is 80.7% of cases from the number of persons with clinical indications for their use. Atorvastatin (89.7%) prevailed in the structure of antihypercholesterolemic therapy in patients with hypercholesterolemia and clinically manifested atherosclerosis. A low adherence to statin therapy has been revealed, reaching only 46.6% of the number of appointments and decreasing to 39.9% in individuals without clinical manifestations of atherosclerosis. The overall frequency of regular statin use in the group average, taking into account prescriptions and adherence, is 37.6% of the number of people with clinical indications and depends on the clinical diagnosis. Conclusion: It is necessary to implement measures to correct the approaches of doctors to the appointment of antihypercholesterolemic therapy and work with patients aimed at increasing adherence to treatment.

Abstract 3734: Modified dietary inflammatory index and increased number of colonic aberrant crypt foci

Abstract Pro-inflammatory dietary intake has been linked to the development of colorectal cancer (CRC). There is a paucity of data, however, concerning dietary behavior and prevalence of colonic aberrant crypt foci (ACF), an emerging pre-polyp intermediate endpoint thought to be on the pathway to CRC. We assessed this question in a cross-sectional study of 130 patients (mean age = 57.1 yrs) who received colonoscopy at the Colon Cancer Prevention Program at University of Connecticut Health. Typical diet intake was ascertained from the Brief Block Food Frequency Questionnaire, which provided 29 of the 45 food items in the standard Dietary Inflammatory Index (DII). Using advanced chromoendoscopy imaging, ACF were counted by an endoscopist and external reviewer for consensus. In bivariate analyses between ACF quartiles and mean number of daily servings in four food groups, using the Kruskal-Wallis Non-Parametric test, we found evidence of an inverse dose response with reduced intake of grains (3.9, 3.6, 3.1, 2.7, mean servings per ACF quartile, respectively, p = 0.06) and fruit (1.4, 1.2, 1.0, 1.1, mean servings per ACF quartile, respectively, p = 0.06). We observed little variation in vegetable or dairy intake across ACF quartiles. The association between the modified DII (mod-DII) and ACF number (continuous) was assessed using latent variable modeling controlling for continuous variables of age and waist-hip ratio, and, categorical variables of sex, regular aspirin use (≥ 1 pill per week in past 12 months), regular statin use (≥ 1 pill per week in past 12 months), cigarette smoking (ever, never), polyp history (yes, no) and education level. The final model had a good fit (CFI = 0.92, RMSEA&amp;lt;0.05), and showed statistically significant direct associations between ACF number and both increasing mod-DII score (β = 0.18) and ever having smoked cigarettes (β = 0.19). No significant effects were found between ACF number and the remaining variables in the model. In summary, these cross-sectional findings support the growing evidence base about the adverse impact of an overall pro-inflammatory diet in CRC development and potential value of ACF as intermediate endpoints in research. A limitation of this study is lack of information on physical activity, a lifestyle behavior known to reduce CRC risk presumably through anti-inflammatory effects. More research is warranted to explore possible mitigating effects of physical activity, and other factors known to have pro- or anti-inflammatory properties, in the context of inflammation-based classification of diet. Citation Format: Helen Swede, Masteneh Sharafi, Rong Wu, Valerie B. Duffy, Daniel W. Rosenberg, David A. Drew, Thomas Devers, Richard G. Stevens. Modified dietary inflammatory index and increased number of colonic aberrant crypt foci. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3734. doi:10.1158/1538-7445.AM2015-3734

Statin use and thyroid cancer: a population-based case-control study.

Several observational studies raised the possibility that the use of statins may decrease the overall risk of cancer and of specific cancers. This study aimed to evaluate the association of statin use with thyroid cancer based on a population-based data set. The data for this case-control study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 500 subjects with thyroid cancer as cases and 2500 gender- and age-matched subjects without thyroid cancer as controls. We used a conditional logistic regression to calculate the odds ratio (OR) and its corresponding 95% confidence interval (CI) for having previously used statins between cases and controls. The OR of prior statin use for cases was 1.39 (95% CI = 1.08-1.78) compared to controls, and thyroid cancer was significantly associated with previous regular statin use (OR = 1.40, 95% CI = 1.05-1.86). However, thyroid cancer was not significantly associated with previous irregular statin use (OR = 1.35; 95% CI = 0.88-2.07). Furthermore, the significant association between thyroid cancer and previous statin use only existed for females (OR: 1.43; 95% CI: 1.07-1.90) but not for males (OR: 1.28; 95% CI: 0.75-2.17). We concluded that statin use was associated with thyroid cancer in female patients.

Association between statin use and Bell's palsy: a population-based study.

Several reports mention that statin (HMG-CoA reductase inhibitor) use seems to be associated with several neurologic disorders and that the lipid-lowering effect of statins may contribute to some neural toxicity. This study aimed to evaluate the association between statin use and Bell's palsy using a population-based health insurance database. This case-control study identified 1,977 subjects with Bell's palsy as cases and 5,931 sex- and age-matched subjects without Bell's palsy as controls from the Taiwan Longitudinal Health Insurance Database 2000. Conditional logistic regressions was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for previous use of statins between the cases and controls. The associations of regular and irregular statin users with Bell's palsy were further analyzed. By Chi-square test, there was a significant difference in the prevalence of statin use between cases and controls (23.2 vs. 16.4%, p < 0.001). Conditional logistic regression analysis revealed that after adjusting for diabetes mellitus, hypertension, and hyperlipidemia, the OR for prior statin use was 1.47 (95% CI 1.28-1.69) for cases compared with controls. Bell's palsy was significantly associated with previous regular statin use (≥60 days within 6 months) (adjusted OR: 1.46, 95% CI 1.28-1.67). However, there was no increased adjusted OR of irregular statin use (<60 days within 6 months) for cases compared with controls (OR: 1.09, 95% CI 0.82-1.46). Our present data suggest a potential association between regular statin use and Bell's palsy.

Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases

Objective To evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention.Design Eight population based cohort studies and...

Effects of statins on incident dementia in patients with type 2 DM: a population-based retrospective cohort study in Taiwan.

BackgroundPatients with Type 2 diabetes (T2DM) are prone to develop dementia. Results from a recent study indicated that statin users had lower chance of developing incident dementia. However there is little information on the potential benefits of statin use on dementia in patients with T2DM cohort.MethodA population-based retrospective study using a nationwide cohort of National Health Insurance Research Database in Taiwan was performed. T2DM cohort with regular use of statins was followed up to 8 years. Multivariate cox-proportional hazards regression model was used to estimate the association between statin use and incidence of dementia including Alzheimer's disease and non-Alzheimer dementia after adjusting for several potential confounders.ResultsAmong 28,321 patients diagnosed with T2DM age above 50 and without history of dementia before 2000/1/1, 15,770 patients who had never used statin and 2,400 patients who regularly used statin drugs were enrolled. After adjusting for age group, gender, CCI (Charlson-Deyo comorbidity index) group, stroke types and anti-diabetic drugs, regular statin use was associated with a decreased risk of developing incident Alzheimer's disease dementia (adjusted HR: 0.48, 95% CI 0.30 – 0.76, p<0.001), but not in non-Alzheimer dementia (adjusted HR: 1.07, 95% CI 0.54–2.12 p = 0.844) in patients with T2DM. Further analysis showed significant protective effects of the use of atorvastatin and simvastatin.ConclusionRegular use of statins might decrease the risk of developing Alzheimer's disease in patients with T2DM while no benefit was observed in non-Alzheimer dementia. Among statins, both atorvastatin and simvastatin showed significant benefits.

Statin Use Is Associated With Reduced Risk of Histologic Subtypes of Esophageal Cancer: A Nested Case-Control Analysis

Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups.

The Differential Effects of Statins on the Risk of Developing Pancreatic Cancer: A Case–Control Study in Two Centres in the United Kingdom

There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes. A matched case-control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants' medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes. Two hundred fifty-two cases (median age 71 years, range 48-73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p = 0.80), with no gender effects. In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

Regular statin users and colorectal cancer (CRC) prognosis.

3554 Background: Statins are frequently used for the control of hyperlipidemia. Statins have multiple anti-cancer properties and may be associated with lower CRC risks among their users. This study tries to go a step further and explores whether statin use affects the prognosis of curatively resected CRC. Methods: We established a population cohort with patients (age ≥ 40 y) who were diagnosed as having stage I or II CRC from 2004 to 2008 and received curative surgery from the database of Taiwan Cancer Registry. Data of medication prescription and co-morbidities were retrieved from the database of National Health Insurance, Taiwan. Regular statin use was defined as taking statins for &gt; 180 days within the observation period from one year before the cancer diagnosis to one year afterward. The database of National Death Registry was used for survival outcomes. Another similar cohort consisting of patients with hepatocellular carcinoma (HCC) was used for comparison. Results: In total, 10762 patients with CRC were enrolled; 891 (8%) patients were regular stain users, 812 (8%) patients took statins but were not regular users, and 9059 (84%) patients never used statins. Regular statin users, compared to never users, were more likely to be female (p &lt; 0.001), older (p &lt; 0.001), have stage I disease (p &lt; 0.001) and co-morbidities such as diabetes, coronary artery disease, and renal disease. Adjuvant therapy was less frequently administered in regular statin users. In univariate analysis, cancer-specific survival (CSS) of regular stating users was significantly longer than that of never users (5-y CSS, 87% vs. 84%, p = 0.022), but overall survival (OS) was not significantly different (5-y OS, 80% vs. 77%, p = 0.156). In multivariate analysis adjusting for age, gender, stage, adjuvant therapy, co-morbidities, and the use of aspirin, regular stating use was an independent predictor both for better CSS (hazard ratio [HR] 0.72, p &lt; 0.001) and for better OS (HR 0.71, p&lt; 0.001). In contrast, no associations were found between statin use and CSS or OS in the HCC comparison cohort. Conclusions: Regular statin use was associated with better prognosis in CRC patients who received curative therapy. (This study was supported by grants DOH-101-TD-B-111-001 and DOH-102-TD-B-111-001).

Regular statin and aspirin use in patients with Barrett’s oesophagus is associated with a reduced incidence of oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) has a poor prognosis, and chemoprevention is an attractive option to reduce the burden of the disease. Hydroxyl-methyl-CoA reductase inhibitors (statins) have been shown to exert potentially useful anticancer effects against OAC cell lines, but there are only limited clinical data examining the effects of statins on the incidence of OAC. To examine the association between statin use and the incidence of OAC. We have carried out a case-control study comparing statin use between patients with an incident diagnosis of OAC and controls with nonprogressive Barrett's oesophagus. Eighty-five cancer cases were compared with 170 age-matched and sex-matched controls. Risk factors and drug exposure were established using standardized interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. Regular statin use was associated with a significantly lower incidence of OAC [uncorrected odds ratio (OR) 0.45, 95% confidence intervals 0.24-0.84)]. After correction for confounding variables including aspirin and NSAID use, statin use was still associated with a reduced incidence of OAC (OR 0.57, 0.28-0.94). Longer duration of statin use and higher doses were both associated with a significantly greater reduction in OAC. The combination of regular statin and aspirin use was associated with a significantly further reduced incidence of OAC (OR 0.31, 0.04-0.69). In this observational case-control study, the regular use of statins was associated with a reduced incidence of OAC. The chemopreventative actions of statins, especially in conjunction with aspirin, deserve further study.

Statin use and the risk of renal cell carcinoma in 2 prospective US cohorts

Statins are widely used cholesterol-lowering agents that may have potential antitumor effect. Epidemiological studies on statin use and renal cell carcinoma (RCC) risk have been inconsistent. The authors investigated the association between statin use and RCC risk in the Nurses' Health Study and Health Professionals Follow-Up Study. In total, 80,782 women and 37,869 men were followed for 14 years and 16 years, respectively. Regular statin use was assessed at baseline and was updated biennially during follow-up. RCC diagnosis was confirmed by medical record review. Two hundred seventy-seven incident RCC cases (164 women and 113 men) were identified. Compared with no current use, the multivariate relative risks of current statin use were 0.68 (95% confidence interval, 0.46-1.00) in women and 1.17 (95% confidence interval, 0.75-1.82) in men. The results for ever versus never users of statins were similar. No dose-response relation with duration of statin use and RCC risk was observed. On subgroup analyses, statin use was associated with a reduced RCC risk among women who had no history of hypertension. The current study indicated that statin use may be associated with a lower risk of RCC in women, although these results need to be investigated further.