Beneficial Effects Of Statin Therapy Research Articles

Improvement of clinical outcomes in patients undergoing peritoneal dialysis using hydroxymethylglutaryl-CoA reductase inhibitors: A systematic review and meta-analysis.

It is unclear whether hydroxymethylglutaryl-CoA reductase inhibitor (statin) therapy decreases the risk of mortality and cardiovascular disease (CVD) in patients undergoing peritoneal dialysis (PD). We performed a literature search of PubMed, Cochrane Library, Embase, and other databases for research publications up to June 2022. The outcomes of interest were fatal and nonfatal CVDs, all-cause mortality, and changes in the biochemical profiles. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled and synthesized using a random-effects model. The certainty of the evidence was determined using Grading of Recommendations, Assessment, Development, and Evaluation. Nine studies, including 2,933 patients undergoing PD, were included. Among them, three studies, including 2,099 patients, reported all-cause mortality, and three, including 1,571 patients, reported CVDs. In these patients, pooling results of two observational studies (very low-certainty evidence) showed that statin therapy significantly reduced CVDs (HR = 0.67; 95% CI = 0.54-0.84; p = 0.0004). Moreover, statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels (very low certainty of evidence). However, the effects of statin therapy on triglyceride, high-density lipoprotein, and albumin levels were not statistically significant. Although statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels, the probable beneficial effect of statins on CVD risk in patients undergoing PD could not be concluded firmly. Additional high-quality studies are required to assess the potential beneficial effects of statin therapy in PD patients.

PSAT161 Effect of Hyperlipidemia and Statin Use on the Risk of Dementia and Functional Dependence in the Vietnamese Immigrants

Abstract The role of cholesterol in the etiology of dementia is still controversial. Some studies aiming to explore the association between lipids and/or lipid-lowering treatment and dementia indicated a harmful effect of dyslipidemia and a beneficial effect of statin therapy on the risk for dementia. Still, it is not well studied in the Vietnamese population. We sought to evaluate the impact of hyperlipidemia and statin use on the risk of dementia and functional frailty in Vietnamese immigrants.We identified 38(female(F) 26, male(M) 12) community-dwelling Vietnamese patients aged ≥ 55 seen at the cognitive assessment clinic in a community health center 1/2021-8/2021 through chart review. This cohort's mean age(±SD) was 72.3(±9.35). Because lipid panel results were unavailable, 1 patient (F 1) was excluded. We assigned the patients with normal cognitive tests results or a diagnosis of mild cognitive impairment to the control group and those diagnosed with dementia to the study group. To assess function, we obtained ADLs (activities of daily living) and IADLs (instrumental activities of daily living). This study defined hyperlipidemia (HLD) as LDL >100 and functional dependence as dependence in ADLs and/or IADLs.Among 37 patients (F25, M12), 21 patients were diagnosed with dementia (F15, M 6), and 16 patients (F10, M6) were assigned to the control group. In the study group, 19 patients (F13, M 6) were diagnosed with HLD, and 13 patients (F 8, M 5) were taking statins. Fifteen patients (F 10, M 5) were diagnosed with HLD, and 14 patients (F9, M5) were taking statins in the control group. Thirty-three patients (F 23, M 10) were functional dependent. Among them, 31 patients (F 21, M 10) were diagnosed with HLD, and 24 patients (F 15, M 9) were taking statins. Four patients (F 2, M2) were functionally independent, and 3 patients (F 2, M1) were diagnosed with HLD, and all of them were taking statins.The persons with HLD had an about 12% reduction in risk of dementia (RR 0.8382, P=0.6855), but they were about 37% likely to develop functional dependence (RR 1.3676, P=0.4470). Statin users had a nearly 40% reduction in risk of dementia (RR 0.6019, P=0.0462) but the risk for developing functional dependence was not significantly different from non-users (RR 0.9877, P=0.9211). These findings suggested statin treatment has a beneficial effect on decreasing the risk for dementia in patients with HLD, and HLD has a harmful impact on developing functional frailty. This study showed a risk reduction of dementia in patients with HLD, which was different from other study results. More studies with a larger number of patients in this cohort are needed to investigate this further. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

Beneficial Effect of Statin Therapy on Arterial Stiffness

Arterial stiffness describes the increased rigidity of the arterial wall that occurs as a consequence of biological aging and several diseases. Numerous studies have demonstrated that parameters to assess arterial stiffness, especially pulse-wave velocity, are predictive of those individuals that will suffer cardiovascular morbidity and mortality. Statin therapy may be a pharmacological strategy to improve arterial elasticity. It has been shown that the positive benefits of statin therapy on cardiovascular disease is attributable not only to their lipid-lowering capacity but also to various pleiotropic effects, such as their anti-inflammatory, antiproliferative, antioxidant, and antithrombotic properties. Additionally, statins reduce endothelial dysfunction, improve vascular and myocardial remodeling, and stabilize atherosclerotic plaque. The aim of the present review was to summarize the evidence from human studies showing the effects of statins on arterial stiffness.

The Evolving Role of Omega 3 Fatty Acids in Cardiovascular Disease: Is Icosapent Ethyl the Answer?

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality globally. Despite significant advances in pharmacotherapies and the beneficial effects of statin therapy on ASCVD outcomes and progression of atherosclerosis, residual cardiovascular (CV) risk remains. Extensive evidence has identified the contribution of atherogenic dyslipidaemia, which is particularly characterised by elevated triglycerides (TGL) as a key driver of CV risk, even if low-density lipoprotein cholesterol levels are well controlled. Epidemiologic and genetic/Mendelian randomisation studies have demonstrated that elevated TGL levels serve as an independent marker for an increased risk of ischaemic events, highlighting TGLs as a suitable therapeutic target. Clinical studies have shown that omega 3 fatty acids (OM3FA) are effective in lowering TGLs; however, to date, trials and meta-analyses of combined OM3FA products have not demonstrated any clinical CV outcome benefit in patients receiving statins. However, icosapent ethyl (IPE) - a highly purified, stable ethyl ester of eicosapentaenoic acid (EPA) - has been rigorously demonstrated in multiple studies to be a useful adjunctive therapy to address residual CV risk. EPA is an omega-3 polyunsaturated fatty acid that is incorporated into membrane phospholipid bilayers and is reported to exert multiple beneficial effects along the pathway of coronary atherosclerosis. In this brief review, we will provide an overview of the mode of action of IPE in coronary atherosclerosis, the robust clinical evidence and trial data supporting its use, and expert consensus/recommendations on its use in specific populations, as an adjunct to existing anti-atherosclerotic therapies.

Statin therapy among chronic kidney disease patients presenting with acute coronary syndrome

Background and aimsThe beneficial effect of statin therapy has been well established for both primary and secondary prevention of cardiovascular disease. Nevertheless, it remains under-used among patients with chronic kidney disease (CKD).We aimed to investigate the impact of statin therapy across a wide spectrum of CKD patients presenting with acute coronary syndrome (ACS). MethodsWe included all patients with ACS enrolled in the Acute Coronary Syndrome Israel Survey (ACSIS) between the years 2006 and 2016, and allocated them to 3 groups according to their renal function based on an estimated glomerular filtration rate (eGFR) calculation on admission (MDRD formula): eGFR<30 ml/min/1.73 m2 (n = 525, 6%), eGFR 30–59 ml/min/1.73 m2 (n = 1919, 21%), and eGFR>60 ml/min/1.73 m2 (n = 6501, 73%). Primary outcome included in-hospital, 30-day, and 1-year major adverse cardiovascular events (MACE), and the independent prognostic effect of statins among CKD patients with ACS, by Cox regression analysis. ResultsAll 8945 consecutive ACS patients were included in our analysis. On hospital discharge, statin prescriptions were negatively associated with eGFR ]eGFR>60 ml/min/1.73 m2 -95%, eGFR 30–59 ml/min/1.73 m2 -90%, eGFR<30 ml/min/1.73 m2 -78% (p < 0.001 for trend). Kaplan-Meier curves demonstrated both short and long-term higher mortality rates in those prescribed compared with those not prescribed statins (p < 0.001), regardless of renal function. Cox regression analysis revealed the protective effect of discharge statins (HR-0.25, 95% C.I 0.2–0.3, p < 0.001). ConclusionsIn our study, the beneficial effect of statins was maintained among CKD patients presenting with ACS. Therefore, these patients should be treated with statins regardless of their eGFR.

Influence of statin therapy on antiphospholipid antibodies and endothelial dysfunction in young patients with coronary artery disease and systemic lupus erythematosus.

IntroductionAntiphospholipid antibodies (aPL) affect atherogenesis and may cause thromboembolism in systemic lupus erythematosus (SLE) and coronary artery disease (CAD). Intensive treatment with statins may reduce inflammation and decrease the number of thrombotic events. That may explain the beneficial effect of statin therapy in SLE and CAD. This study was established to investigate the influence of statin treatment on aPL antibody levels and selected endothelial dysfunction markers in CAD and SLE patients.Material and methodsFifty-eight patients – 40 after coronary revascularization (age 38.9 (27–46), 35 males) and 18 with clinically stable SLE (age 38.8 (18–62), 1 male) – were enrolled in the study. In both groups intensive atorvastatin treatment was administered. At baseline and after 1 year of follow-up serology tests were performed: anticardiolipin antibodies (aCL), anti-β2 glycoprotein I (aβ2GPI), lupus anticoagulant (LA), C-reactive protein (CRP), soluble form of intracellular adhesion molecule-1 (sICAM-1), vWF:Ag.ResultsCoronary artery disease patients in 1 year follow-up revealed a decrease of aβ2GPI IgG and CRP. There was a significant increase in aCL IgG, sICAM-1 and vWF:Ag. In SLE patients aPL levels showed no significant reduction after treatment.ConclusionsIn clinically stable patients IgM and IgG class aβ2GPI levels are higher in CAD than in SLE, whereas IgG class aCL levels are lower. Statin treatment decreases the CRP level in both SLE and CAD patients, while decreasing the aβ2GPI IgG level only in CAD patients.

Perioperative Statin Use and Acute Kidney Injury in Patients Undergoing Partial Nephrectomy.

Background:Statin use is widespread among the general population. Data suggest a potentially beneficial effect of statin therapy on renal function following surgery. The impact of statins on post-partial nephrectomy (PN) renal function is unknown. We hypothesized that perioperative statin use may be associated with reduced rates of acute kidney injury (AKI) in patients undergoing PN.Objectives:To evaluate the effect of perioperative statin use on AKI rates in patients undergoing PN.Materials & Methods:1,056 patients undergoing PN were identified from a prospectively-maintained institutional renal mass database. Exclusion criteria included lack of preoperative serum creatinine (Cr), concurrent surgeries, and those with baseline Cr <0.4. The binary outcome was AKI, defined using modified Kidney Disease Improving Global Outcomes (KDIGO) criteria. Chi-Square and Cochran-Armitage trend tests were used to evaluate the strength of associations. A multivariate logistic regression model was used to determine predictors of AKI.Results:Statin use was reported by n = 346 (32.8%) patients at the time of surgery. Univariate analysis demonstrated that statin use was associated with an increased risk of AKI following PN (OR 1.38, CI 1.01–1.88, p = 0.04). On multivariate analysis, statin use was no longer associated with AKI following PN (OR 1.09, CI 0.76–1.56, p = 0.65). Gender, BMI, comorbidity index, hypertension, surgical approach, ischemia temperature/time, and nephrometry “R” score were all independently associated with AKI.Conclusions:Perioperative statin use at the time of PN was not associated with rates of post-operative AKI. Prospective studies are needed to elucidate the effects of statins on functional outcomes following PN.

The Use of Primary Prevention Statin Therapy in Those Predisposed to Atherosclerosis.

Many guidelines exist for the use of statins in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Few have focused on disease specific states that predispose to ASCVD. This review is intended to focus on the recommendations and evidence in inflammatory diseases that predispose to an increased risk of ASCVD beyond what conventional cardiac risk scores would predict. Certain autoimmune inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE), and psoriasis/psoriatic arthritis have all been shown to increase the risk of ASCVD. Other diseases such as human immunodeficiency virus (HIV) and mediastinal radiation have also been correlated with increased ASCVD. In RA and HIV, the evidence suggests a benefit to added statin therapy and society guidelines favor early initiation. The evidence for statin therapy in RA is limited to observational studies with small secondary analysis. In HIV, there is a large ongoing clinical trial to assess efficacy. In those with psoriasis and psoriatic arthritis, there is limited evidence for or against statin therapy independent of a calculated cardiac risk score. Finally, in SLE and in those with exposure to mediastinal radiation, cardiac events remain high, but evidence is limited on the beneficial effects of statin therapy. There are many individuals who have an increased risk for ASCVD above what is predicted from a cardiac risk score. It would be beneficial to create risk prediction models with statin therapy recommendations that are tailored to those predisposed to accelerated atherosclerosis.

Patterns of statin non-prescription in patients with established coronary artery disease: A report from a contemporary multicenter Japanese PCI registry

Statin therapy is regarded as an effective medication to reduce cardiovascular events in patients at higher risk for future incidence of coronary artery disease. However, very few studies have been conducted to examine its implementation in non-Western real-world practice. In this study, we sought to describe statin prescription patterns in relation to patient characteristics in a Japanese multicenter percutaneous coronary intervention (PCI) registry as a foundation for quality improvement. We studied 15,024 patients that were prospectively enrolled in the Japan Cardiovascular Database-Keio interhospital Cardiovascular Study Registry from January 2009 to August 2014. The overall discharge statin non-prescription rate was 15.2%, without significant interhospital (MOR = 1.01) or annual differences (MOR = 1.13) observed. Hierarchical multivariable logistic regression analysis accounting for regional differences revealed that the presence of chronic kidney disease was associated with higher rates of statin non-prescription (OR 1.87, 95% confidence interval, 1.69–2.08, p value <0.001), and higher age (per 1-year increase) showed a trend for prescription of low-intensity statin (OR 1.00, 95% confidence interval, 1.00–1.01, p value = 0.045) within the subset of PCI patients (N = 4,853) enrolled after the year 2011. Our study indicates that patients with chronic kidney disease and elderlies may be the primary targets for maximizing the beneficial effect of statin therapy in post PCI patients.

Modulation of carotid strain by statin therapy in atherosclerosis patients.

The beneficial effect of statin therapy on the progress of atherosclerotic disease has been demonstrated by numerous studies. Vascular strain imaging is an arising method to evaluate arterial stiffness. Our study examined whether an influence of statin therapy on the vessel wall could be detected by vascular strain imaging. 88 patients with recently detected atherosclerosis underwent an angiological examination including ankle-brachial index (ABI), pulse wave index (PWI), central puls ewave velocity and duplex ultrasound. Captures for vascular strain analysis were taken in B-mode during ultrasound examination of the common carotid artery and evaluated using a workstation equipped with a speckle tracking based software. A statin therapy was recommended and after six months a follow-up examination took place. Meanwhile, the non-adherence of a group of patients (N = 18) lead to a possibility to observe statin effects on the vascular strain. In the statin non-adherent group the ABI decreased significantly to a still non-pathological level (1.2 ± 0.2 vs. 1.0 ± 0.2; p = 0.016) whereas it stagnated in the adherent group (1.0 ± 0.2 vs. 1.0 ± 0.2; p = 0.383). The PWI did not differ in the non-adherent group (180.5 ± 71.9 vs. 164.4 ± 75.8; p = 0.436) but under statin therapy it decreased significantly (261.8 ± 238.6 vs. 196.4 ± 137.4; p = 0.016). In comparison to the adherent group (4.2 ± 2.0 vs. 4.0 ± 1.8; p = 0.548) under statin therapy the radial strain decreased significantly in the non-adherent group (4.7 ± 2.0 vs. 3.3 ± 1.1; p = 0.014). Our findings reveal a beneficial influence of statin therapy on the arterial wall detected by vascular strain analysis.

Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials.

BackgroundSeveral studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery. However, recent randomized controlled trials (RCTs) show potential detrimental effects. The objective of this systematic review is to examine the association between perioperative statin therapy and clinical outcomes in cardiac surgery patients.MethodsElectronic databases were searched up to 1 November 2016 for RCTs of preoperative statin therapy versus placebo or no treatment in adult cardiac surgery. Postoperative outcomes were acute kidney injury, atrial fibrillation, myocardial infarction, stroke, infections, and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using fixed-effects meta-analyses. Primary analysis was restricted to trials with low risk of bias according to Cochrane methodology, and sensitivity analyses examined whether the risk of bias of included studies was associated with different results. We performed trial sequential analysis (TSA) to test the strength of the results.ResultsWe included data from 23 RCTs involving 5102 patients. Meta-analysis of trials with low risk of bias showed that statin therapy was associated with an increase in acute kidney injury (314 of 1318 (23.82%) with statins versus 262 of 1319 (19.86%) with placebo; OR 1.26 (95%CI 1.05 to 1.52); p = 0.01); these results were supported by TSA. No difference in postoperative atrial fibrillation, myocardial infarction, stroke, infections, or mortality was present. On sensitivity analysis, statin therapy was associated with a slight increase in hospital mortality. Meta-analysis including also trials with high or unclear risk of bias showed no beneficial effects of statin therapy on any postoperative outcomes.ConclusionsThere is no evidence that statin therapy in the days prior to cardiac surgery is beneficial for patients’ outcomes. Particularly, statins are not protective against postoperative atrial fibrillation, myocardial infarction, stroke, or infections. Statins are associated with a possible increased risk of acute kidney injury and a detrimental effect on hospital survival could not be excluded. Future RCTs should further evaluate the safety profile of this therapy in relation to patients’ outcomes and assess the more appropriate time point for discontinuation of statins before cardiac surgery.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1560-6) contains supplementary material, which is available to authorized users.

Moderate-intensity statin therapy seems ineffective in primary cardiovascular prevention in patients with type 2 diabetes complicated by nephropathy. A multicenter prospective 8years follow up study.

BackgroundAlthough numerous studies and metanalysis have shown the beneficial effect of statin therapy in CVD secondary prevention, there is still controversy such the use of statins for primary CVD prevention in patients with DM. The purpose of this study was to evaluate the occurrence of total major adverse cardio-vascular events (MACE) in a cohort of patients with type 2 diabetes complicated by nephropathy treated with statins, in order to verify real life effect of statin on CVD primary prevention.MethodsWe conducted an observational prospective multicenter study on 564 patients with type 2 diabetic nephropathy free of cardiovascular disease attending 21 national outpatient diabetes clinics and followed them up for 8 years. 169 of them were treated with statins (group A) while 395 were not on statins (group B).ResultsNotably, none of the patients was treated with a high-intensity statin therapy according to last ADA position statement. Total MACE occurred in 32 patients from group A and in 68 patients from group B. Fatal MACE occurred in 13 patients from group A and in 30 from group B; nonfatal MACE occurred in 19 patients from group A and in 38 patients from group B. The analysis of the Kaplan–Meier survival curves showed a not statistically significant difference in the incidence of total (p 0.758), fatal (p 0.474) and nonfatal (p 0.812) MACE between the two groups. HbA1c only showed a significant difference in the incidence of MACE between the two groups (HR 1.201, CI 1.041–1.387, p 0.012).ConclusionsThese findings suggest that, in a real clinical setting, moderate-intensity statin treatment is ineffective in cardiovascular primary prevention for patients with diabetic nephropathy. Trial registration ClinicalTrials.gov Identifier NCT00535925. Date of registration: September 24, 2007, retrospectively registered

Dyslipidemia and Dementia

Several lines of evidences support a possible involvement of serum cholesterol in the development of dementia/Alzheimer's disease (AD), with hypercholesterolemia as one of the risk factors that can be targeted by therapeutic interventions. It has also been suggested that statins, prescribed as lipid-lowering drugs to patients at risk for cardiovascular conditions, may be useful in both the prevention and treatment of AD. Currently, conflicting evidences from epidemiological studies indicate a controversial association between dyslipidemia and dementia/AD risk. In randomized clinical trials, virtually no beneficial effect of statin therapy has been observed. On the other hand, in vitro and in vivo animal experiments have revealed that statins suppress amyloid β protein (Aβ) generation. All these findings suggest that statins can be potentially used as preventive or therapeutic agents for AD. In addition, currently the pathophysiological process of AD is thought to begin many years before the diagnosis of AD dementia. Then, statin treatment as well as some disease-modifying therapies may be more efficacious at an early stage of AD including preclinical AD or mild cognitive impairment due to AD.

Use of Statins and the Risk of Incident Diabetes: A Retrospective Cohort Study.

Even though several landmark statin trials have demonstrated the beneficial effects of statin therapy in both primary and secondary prevention of cardiovascular disease, several studies have suggested that statins are associated with a moderate increase in risk of new-onset diabetes. These observations prompted the US FDA to revise statin labels to include a warning of an increased risk of incident diabetes mellitus as a result of increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose. However, few studies have used US-based data to investigate this statin-associated increased risk of diabetes. The primary objective of our study was to examine whether the use of statins increases the risk of incident diabetes mellitus using data from the Thomson Reuters MarketScan (®) Commercial Claims and Encounters Database. This study was a retrospective cohort analysis utilizing data for the period 2003-2004. The study population included new statin users aged 20-63years at index who did not have a history of diabetes. The proportion (3.4%) of statin users (N=53,212) who had incident diabetes was higher than the proportion (1.2%) of non-statin users (N=53,212) who had incident diabetes. Compared with no statin use and controlling for demographic and clinical covariates, statin use was significantly associated with increased risk of incident diabetes (hazard ratio 2.01; 99% confidence interval 1.74-2.33; p<0.0001). In addition, risk of diabetes was highest among users of lovastatin, atorvastatin, simvastatin, and fluvastatin. Diabetes risk was lowest among pravastatin and rosuvastatin users. Because the potential for diabetogenicity differs among different statin types, healthcare professionals should individualize statin therapy by identifying patients who would benefit more from less diabetogenic statin types.

PDB15 - USE OF STATINS AND THE RISK OF INCIDENT DIABETES: A RETROSPECTIVE COHORT STUDY

Even though several landmark statin trials have demonstrated the beneficial effects of statin therapy in both primary and secondary prevention of cardiovascular disease, several studies have suggested that statins are associated with a moderate increase in risk of new-onset diabetes. These observations prompted the US FDA to revise statin labels to include a warning of an increased risk of incident diabetes mellitus as a result of increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose. However, few studies have used US-based data to investigate this statin-associated increased risk of diabetes. The primary objective of our study was to examine whether the use of statins increases the risk of incident diabetes mellitus using data from the Thomson Reuters MarketScan ® Commercial Claims and Encounters Database. This study was a retrospective cohort analysis utilizing data for the period 2003–2004. The study population included new statin users aged 20–63 years at index who did not have a history of diabetes. The proportion (3.4 %) of statin users (N = 53,212) who had incident diabetes was higher than the proportion (1.2 %) of non-statin users (N = 53,212) who had incident diabetes. Compared with no statin use and controlling for demographic and clinical covariates, statin use was significantly associated with increased risk of incident diabetes (hazard ratio 2.01; 99 % confidence interval 1.74–2.33; p < 0.0001). In addition, risk of diabetes was highest among users of lovastatin, atorvastatin, simvastatin, and fluvastatin. Diabetes risk was lowest among pravastatin and rosuvastatin users. Because the potential for diabetogenicity differs among different statin types, healthcare professionals should individualize statin therapy by identifying patients who would benefit more from less diabetogenic statin types.

Abstract 623: Effect of High-intensity Statin Therapy on High-density Lipoprotein (HDL) Subfractions and Regression of Coronary Atheroma: The SATURN Trial

Aim: Statin therapy can slow the progression of coronary atherosclerosis. However, the clinical factors underlying the beneficial effects of statin therapy on disease progression remain poorly understood. We examined the relationship of circulating HDL subfractions with measures of coronary atheroma following long-term high-intensity statin therapy. Methods: Serial coronary intravascular ultrasound (IVUS) was utilized in SATURN to monitor changes in atheroma burden [percent atheroma volume (PAV)] in 915 patients with coronary artery disease, treated with rosuvastatin (40 mg) or atorvastatin (80 mg) daily for 24 months. Results: Baseline levels of total HDL-C, apo E-containing HDL-C (apoE HDL-C), HDL 3 -C and HDL 2 -C did not differ significantly between treatment groups. Compared with the atorvastatin-treated group, rosuvastatin-treated patients demonstrated greater increases in levels of total HDL-C (4.4% vs. -1.8%, p&lt;0.001), apoE HDL-C (8.5% vs. -3.3%, p&lt;0.001), HDL 3 -C (3.3% vs. -2.7%, p&lt;0.001) and HDL 2 -C (7.0% vs. -0.7%, p&lt;0.001). The alterations in apo E HDL-C and HDL 3 -C levels were associated with PAV regression in rosuvastatin-treated patients (β=-0.84, p=0.018 and β=-1.10, p=0.056, respectively) but not in the atorvastatin-treated group (β=0.41, p=0.22 and β=0.71, p=0.22 for apo E HDL-C and HDL 3 -C, respectively). Conclusions: Rosuvastatin therapy resulted in favorable changes in HDL subfractions and on-treatment levels of apoE HDL-C and HDL 3 -C were associated with greater disease regression.

Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failure model rats

Clinical studies have suggested the beneficial effects of statin therapy on diastolic heart failure. However, the mechanism of the beneficial effects of statin on diastolic heart failure remains unknown. We examined the effect of atorvastatin on the cardiac function of Dahl salt-sensitive rat, a model of hypertensive diastolic heart failure. Dahl salt-sensitive rats were divided into three groups: the low-salt group (given standard diet), the high-salt group (given 8% NaCl diet from 7 weeks of age), and the high-salt + atorvastatin (HS + Ato) group (given 8% NaCl diet from 7 weeks of age and atorvastatin from 17 weeks of age). We evaluated left ventricular hypertrophy (LVH), fibrosis, and function by using echocardiography and histology. We also examined the expression of molecules related to fibrosis in the hearts of Dahl salt-sensitive rats and cultured rat cardiac fibroblasts. Left ventricular hypertrophy, diastolic dysfunction, and cardiac fibrosis were observed in the high-salt group. Atorvastatin ameliorated cardiac fibrosis and normalized left ventricular diastolic function without altering blood pressure. Atorvastatin also decreased the expression of heat shock protein 47 (HSP47), an essential chaperone for type 1 collagen processing, without changing in expression of transforming growth factor beta. In rat cardiac fibroblast cells, atorvastatin also reduced HSP47 level induced by transforming growth factor beta. The effect of atorvastatin was reversed by mevalonate and geranylgeranyl-pyrophosphate and mimicked by Rho kinase inhibitor. Atorvastatin administration ameliorates cardiac fibrosis and improves left ventricular diastolic function in Dahl salt-sensitive rats. Lowering HSP47 by atorvastatin via inhibition of Rho-Rho kinase pathway is suggested as a mechanism.

Mobilization of CD133+ Progenitor Cells in Patients with Acute Cerebral Infarction

Progenitor cells (PCs) contribute to the endogenous repair mechanism after ischemic events. Interleukin-8 (IL-8) as part of the acute inflammatory reaction may enhance PC mobilization. Also, statins are supposed to alter number and function of circulating PCs. We aimed to investigate PC mobilization after acute ischemic stroke as well as its association with inflammatory markers and statin therapy. Sixty-five patients with ischemic stroke were enrolled in the study. The number of CD133+ PCs was analyzed by flow cytometry. Blood samples were drawn within 24 hours after symptom onset and after 5 days. The number of CD133+ PCs increased significantly within 5 days (p<0.001). We found no correlation between CD133+ PCs and the serum levels of IL-8, IL-6, or C-reactive protein (CRP). Multivariate analysis revealed that preexisting statin therapy correlated independently with the increase of CD133+ PCs (p = 0.001). This study showed a mobilization of CD133+ PCs in patients with acute cerebral infarction within 5 days after symptom onset. The early systemic inflammatory response did not seem to be a decisive factor in the mobilization of PCs. Preexisting statin therapy was associated with the increase in CD133+ PCs, suggesting a potentially beneficial effect of statin therapy in patients with stroke.

The role of statins in chronic heart failure.

The efficacy of statins in reducing morbidity and mortality in patients with documented coronary artery disease is unquestionable. However, in chronic heart failure (CHF), evidence regarding the beneficial effects of statin therapy remains contradictory. Although numerous retrospective studies have demonstrated improved prognosis in CHF patients treated with statins, two randomized trials, GISSI-HF and CORONA, have not confirmed the benefit of rosuvastatin in this group of patients. The benefits of using statins in CHF probably result mostly from their pleiotropic action, including the improvement of endothelial function, the inhibition of neurohormonal activation, and the reduction of proinflammatory activation. On the other hand, it has been recognized that low cholesterol is associated with worse morbidity and mortality in patients with CHF. It appears that it is necessary to conduct further randomized clinical trials using different kinds of statins in different populations of patients with CHF.