Long-term Statin Use Research Articles

Long-term statin use reduces pancreatic cancer risk in men

Long-term statin use reduces pancreatic cancer risk in men

Statin therapy and Vitamin D

Background: Statins are well-known drugs used in dyslipidemia and cardiac disorders since several years. Recently, it has been reported that long-term use of statins reduce serum vitamin D level. When statins are administered to patients with low vitamin D more muscular side effects have been reported. On the contrary, a few studies report that statins might increase vitamin D level competing with its metabolism. Hence, this study was conducted to evaluate the association between statins and vitamin D. Methods: 125 participants who fulfilled the selection criteria were enrolled in the study. 65 subjects belonged to control group and 60, statin group. The blood sample was collected for Vitamin D estimation. The results were correlated with a demographic profile, nature of statin and the muscular side effects and compared with control group. Results: The mean vitamin D level in statin group was 15.82 ng/ml±11.51 and 20.57 ng/ml±7.007 in the control group. The difference was found to be statistically significant. 13.85% in the control group and 10% in statin group had sufficient vitamin D level. 18.33% and 36.92 % had insufficient levels and 71.67% and 49.23% had a deficiency in the statin and control groups respectively. Myalgia was reported by 30 among 60 subjects (50%) in statin group and 5 among 65 subjects (7.69%) in the control group. Conclusion: The present study has shown that statin therapy is associated with low vitamin D level and that this could contribute to the increased incidence of myalgia in the statin group.

Endothelial dysfunction as a predictor of cardiovascular disease in type 1 diabetes.

Macro and microvascular disease are the main cause of morbi-mortality in type 1 diabetes (T1DM). Although there is a clear association between endothelial dysfunction and atherosclerosis in type 2 diabetes, a cause-effect relationship is less clear in T1DM. Although endothelial dysfunction (ED) precedes atherosclerosis, it is not clear weather, in recent onset T1DM, it may progress to clinical macrovascular disease. Moreover, endothelial dysfunction may either be reversed spontaneously or in response to intensive glycemic control, long-term exercise training and use of statins. Acute, long-term and post-prandial hyperglycemia as well as duration of diabetes and microalbuminuria are all conditions associated with ED in T1DM. The pathogenesis of endothelial dysfunction is closely related to oxidative-stress. NAD(P)H oxidase over activity induces excessive superoxide production inside the mitochondrial oxidative chain of endothelial cells, thus reducing nitric oxide bioavailability and resulting in peroxynitrite formation, a potent oxidant agent. Moreover, oxidative stress also uncouples endothelial nitric oxide synthase, which becomes dysfunctional, inducing formation of superoxide. Other important mechanisms are the activation of both the polyol and protein kinase C pathways as well as the presence of advanced glycation end-products. Future studies are needed to evaluate the potential clinical applicability of endothelial dysfunction as a marker for early vascular complications in T1DM.

Statin use and survival following glioblastoma multiforme

AimWhile some studies indicate a potential chemopreventive effect of statin use on the risk of glioma, the effect of statins on the prognosis of brain tumours has not yet been examined. We thus conducted a cohort study evaluating the influence of statin use on survival in patients with glioblastoma multiforme (GBM). MethodsWe identified 1562 patients diagnosed with GBM during 2000–2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥2 redeemed prescriptions) was matched to two statin non-users (<2 redeemed prescriptions) by propensity scores based on age, gender, year of diagnosis, comorbidity, and use of selected drugs. Cox proportional hazard models were used to compute hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause death associated with prediagnostic statin use. ResultsA total of 339 GBM patients were included in the analyses. Of these, 325 died during median follow-up of 6.9 months (interquartile range: 3.8–13.4 months). Prediagnostic statin use was associated with a reduced HR of death (0.79; 95% CI: 0.63–1.00). The HRs decreased with increasing duration or intensity of prediagnostic statin use [long-term (≥5 years) statin use: HR 0.75 (95% CI: 0.47–1.20); high-intensity statin use: HR 0.66 (95% CI: 0.44–0.98)]. Additional adjustment for oncotherapeutic modalities yielded similar results (overall HR 0.80, 95% CI: 0.63–1.01). ConclusionLong-term prediagnostic statin use may improve survival following GBM.

Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress

Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.

Is there sufficient enhancement of the reduction in CVD rates after a decade of statin therapy to justify continuation?

Randomized, controlled clinical trials have shown significant benefits of statin therapy in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD). But these trials typically enroll patients for only 5years or so, prompting some clinicians to ask what the longer term follow-up of these patients will show. While most trials have a duration of only approximately 5years, four large trials report extended post-trial follow-up to 10years, and these trials, as well as multiple large cohort studies, suggest an expected benefit of statins' effects beyond 10years. In this review we will summarize the current state of the literature, the benefits noted to date, and the potentially accumulating, adverse effects of long-term statin use.

Statin Use in Patients With Acute Pancreatitis and Symptomatic Gallstone Disease

The long-term use of statins may be associated with a decreased risk for gallstones and biliary-induced acute pancreatitis (AP). Our aim was to study the relationship of statin use and outcome of AP. We investigated the records of 461 consecutive patients with AP and 1140 patients with symptomatic gallstones during 2008 to 2010. The use of lipid-lowering drugs, patient's characteristics, and outcome of patients were recorded. All known risk factors for AP and particularly statin use in idiopathic AP were analyzed. Statin use was comparable between the patients with AP (22%) and patients with cholelithiasis (24%). The frequencies of surgical treatment, duration of hospital stay, or mortality were not different between the statin users compared with the nonusers. Idiopathic AP was more often associated with the use of statins than alcohol- or gallstone-induced AP (44% vs 30% vs 13%, P < 0.002). The etiology of AP was alcohol in 56% of the patients, gallstones in 28% of the patients, and unknown (idiopathic) or miscellaneous in 16% of the patients. No beneficial effect of statins was observed in mortality or other outcome parameters of patients with AP. Statin use was more frequent in patients with idiopathic AP than in patients with biliary- or alcohol-induced AP.

HMG CoA Reductase Inhibitor Treatment Induces Dysglycemia in Renal Allograft Recipients

Dysglycemia and dyslipidemia are important metabolic complications of organ transplantation. Statins are widely used to control dyslipidemia; however, long-term use of statins is related to diabetes mellitus (DM) and impaired fasting glucose (IFG). The aim of this study was to evaluate the influence of statins on the development of dysglycemia (IFG and/or DM) in renal allograft recipients. A total of 394 patients without previously known DM or IFG who underwent kidney transplantation were enrolled. Patients were grouped into the two groups according to the use of statin (control, n=149; statin, n=245). The major statins used were fluvastatin (80 mg/d, n=134) and atorvastatin (20 mg/d, n=111). We compared the incidence of IFG or DM during the follow-up period. The incidence of IFG was higher in the statin group than that in the control group (28.6% vs. 8.7%, P<0.001). The incidence of dysglycemia was significantly higher in the statin group (40.0% vs. 15.4%, P=0.001). Time to development of dysglycemia after transplantation was shorter in the statin group than in the control group (38.8±29.7 vs. 47.2±23.3 months, P=0.002). Statin use was associated with an increased risk for dysglycemia after adjustment for age, sex, body mass index, hypertension, cholesterol levels, hepatitis C infection, and type of immunosuppressant (hazard ratio=3.08, 95% confidence interval=1.91-4.98). The dysglycemic effect was more profound in the patients who used atorvastatin than in those who used fluvastatin (hazard ratio=2.21, 95% confidence interval=1.02-4.76). Statin treatment is associated with an elevation in fasting plasma glucose and in the development of dysglycemia in renal allograft recipients.

Long-Term Statin Use and Dementia Risk in Taiwan

The effect of statin use on dementia risk remains unclear. This study aims to examine the association between long-term statin use and dementia risk. A nest case-control study within a nationwide representative population-based cohort. Individuals aged 50 years and older participating in Taiwan's National Health Insurance program between 1998 and 2009 were enrolled. A total of 9257 patients with at least 3 outpatient or 1 inpatient claims records for dementia were identified. Comparison patients were selected at a 1:2 ratio from age- and sex-matched participants without dementia. The cumulative period and average daily dosages of statins, fibrates, and other lipid-lowering agents were measured. The authors found a duration-response relationship, as dementia risk decreased by 9% per year of treatment of statins (adjusted odds ratio = 0.91; 95% confidence interval, 0.85-0.97). Use of high average dose statins for more than 1 year was associated with a lower risk of dementia than use of low average dose. However, there was no significant difference in dementia risks between lipophilic and hydrophilic statins. Fibrates or other lipid-lowering agents had no significant association with dementia risk. Our results suggest that long-term use of statin is associated with a reduced dementia risk.

A two-year follow-up for Chinese patients with abdominal aortic aneurysm undergoing open/endovascular repair

Background A number of studies have demonstrated the rates of overall and aneurysm-related mortality and morbidity in Western populations. The cardiovascular risk factors influencing postoperative outcome have been also reported. Until recently, little has been known about the prognosis in this patient cohort in the Chinese population. We evaluated the independent predictors of mortality and morbidity in abdominal aortic aneurysm (AAA) patients undergoing elective surgical treatment and emphasized whether the coronary artery revascularization could have any effect on the overall mortality and morbidity in patients following the current guideline recommendation. Methods A total of 386 patients (174 women) undergoing surgery in Beijing Anzhen Hospital from January 2008 to June 2010 were enrolled (mean age (70.6±10.5) years). Kaplan-Meier curves were constructed to compare the mortality and morbidity of AAA patients with coronary artery revascularization and those without. A Cox proportional hazards model was constructed to identify clinical factors associated with two-year outcomes. The primary outcomes were death from any cause, the pre-specified morbidity was re-hospitalization for pulmonary conditions, congestive heart failure, angina, ischemic/hemorrhagic stroke. Results During the two-year follow-up, 34 patients died and 65 experienced re-hospitalization with pulmonary conditions, congestive heart failure, angina, or ischemic/hemorrhagic stroke. Kaplan-Meier survival analysis showed that the AAA patients with cardiac revascularization had no higher incidence of overall mortality and major morbidity than those without (log-rank test P=0.35 and P=0.40, respectively). Cox proportional hazards regression analysis showed that level of lowdensity lipoprotein (HR, 4.06; 95% CI: 1.19-18.7, P=0.027) and AAA size (HR, 2.18; 95% CI: 1.28-11.65, P=0.036) were independently associated with the incidence of overall mortality. Long-term use of angiotensin converting enzyme inhibitors, statins, AAA size and systolic blood pressure were independent predictors of the secondary pre-specified outcomes. Conclusions Coronary artery revascularization following the guideline recommendations did not increase the mortality and morbidity of Chinese with AAA who were undergoing repair. Absence of angiotensin converting enzyme inhibitors and statins, AAA size, and systolic blood pressure were powerful predictors of the clinical events.

Long-term Statin Use and Risk of Breast Cancer—Letter

We read with great interest the work of McDougall and colleagues recently appeared on your journal reporting that current users of statins for 10 years or longer had a 1.83-fold increased risk of invasive ductal carcinoma (IDC) and a 1.97-fold increased risk of invasive lobular carcinoma (ILC)

Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies

There is a long-standing debate about whether statins have chemopreventive properties against colorectal cancer (CRC), but the results remain inconclusive. We therefore present a meta-analysis to investigate the association between statin use and risk of CRC. A comprehensive literature search was undertaken through July 2013 looking for eligible studies. Pooled relative risk (RR) estimates and 95 % confidence intervals (CIs) were used to calculate estimated effect. Forty-two studies [18 case-control studies, 13 cohort studies, and 11 randomized controlled trials (RCTs)] were included in this analysis. Overall, statin use was associated with a modest reduction in the risk of CRC (RR = 0.90, 95 % CI 0.86-0.95). When the analyses were stratified into subgroups, a significant decreased association of CRC risk was observed in observational studies (RR = 0.89, 95 % CI 0.84-0.95), rectal cancer (RR = 0.81, 95 % CI 0.66-0.99), and lipophilic statin (RR = 0.88, 95 % CI 0.85-0.93), but not in RCTs (RR = 0.96, 95 % CI 0.85-1.08), colon cancer, and hydrophilic statin. However, long-term statin use (≥5 years) did not significantly affect the risk of CRC (RR = 0.96, 95 % CI 0.90-1.03). Cumulative meta-analysis showed that statin use significantly reduces the risk of CRC, which has been available between 2007 and 2013. Our results suggest that statin use is associated with a modest reduced risk of CRC; apparent associations were found for lipophilic statin use. However, long-term statin use did not appear to significantly affect the risk of CRC.

Statin use and peripheral sensory perception: A pilot study

Objectives. Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins.Methods. Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10 g monofilament and neurothesiometer.Results. There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p = 0.031) and medial malleolus (p = 0.003) than the control group. Results at the hallux were not statistically significant (p = 0.183).Conclusion. This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations.

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.

Long-Term Statin Use and Risk of Breast Cancer—Letter

Long-Term Statin Use and Risk of Breast Cancer—Letter

Statin use and incident prostate cancer risk: does the statin brand matter? A population-based cohort study

Statins have known anticarcinogenic effects; evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent. We conducted a population-based cohort study to examine the association between statin use and risk of prostate cancer using the Database of Clalit Health Services. A total of 66,741 eligible participants were identified at 1 January 2001 and followed through to 31 December 2009. Cox proportional hazard models were used to compute hazard ratios (HRs) of incident prostate cancer associated with statin therapy controling for patients' clinical and sociodemographic characteristics. A total of 1813 cases of prostate cancer were diagnosed. Statin use was associated with a decreased incidence of prostate cancer, the association was stronger with increasing total dose, hydrophobic statins use and longer periods of treatment. When comparing statin use of over 6 months, this association was strongest for simvastatin (HR 0.51, 95% confidence interval (CI) 0.47-0.56), atorvostatin (HR 0.48, 95% CI 0.33-0.68) and rosuvastatin (HR 0.22, 95% CI 0.08-0.75). Our findings suggest that prolonged statin use is associated with a reduced risk of prostate cancer; however, this was not true for all types of statin.

Factors influencing adherence in long‐term use of statins

To assess the factors influencing adherence in long-term medication use as exemplified by statins. Data from an in-depth survey of Australians aged 45 years and over were linked to national prescription reimbursement data to assess medication possession ratio (MPR) for statins for the middle two years of a four-year period of statin possession. Poisson regression was used to calculate the relative risk (RR) for adherence (MPR ≥ 80%) for patient characteristics and factors related to access to and need for health care services. Separate models were fit for patients receiving healthcare concession subsidies and those who do not ('general beneficiaries'). In the analysis, 42 492 concessional and 16 110 general beneficiary patients were included, with 80.1% and 56.7% showing MPR ≥ 80%, respectively. In both models, RR for adherence was significantly elevated for older (age 65+) and less healthy (worse self-rated health, pre-existing heart condition or obese) individuals, and for those who had private health insurance. Significantly lower RR (i.e. more non-adherence) was found for individuals reporting speaking a language other than English at home, who were smokers, were employed, and had higher levels of education, and for those who reported psychological distress. Income had no significant relationship with adherence, and the pattern of adherence by remoteness of area of residence was inconsistent. Poor adherence in long-term use of statins is commonplace, but a number of key predictors-including age, language other than English spoken at home, smoking status and psychological distress-are readily assessable by the prescribing practice.

Long-Term Statin Use and Risk of Ductal and Lobular Breast Cancer among Women 55 to 74 Years of Age

Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use. We used data from a population-based case-control study of breast cancer conducted in the Seattle-Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. Nine hundred sixteen invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases in patients 55 to 74 years of age diagnosed between 2000 and 2008 were compared with 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid-lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression. Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14-2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25-3.12) compared with never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC (OR: 2.04, 95% CI: 1.17-3.57) and ILC (OR: 2.43, 95% CI: 1.40-4.21) compared with never users. In this contemporary population-based case-control study, long-term use of statins was associated with increased risks of both IDC and ILC. Additional studies with similarly high frequencies of statin use for various durations are needed to confirm this novel finding.

Declining Cholecystectomy Rate During the Era of Statin Use in Finland: A Population-Based Cohort Study Between 1995 and 2009

Aging with comorbidities, obesity, and rapid recovery from operation may increase the need for laparoscopic cholecystectomy, but long-term use of statins may be associated with a decreased risk of gallstones. This population-based cohort study presents the changing rate and causative factors of laparoscopic cholecystectomy in Finland during the era of statin use. Age structure of the population, changes in body mass index and diabetes, and the number of all cholecystectomies in 1995-2009 were retrieved from the registers of National Institute for Health and Welfare. Additionally, these results were supplemented by a population-based retrospective cohort (1581 laparoscopic cholecystectomy) in one community-based hospital area. The risk factors for laparoscopic cholecystectomy, use of statins, and surgical outcome were analyzed. During the 15 years, 123,794 cholecystectomies were performed in Finland, of which 94,740 (76.5%) were performed using laparoscopic technique. The median rate of laparoscopic cholecystectomy varied between 110 and 140 operations per 100,000 inhabitants. In 1995-2009, the annual number of cholecystectomies decreased from 8600 to 7500, the number of laparoscopic cholecystectomies increased by 10%, and the number of open cholecystectomies declined by 60%. In a cohort of 1581 laparoscopic cholecystectomies, the proportion of elderly (>65 years of age), obese (body mass index > 30 kg/m(2)), and diabetic patients increased from 17% to 28%, 9% to 34%, and 4% to 8%, respectively. Use of statins increased more than fourfold during the 15 years. The rates of all cholecystectomies decreased despite marked increase in laparoscopic cholecystectomies performed. The increase in risk factors for gallstones in Finland implied more marked increase in laparoscopic cholecystectomies. The possible role of statins on gallstone disease is discussed.

Long-term use of statins reduces the risk of hospitalization for dementia

BackgroundDementia is a major public health problem because of its high prevalence in elderly individuals, particularly in the growing category of subjects aged 80 years or more. There is accumulating evidence that cholesterol may be implicated in the pathogenesis of dementia, and this has led us to assess the relationship between time spent with statins available and the risk of hospitalization for dementia. MethodsA population-based, nested case-control study was carried out by including the cohort of 152,729 patients from Lombardy (Italy) aged 40 years or older who were newly treated with statins between 2003 and 2004. Cases were the 1380 patients who experienced hospitalization for dementia disease from initial prescription until 2010. Up to twenty controls were randomly selected for each case. Logistic regression was used to model the risk of dementia associated with the cumulative time during which statins were available. Monte-Carlo and rule-out sensitivity analyses were performed to account for unmeasured confounders. ResultsCompared with patients who had very short statins coverage (less than 6 months), those on 7–24, 25–48, and >48 months of coverage respectively had risk reductions of 15% (OR: 0.85; 95% CI: 0.74 to 0.98), 28% (OR: 0.72; 95% CI: 0.61 to 0.85), and 25% (OR: 0.75; 95% CI: 0.61 to 0.94). Simvastatin and atorvastatin were both associated with a reduced risk of dementia, while no similar evidence was observed for fluvastatin and pravastatin. ConclusionsLong-term use of statins seems effective for the prevention of dementia.