Statin Intake Research Articles

Statins Increase the Bioavailability of Fixed-Dose Combination of Sofosbuvir/Ledipasvir by Inhibition of P-glycoprotein.

Coadministration of statins and direct acting antiviral agents is frequently used. This study explored the effects of both atorvastatin and lovastatin on pharmacokinetics of a fixed-dose combination of sofosbuvir/ledipasvir "FDCSL". 12 healthy volunteers participated in a randomized, three-phase crossover trial and were administered a single atorvastatin dose 80 mg plus tablet containing 400/90 mg FDCSL, a single lovastatin dose 40 mg plus tablet containing 400/90 mg FDCSL, or tablets containing 400/90 mg FDCSL alone. Liquid chromatography-tandem mass spectrometry was used to analyze plasma samples of sofosbuvir, ledipasvir and sofosbuvir metabolite "GS-331007" and their pharmacokinetic parameters were determined. Atorvastatin caused a significant rise in sofosbuvir bioavailability as explained by increasing in AUC0-∞ and Cmax by 34.36% and 11.97%, respectively. In addition, AUC0-∞ and Cmax of GS-331007 were increased by 73.73% and 67.86%, respectively after atorvastatin intake. Similarly, co-administration of lovastatin with FDCSL increased the bioavailability of sofosbuvir, its metabolite (AUC0-∞ increase by 17.2%, 17.38%, respectively, and Cmax increase by 12.03%, 22.24%, respectively). However, neither atorvastatin nor lovastatin showed a change in ledipasvir bioavailability. Hepatic elimination was not affected after statin intake with FDCSL. Compared to lovastatin, atorvastatin showed significant increase in AUC0-∞ and Cmax of both sofosbuvir and its metabolite. Both atorvastatin and lovastatin increased AUC of sofosbuvir and its metabolite after concurrent administration with FDCSL. Statins' P-glycoprotein inhibition is the attributed mechanism of interaction. The increase in sofosbuvir bioavailability was more pronounced after atorvastatin intake. Close monitoring is needed after co-administration of atorvastatin and FDCSL.

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.

PD50-03 NO ASSOCIATION BETWEEN STATINS AND INCREASED NEPHROLITHIASIS RISK

You have accessJournal of UrologyCME1 May 2022PD50-03 NO ASSOCIATION BETWEEN STATINS AND INCREASED NEPHROLITHIASIS RISK Wilson Sui, Christina J. Peterson, Naren Nimmagadda, Nicholas L. Kavoussi, Nicole L. Miller, S. Duke Herrell, and Ryan S. Hsi Wilson SuiWilson Sui More articles by this author , Christina J. PetersonChristina J. Peterson More articles by this author , Naren NimmagaddaNaren Nimmagadda More articles by this author , Nicholas L. KavoussiNicholas L. Kavoussi More articles by this author , Nicole L. MillerNicole L. Miller More articles by this author , S. Duke HerrellS. Duke Herrell More articles by this author , and Ryan S. HsiRyan S. Hsi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002621.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently studies have shown inconclusive evidence for the association of statin intake and risk of nephrolithiasis in large cohort studies, while the impact of statin use on urinary chemistry factors related to stone risk are unknown. Therefore, we sought to examine the association between statin use and incident kidney stone risk and evaluate statin use on 24-hour urine analysis. METHODS: We performed a single center, retrospective study of patients with the diagnosis of hyperlipidemia (HLD) and without a history of kidney stones across the electronic health record (EHR). Medication information on statin use was extracted and then the occurrence of an incident kidney stone diagnosis or procedure was identified. Kaplan-Meier analysis was used to estimate risk of incident kidney stone diagnoses. Then, among patients with HLD and kidney stones undergoing 24-hour urine metabolic testing, we compared 24-hour urine parameters with and without concurrent statin use. RESULTS: We identified n=109,866 patients with HLD without prior medical therapy and without kidney stone history, of which 89,599 (81.6%) were exposed to statin over a median 6.5 years of follow-up. The statin exposed were more likely to have history of stroke, coronary artery disease, gout, hypertension, and diabetes. On survival analysis, statin use was not associated with improved stone-free survival (log rank p=0.84). Among patients with 24-hour urine profiles (n=539), those with statin exposure had higher mean BMI, were more often male, and more likely to have a history of hypertension or coronary artery disease. Comparing 24-hour urine parameters, the statin-exposed had higher mean calcium (234 vs 206.1 mg, p=0.02), but there were no other differences in other analytes observed. CONCLUSIONS: Contrary to prior studies, statin use does not appear to be associated with decreased risk of kidney stones. Additionally, there are no identifiable differences in urinary metabolites on 24-hour urine analysis that would suggest a benefit in reducing stone risk. Source of Funding: The project described was supported by CTSA award No. UL1 TR002243 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e836 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wilson Sui More articles by this author Christina J. Peterson More articles by this author Naren Nimmagadda More articles by this author Nicholas L. Kavoussi More articles by this author Nicole L. Miller More articles by this author S. Duke Herrell More articles by this author Ryan S. Hsi More articles by this author Expand All Advertisement PDF DownloadLoading ...

IDF21-0537 Prevalence of normo‐albuminuric renal dysfunction and associations with other clinical parameters in diabetic population

Background: There is paucity of studies regarding normoalbuminuric form of renal dysfunction in diabetic subjects in India. Aim: To find out the prevalence of normo‐albuminuric renal dysfunction and its associations with various clinical and biochemical parameters in a cohort of Indian diabetic population. Method: This is a cross sectional observational study with Indian subjects with type 2 diabetes mellitus. After ruling out other causes of renal dysfunction, based on urinary albumin creatinine ratio and e‐GFR, patients were classified as having no kidney disease (NKD), albuminuria alone (ALB), normoalbuminuric low e‐GFR (NACKD) and albuminuria with low e‐GFR (ACKD). Clinical and biochemical data of these groups were compared. Results: Data from 3000 diabetic subjects with a mean age and duration of diabetes of 53.8 ± 10.9 years and 10.3 ± 7.5 years respectively was analysed. Among the total patients 1750 (58.3%) had NKD and 1250 (41.7%) had renal dysfunction. Among the renal dysfunction patients 430 (34.4%) patients had NACKD and 820 (65.6%) had ACKD. Out of 1250 renal dysfunction patients 537(42.96%) patients had eGFR < 60 ml/min and among them 137 (25.5%) were NACKD. Among 1750 patients of renal dysfunction, the proportion of patients with NACKD was 4.6% where as ACKD was 14.3%. Regression analysis revealed that, NACKD was found to have an independent association with higher age [OR (95% CI)= 1.01 (1.02–1.03); p < 0.001], male sex [OR (95% CI)= 1.23 (1.12–1.35); p < 0.001], body weight [OR (95% CI)= 1.35 (1.17–2.1); p = 0.001] and with statin intake [OR (95% CI)= 1.1 (1.03–1.2); p < 0.00]. None of the glycaemic parameters like HbA1c, FPG, PPPG showed an association with NACKD. When compared to ACKD subjects, only the higher age was found to have an association with NACKD [OR (95% CI) = 1.02 (1.03–1.07); p < 0.001]). Retinopathy was more prevalent in the ACKD patients (p<0.001), whereas the rates of macrovascular complications were similar between the ACKD and NACKD groups (P=0.77). When considering more severe chronic kidney disease (CKD, stage 3b or worse) the prevalence of normoalbuminuric CKD decreased compared to that of albuminuric CKD. Discussion: Normoalbuminuric CKD constitutes more than one third of Indian patients with diabetes and decreased e‐GFR and is strongly related to age but lacks association with duration or severity of hyperglycemia or the presence of retinopathy whereas it has similar association with macrovascular disease as albuminuric CKD.

Lipoprotein(a), Immune Cells and Cardiovascular Outcomes in Patients with Premature Coronary Heart Disease.

The detection of lipoprotein(a) [Lp(a)] in the artery wall at the stage of lipid-bands formation may indicate that it participates in the atherosclerosis local nonspecific inflammatory process. Innate immune cells are involved in atherogenesis, with monocytes playing a major role in the initiation of atherosclerosis, while neutrophils can contribute to plaque destabilization. This work studies the relationship between Lp(a), immune blood cells and major adverse cardiovascular events (MACE) in patients with the early manifestation of coronary heart disease (CHD). The study included 200 patients with chronic CHD, manifested up to the age of 55 in men and 60 in women. An increased Lp(a) concentration [hyperLp(a)] was shown to predict cardiovascular events in patients with premature CHD with long-term follow-up. According to the logistic regression analysis results, an increase in the monocyte count with OR = 4.58 (95% CI 1.04–20.06) or lymphocyte-to-monocyte ratio with OR = 0.82 (0.68–0.99), (p < 0.05 for both) was associated with MACE in patients with early CHD, regardless of gender, age, classical risk factors, atherogenic lipoproteins concentration and statin intake. The combination of an increased monocyte count and hyperLp(a) significantly increased the proportion of patients with early CHD with subsequent development of MACE (p = 0.02, p trend = 0.003). The odds of cardiovascular events in patients with early CHD manifestation were highest in patients with an elevated lymphocyte-to-monocyte ratio and an elevated Lp(a) level. A higher neutrophil blood count and an elevated neutrophil-to-lymphocyte ratio determined the faster development of MACE in patients with a high Lp(a) concentration. The data obtained in this study suggest that the high atherothrombogenicity of Lp(a) is associated with the “inflammatory” component and the innate immune cells involvement in this process. Thus, the easily calculated immunological ratios of blood cells and Lp(a) concentrations can be considered simple predictors of future cardiovascular events.

Prevalence of normoalbuminuric chronic kidney disease among individuals with type 2 diabetes mellitus from India.

A subset of diabetic individuals are known to develop progressive renal insufficiency without albuminuria, referred to as normoalbuminuric chronic kidney disease (NACKD). There is, however, a paucity of studies regarding this condition in India. So, this study, aimed to find the prevalence of normoalbuminuric renal dysfunction and its clinical associations in diabetic Indian population. Medical record search of patients with type 2 diabetes mellitus at a tertiary care centre was done. Based on the urinary albumin:creatinine ratio (>30 mg/g creatinine) and estimated glomerular filtration rate (e-GFR) (<60 ml/min/1.73m2), individuals were classified as having, (i) no kidney disease (NKD), (ii) chronic kidney disease (CKD), (iii) albuminuria alone (ALB), (iv) normoalbuminuric low e-GFR (NACKD) and (v) albuminuria with low e-GFR albuminuric CKD (ACKD). Furthermore, the clinical and biochemical parameters of these groups were also compared. Data from 3534 diabetes patients with a mean age of 53.8±10.9 yr and mean duration of diabetes of 10.3±7.5 yr were available for the analysis. NACKD constituted 39.1 per cent of the patients with reduced e-GFR, NACKD was found in 2.1 per cent and ACKD in 3.4 per cent of all diabetic patients. Compared to NKD patients, was found an independent association between NACKD and higher age, male sex, lower body weight and statin intake but not with glycated haemoglobin, fasting and postprandial plasma glucose. Patients with NACKD were found to be older than those with ACKD. Retinopathy was found to be more prevalent in the ACKD patients, whereas the rates of macrovascular complications were found to be similar between the groups. The prevalence of NACKD relative to ACKD decreased in CKD stages 3b, 4 and 5. The results of this study suggest that NACKD constituted greater than one third of patients with diabetes and decreased e-GFR, which showed a strong association with age but not with duration or severity of hyperglycaemia or the presence of retinopathy. Both NACKD and ACKD showed similar associations with macrovascular disease.

Factors Associated with 90-Day Mortality in Invasively Ventilated Patients with COVID-19 in Marseille, France.

Objectives: To describe clinical characteristics and management of intensive care units (ICU) patients with laboratory-confirmed COVID-19 and to determine 90-day mortality after ICU admission and associated risk factors. Methods: This observational retrospective study was conducted in six intensive care units (ICUs) in three university hospitals in Marseille, France. Between 10 March and 10 May 2020, all adult patients admitted in ICU with laboratory-confirmed SARS-CoV-2 and respiratory failure were eligible for inclusion. The statistical analysis was focused on the mechanically ventilated patients. The primary outcome was the 90-day mortality after ICU admission. Results: Included in the study were 172 patients with COVID-19 related respiratory failure, 117 of whom (67%) received invasive mechanical ventilation. 90-day mortality of the invasively ventilated patients was 27.4%. Median duration of ventilation and median length of stay in ICU for these patients were 20 (9–33) days and 29 (17–46) days. Mortality increased with the severity of ARDS at ICU admission. After multivariable analysis was carried out, risk factors associated with 90-day mortality were age, elevated Charlson comorbidity index, chronic statins intake and occurrence of an arterial thrombosis. Conclusion: In this cohort, age and number of comorbidities were the main predictors of mortality in invasively ventilated patients. The only modifiable factor associated with mortality in multivariate analysis was arterial thrombosis.

Sex-related differences in outcome after endovascular revascularization for lower extremity artery disease.

Background: Sex-related differences may influence the outcome of endovascular revascularization (EVR) in patients with lower extremity arterial disease (LEAD) even under optimized healthcare supply. Patients and methods: LEAD patients who underwent EVR at the Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Germany between 2014 and 2016 were included into the retrospective study. Detailed information on risk factors and co-morbidities, medication, LEAD related measures, and interventional parameters were assessed. Outcome defined as technical success rate, complications, and mortality was analyzed up to 12 months follow-up. Results: In total, 165 female and 437 male LEAD patients were included. Women and men presented with comparable severity of LEAD in terms of critical limb threatening ischemia (46.2%), wound status (34.9%), and amputation rate (9.6%, all n.s.) at index. Intake of platelet inhibitors (65.8% female vs. 70.0% male), oral anticoagulants (21.3% vs. 25.4%), and statins (65.6% vs. 76.0%) was observed less frequently in female patients. Against the background of high technical success (85%), in-hospital death (0.8%), severe adverse cardiac (MCE; 1.7%), and limb events (MALE; 6.1%) occurred at low rates in either sex. Adjusted long-term mortality was not affected by patients' sex (female HR 0.755; p=0.312). Conclusions: Despite critical LEAD stages in every second patient, EVR was performed safe with high technical success rates in female and male patients. Long-term outcomes were observed at comparatively low rates in both sexes at the specialized vascular center. During aftercare, supply with statin therapy turned out improvable particularly in female LEAD patients.

Abstract 8938: The New Myokine Myonectin is Significantly Associated with Type 2 Diabetes in Elderly Patients

Introduction: The novel myokine myonectin is predominantly expressed in skeletal muscle and is involved in the regulation of metabolic homeostasis. A putative association between myonectin and type 2 diabetes mellitus (T2DM) has been discussed controversially in current literature. Hypothesis: We hypothesize that there is an association between myonectin and T2DM at different ages - this is addressed in the present study. Methods: We measured myonectin in 410 vascular risk patients with a mean age of 66 years. Results: Myonectin did not correlate with age (r=-0.19; p=0.697). From our patients 219 (53%) were &gt;65 years, with a mean age of 74 years and 191 ≤65 years, with a mean age of 57 years. The prevalence of T2DM was 40.6% vs. 42.4% in the older as compared to the younger age group. Myonectin concentrations were significantly decreased in elderly patients with T2DM compared to non-diabetic subjects (1.8 vs. 4.2 ng/ml; p=0.002), whereas no significant difference was observed in younger patients (2.6 vs. 2.3 ng/ml; p=0.183). Concordantly, regression analysis revealed an unadjusted odds ratio (OR) of 0.24 [0.07-0.81] (p=0.021) for the association between myonectin and T2DM in elderly patients but not in younger patients (OR=1.08 [0.80-1.45]; p=0.609). The association between myonectin and T2D remained significant after adjusting for sex, body mass index, LDL cholesterol, HDL cholesterol, current smoking, as well as statin intake in elderly but remained non-significant in younger patients (OR=0.23 [0.07-0.81]; p=0.021 vs. OR=1.05 [0.76-1.46]; p=0.769). Conclusions: We conclude that plasma myonectin levels are significantly associated with T2DM, particularly in elderly vascular risk patients.

A Randomized Open Clinical Study of the Atherosclerosis Treatment Information Video Effect on Adherence to Long-Term Therapy in Patients with Cardiovascular Diseases

Aim. Study the effect of a study video, which was created by researchers and devoted to the atherosclerosis development and the effect of statin therapy on atherosclerotic plaque, on adherence to long-term therapy in patients with high or very high risk of cardiovascular complications.Material and methods. 120 patients admitted to hospital with cardiovascular diseases were included in the study. Patients were randomized into 2 groups: in the main group (n=60), the information video edited by the researchers was shown to patients on the eve of discharge, in addition to a printed brochure on lifestyle and diet modification, and in the control group (n=60), patients were given only a standard brochure. The motivating video shows the damage to the cardiovascular system by the atherosclerotic process and the beneficial effect on the body of constant intake of statins. After 1 and 3 months after discharge from the hospital, telephone calls were made, after which the patients had to visit the center for an objective examination by a researcher and control of laboratory parameters. After 1 month, 110 patients visited the center, after 3 months, 98 respondents visited the center.Results. The group with the information video demonstration noted more frequent adherence to medical recommendations compared to the control: after 1 month, 52 (96%) patients continued treatment versus 48 (86%) patients, 3 months after discharge 48 (96%) patients continued treatment versus 38 (79%) patients (p&lt;0.05). After 1 month, 38 (70%) patients in the intervention group continued taking statins versus 29 (43%) respondents in the control group (p&lt;0.05), 3 months after discharge, 40 (80%) patients in the intervention group continued to take statins versus 33 (69%) control patients (p&lt;0.09).Conclusion. Demonstration of a motivating video about the effect of statins on the atherosclerosis course increases patient adherence to medicinal therapy, including adherence to statins.

Peri-implant marginal bone loss and systemic statin use: A retrospective cohort pilot study.

ObjectivesThe aim was to analyze clinical parameters of peri‐implantitis in human subjects exposed and non‐exposed to use of systemic statins.Material and methodsThis retrospective cohort pilot study compared patient records of 60 exposed individuals to 196 non‐exposed individuals as of 2011 throughout 2017. Source of records were specialist and general dentistry clinics in Public Dental Service, Stockholm County, Sweden. Extent/severity of peri‐implantitis and peri‐implant bone loss were registered as well as intake of systemic statins. Background variables considered were bleeding on probing, bone‐loss, age, gender, earlier periodontitis, prosthetic quality, and smoking. Stepwise linear and logistic regression analysis at the individual level was adopted in order to study the influence of statin use on the severity of peri‐implantitis and the incidence of peri‐implant bone loss. Results were considered statistically significant at p < 0.05.ResultsPeri‐implant bone loss was significantly correlated to use of statin after compensation for age and sex.ConclusionsThe results render an actual effect of statins on peri‐implant bone loss plausible. Further research is warranted.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD

Background and aimsThe optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and resultsA total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression.During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. ConclusionsThis study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

The new myokine myonectin is significantly associated with type 2 diabetes in elderly patients

Abstract The novel myokine myonectin is predominantly expressed in skeletal muscle and is involved in the regulation of metabolic homeostasis. A putative association between myonectin and type 2 diabetes mellitus (T2DM) has been discussed controversially in current literature. The purpose of this study was to investigate the association between myonectin and T2DM at different ages. We measured myonectin in 410 vascular risk patients with a mean age of 66 years. Myonectin did not correlate with age (r=−0.19; p=0.697). From our patients 219 (53%) were &amp;gt;65 years, with a mean age of 74 years and 191 ≤65 years, with a mean age of 57 years. The prevalence of T2DM was 40.6% vs. 42.4% in the older as compared to the younger age group. Myonectin concentrations were significantly decreased in elderly patients with T2DM compared to non-diabetic subjects (1.8 vs. 4.2 ng/ml; p=0.002), whereas no significant difference was observed in younger patients (2.6 vs. 2.3 ng/ml; p=0.183). Concordantly, regression analysis revealed an unadjusted odds ratio (OR) of 0.24 [0.07–0.81] (p=0.021) for the association between myonectin and T2DM in elderly patients but not in younger patients (OR=1.08 [0.80–1.45]; p=0.609). The association between myonectin and T2D; remained significant after adjusting for sex, body mass index, LDL cholesterol, HDL cholesterol, current smoking, as well as statin intake in elderly but remained non-significant in younger patients (OR=0.23 [0.07–0.81]; p=0.021 vs. OR=1.05 [0.76–1.46]; p=0.769). We conclude that plasma myonectin levels are significantly associated with T2DM, particularly in elderly vascular risk patients. Funding Acknowledgement Type of funding sources: None.

The associations of statin intake and the trabecular bone score and bone mineral density status in elderly Iranian individuals: a cross-sectional analysis of the Bushehr Elderly Health (BEH) program.

In recent years, a growing interest has been established to evaluate the impact of statin intake on bone health, although the reported results are controversial. This study aimed to evaluate the association of statin intake with bone health status according to BMD and TBS. This cross-sectional analysis used data from the elderly Iranian individuals who participated in the Bushehr Elderly Health (BEH) program. Dual x-ray absorptiometry (DXA) device was used to evaluate the BMD at lumbar spine (L1-L4), femoral neck, and total hip, as well as TBS at lumbar spine. Among 2426 (1260 women and 1166 men) study participants, 778 were statin users. A positive significant association, irrespective of sex, was observed between statin intake and BMD at L1-L4, even after controlling for potential variables in total population (β = 0.016, p = 0.013). The mean TBS values at L1-L4 were negatively associated with statin intake in total population (β = - 0.009, p = 0.001), while in the full adjusted model, significant positive association between TBS and statin intake was detected only in men (β = 0.013, p = 0.02). The results of this study revealed that BMD at lumbar spine has a significant association with statin intake. However, such an association appears to be weaker regarding TBS values compared to BMD.

Usefulness of red cell distribution width to predict mortality in patients undergoing endovascular repair of abdominal aortic aneurysms.

Red cell distribution width (RDW) reflecting impaired erythropoyesis, has been associated with poor prognosis and mortality in several conditions. The aim of this study was to determine the relationship between RDW and the 5-year survival after the endovascular repair of abdominal aortic aneurysms (EVAR) and its ability to improve the discriminative power of a survival predictive score. Retrospective analysis of 284 patients undergoing EVAR at a single centre. The pattern of relationship between RDW and survival was assessed with penalized smoothing splines. Categorized RDW values were added to a predictive score based in standard preoperative variables, whose improvement in discriminative power was calculated on the basis of changes in the C-statistics and the continuous Net Reclassification Index (c-NRI). The survival rate at 5 years was 66.2% and was independently associated with hemoglobin (HR=0.85, P<0.004), statin intake (HR=0.54, P<0.004), heart failure (HR=2.53, P<0.018), atrial fibrillation (HR=2.53, P<0.000) and the non-revascularized coronary artery disease (HR=2.15, P<0.005). The relationship between RDW values and 5-year survival was linear. RDW-CV and RDW-SD were categorized to cut-off values of ≥15% (N.=83, 29.2%) and ≥50 fL (N.=82, 28.9%) that were independently associated with poorer 5-year survival rates (HR=2.03, CI 95%=1.29-3.19, P=0.002 and HR=1.89, CI 95%=1.21-2.95, P=0.005, respectively). The addition of the RDW CV or the RDW-SD to the baseline predictive score significantly improved the c-NRI (0.437, P<0.001 and 0.442, P<0.001, respectively). High preoperative RDW levels were linear and adversely related to 5-year survival after EVAR, improved the discriminative power of a predictive score based in standard preoperative variables and may help in decision-making at the time of surgical planning.

Modulation of Phospholipid Bilayer Properties by Simvastatin

Simvastatin (Zocor) is one of the most prescribed drugs for reducing high cholesterol. Although simvastatin is ingested in its inactive lactone form, it is converted to its active dihydroxyheptanoate form by carboxylesterases in the liver. The dihydroxyheptanoate form can also be converted back to its original lactone form. Unfortunately, some of the side effects associated with the intake of simvastatin and other lipophilic statins at higher doses include statin-associated myopathy (SAM) and, in more severe cases, kidney failure. While the cause of SAM is unknown, it is hypothesized that these side effects are dependent on the localization of statins in lipid bilayers and their impact on bilayer properties. In this work, we carry out all-atom molecular dynamics simulations on both the lactone and dihydroxyheptanoate forms of simvastatin (termed "SN" and "SA", respectively) with a pure 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer and a POPC/cholesterol (30 mol %) binary mixture as membrane models. Additional simulations were carried out with multiple simvastatin molecules to mimic in vitro conditions that produced pleiotropic effects. Both SN and SA spontaneously diffused into the lipid bilayer, and a longer simulation time of 4 μs was needed for the complete incorporation of multiple SAs into the bilayer. By constructing potential mean force and electron density profiles, we find that SN localizes deeper within the hydrophobic interior of the bilayer and that SA has a greater tendency to form hydrogen-bonding interactions with neighboring water molecules and lipid headgroups. For the pure POPC bilayer, both SN and SA increase membrane order, while membrane fluidity increases for the POPC/cholesterol bilayer.

Chronic Onset Form of Anti-HMG-CoA Reductase Myopathy.

We report a case of anti-HMGCR myopathy mimicking limb-girdle muscular dystrophy in a 27-year-old male patient with no history of statin intake and presenting with a chronic onset form over 3 years. Treatment with prednisone and methotrexate was initiated with an insufficient response, so intravenous immunoglobulin was added. One year after initial treatment was started, as levels of creatine kinase (CK) were >1000 U/l, treatment with rituximab was added. Despite a 3-year delay before treatment, muscle strength improved even though CK levels remain elevated.LEARNING POINTSWe describe a case of anti-HMGCR myopathy mimicking limb-girdle muscular dystrophy, which resulted in delayed diagnosis and management.The patient’s muscular strength improved but creatine kinase levels remain elevated despite comprehensive treatment.

1188-P: The New Myokine Myonectin Is Significantly Associated with Type 2 Diabetes in Elderly Patients

The novel myokine myonectin is predominantly expressed in skeletal muscle and is involved in the regulation of metabolic homeostasis. A putative association between myonectin and type 2 diabetes mellitus (T2DM) has been discussed controversially in current literature. The association between myonectin and T2DM at different ages is still obscure and thus is addressed in the present study. We measured myonectin in 410 vascular risk patients with a mean age of 66 years. Myonectin did not correlate with age (r=-0.19; p=0.697). Half of our patients (53%) were elderly (≥66 years; n=219) with a mean age of 74 years. The younger ones (≤65 years; n=191) had a mean age of 57 years. 40.6% (n=89) of elderly patients had T2DM and 42.4% (n=81) of the younger ones. Myonectin concentrations were significantly decreased in elderly patients with T2DM compared to nondiabetic ones (1.8 vs, 4.2 ng/ml; p=0.002), whereas no significant difference was seen in younger patients (2.6 vs. 2.3 ng/ml; p=0.183). Regression analysis revealed an unadjusted odds ratio (OR) of 0.24 [0.07-0.81] (p=0.021) for the association between myonectin and T2DM in elderly patients but not in younger patients (OR=1.08 [0.80-1.45]; p=0.609). This association remained significant after adjusting for sex, body mass index, LDL-cholesterol, HDL-cholesterol, current smoking, as well as statin intake in elderly but not in younger patients (OR=0.23 [0.07-0.81]; p=0.021 vs. OR=1.05 [0.76-1.46]; p=0.769). We conclude that plasma myonectin levels are significantly associated with T2DM particularly in elderly vascular risk patients. Disclosure A. Leiherer: None. P. Fraunberger: None. H. Drexel: None. A. Muendlein: None. K. Geiger: None. C. H. Saely: None. B. Larcher: None. A. Mader: None. M. Maechler: None. L. Sprenger: None. B. Mutschlechner: None.

MO474PCSK9 LEVELS AND MARKERS OF INFLAMMATION, OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION IN A POPULATION OF NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS: IS THERE AN ASSOCIATION?

Abstract Background and Aims Proprotein convertase subtilisin / kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress and endothelial damage in patients with CKD. Method Ninety-two patients with CKD stage II-ΙV (eGRF CKD-EPI 47.3 ±25.7ml/min/1,73m2, mean age 66 years, 51 men) were included. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension; diabetes mellitus, history of cardiovascular disease), renal function indices (eGFR, proteinuria – UPR/24h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp (a), APO-A1, APO-B), as well as soluble biomarkers of inflammation, oxidative stress and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, sVCAM-1). Results The mean plasma value of PCSK9 was 278.1ng/ml. PCSK9 levels showed direct correlation with serum triglycerides (p = 0.03), Lp(a) (p = 0.01), and sICAM-1 levels (p = 0.03). There was no significant correlation between PCSK9 levels and indices of renal function, other lipid profile parameters, inflammatory markers or co-morbidities. Multiple regression analysis showed a significant effect of the Lp(a) on PCSK9 levels, for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935 - 5.228, p=0.006). At the same time, patients receiving statins are expected to have on average 63.8ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6 - 113.5 p=0.012). Conclusion Plasma levels of PCSK9 in non-dialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD

Evaluation of Drug-Drug Interactions in EGFR-Mutated Non-Small-Cell Lung Cancer Patients during Treatment with Tyrosine-Kinase Inhibitors.

(1) Background. The onset of a drug–drug interaction (DDI) may affect treatment efficacy and toxicity of advanced non-small-cell lung cancer (aNSCLC) patients during epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) use. Here we present the use of Drug-PIN® (Personalized Interactions Network) software to detect DDIs in aNSCLC patients undergoing EGFR-TKIs. (2) Methods. We enrolled patients with Stage IV aNSCLC already treated with or candidates to receive EGFR-TKIs, in any line; ECOG PS 0–2; taking at least one concomitant drug. Cancer treatments, concomitant drugs, and clinical and laboratory data were collected and inserted in Drug-PIN®. (3) Results. Ninety-two patients, median age of 68.5 years (range 43–89), were included. In total, 20 clinically relevant DDIs needing medical intervention in a total of 14 patients were identified; the 14 major DDIs were related to a high-grade interaction between TKIs and SSRIs, antipsychotics, antiepileptics, H2-receptor antagonist and calcium antagonists. A negative association between statin intake and PFS was identified (p = 0.02; HR 0.281, 95% CI 0.096–0.825). (4) Conclusions. This is the first retrospective study assessing the prevalence of DDIs, the clinical need for medical intervention and the impact of concomitant drugs on EGFR-TKIs survival in aNSCLC.