Statin Nonusers Research Articles

Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk.

Statins lower low-density lipoprotein cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced low-density lipoprotein reduction increases risk of intracerebral haemorrhage has been debated for almost two decades. Here, we explored whether genetically predicted on-statin low-density lipoprotein response is associated with intracerebral haemorrhage risk using Mendelian randomization. Using genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms of on-statin low-density lipoprotein response and tested it in the population-based UK Biobank. We extracted statin drug and dose information from primary care data on a subset of 225 195 UK Biobank participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal low-density lipoprotein measurements with generalized mixed models and explored associations with incident intracerebral haemorrhage using Cox regression analysis. Statins were prescribed at least once to 75 973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean low-density lipoprotein decreased by 3.45 mg/dl per year [95% confidence interval (CI): (-3.47, -3.42)] over follow-up. A higher genetic score of statin response [1 standard deviation (SD) increment] was associated with significant additional reductions in low-density lipoprotein levels [-0.05 mg/dl per year, (-0.07, -0.02)], showed concordant lipidomic effects on other lipid traits as statin use and was associated with a lower risk for incident myocardial infarction [hazard ratio per SD increment 0.98 95% CI (0.96, 0.99)] and peripheral artery disease [hazard ratio per SD increment 0.93 95% CI (0.87, 0.99)]. Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher intracerebral haemorrhage risk in a model adjusting for statin dose [hazard ratio per SD increment 1.16, 95% CI (1.05, 1.28)]. On the contrary, there was no association with intracerebral haemorrhage risk among statin non-users (P = 0.89). These results provide further support for the hypothesis that statin-induced low-density lipoprotein reduction may be causally associated with intracerebral haemorrhage risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacological low-density lipoprotein lowering in the pathogenesis of intracerebral haemorrhage.

Effects of statins on the risks of ischemic stroke and heart disease in human immunodeficiency virus infection, influenza and severe acute respiratory syndrome–associated coronavirus: respiratory virus infection with steroid use

Objectives We sought to fill the research gap on the effects of statins on the risks of ischemic stroke and heart disease among individuals with human immunodeficiency virus infection, influenza, and severe acute respiratory syndrome associated–coronavirus (HIS) disorders. Methods We enrolled a HIS cohort treated with statins (n = 4921) and a HIS cohort not treated with statins (n = 4921). The cumulative incidence of ischemic stroke and heart disease was analyzed using a time-dependent Cox proportional regression analysis. We analyzed the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of ischemic stroke and heart disease for statins users relative to nonusers based on sex, age, comorbidities and medications. Results The aHR (95% CI) was 0.38 (0.22–0.65) for ischemic stroke. The aHR (95% CI) of heart disease was 0.50 (0.46–0.55). The aHRs (95% CI) of statin users with low, medium, and high adherence (statin use covering <33%, 33%–66%, and >66%, respectively, of the study period) for the risks of ischemic stroke were 0.50 (0.27–0.92), 0.31 (0.10–1.01), and 0.16 (0.04–0.68) and for heart disease were 0.56 (0.51–0.61), 0.40 (0.33–0.48), and 0.44 (0.38–0.51), respectively, compared with statin nonusers. Conclusion Statin use was associated with lower aHRs for ischemic stroke and heart disease in those with HIS disorders with comorbidities.

Statins Are Associated with Improved Survival of Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.

Statins are associated with gastric cancer (GC) risk. The present study aimed to clarify the efficacy of statins on the overall survival (OS) benefits in patients with GC. Publications were retrieved from PubMed, Embase, and the Cochrane Library as of April 2022. Data from the eligible cohort, case-control studies, and randomized control trials (RCTs) were extracted for the meta-analysis. Hazard ratio (HR) and 95% confidence intervals (CI) were used to assess the association between statins users and OS in GC patients. Subgroup analysis was performed based on the study design (prospective vs. retrospective). A total of 6 studies encompassing 5693 GC patients were included. Statins added to the standard treatment prolonged the patient's OS outcome (HR (95% CI): 0.72 (0.53–0.97), p = 0.032; I2 = 88.0%, pheterogeneity < 0.001). A prospective study did not find any statistically significant difference in OS between statins users vs. nonstatin users (HR (95% CI): 0.92 (0.68–1.26), p = 0.614; I2 = 11.7%, pheterogeneity = 0.322), whereas the retrospective studies showed prolonged OS in statins users (HR (95% CI): 0.63 (0.42–0.961), p = 0.032; I2 = 94.6%, pheterogeneity < 0.001). Statin users had significantly improved OS compared to nonstatin users in GC treatment. This long-term survival benefit was only observed in the pooled analysis of retrospective studies but not in prospective studies.

Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008-2018.

Background Despite early goal-directed therapy, sepsis mortality remains high. Statins exhibit pleiotropic effects. Objective We sought to compare mortality outcomes among statin users versus nonusers who were hospitalized with sepsis. Methods Retrospective cohort study of patients (age ≥18 years) during 1/1/2008–9/30/2018. Mortality was compared between statin users and nonusers and within statin users (hydrophilic versus lipophilic, fungal versus synthetic derivation, and individual statins head-to-head). Multivariable Cox regression models were used to estimate hazard ratios (HR) for 30-day and 90-day mortality. Inverse probability treatment weighting (IPTW) analysis was performed to account for indication bias. Results Among 128,161 sepsis patients, 34,088 (26.6%) were prescribed statin drugs prior to admission. Statin users compared to nonusers had a 30-day and 90-day mortality HR (95% CI) of 0.80 (0.77–0.83) and 0.79 (0.77–0.81), respectively. Synthetic derived statin users compared to fungal derived users had a 30- and 90-day mortality HR (95% CI) of 0.86 (0.81–0.91) and 0.85 (0.81–0.89), respectively. Hydrophilic statin users compared to lipophilic users had a 30-day and 90-day mortality HR (95% CI) of 0.90 (0.81–1.01) and 0.86 (0.78–0.94), respectively. Compared to simvastatin, 30-day mortality HRs (95% CI) were 0.85 (0.66–1.10), 0.87 (0.82–0.92), 0.87 (0.76–0.98), and 1.22 (1.10–1.36) for rosuvastatin, atorvastatin, pravastatin, and lovastatin, respectively. Conclusion Statin use was associated with lower mortality in patients hospitalized with sepsis. Hydrophilic and synthetic statins were associated with better outcomes than lipophilic and fungal-based preparations.

The Impact of Age on Statin-Related Glycemia: A Propensity Score-Matched Cohort Study in Korea.

The aim of this study was to investigate the influence of statin on glycemic control in different age groups. Patients admitted for suspected or confirmed coronary artery disease between January 2005 and December 2013 in Seoul, Korea were initially enrolled. After propensity score matching, 2654 patients (1:1 statin users and non-users) were selected out of total 5041 patients, including 1477 “young” patients (≤60 y) and 1177 elderly patients (>60 y). HbA1c was decreased by 0.04% (±0.86%) in statin non-users. On the contrary, a slight increment of 0.05% (±0.71%) was found in statin users (p < 0.001). The change patterns of HbA1c were constant in both young and elderly patient groups. Furthermore, elderly statin users demonstrated significantly worse glycemic control in serum insulin and homeostatic model assessment—insulin resistance (HOMA-IR) index. In elderly patients, statin users were found to have a 2.61 ± 8.34 μU/mL increment in serum insulin, whereas it was 2.35 ± 6.72 μU/mL for non-users (p = 0.012). Statin users had a 0.78 ± 3.28 increment in HOMA-IR, in contrast to the 0.67 ± 2.51 increment in statin non-users (p = 0.008). In conclusion, statin treatment was associated with adverse glycemic control in the elderly population.

Parkinson's Disease Progression and Statins: Hydrophobicity Matters.

Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson's disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance. Investigate a potential effect of statins on PD progression. Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participating in the PD Biomarker Program (PDBP, 2012-2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the "on" drug state. R2* values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions. Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2* (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= -7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2* did not reach statistical significance (β= 2.5, p = 0.24). This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.

420 Comparison of Statin Use to Non-Use on Cerebral Blood Flow Velocity in Older Adults at Risk for Alzheimers Disease: Data from a Phase II Multisite Clinical Trial

OBJECTIVES/GOALS: Reduced cerebral blood flow (CBF) along with vascular risk factors (e.g., dyslipidemia) are prevalent in Alzheimers disease (AD) and related dementias. Statins are one of the most effective pharmacologic treatments for vascular risk reduction, which may contribute to CBF in individuals with an increased risk for AD. METHODS/STUDY POPULATION: Cross-sectional analysis of 212 older adults with a family history of dementia. Heart rate via electrocardiogram, mean arterial pressure (MAP) via brachial sphygmomanometers, end-tidal CO2 via capnograph, and CBF velocity at the middle cerebral artery (MCAv) via transcranial Doppler ultrasound were collected following 20-minutes of supine rest. Mean MCAv (cm/s) was measured within each cardiac cycle and averaged over an 8-minute duration. Cerebrovascular conductance was calculated by dividing mean MCAv by MAP. Pulsatility Index was calculated by subtracting systolic MCAv from diastolic MCAv and then dividing by mean MCAv. RESULTS/ANTICIPATED RESULTS: 125 females (68 ± 6 years; 49 statin) and 87 males (70 ± 6 years; 47 statin) were included in analyses. There were no significant differences between heart rate, MAP, or end-tidal CO2 between statin and non-statin users. After controlling for age, sex, and low-density and high-density lipoprotein, statin use did not significantly contribute to MCAv (p = 0.09). However, statin use did significantly contribute to cerebrovascular conductance (MCAv/MAP; p = 0.03) as well as Pulsatility Index (assessment of cerebral health, p &lt; 0.01). DISCUSSION/SIGNIFICANCE: Our findings suggest statin use significantly and positively contributes to resting cerebral blood flow velocity and cerebrovascular health. Further investigation is warranted into statin interventions with other components of cerebrovascular function, as differences may have implications for brain health and disease pathogenesis.

Association of Use of Statins with Progression of Diabetic Retinopathy at a Tertiary Care Hospital in Southern India.

Purpose:To study the role of statin therapy on diabetic retinopathy (DR) progression.Methods:This retrospective study was carried out at a tertiary care hospital in southern India. Data were collected from the medical records of patients admitted from January 2013 to December 2018. Out of 1673 patients of DR enrolled in the study, 171 met the inclusion criteria. Patients' demographic data, drug history, clinical characteristics, and laboratory investigations were recorded as per the pro forma. The patients were divided into statin users and nonusers. The results were analyzed to compare the DR progression between the two groups.Results:DR progressed in 67% of nonstatin users and 37% of statin users (P < 0.001). The use of statins decreased the risk of DR progression (P < 0.001). Center-involving macular edema was seen in 8 of 79 statin users (10%) and 16 of 92 statin nonusers (16%) based on optical coherence tomography findings during the follow-up period (P = 0.17).Conclusion:In patients with type 2 diabetes, lipid-lowering therapy with statins has the potential to retard DR progression.

The association between statin and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

There currently exist limited and conflicting clinical data on the use of statins in coronavirus disease 2019 (COVID-19) patients. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins. We performed a population-based retrospective cohort study using South Korea's nationwide healthcare claim database. We identified consecutive patients hospitalized with COVID-19 and aged 40 years or older. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry to capture patients who are chronic statin users and, therefore, receive statin prescriptions as infrequently as every 8 months. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes [myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke]. We compared the risk of outcomes between statin users and non-users using logistic regression models after inverse probability of treatment weighting (IPTW) adjustment. Of 234,427 subjects in the database, 4,349 patients were hospitalized with COVID-19 and aged 40+ years. In total, 1,115 patients were statin users (mean age =65.9 years; 60% female), and 3,234 were non-users (mean age =58.3 years; 64% female). Pre-hospitalization statin use was not significantly associated with increased risk of the primary endpoint [IPTW odds ratio (OR) 0.82; 95% confidence interval (CI): 0.60-1.11]. Subgroup analysis showed a protective role of antecedent statin use for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, P for interaction: 0.0087). Pre-hospitalization statin use is not detrimental and may be beneficial amongst hypertensive COVID-19 patients. Further investigation into statin is needed for more conclusive effects of statins for treatment of COVID-19.

The Impact of Statin Use and Breast Cancer Recurrence -A Retrospective Study in Singapore.

IntroductionStatins, HMG-CoA reductase inhibitors, are commonly used cholesterol-lowering medications which are also increasingly recognized to have anti-cancer properties for various cancers, including breast cancer. Most clinical evidence supports a protective effect of statin on reducing breast cancer recurrence, particularly in hormone-receptor positive breast cancers.This study seeks to study the impact of statin use on breast cancer recurrence in an Asian population.MethodsThis is a retrospective study of patients diagnosed with breast cancer at the National Cancer Centre and Singapore General Hospital from 2005-2015. Statin use was defined as use after surgery. Associations between statin use, breast cancer recurrence and overall survival were estimated using Cox proportional hazards regression with adjustment for age, TNM stage, grade, ER/HER2 status, and co-morbidities. Associations between statin-use and disease-specific survival were estimated using competing risks regression.ResultsA total of 7858 females with breast cancer were studied, 1353(17.2%) were statin users, 6505(82.8%) were non-statin users, with a median follow-up of 8.67 years. Distribution of cancer stage, histology, molecular subtypes and grades were similar in both groups. Estrogen receptor(ER) positive (HR 0.57,95%CI 0.43-0.76,p<0.001) and HER2 negative (HR 0.74,95%CI 0.57-0.96,p=0.026) invasive cancers had a lower risk of recurrence in statin users. Statin users trended towards a long term recurrence-risk reduction (all subtypes,HR 0.48,p=0.002; ER-, HR 0.34,p=0.036; HER2+,HR 0.10,p=0.002). The risk-reduction benefit is not appreciated in statin users with DCIS, possibly due to small recurrence event numbers. Disease-specific survival benefit was seen in statin users with ER+ cancers (adjusted SHR 0.71,95%CI 0.53-0.96,p=0.027), especially ER+ invasive cancers (adjusted SHR 0.72, 95%CI 0.53-0.97,p=0.028), but with no statistically significant benefit in overall survival for statin users (all subtypes).ConclusionThis is the first known retrospective study on the effect of statin use and breast cancer recurrence in an Asian population. Similar to previous international studies, statin use is associated with a risk reduction in breast cancer recurrence. This is especially beneficial in patients who have ER+ and HER2- invasive breast cancer. Statin use is also associated with a reduced risk of breast cancer recurrence in all subtypes of breast cancer in the long term (>6 years post diagnosis).

Association between statin use and physical performance in home-dwelling older patients receiving polypharmacy: cross-sectional study

BackgroundIn older patients with polypharmacy and multiple comorbidities, even low grades of statin-associated muscle symptoms may have clinical implications. The aim of this study was therefore to investigate the potential associations between statin use and measures of physical performance and muscle function.MethodsParticipants were aged 70+, treated with at least seven regular systemic medications, and not expected to die or become institutionalized within 6 months. Physical performance measured as gait speed and Short Physical Performance Battery (SPPB) score, and muscle function measured as grip strength, were compared between users and non-users of statins. In the subgroup of statin users, the dose-response relationship was assessed using harmonized simvastatin equivalents adjusted for statin potency, pharmacokinetic interactions and SLCO1B1 c.521 T > C genotype. Multiple linear regression analyses were applied to investigate potential associations between stain use and exposure as independent variables, and physical performance and muscle function as outcomes, adjusted for age, gender, body mass, comorbidity, disability and dementia.Results174 patients (87 users and 87 non-users of statins) with a mean (SD) age of 83.3 (7.3) years were included. In analyses adjusted only for gender, grip strength was significantly higher in users than in non-users of statins [regression coefficient (B) 2.7, 95% confidence interval (CI) 1.0 to 4.4]. When adjusted for confounders, the association was no longer statistically significant (B 1.1, 95% CI − 0.5 to 2.7). SPPB and gait speed was also better in statin users than in non-users, but the differences were not statistically significant. In dose-response analyses adjusted for confounders, we found a statistically significant increase in SPPB score (B 0.01, 95% CI 0.00 to 0.02) and gait speed (B 0.001, 95% CI 0.000 to 0.002) per mg increase in simvastatin equivalents.ConclusionsIn contrast to our hypothesis, statin use and exposure was associated with better measures of physical performance and muscle function in older patients with complex drug treatment. The unexpected findings of this cross-sectional, observational study should be further investigated by comparing physical performance before and after statin initiation or statin withdrawal in prospective studies.Trial registrationClinicalTrials.gov identifier: NCT02379455, registered March 5, 2015.

Atorvastatin Reduces the Severity of COVID-19: A Nationwide, Total Population-Based, Case-Control Study

Background: Statins have a pleiotropic effect in addition to a lipid-lowering effect. Several studies have demonstrated that statins may reduce the mortality and severity of infectious diseases, such as pneumonia or sepsis. We investigated the protective effects of various statins on the coronavirus disease 2019 (COVID-19) using a population-based cohort covering the entire Korean population. Methods: Consecutive patients diagnosed with COVID-19 between January 2020 and May 2020 were enrolled from the Korean National Health Insurance Service database. Current statin users were defined as patients who used statins within 30 days before the diagnosis of COVID-19. We compared the mortality and severity of COVID-19 between statin users and non-users to confirm the efficacy of statins. Results: Of the 7723 patients with COVID-19 who were enrolled, 255 died due to COVID-19 and 493 had severe COVID-19 (defined as mortality, admission to the intensive care unit, or mechanical ventilator use). Compared with non-users, atorvastatin users had a lower risk of COVID-19 mortality (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.34–0.86) and severe COVID-19 (OR, 0.65; 95% CI, 0.45–0.93). However, other statins did not reduce the COVID-19 mortality and severity. Conclusions: Among the statins, only atorvastatin was effective in reducing the COVID-19 mortality and severity. Further randomized controlled trials are required to clarify the protective effects of atorvastatin.

Statin Use Is Associated With a Lower Risk of Blepharitis: A Population-Based Study.

BackgroundBlepharitis is a common eye disorder that may be overlooked by patients and clinical practitioners. The symptoms of blepharitis often manifest as irritation, a burning sensation, grittiness, and itchiness and may decrease visual acuity if not treated promptly. Meibomian gland dysfunction (MGD), a common cause of blepharitis, is believed to be associated with increased inflammatory marker levels that may disrupt the composition of lipids produced by the sebaceous glands in the eyelids and ultimately cause tear film instability.MethodsThis is a retrospective, population-based study using National Health Insurance Research Database (NHIRD) data from a 14-year period (2000–2015). Pearson chi-squared and Student's t-tests were used to assess the differences in categorical and continuous variables, respectively, between statin users and non-statin users. Univariate and multivariate Cox regression analyses were performed to calculate the hazard ratios (HRs) after adjusting for confounders. Kaplan-Meier analysis was used to assess the cumulative risk of blepharitis between the two cohorts.ResultsA total of 67,014 patients who used statins were enrolled as the study cohort, and 268,056 patients who did not use statins were enrolled as the comparison cohort. The incidence of blepharitis was 3.04% with statin treatment and 3.72% without statin treatment (p < 0.001). Patients who used statins had a lower risk of developing blepharitis [adjusted hazard ratio (aHR): 0.746, p < 0.001] than those who did not. In addition, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), stroke, chalazion, rosacea, Sjogren syndrome, psoriasis and atopy were found to be possible risk factors for blepharitis.ConclusionStatin use can decrease the risk of developing blepharitis. However, further prospective studies are needed to evaluate statin treatment for various subtypes of blepharitis and to identify the associated mechanism.

Statin use and the risk of progression to vision threatening diabetic retinopathy.

This study aims to assess the effect of statins on progression from nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). Two cohort studies using a U.S. medical claims database from 2002 to 2019 including NPDR patients 18 years or older. A risk factor analysis performed a time-updating cox regression model assessing statin usage. A second new-user active comparator design analysis replicating a previously published study. Main outcomes included a new diagnosis of VTDR (composite of either PDR or DME) or DME and PDR individually for the risk factor study and included additional outcomes of new DR, NPDR, vitreous hemorrhage (VH) and tractional retinal detachment (TRD) for the new user study. Risk factor analysis included 66 617 statin users with NPDR at baseline and 83 365 nonstatin users. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After multivariable analysis, no protective effect of statin use was found for progression to VTDR, PDR, or DME (HR=1.01-3, p >0.33 for all comparisons). Replicated new user design analysis also showed no protective effect for statins on risk of development of DR (HR=1.03, 95% CI: 0.99-1.07, p=0.13), PDR (HR=0.89, 95% CI: 0.79-1.02, p=0.09), DME (HR=0.94, 95% CI: 0.86-1.03, p=0.21), VH (HR=1.00, 95% CI: 0.86-1.16, p=0.99), and TRD (HR=1.11, 95% CI: 0.89-1.38, p=0.36). Statin use was found not to be protective for progression of DR regardless of study methodology. These results suggest that the specifics of the population studied rather than differing study methodology are important in assessing the effect of statins on DR progression.

Statin Therapy for Hyperlipidemic Patients With Chronic Kidney Disease and End-Stage Renal Disease: A Retrospective Cohort Study Based on 925,418 Adults in Taiwan.

Background: For non-dialysis patients with hyperlipidemia, statins may provide clinical benefits in reducing mortality risk; however, the optimal treatment for dialysis patients with hyperlipidemia remains debatable. We evaluated the mortality risks for hyperlipidemic patients with renal disorders associated with statin therapy (ST), using the insurance claims data of Taiwan. Methods: From hyperlipidemic patients diagnosed in 2000–2011, we identified 555,153 patients receiving statin treatment for at least 90 days continuously and 1,141,901 non-statin users, and then randomly selected, from both groups, the propensity score-matched subcohorts of statin users and nonusers in a 1:1 pair by renal function: 415,453 pairs with normal renal function , 43,632 pairs with chronic kidney disease (CKD), and 3,624 pairs with end-stage renal disease (ESRD). We compared the mortalities, by the end of 2016, from all causes, cancer, heart disease, and septicemia between statin users and non-users and between hydrophilic-statin users and lipophilic-statin users. The Cox method estimated ST users to non-user hazard ratios. The time-dependent model was also conducted as sensitivity analysis. Results: The mean ages were 58.7 ± 10.7, 64.2 ± 10.7, and 62.2 ± 10.8 years in normal renal function, CKD, and ESRD groups, respectively. Compared with non-users, statin users had reduced mortality risks from all causes for 32%–38%, from cancer for 37%–46%, from heart disease for 6%–24%, and from septicemia for 17%–21% in all three renal groups. The hydrophilic statin therapy was superior than the lipophilic statin therapy, particularly for reducing deaths from all-causes and cancer. The results under the time-dependent model were similar. Conclusion: Statin therapy is associated with reduced all-causes and non-cardiovascular mortality in ESRD patients.

Association between low-density lipoprotein cholesterol and cardiovascular mortality in statin non-users: a prospective cohort study in 14.9 million Korean adults.

Limited information is available on detailed sex/age-specific associations between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) mortality and 'the optimal range' associated with the lowest CVD mortality in the general population. Korean adults (N = 14 884 975) who received routine health screenings during 2009-2010 were followed until 2018 for CVD mortality. During 8.8 years (mean) of follow-up, 94 344 individuals died from CVD. LDL-C had U-curve associations with mortality from CVD and its subtypes, except haemorrhagic stroke. Optimal range was 90-149 mg/dL for CVD; 70-114 for ischaemic heart disease; 85-129 for ischaemic stroke; ≥85 for subarachnoid haemorrhage; ≥130 for intracerebral haemorrhage; 115-159 for hypertension and heart failure; and 100-144 for sudden cardiac death. Assuming linear associations between 100 and 300 mg/dL, LDL-C was positively associated with CVD mortality [hazard ratio (HR) per 39-mg/dL (1-mmol/L) higher LDL-C = 1.10], largely due to ischaemic heart disease (HR = 1.26), followed by sudden cardiac death (HR = 1.13), ischaemic stroke (HR = 1.11) and heart failure (HR = 1.05). Intracerebral haemorrhage (HR = 0.90), but not subarachnoid haemorrhage, had inverse associations. Women and older adults had weaker positive associations than men and younger adults (Pinteraction < 0.001 for both sex and age). Individuals aged 75-84 years had modest positive associations with CVD mortality, especially ischaemic heart disease and ischaemic stroke. LDL-C had U-curve associations for CVD mortality. The associations and optimal ranges differed across CVD subtypes. Women and older adults had weaker positive associations than men and younger adults. Positive associations with ischaemic heart disease and ischaemic stroke were maintained in adults aged 75-84 years.

Association between statin use and Parkinson's disease in Korean patients with hyperlipidemia

IntroductionFindings on the association between statin therapy and Parkinson's disease (PD) occurrence have been inconsistent. This study aimed to identify the association between statin use and PD in participants with a history of hyperlipidemia or blood cholesterol >200 in a Korean population to exclude nonstatin users owing to normal lipid values. MethodsWe conducted a nested case-control analysis using the Korean National Health Insurance Service-National Sample Cohort assessed between 2002 and 2015. We identified 3026 PD cases. A total of 12,104 controls were then individually matched by age, sex, income, and region of residence at a ratio of 1:4. Potential confounders comprised basic demographic factors, lifestyle factors, various medical conditions and comorbidities. A conditional/unconditional logistic regression method was applied. ResultsCompared with statin use for <6 months, adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for 6–12 months of statin use and ≥12 months of statin use were 1.03 (0.92–1.15) and 1.61 (1.35–1.93) after adjustment for confounders, respectively (P = 0.664 and P < 0.001). In analyses according to statin solubility, only the association between lipophilic statin use for ≥12 months and PD maintained statistical significance, with an aOR of 1.64 (95% CI = 1.34–2.01, P < 0.001). These relations were consistent in subgroup analyses by covariates. ConclusionsStatin use for more than 12 months was associated with a higher probability of PD in the Korean population with hyperlipidemia. This probability was significant for lipophilic statins but not hydrophilic statins.

Statin Use and Reduced Hepatocellular Carcinoma Risk in Patients With Nonalcoholic Fatty Liver Disease

Recent evidence suggests potential clinical benefits of statin in cancer chemoprevention and treatment. Nonalcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC). We aimed to investigate the association between statin initiation and the risk of HCC among patients with NAFLD. In this study using the Optum de-identified Clinformatics database, Cox proportional hazards regression model was performed to determine the risk of HCC in statin initiators versus nonusers. We incorporated inverse probability of treatment weighting (IPTW) to minimize potential confounding. Among 272,431 adults with NAFLD diagnosis, IPTW model shows that statin initiators had 53% less risk of developing HCC compared with nonusers (hazard ratio [HR], 0.47; 95% confidence interval, 0.36-0.60). In the subcohort with fibrosis-4 index data available, statin initiation was associated with 56% hazard reduction of developing HCC in NAFLD after adjusting for fibrosis-4 index score (HR, 0.44; 0.30-0.65). The association between statin initiation and lower risk of HCC development was observed for both lipophilic statin (HR, 0.49; 0.37-0.65) and hydrophilic statin (HR, 0.40; 0.21-0.76). Moreover, we observed greater hazards reduction as the dose and duration of statin use increased. NAFLD patients with more than 600 cumulative defined daily doses of statin had 70% reduction in hazards of developing HCC (HR, 0.30; 0.20-0.43). Our study provides strong evidence for the association between statin initiation and reduced risk of HCC development in NAFLD patients. These findings imply that statin can be used as a protective medication for NAFLD patients to reduce the risk of HCC.

Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicenter study.

We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy. We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumor, disease recurrence, disease progression and overall mortality (OM) rates. Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rate of high-grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; P=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; P=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; P=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; P=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users. Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

Moderate-intensity statin use for primary prevention for more than 5 years is associated with decreased all-cause mortality in 75 years and older

ObjectiveEvidence regarding the primary preventive effects of statin in the elderly is inadequate. This study aimed to determine the duration and intensity of statins beneficial in adults aged ≥75 years for primary prevention. MethodsThis is a retrospective longitudinal study, using the National Health Insurance Corporation-Senior Cohort data from 2002 to 2015. Exact block matching was used to select comparable subjects from statin users and non-users. ResultThe study subjects consisted of 685 pairs of statin non-users and users (total number of 1,370). During the follow-up (mean 8.7 years) period, the adjusted HR for mortality compared to non-user was 0.95 (p = 0.71) in low intensity statin users and 0.80 (p = 0.002) in the moderate intensity statin groups. The adjusted HR for MACE (Major Adverse Cardiovascular Events) compared to non-users was 1.10 (p = 0.39) in the low intensity statin group and 1.29 (p = 0.001) in the moderate intensity statin group. The risk of MACE disappeared five years after in moderate intensity statin users. Moderate intensity statin use was significantly associated with an increased risk of NODM (New Onset Diabetes Mellitus) (HR 1.50, p < 0.001) for up to three years, but the risk faded away after five years (HR 0.90, p = 0.52). ConclusionModerate intensity statins taken for five or more years for primary prevention would be associated with low risk of all-cause mortality in the 75+ years old. This result may support the evidence that initiation of statin for primary prevention in patients aged over 75 years is beneficial and tolerable.