Patients Receiving Statin Treatment Research Articles

The Effect of Chronic Laxative Use on Lipid Profile and HbA1c: A Hospital-Based Retrospective Study.

Laxatives are over-the-counter medications used as a treatment for constipation. The lipid-lowering effect of the long-term use of laxatives has been proposed. To investigate the possible impact of the chronic use of laxatives on serum lipid profile, body mass index (BMI), and hemoglobin A1c (HbA1c). An observational retrospective cohort study was conducted to analyze data related to patients who received laxatives for six or 12 months or more in the KAUH database system. BMI, weight, cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and HbA1c data were collected retrospectively from hospital records for three time points: baseline, six months, and 12 months of laxative treatment from the starting date for each patient. A total of 106 patients' records fulfilled the inclusion criteria, 46 (43%) males with a mean age of 66 and 60 (57%) females with a mean age of 63. A significant decrease in plasma cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels was observed in those who used laxatives for 12 months. Furthermore, an overall BMI and ALT reduction was seen in the combined. On the other hand, HbA1c levels appeared to improve in the combined group but not statistically significant. The change in the cholesterol level could be observed in patients receiving statin treatment and those without, with no statistical significance between the two groups. Chronic laxative use for 12 months or more is associated with a decreased total and LDL-C level with no significant effect on high-density lipoprotein-cholesterol (HDL-C) levels. Additionally, there was a significant reduction in BMI and ALT. This effect is more prominent with combined therapy. Further multicentric studies on larger sample sizes are recommended to confirm our findings.

Effect of statin treatment on clinical outcomes in cardioembolic stroke with endovascular thrombectomy

BackgroundWhile statins have been widely used in patients with large-artery atherosclerotic stroke, their effectiveness in patients with cardioembolic large vessel occlusion (CE-LVO) undergoing endovascular treatment (EVT) remains unclear. This study...

Efficacy and safety of pemafibrate versus bezafibrate in coronary artery disease patients receiving statin treatment: a randomized, open-label, cross-over study

Abstract Background Fibrates activate peroxisome proliferator-activated receptor (PPAR)-α which is associated with lipid metabolism. Bezafibrate is a non-selective PPAR-α agonist, whereas pemafibrate has been developed as a higher selective PPAR-α agonist. Objective The efficacy and safety of pemafibrate for 24-week in patients with dyslipidemia was examined in comparison with bezafibrate. Methods Sixty patients with hypertriglyceridemia (fasting triglyceride (TG) level of ≥150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24-week in a randomized cross-over study. Percent change from baseline in TG levels was the primary endpoint, and that in HDL-C and apolipoprotein A-I (Apo A-I) levels was the secondary endpoints. Results A significantly greater reduction in TG percent change was observed in pemafibrate than in bezafibrate (−46.1% vs. −34.7%, p<0.001). There was no significant difference in HDL-C percent change between pemafibrate and bezafibrate (18.4% vs. 14.0%, p=0.067), whereas Apo A-I percent change was significantly greater in pemafibrate than in bezafibrate (9.2% vs. 5.7%, p=0.018). Pemafibrate and bezafibrate significantly decreased alanine aminotransferase (ALT) and gamma-glutamyltransferase (γ-GT) levels, and pemafibrate showed a greater reduction than bezafibrate (ALT: −21.9% vs. −10.6%, p=0.048; γ-GT: −43.5% vs. −33.1%, p=0.025). Creatinine levels significantly increased in both treatments (both p<0.001), however, creatinine percent change was significantly smaller in pemafibrate than in bezafibrate (5.72% vs. 15.5%, p<0.001). There was no difference in frequency of adverse event (AE) or serious AE between two treatments, but frequency of creatinine elevation (≥0.5 mg/d and/or 25%) was significantly higher in bezafibrate than in pemafibrate (16/60 vs. 3/60, p=0.004). Conclusion As compared with bezafibrate, pemafibrate is more effective to reduce TG levels and to elevate Apo A-I levels, and it is safer in terms of liver and renal function. Funding Acknowledgement Type of funding sources: None.

Comorbidity and medication use in patients with angina due to a coronary vasomotion disorder

Abstract Background Microvascular angina and vasospastic angina are disorders of coronary vasomotion. The associations between these conditions, comorbidity and medication use in relatively unselected populations is not well described. Aim To describe the proportions of patients with concomitant morbidity and related medication use in an international, contemporary, clinical database. Methods TriNetX, a global federated health research network with access to anonymized electronical medical records (EMRs) from participating healthcare organizations including academic medical centres, specialty physician practices, and community hospitals, predominantly in the USA was used. The ICD10 code (I20.1) representing “Angina pectoris with documented spasm” was used as a primary search term. ICD10 codes were also used for cardiorenal and metabolic conditions. Medication use was classified as occurring prior to or on the date of the angina episode. The time-period for defining the analysis population was 01.01.2017–31.12.2019. The population age was ≥18 years. Results Data were available on 12,200 individuals (mean (SD) age 63 (13) years; 63% female). The % of individuals with a concomitant diagnosis is described in Table 1. Hypertension occurred in almost two thirds of individuals, an anxiety disorder affected more than one quarter and type 2 diabetes and/or obesity occurred in one fifth. Medication use is described in Table 2. Half of patients received a calcium channel blocker therapy. Nitroglycerin, beta-blockers, and isosorbide mononitrate were less commonly used (45%, 45% and 23%, respectively). Most (58%) patients were prescribed an antacid. Half of patients received statin treatment (50% overall; 36% atorvastatin) and insulin (12%) and metformin (9%) were the most commonly prescribed antidiabetic medications. Conclusions Angina associated with coronary spasm associates with female sex and cardio-metabolic risk factors. Contemporary pharmacotherapy for diabetes and statins appear to be under-used. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca

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 of Lipoprotein(a) With Recurrent Ischemic Events Following Percutaneous Coronary Intervention.

This study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI). Elevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study. A prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke. From the registry, 3,747 (31.1%) patients had high Lp(a) (>30mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95%CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95%CI: 1.02-1.25; P = 0.022). Elevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI.

Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

BackgroundType 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target.MethodsCarotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers.ResultsPlaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p < 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a).ConclusionsThis study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.

Association between statin use and osteoporotic fracture in patients with chronic obstructive pulmonary disease: a population-based, matched case-control study

BackgroundIn the recent years, chronic obstructive pulmonary disease (COPD) has been found to be associated with a higher risk of new-onset osteoporotic fracture (NOF). However, the existence of such an association in the COPD patients receiving statin treatment remains unknown. The present study aimed to investigate the association between COPD and NOF in statin-treated patients.MethodsThe present study was conducted over a period of 10 years (January 2004 to December 2013) in Taiwan. COPD patients receiving statin treatment were included in the statin user group, whereas the randomly selected statin non-users, with 1:1 matching for sex, age, index date, and Charlson Comorbidity Index, were included in the statin non-user group. The hazard ratio (HR) of NOFs in COPD patients was estimated between statin user and non-user groups.ResultsA total of 86,188 cases were identified as the statin-treated patients, and 86,188 subjects were included in the control group of statin non-users. Initially, the risk of NOF was found to be higher among the statin users as compared to non-users [HR, 1.12; 95% confidence interval (CI), 1.01–1.25]. However, the calculation of risk for NOFs after the adjustment for age, sex, comorbidities, and concurrent medications indicated no association of NOF (HR, 0.81; 95% CI, 0.55–1.21) with COPD in patients receiving statin treatment as compared to statin non-users.ConclusionThe results of the study provided first evidence for the absence of any association between COPD and NOFs in statin-treated patients during a follow-up period of 10 years. Thus, the findings of this study might support the hypothesis stating the potent pleiotropic effects of statins. In clinical practice, these drugs might prove beneficial for the patients with COPD.

Guideline adherence is associated with long-term all-cause mortality in patients after an acute coronary syndrome

Abstract Background/Introduction Guideline-directed medical therapy (GDMT) remains the mainstay in the long-term management of patients after an acute coronary syndrome (ACS). Data on the association of adherence to GDMT with clinical outcomes are scarce. Purpose To assess the adherence to GDMT and its relation to all-cause mortality in a population of patients after an ACS. Methods In this post-hoc analysis of the prospective, randomised IDEAL-LDL trial (NCT02927808) we analyzed data of 360 ACS patients discharged from a cardiology clinic. Median follow-up period was 35.9 (IQR 25.7–41.6) months. GDMT was assessed at discharge and at the 1-year follow-up, at which time data was collected by telephone interviews or ambulant visits. GDMT was defined as compliance with secondary prevention therapies (statin, antiplatelet, b-blocker, angiotensin-converting enzyme inhibitor (ACE-i) or angiotensin II receptor blocker (ARB)), as per their respective indication in the 2017 STEMI and 2015 NSTE-ACS ESC Guidelines. Extended follow-up data for mortality was collected from the national health insurance electronic prescription system. Results Median age of the entire cohort was 60 (IQR-53–71) years, 18.6% were female and 55.6% suffered a STEMI. At discharge, 342 patients (95%) received statins, 331 (91.9%) proper antithrombotic therapy (86.4% on dual antiplatelet therapy (DAPT), 2.5% on antiplatelet plus anticoagulant and 3% on triple therapy), 309 (85.8%) β-blockers and 217 (60.3%) ACE-i or ARB. GDMT at discharge was prescribed to 272 (75.6%) patients. The 1-year mortality rate was 4.7% (IQR, 2.5–6.9) and there was no mortality benefit for GDMT (HR=0.77 95% CI 0.27 - 2.2) (Figure 1a). At the one-year follow up, 323 (94.2%) of 343 alive patients received statin treatment (72.4% of which a high-intensity statin), 330 (96.2%) any antithrombotic therapy (59.8% on DAPT, 5.2% on any anticoagulant), 263 (76.7%) a β-blocker and 194 (56.6%) an ACE-I or ARB. GDMT at one-year follow up was prescribed to 248 (72.3%) patients. Beyond one year, all-cause mortality was significantly reduced in patients receiving GDMT adjusted for age, STEMI, revascularization with percutaneous coronary angioplasty, history of diabetes mellitus and arterial hypertension. (1.6% vs 9.5%, aHR 0.3 95% CI 0.08 - 0.92) (Figure 1b). Conclusions Adherence to GDMT remains stable one year after an ACS. GDMT was associated with a significant decrease in long-term mortality, but not associated with one-year mortality. Figure 1. GDMT at baseline, at 1 year and mortality Funding Acknowledgement Type of funding source: None

Role of statins in preventing cardiac surgery-associated acute kidney injury: an updated meta-analysis of randomized controlled trials.

BackgroundThe prevention of cardiac surgery-associated acute kidney injury (CSA-AKI) by statins remains controversial. Therefore, the present meta-analysis including randomized controlled trials (RCTs) was performed to assess the effect of perioperative statin on CSA-AKI.MethodsTwo reviewers independently searched for RCTs about perioperative statin for prevention of CSA-AKI. The primary endpoint was CSA-AKI. Relative risk was calculated between statin and placebo for preventing CSA-AKI using the random-effect model or fixed-effect model according to different heterogeneity.ResultsEight RCTs met inclusion criteria, including five studies with atorvastatin, two with rosuvastatin, and one with simvastatin. There were 1,603 patients receiving statin treatment and 1,601 with placebo. Perioperative statin therapy did not reduce the incidence of CSA-AKI (relative risk =1.17, 95% CI: 0.98–1.39, p=0.076). Furthermore, perioperative statin increased the risk of CSA-AKI in the subgroup analysis with clear definition of CSA-AKI and those with JADAD score >3. Perioperative rosuvastatin produced slightly significantly higher risk of AKI than atorvastatin therapy (p=0.070). Statin intervention both pre and post surgery slightly increased the risk of CSA-AKI versus preoperative statin therapy alone (p=0.040).ConclusionsPerioperative statin therapy might increase the risk of CSA-AKI after cardiac surgery.

ABT-737 and pictilisib synergistically enhance pitavastatin-induced apoptosis in ovarian cancer cells.

There is considerable interest in redeploying drugs for use in combination with other oncology therapeutics. The single-agent activity of statins in ovarian cancer has been widely reported, however the drug concentration required to cause cell death is considerably higher than that achieved in patients receiving statin treatment for hypercholesterolemia. Unfortunately, statins can cause myopathy when administered in high doses. One solution to this is to identify drugs that could be used in combination with statins to reduce the dose required and those that may potentially reduce the incidence of adverse side effects. When the BH3 mimetic ABT-737, or the phosphatidylinositol 3-kinase inhibitor pictilisib, were combined with pitavastatin in cell growth assays using Ovcar-3 and Igrov-1 cells, the drug combinations were more effective than pitavastatin alone. In support of this, ABT-737 or pictilisib markedly increased cell death induced by pitavastatin in several ovarian cancer cell lines. The drugs were also synergistic in apoptosis assays. These observations suggested that either BH3 mimetics or pictilisib in combination with pitavastatin could be used in a subset of ovarian tumours, particularly those sensitive to BH3 mimetics, and phosphatase and tensin homolog inhibition, in the treatment of ovarian cancer.

Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease.

Many susceptibility loci associated with coronary artery disease (CAD) have been identified using genome-wide association studies (GWAS). This study aimed to examine whether a composite of single nucleotide polymorphisms (SNPs) derived from GWAS could identify the risk of major adverse cardiovascular events (MACEs) in patients with established CAD. There were 1059 patients with CAD were included in the analysis. Of the participants, 686 were on statin treatment at the start of follow-up. A weighted genetic risk score (wGRS) was calculated as the sum of risk alleles multiplied by the hazard ratio for a particular SNP. In single variant analyses, rs579459, rs4420638, and rs2107595 were associated with an increased risk of MACE. A wGRS was further constructed to evaluate the cumulative effect of the 3 SNPs on the prognosis of CAD. The risk of MACE among patients with high and intermediate wGRS was 1.968- and 1.838-fold, respectively, higher than those with low wGRS. This effect was more evident in patients using lipid-lowering medication and with hypertension. Furthermore, the interaction analysis revealed that lipid-lowering medication and hypertension interacted with the genetic effect off wGRS on the risk of MACE in patients using lipid-lowering medication or with hypertension (Pinteraction < .001). We further analyzed the follow-up change in low-density lipoprotein cholesterol (LDL-C) level at 6 months after CAD disclosure and evaluated whether that was due to wGRS or statin use. The lowest reduction in LDL-C was observed in patients with high GRS who received statin treatment. Furthermore, LDL-C reduction of patients with intermediate wGRS was less than those with low wGRS in patients treated with statin. Taken together, a wGRS comprised of SNPs significantly predicts MACE in CAD patients receiving statin treatment and hypertension.

The association of HDL-apoCIII with coronary heart disease and the effect of statin treatment on it.

BackgroundApolipoprotein CIII (apoCIII) is considered to impair the anti-atherogenic effect of high density lipoprotein (HDL) in coronary heart disease (CHD) patients, and apoCIII content in HDL (HDL-apoCIII) predicts CHD more accurately. However, the relationship between HDL-apoCIII and CHD, and the effect of statin treatment on HDL-apoCIII are still unclear. The aims of the study are to establish the association of HDL-apoCIII with CHD, and investigate the effect of statin treatment on HDL-apoCIII in CHD patients.MethodsWe conducted a hospital-based observational study. Totally 80 non-CHD patients and 120 CHD patients without statin treatment were previously enrolled in this study. All the CHD patients received statin treatment, and 63 of them were followed after 3 months of regular statin treatment. HDL sample of each patient was isolated by density gradient ultracentrifugation from fasting venous plasma, and HDL-apoCIII of each patient was measured by ELISA method.ResultsHDL-apoCIII was significantly higher in CHD patients than non-CHD patients (p < 0.05), and it was still an independent predictor of CHD after adjusting for other factors. Total plasma apoCIII, especially HDL-apoCIII was significantly elevated after statin treatment in CHD patients, whereas total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and apolipoprotein B (apoB) were decreased significantly (p < 0.05). Compared with CHD patients without diabetes mellitus (DM), the effect of statin treatment on apoCIII markers was minor in CHD patients with DM. And HDL-apoCIII correlated with plasma TG significantly in non-CHD and CHD patients (p < 0.05), but the correlation in CHD patients did not exist after statin treatment (p > 0.05).ConclusionsHDL-apoCIII has a significant and positive association with CHD. Although conventional atherogenic lipid markers have a significantly decrease in CHD patients after statin treatment, HDL-apoCIII has a further elevation at the same time.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0129-8) contains supplementary material, which is available to authorized users.

Association between Statin Use and Short-Term Outcome Based on Severity of Ischemic Stroke: A Cohort Study

BackgroundStatins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity.MethodsA total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0–5) at 3 months after onset using multivariable logistic regression models.ResultsA total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38–0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81–1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31–0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57–0.92) at 3 months in the non-minor stroke group.ConclusionsStatin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.

Increased levels of circulating endothelial progenitor cells in patients with ischaemic stroke treated with statins during acute phase

Endothelial progenitor cells (EPCs) have been suggested to be a therapeutic option in ischaemic stroke. Our aim was to study whether statin treatment during acute phase could increase circulating EPCs after acute ischaemic stroke. We studied 48 patients with a first-ever non-lacunar ischaemic stroke (<12h from stroke onset). Sixteen patients received statin treatment (20mg atorvastatin/day) during the first 4days. We defined the EPC increment during the first week as the difference in the number of early outgrowth colony-forming unit-endothelial cell (CFU-EC) between day 7 and at admission (previous to atorvastatin treatment). Serum levels of vascular endothelial growth factor and active matrix metalloproteinase 9 (determined by ELISA), and nitric oxide metabolites (NOx) (determined by high-performance liquid chromatography) were measured at admission, 24 and 72h, and day 7. Colony-forming unit-endothelial cells were similar at baseline between patients treated (n=16) and non-treated (n=32) with statins (10.1±3.9 vs. 7.9±6.9CFU-EC, P=0.223). However, patients treated with statins showed a higher EPC increment (24.0±17.3 vs. 6.0±17.8CFU-EC, P=0.002) during the first week. An EPC increment≥4CFU-EC predicted with the highest sensitivity (88%) and specificity (92%) the probability of good outcome (area under the curve 0.903, P<0.0001). Statin treatment (OR, 13.1; CI 95%, 2.2-76.9, P=0.004) was independently associated with an EPC increment≥4CFU-EC after adjustment for confounder factors, but this association was lost when adjusting for NOx levels. Statin treatment for 4days may increase circulating EPC levels, probably by NO-related mechanisms.

Statins Improve Outcome in Isolated Heart Valve Operations: A Propensity Score Analysis of 3,217 Patients

Whether statins can improve postoperative outcome in patients without coronary artery disease undergoing heart valve operations was assessed. Data for 3,217 patients undergoing isolated valve procedures at 2 institutions between May 2003 and May 2009 were reviewed. Clinical follow-up was completed. Two propensity-matched cohorts of 1,104 patients each were identified. Multivariable regression and Kaplan-Meyer survival analysis were performed to investigate risk factors correlated with death, stroke, myocardial infarction, and cardiac arrhythmias. The overall 30-day mortality rate was 2.7%, and 2,096 of 2,149 hospital survivors were alive at a median follow-up of 27 months. Preoperative statin treatment was independently associated with a significant reduction in the risk of hospital death (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32 to 0.89; p=0.001), postoperative cardiac arrhythmias (OR, 0.76; 95% CI, 0.62 to 0.93; p<0.006), and stroke (OR, 0.54; 95% CI, 0.32 to 0.92; p=0.02) but was not independently associated with a reduced risk of postoperative myocardial infarction. At follow-up, Kaplan-Meyer survival analysis showed statistically significant lower rates of mortality (χ2, 4.41; hazard ratio [HR], 1.59; 95% CI, 1.13 to 2.27; p=0.03), stroke (χ2, 11.42; HR, 2.15; 95% CI, 1.37 to 3.27; p=0.0007), cardiac arrhythmias (χ2, 19.9; HR, 2.13; 95% CI, 1.81 to 2.72; p<0.0001), and major adverse cardiac and cerebrovascular events (χ2, 3.74; HR, 1.37; 95% CI, 0.99 to 1.74; p=0.05) in patients receiving statin treatment. No statistically significant difference was found between groups in myocardial infarction incidence at follow-up. Statin therapy is associated with a lower rate of adverse cardiovascular events after isolated heart valve operations.

58 CHANGES IN HUMAN LIPOPROTEIN COMPOSITION IN PATIENTS WITH ACUTE CORONARY SYNDROME

The protein composition of lipoproteins may serve as biomarkers or reveal underlying mechanisms during different states of disease. Here we have analysed the protein composition of LDL and HDL from patients with acute coronary syndrome (ACS) and patients receiving statins after previous ACS. Plasma samples were obtained from males, namely 12 healthy donors, 9 patients with ACS and 7 stable patients receiving statin treatment after previous ACS. LDL and HDL were isolated by two-step density ultracentrifugation. LDL proteins were analysed with two-dimensional gel electrophoresis and mass spectrometry. Paraoxonase 1 (PON-1) in HDL was analyzed with SDSPAGE/Western Blot.Concentrations of apo A-IV, a1-antitrypsin and transthyretin were significantly increased (P < 0.05) in LDL from patients with ACS compared to healthy controls. In patients receiving statins, a1-antitrypsin remained increased while serum amyloid A4 was decreased. By western blot analysis, a non-significant increase in PON-1 was found in HDL from patients with ACS. Interestingly, a truncated form of PON-1 was detected in all patients with ACS but not in any of the controls.In conclusion, we confirm previous findings that LDL-associated transthyretin is a possible biomarker of myocardial infarction. Moreover, the increased concentration of the inflammatory marker a1-antitrypsin in LDL from both ACS patients and stable patients after ACS indicate that the enrichment does not only reflect an acute phase response. The presence of a truncated form of the antioxidant protein PON-1 in HDL may explain previous findings showing increased amounts but lower activity of PON-1 in patients with ACS.

Cardiovascular and Cancer Mortality in Very Elderly Post-Myocardial Infarction Patients Receiving Statin Treatment

The purpose of this study was to determine whether statin treatment is effective and safe in very elderly (80 years and older) acute myocardial infarction (AMI) patients. Elderly individuals constitute an increasing percentage of patients admitted to hospitals for AMI. Despite that these patients have a higher mortality risk, the application of evidence-based medicine remains much lower than for younger patients. We included all patients 80 years and older who were admitted with the diagnosis of AMI in the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions between 1999 and 2003 (n = 21,410). Of these, complete covariate and follow-up data were available for 14,907 patients (study population A). To limit the bias related comorbidity on statin therapy, we also performed analyses excluding patients who died within 14 days of the acute event (study population B) and all patients who died within 365 days (study population C). A propensity score was used to adjust for initial differences between treatment groups. All-cause mortality was significantly lower in patients receiving statin treatment at discharge in study population A (relative risk: 0.55, 95% confidence interval: 0.51 to 0.59), in study population B (relative risk: 0.65; 95% confidence interval: 0.60 to 0.71), and in study population C (relative risk: 0.66; 95% confidence interval: 0.59 to 0.76). Similar observations were made for cardiovascular mortality as well as for AMI mortality. There was no increase in cancer mortality in statin-treated patients. Statin treatment is associated with lower cardiovascular mortality in very elderly post-infarction patients without increasing the risk of the development of cancer.

Statin therapy is associated with reduced total and cardiovascular mortality after coronary artery bypass grafting surgery

In an observational study, we evaluated the association between postoperative statin therapy and long-term mortality among patients undergoing a first-ever coronary artery bypass grafting (CABG) surgery. In an outpatient clinic setting, we assessed 1869 consecutive patients (age 58.7+/-9.6 years; 1657 men), who survived the 1st month after a first-ever CABG, within a 17-year period. Cox proportional hazard analysis was used to calculate the adjusted hazard ratios (adjusting for age, smoking, the presence of hypertension, diabetes mellitus, lipid profile at the time of the procedure, vessel disease, number and kind of grafts used, and concomitant treatment) for patients receiving statin treatment during follow-up and adjusted Kaplan-Meier survival curves were constructed. During a 9345 patient-years follow-up, 48% of the patients were on a statin. In a total of 222 deaths, 80.6% were because of cardiovascular causes. Total and cardiovascular mortality were significantly reduced in patients receiving statin therapy [adjusted hazard ratio, 0.48 (95% confidence interval, 0.28-0.82); P=0.007), and 0.43 (95% confidence interval, 0.23-0.80); P=0.007, respectively]. The estimated 16-year Kaplan-Meier survival curves diverged at 2 years and thereafter. Taking into account the potential limitations of observational data, statin treatment postoperatively is associated with a 50% reduction in total and cardiovascular mortality in patients undergoing a first-ever CABG.

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells

BackgroundA number of recent studies have suggested that cancer incidence rates may be lower in patients receiving statin treatment for hypercholesterolemia. We examined the effects of statin drugs on in vitro proliferation, migration and invasion of melanoma cells.MethodsThe ability of lovastatin, mevastatin and simvastatin to inhibit the melanoma cell proliferation was examined using cytotoxicity and apoptosis assays. Effects on cell migration and invasion were assessed using transwell invasion and migration chambers. Hypothesis testing was performed using 1-way ANOVA, and Student's t-test.ResultsLovastatin, mevastatin and simvastatin inhibited the growth, cell migration and invasion of HT144, M14 and SK-MEL-28 melanoma cells. The concentrations required to inhibit proliferation of melanoma cells (0.8–2.1 μM) have previously been achieved in a phase I clinical trial of lovastatin in patients with solid tumours, (45 mg/kg/day resulted in peak plasma concentrations of approximately 3.9 μM).ConclusionOur results suggest that statin treatment is unlikely to prevent melanoma development at standard doses. However, higher doses of statins may have a role to play in adjuvant therapy by inhibiting growth and invasion of melanoma cells.