The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol Statins, systemic inflammation and risk of death in COPD: the Rotterdam study. Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness. The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease. Effect of 24 weeks of statin therapy on systemic and vascular inflammation in HIV-infected subjects receiving antiretroviral therapy. Effect of statin dose on incidence of atrial fibrillation: data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials. Inflammation, Statin Therapy, and Risk of Stroke After an Acute Coronary Syndrome in the MIRACL Study Diabetes mellitus is a major negative determinant of coronary plaque regression during statin therapy in patients with acute coronary syndrome--serial intravascular ultrasound observations from the Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome Trial (the JAPAN-ACS Tria Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Effect of intensive lipid-lowering therapy on cardiovascular outcome in patients with and those without inflammatory joint disease. Genome-Wide Association of Lipid-Lowering Response to Statins in Combined Study Populations High-Dose Atorvastatin Enhances the Decline in Inflammatory Markers in Patients With Acute Coronary Syndromes in the MIRACL Study Statin therapy and levels of hemostatic factors in a healthy population: the Multi-Ethnic Study of Atherosclerosis. Statin therapy is associated with improved cardiovascular outcomes and levels of inflammatory markers in patients with heart failure. Cardiovascular disease risk factors in HIV patients – association with antiretroviral therapy. Results from the DAD study Primary prevention of vascular events in patients with high levels of C-reactive protein: the JUPITER study
We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome ( ACS ) patients with low low-density lipoprotein ( LDL ) cholesterol level . One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study ( mean 78.2 ± 12.3 mg/dl ) . While 70 r and omly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their st and ard treatment as the atorvastatin group , the remaining 42 patients considered as the control group were given the st and ard treatment only , i.e. , without any lipid-lowering drug therapy .  Lipid profile , high-sensitivity C-reactive protein ( hsCRP ) , and plasma amyloid A ( SAA ) levels were measured in all patients within the first 24 h of chest pain , on the 5th day , and in the 6th month . During the inpatient period and subsequent 6-month follow-up , all episodes of angina , reinfa rct ion , revascularization , heart failure , rehospitalization , cardiac mortality , and total number of cardiac events were recorded . In the atorvastatin group , hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group ( P < 0.0001 ) . Mean LDL cholesterol level was significantly decreased in the atorvastatin group ( 55.7 ± 17.7 mg/dl ) , but there was no significant change in the control group at the 6th month . The frequency of heart failure during the inpatient period and angina , unstable angina pectoris , heart failure , and revascularization in the first 6 months were also significantly reduced in the atorvastatin group . Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels BACKGROUND Studies suggest that statins decrease mortality in COPD patients but it is unknown which patients might benefit most . OBJECTIVES We investigated whether statins were associated with reduced mortality in COPD patients and whether effects differed according to baseline high-sensitivity C-reactive protein ( hsCRP ) concentration , a marker of systemic inflammation . METHODS This nested case-control study was part of the Rotterdam Study , a prospect i ve population -based cohort study among 7983 subjects ≥ 55 years . Using automated pharmacy records , we evaluated statin use of 363 cases ( COPD patients who died during follow-up of 17 years ) with 2345 age and sex matched controls ( COPD patients who survived the follow-up period of the index case ) . RESULTS Compared to never use , long-term statin use ( > 2 years ) was associated with a 39 % decreased risk of death in COPD patients . Stratified according to the level of systemic inflammation , long-term statin use was associated with a 78 % reduced mortality if hsCRP level > 3 mg/L , versus a non significant 21 % reduced mortality if hsCRP level ≤ 3 mg/L. CONCLUSIONS Statin use is associated with a beneficial effect on all-cause mortality in COPD , depending on the baseline level of systemic inflammation Context While the benefits of statins in the primary and secondary prevention of coronary artery disease are clear , the value of statin therapy in acute coronary syndromes is uncertain . Contribution Analyzing data from a large , international observational study of acute coronary syndromes , these investigators identified associations between statin use before and during acute coronary events and favorable outcomes . Caution s While these data suggest a potential benefit of statins during acute coronary events , trials are necessary to determine the most appropriate use of statins in the treatment of acute coronary events . The Editors Data from r and omized clinical trials support the efficacy of lipid-lowering medications , particularly statins , in the primary and secondary prevention of coronary artery disease ( 1 - 3 ) . The benefits of statins , however , were not readily apparent until after several months of therapy , suggesting that the drugs ' lipid-lowering capabilities were largely responsible . In vitro work has suggested that statins may have an abundance of pleiotropic effects ( 4 ) . These include modulation of inflammation , inhibition of platelet function and thrombosis , and enhancement of endothelial cell function . The demonstrated ability of statins to immediately affect basic pathophysiologic mechanisms has result ed in increased interest in their potential role in the setting of acute coronary syndromes . The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) trial found that early treatment with high-dose atorvastatin modestly reduced event rates of recurrent ischemia in statin-naive patients presenting with an acute coronary syndrome ( 5 ) . These observations , while intriguing , did not conclusively establish the role of statins in patients with acute coronary syndromes . In the MIRACL trial , the failure of statins to significantly affect more concrete trial end points ( for example , death or recurrent myocardial infa rct ion [ MI ] ) was disappointing . Whether this reflected a true lack of physiologic impact of early statin treatment or merely indicated that the study was underpowered to detect differences in these end points remains unclear . In a sub study using data from the Platelet Receptor Inhibition for Ischemic Syndrome Management ( PRISM ) trial in patients with acute coronary syndromes , patients already taking statins  had better short-term outcomes ( decreased risk for death or nonfatal MI ) than those not previously receiving statin therapy , unless statin therapy was discontinued in the hospital ( 6 ) . Initiation of statin therapy after the onset of an acute coronary syndrome appeared to be less effective than treatment with statins before symptom onset . Using data from the Global Registry of Acute Coronary Events ( GRACE ) project , a large , multinational , observational study of patients with acute coronary syndromes , we examined the association between previous statin therapy  , presentation characteristics of acute coronary syndromes , and hospital outcomes . We also examined the effect of early in-hospital statin therapy ( or withdrawal of statins ) on important hospital outcomes , including death or the development of recurrent MI or stroke . Methods Full details of the GRACE rationale and methods have been published elsewhere and are outlined below ( 7 - 9 ) . Site Selection The GRACE project is design ed to reflect an unbiased population of patients with acute coronary syndromes , regardless of geographic region . Currently , 94 hospitals located in 14 countries ( Argentina , Australia , Austria , Belgium , Brazil , Canada , France , Germany , Italy , New Zeal and , Pol and , Spain , the United Kingdom , and the United States ) are participating in this observational study . Patients entered in the registry must be at least 18 years of age and alive at the time of hospital presentation ; be admitted with an acute coronary syndrome as a presumptive diagnosis ( that is , have symptoms consistent with acute ischemia ) ; and have at least 1 of the following : electrocardiographic changes consistent with an acute coronary syndrome , serial increases in serum biochemical markers of cardiac necrosis , or documentation of coronary artery disease ( 7 - 9 ) . The qualifying acute coronary syndrome must not be precipitated by a significant noncardiovascular comorbid condition ( for example , trauma or surgery ) . To ensure the enrollment of an unbiased sample , the first 10 to 20 consecutive patients ( depending on each site 's patient volume ) are recruited from each site on a monthly basis . Where required , study investigators received approval from their local hospital ethics or institutional review board . Data Collection At each site , a trained coordinator collected data using a st and ardized case-report form . Data on demographic characteristics , medical history , presenting symptoms , duration of prehospital delay , biochemical and electrocardiographic findings , treatment practice s , and hospital outcome were collected . St and ardized definitions of all patient-related variables and clinical diagnoses were used . All cases were assigned to 1 of the following categories : ST-segment elevation MI , nonST-segment elevation MI , unstable angina , and other cardiac or noncardiac diagnoses that have been previously described ( 7 - 9 ) . St and ardized definitions were also used for selected hospital complications and outcomes . Patient Sample For the current study , patients who were subsequently found to have noncardiac or other cardiac ( nonacute coronary syndrome ) primary diagnoses and those who transferred into or out of GRACE registry hospitals were excluded from further consideration . Treatments defined as previous use were those taken by the patient on a long-term basis at home and within 7 days of the presenting event , based on the review of information contained in medical records and abstract ed by trained study physicians and nurses . Treatments received in the hospital ( within the first 24 hours or thereafter ) were categorized as within hospital . Agents prescribed for use after discharge from participating hospitals were categorized as at discharge . Patient treatment categories were defined according to the following groupings : no previous treatment with statins and no treatment with statins during hospitalization , no previous therapy with statins but statin therapy  instituted during hospitalization , previous therapy with statins and statin therapy continued during hospitalization , and previous  therapy with statins but statin therapy not continued during the index hospitalization . Statistical Analysis We used the chi-square tests for discrete variables to analyze differences in demographic and clinical characteristics , treatment practice s , clinical presentation ( ST-segment elevation vs. nonST-segment elevation , large infa rct [ creatine phosphokinase level > 2 times the upper limit of normal ] vs. small infa rct ) , subsequent diagnosis ( ST-segment elevation MI , nonST-segment elevation MI , unstable angina ) , and hospital complications ( death , congestive heart failure or pulmonary edema , cardiogenic shock , stroke , ventricular tachycardia or ventricular fibrillation , and cardiac arrest ) in relation to statin use . The Wilcoxon rank-sum test was used to analyze differences between respective comparison groups for continuous variables . While controlling for potentially confounding variables , we performed multivariate regression analyses to examine the association between previous statin therapy and hospital presentation ( ST-segment elevation vs. no ST-segment elevation , creatine phosphokinase level 2 times normal vs. creatine phosphokinase level < 2 times the upper limit of normal ) , as well as any association between previous or in-hospital statin therapy and hospital outcomes ( death , recurrent MI or MI after 24 hours , and stroke ) or a composite end point of all 3 outcomes . C and i date variables for inclusion in the regression models evaluating previous statin use and hospital presentation included patient age , sex , smoking status , diabetes , history of vascular disease ( previous MI , stroke , positive angiogram , peripheral vascular disease , percutaneous coronary intervention , or coronary artery bypass graft surgery ) , hypertension , hyperlipidemia , and previous therapies ( aspirin , angiotensin-converting enzyme [ ACE ] inhibitors , -blockers , and other lipid-lowering agents ) . C and i date variables for regression models evaluating previous or in-hospital statin use and hospital outcomes included all of the previously listed characteristics plus characteristics present at the time of hospital admission ( heart rate , systolic blood pressure , Killip class , ST-segment elevation or left bundle-branch block pattern , and positive cardiac enzymes ) and receipt of in-hospital therapies ( aspirin and other antiplatelet agents , -blockers , unfractionated heparin , low-molecular-weight heparin , glycoprotein IIb/IIIa inhibitors , cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass graft surgery ) . C and i date variables possibly associated with the outcomes of interest ( P < 0.25 after univariate analysis ) were included in the multivariate models . Variables for which the P value exceeded 0.05 were eliminated in a stepwise fashion so that only those that had a statistically significant association with the outcome of interest were included in the final regression models . Because of their clinical relevance and potential importance , age , sex , and history of hyperlipidemia were retained in the final multivariable models for clinical outcomes regardless of statistical significance . Final models were evaluated for goodness of fit by the HosmerLemeshow test . Because between-hospital variation in use of statin treatment could be considerable and potentially affect our study results , we adjusted for hospital r and om effects on the observed outcomes . We used a generalized estimating equation modeling technique , assuming patients were repeated measures within each hospital . Variable BACKGROUND As a class , statins are remarkably effective in reducing low-density lipoprotein ( LDL ) cholesterol , and several of these drugs have now been shown to reduce coronary heart disease morbidity and mortality . However , several important controversies in the use of statins remain to be answered by clinical trials . For example , it is controversial whether marked cholesterol reduction to levels below 100 mg/dL would further reduce the incidence of coronary heart disease . Furthermore , concerns about differences among statins for nonlipid effects has raised the concern that the assumption of a class effect is premature until head-to-head clinical trials are completed . METHODS Arterial Biology for the Investigation for the Treatment Effects of Reducing Cholesterol ( ARBITER ) is a single-center , r and omized , active-controlled study comparing the efficacy of high-dose atorvastatin ( 80 mg/d ) and pravastatin ( 40 mg/d ) in patients being treated for either the primary or secondary prevention of coronary heart disease . This trial will enroll up to 200 patients for the primary end point of the mean change in intima-media thickness of the common carotid artery . This effect will be evaluated over a treatment duration of 12 months . Secondary end points include the effects of statin therapy on inflammatory and hemostatic markers ( C-reactive protein and fibrinogen ) . CONCLUSION ARBITER will provide important data on the role of marked LDL reduction and the " class effect " theory of statin therapy in cardiovascular medicine BACKGROUND Non-alcoholic fatty liver disease ( NAFLD ) and its advanced form non-alcoholic steatohepatitis ( NASH ) are the most common causes of elevated liver enzymes in the general population . NASH , and to a lesser extent NAFLD have been associated with increased liver-related , cardiovascular disease ( CVD ) , and allcause mortality . No effective treatment is widely acceptable . OBJECTIVE The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH . METHOD A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH . RESULTS Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial . Post hoc data from three large prospect i ve r and omized clinical trials ( n>11 , 000 ) suggest that specific statins ( mainly atorvastatin ) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function . Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH . Statin treatment may also protect from hepatocellular carcinoma ( HCC ) related to NAFLD/NASH . CONCLUSION Since NAFLD/NASH patients have high CVD risk , they will probably require a statin . Thus , why not select a specific statins ( atorvastatin or rosuvastatin , both generic now ) that offer a substantial liver- and CVDrelated adverse event reduction ? The administration of statins in these patients is as safe as in the general population BACKGROUND Human immunodeficiency virus (HIV)-infected individuals are at increased risk of cardiovascular disease ( CVD ) due in part to inflammation . Statins decrease inflammation in the general population , but their effect during HIV infection is largely unknown . METHODS This is an ongoing r and omized , double-blinded , placebo-controlled trial to evaluate the effect of statin therapy on inflammatory markers during HIV infection . Subjects received rosuvastatin 10 mg daily or placebo for 24 weeks . Subjects were receiving stable ( > 12 weeks ) antiretroviral therapy and had a low-density lipoprotein ( LDL ) cholesterol level of ≤130 mg/dL and evidence of heightened immune activation or inflammation . This was a prespecified interim analysis . RESULTS A total of 147 subjects were enrolled ( 78 % were male , 70 % were black , and the median age was 47 years ) . By 24 weeks , LDL cholesterol levels had decreased in the statin group , compared with an increase in the placebo group ( -28 % vs + 3.8 % ; P < .01 ) . A 10 % reduction in the lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) level was seen in the statin group , compared with a 2 % reduction in the placebo group ( P < .01 ) . In multivariable regression , receipt of statin treatment and having a nadir CD4(+ ) T-cell count of ≤100 cell/µL were the only statistically significant predictors of a decrease in Lp-PLA2 level . Markers of systemic inflammation did not change significantly between groups . CONCLUSIONS Twenty-four weeks of rosuvastatin therapy significantly decreased the level of Lp-PLA2 , a vascular-specific , inflammatory enzyme that predicts cardiovascular events in the general population . Statins may hold promise as a means of attenuating CVD risk in HIV-infected individuals by decreasing Lp-PLA2 levels BACKGROUND Inflammation has been suggested as a factor in the initiation and maintenance of  atrial fibrillation ( AF ) . Several observational studies have suggested that statins , presumably through their anti-inflammatory properties , decrease the risk of AF . METHODS We analyzed 2 large , r and omized trials , PROVE IT-TIMI 22 and phase Z of the A to Z trial , which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up . We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy . From each trial , patients experiencing the onset of AF during follow-up were identified from the adverse event reports . RESULTS Neither study showed a decreased AF risk with higher-dose statin . In PROVE IT-TIMI 22 , 2.9 % versus 3.3 % in the high- versus st and ard-dose statin therapy , respectively , experienced the onset of AF over 2 years ( OR 0.86 , 95 % CI 0.61 - 1.23 , P = .41 ) . In A to Z , rates were 1.6 % versus 0.99 % , respectively ( OR 1.58 , 95 % CI 0.92 - 2.70 , P = .096 ) . In both trials , C-reactive protein levels ( plasma or serum ) tended to be higher among patients experiencing the onset of AF . CONCLUSION Our r and omized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with st and ard dose statin treatment Objective — Patients with acute coronary syndromes have an increased risk of stroke . We measured markers of inflammation in the MIRACL study , a r and omized trial of atorvastatin versus placebo in acute coronary syndromes , to assess the relationship of inflammation to stroke . Methods and Results —Baseline C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin-6 ( IL-6 ) were collected in 2926 ( 95 % ) subjects . Baseline markers were related to stroke risk over the 16 weeks of the study . Subjects who subsequently experienced a stroke had higher CRP ( 27.5 versus 10.2 mg/L , P=0.0032 ) , SAA ( 30.5 versus 16.0 mg/L , P=0.031 ) , IL-6 ( 11 231 versus 6841 pg/L , P=0.004 ) , and troponin ( 6.03 versus 3.19 ng/mL P=0.0032 ) . The risk of stroke was related to greater CRP , SAA , and IL-6 in the placebo group only . Similarly , there was a grade d increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only . Conclusions —In acute coronary syndromes , the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis . Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study , a finding that provides a novel rationale for the use of statins in acute coronary syndromes BACKGROUND The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ( JAPAN-ACS ) trial has found that early aggressive statin therapy in patients with acute coronary syndrome ( ACS ) significantly reduces the plaque volume ( PV ) of non-culprit coronary lesions . The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy . METHODS AND RESULTS Serial intravascular ultrasound observations over 8 - 12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin .  Linear regression analysis identified the presence of diabetes mellitus ( DM ) and PV at baseline as inhibiting factors , and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression . Significant correlation between % change of PV and low-density lipoprotein cholesterol ( LDL-C ) level was found in patients with DM ( n=73 , P<0.05 , r=0.4 ) , whereas there was no significant correlation between the 2 parameters in patients without DM ( n=178 ) . CONCLUSIONS The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts . Moreover , vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia . This was a multicenter , r and omized , open-label , parallel- design study of patients with total cholesterol > 200 mg/dl , triglycerides between 200 and 800 mg/dl , and apolipoprotein B > 110 mg/dl . Patients were r and omly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period . Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy . Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein ( VLDL ) particles ( -31 % and -29 % , respectively ) and small low-density lipoprotein ( LDL ) particles ( -44 % and -35 % , respectively ) . Niacin increased the concentration of large LDL ( + 75 % ) . Atrovastatin reduced the number of LDL particles more than niacin ( 31 % vs 14 % ) . In patients with atherogenic dyslipidemia , both drugs had important effects on lipoprotein subfractions , which contributed to a reduction in coronary heart disease risk . The drugs equally reduced VLDL subclass levels . Niacin shifted the LDL subclass distribution toward the larger particles , more effectively converted patients from LDL phenotype B to phenotype A , and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles . In contrast , atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL , and more effectively , reduced LDL particle numbers .  Atorvastatin had a preferred LDL effect , whereas niacin had a preferred high-density lipoprotein effect OBJECTIVE To examine the effect of intensive lipid-lowering therapy on a composite cardiovascular outcome ( cardiovascular disease [ CVD ] ) , consisting of mortality and morbidity end points , in patients with inflammatory joint disease ( rheumatoid arthritis [ RA ] , ankylosing spondylitis [ AS ] , or psoriatic arthritis [ PsA ] ) by post hoc analysis of 2 prospect i ve trials of statins with a secondary end point of CVD outcome ( the Treating to New Targets [ TNT ] and Incremental Decrease in End Points Through Aggressive Lipid Lowering [ IDEAL ] studies ) . METHODS Of the 18,889 patients participating in the 2 trials , 199 had RA , 46 had AS , and 35 had PsA.  Lipid-lowering therapy consisted of an intensive regimen of atorvastatin 80 mg or a conventional/low-dose regimen of atorvastatin 10 mg or simvastatin 20 - 40 mg . The median duration of followup was nearly 5 years . Changes in lipid levels were examined by analyses of covariance . The effect on CVD was examined by Cox regression analyses , and heterogeneity tests were performed . RESULTS Patients with RA and those with AS had lower baseline cholesterol levels than patients without inflammatory joint disease ( least squares mean ± SEM 180.7 ± 2.3 mg/dl and 176.5 ± 4.7 mg/dl , respectively , versus 185.6 ± 0.2 mg/dl ; P = 0.03 and P = 0.05 , respectively ) . Statin treatment led to a comparable decrease in lipid levels and a 20 % reduction in overall risk of CVD in both patients with and those without inflammatory joint disease . CONCLUSION Our findings indicate that patients with and those without inflammatory joint disease experience comparable lipid-lowering effects and CVD risk reduction after intensive treatment with statins Background Statins effectively lower total and plasma LDL-cholesterol , but the magnitude of decrease varies among individuals . To identify single nucleotide polymorphisms ( SNPs ) contributing to this variation , we performed a combined analysis of genome-wide association ( GWA ) results from three trials of statin efficacy . Methods and Principal Findings Bayesian and st and ard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol , total cholesterol , HDL-cholesterol , and triglyceride on a total of 3932 subjects using data from three studies : Cholesterol and Pharmacogenetics ( 40 mg/day simvastatin  , 6 weeks ) , Pravastatin/Inflammation CRP Evaluation (  40 mg/day pravastatin , 24 weeks ) , and Treating to New Targets ( 10 mg/day atorvastatin , 8 weeks ) . Genotype imputation was used to maximize genomic coverage and to combine information across studies . Phenotypes were normalized within each study to account for systematic differences among studies , and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies . Two SNP associations were assessed as having posterior probability greater than 50 % , indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response . SNP rs8014194 , located within the CLMN gene on chromosome 14 , was strongly associated with statin-mediated change in total cholesterol with an 84 % probability by Bayesian analysis , and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis ( P = 1.8 × 10−8 ) . This SNP was less significantly associated with change in LDL-cholesterol ( posterior probability = 0.16 , P = 4.0 × 10−6 ) . Bayesian analysis also assigned a 51 % probability that rs4420638 , located in APOC1 and near APOE , was associated with change in LDL-cholesterol . Conclusions and Significance Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin , pravastatin , or atorvastatin  , we have identified SNPs that may be associated with variation in the magnitude of statin-mediated reduction in total and LDL-cholesterol , including one in the CLMN gene for which statistical evidence for association exceeds conventional levels of genome-wide significance . Trial Registration PRINCE and TNT are not registered . CAP is registered at Clinical trials.gov Background —Inflammation promotes acute coronary syndromes and ensuing clinical complications . Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina , the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown . Methods and Results —We measured C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin 6 ( IL-6 ) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) study . Subjects with unstable angina or non – Q-wave myocardial infa rct ion were r and omized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks . The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome , country , and initial level of marker . All 3 markers were markedly elevated at r and omization and declined over the 16 weeks in both treatment groups . Compared with placebo , atorvastatin significantly reduced CRP , −83 % ( 95 % CI , −84 % , −81 % ) versus −74 % ( 95 % CI , −75 % , −71 % ) ( P < 0.0001 ) and SAA , −80 % ( 95 % CI , −82 % , −78 % ) versus −77 % ( −79 % , −75 % ) ( P = 0.0006 ) but not IL-6 , −55 % ( 95 % CI , −57 % , −53 % ) versus −53 % ( 95 % CI , −55 % , −51 % ) ( P = 0.3 ) . Reductions in CRP and SAA were observed in patients with unstable angina and non – Q-wave myocardial infa rct ion , with initial LDL cholesterol < 3.2 or ≥3.2 mmol/L ( 125 mg/dL ) , age ≥65 or < 65 years , and in men and women . By 16 weeks , CRP was 34 % lower with atorvastatin than with placebo . Conclusions —High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes . This supports the value of early statin therapy in these patients BACKGROUND HMG-CoA reductase inhibitors ( statins ) reduce the risk of venous thromboembolism ( VTE ) in healthy people .  Statins reduce levels of inflammation biomarkers ; however , the mechanism for the reduction in VTE risk is unknown . AIM In a large cohort of healthy people , we studied associations of statin use with plasma hemostatic factors related to VTE risk . METHODS Cross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis ( MESA ) , a cohort study of 6814 healthy men and women aged 45 - 84 years , free of clinical cardiovascular disease at baseline ; 1001 were using statins at baseline . Twenty-three warfarin users were excluded . Age , race and sex-adjusted mean hemostatic factor levels were compared between statin users and non-users , and multivariable linear regression models were used to assess associations of statin use with hemostatic factors , adjusted for age , race/ethnicity , education , income , aspirin use , hormone replacement therapy ( in women ) , and major cardiovascular risk factors . RESULTS Participants using statins  had lower adjusted levels of D-dimer ( - 9 % ) , C-reactive protein ( - 21 % ) and factor VIII ( - 3 % ) than non-users ( P < 0.05 ) . Homocysteine and von Willebr and factor levels were non-significantly lower with statin use . Higher fibrinogen ( 2 % ) and plasminogen activator inhibitor-1 ( 22 % ) levels were observed among statin users than among non-users ( P < 0.05 ) . Further adjustment for LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use . CONCLUSIONS Findings of lower D-dimer , FVIII and C-reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk . A prospect i ve study or clinical trial linking these biochemical differences to VTE outcomes in  statin users and non-users is warranted BACKGROUND We wished to determine whether the addition of statins affect cardiovascular events and markers of inflammation in patients with heart failure . METHODS AND RESULTS A total of 446 patients with heart failure and ejection fraction < or = 35 % were followed in a prospect i ve , nonr and omized fashion and were classified according to treatment with a statin . We determined all-cause mortality , cardiovascular morbidity , and serum markers of inflammation over a 24-month period . Statin therapy  in patients with heart failure was associated with decreased all-cause mortality at 2 years compared with those not on statin therapy ( 15 % versus 33 % , P < .005 ) as well as hospitalizations for heart failure ( 22 % versus 38 % , P = .001 ) and nonfatal myocardial infa rct ion ( 11 % versus 15 % , P < .001 ) . In addition , statin therapy was associated with a decrease in serum levels of C-reactive protein ( 1.12 + /- 0.13 versus 1.47 + /- 0.11 mg/dL , P = .001 ) , interleukin-6 ( 13.3 + /- 0.8 versus 17.3 + /- 1.4 ng/dL , P = .001 ) , and tumor necrosis factor-alpha receptor II ( 24.3 + /- 1.0 versus 34.5 + /- 3.0 ng/dL , P = .001 ) . CONCLUSION The use of statin therapy in this nonr and omized trial was associated with a significant reduction in all-cause mortality and cardiac morbidity . In addition , the improvement in levels of several serum inflammatory markers with statin therapy suggests in part possible mechanisms by which these agents may exert their benefits Objective : To determine the prevalence of risk factors for  cardiovascular disease ( CVD ) among HIV-infected persons , and to investigate any association between such risk factors , stage of HIV disease , and use of antiretroviral therapies . Design : Baseline data from 17 852 subjects enrolled in DAD , a prospect i ve multinational cohort study initiated in 1999 . Methods : Cross-sectional analyses of CVD risk factors at baseline . The data collected includes data on demographic variables , cigarette smoking , diabetes mellitus , hypertension , dyslipidaemia , body mass index , stage of HIV infection , antiretroviral therapy . Results : Almost 25 % of the study population were at an age where there is an appreciable risk of CVD , with those receiving a protease inhibitor ( PI ) and /or non-nucleoside reverse transcriptase inhibitor ( NNRTI ) tending to be older . 1.4 % had a previous history of CVD and 51.5 % were cigarette smokers . Increased prevalence of elevated total cholesterol ( ⩾ 6.2 mmol/l ) was observed among subjects receiving an NNRTI but no PI [ odds ratio ( OR ) , 1.79 ; 95 % confidence interval ( CI ) , 1.45–2.22 ] , PI but no NNRTI ( OR , 2.35 ; 95 % CI , 1.92–2.87 ) , or NNRTI + PI ( OR , 5.48 ; 95 % CI , 4.34–6.91 ) compared to the prevalence among antiretroviral therapy (ART)-naive subjects . Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects . Higher CD4 cell count , lower plasma HIV RNA levels , clinical signs of lipodystrophy , longer exposure times to NNRTI and PI , and older age were all also associated with elevated total cholesterol level . Conclusion : HIV-infected persons exhibit multiple known risk factors for CVD . Of specific concern is the fact that use of the NNRTI and PI drug classes ( alone and especially in combination ) , particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication , was associated with a lipid profile known to increase the risk of coronary heart disease The Justification for the Use of Statins in Primary Prevention : An Intervention Trial Evaluating Rosuvastatin ( JUPITER ) study was the first large-scale , prospect i ve study to examine the benefits of statin therapy in subjects with elevated levels of high-sensitivity C-reactive protein but with low-to-normal LDL-cholesterol levels , who were not qualified for lipid-lowering treatment according to the current guidelines for primary prevention . The JUPITER study aim ed to determine whether rosuvastatin 20 mg daily would reduce the rate of first major cardiovascular events , including cardiovascular death , nonfatal stroke , nonfatal myocardial infa rct ion , hospitalization for unstable angina or arterial revascularization .  Rosuvastatin reduced LDL-cholesterol levels by 50 % and high-sensitivity C-reactive protein by 37 % . Compared with placebo , the combined primary end point was reduced in 44 % ( p < 0.00001 ) , and total mortality in 20 % ( p = 0.02 ) . The trial confirmed the relationship between the rates of major cardiovascular events with both high-sensitivity C-reactive protein and LDL-cholesterol levels achieved after statin treatment . Interestingly , this was the first large , prospect i ve statin trial to show benefit in the reduction of venous thromboembolism
Our meta‐ analysis showed beneficial effects  of statin use  on reducing inflammatory markers in patients with MetS and related disorders
& NA ; Current evidence suggests that statin use decreases the incidence of cardiovascular diseases ( CVD ) through reducing LDL cholesterol and decreasing inflammation .
Metabolic syndrome ( MetS ) is usually associated with increased inflammatory markers and increased risk of CVD .