Impact of Combination Therapy with Amlodipine and Atorvastatin on Plasma Adiponectin Levels in Hypertensive Patients with Coronary Artery Disease: Combination Therapy and Adiponectin Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk. Combination of an ACE inhibitor and indapamide improves blood pressure control, but attenuates the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Atorvastatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes The Effect of HMG-CoA Reductase Inhibitor on Insulin Resistance in Patients Undergoing Peritoneal Dialysis Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. [Effect of various approaches to therapy with statins in high risk patients from the point of view of vascular endothelium]. Effects of miglitol, sitagliptin, and initial combination therapy with both on plasma incretin responses to a mixed meal and visceral fat in over-weight Japanese patients with type 2 diabetes. "the MASTER randomized, controlled trial". Effects of ARB or ACE-inhibitor administration on plasma levels of aldosterone and adiponectin in hypertension. The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study. Effects of pravastatin and rosuvastatin on the generation of adiponectin in the visceral adipose tissue in patients with coronary artery disease. High-dose statin therapy does not induce insulin resistance in patients with familial hypercholesterolemia. Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy. Effect of High-Dose Statin Treatment on Plasma Concentrations of Endogenous Nitric Oxide Synthase Inhibitors Effects of long-term exercise and diet intervention on plasma adipokine concentrations. The effect of statin therapy on ventricular late potentials in acute myocardial infarction. Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study
Abstract Background : In many countries , combination therapy with amlodipine and atorvastatin is indicated for the treatment of patients with hypertension and hypercholesterolemia . The aim of this study was to investigate the impact of this combination therapy on plasma adiponectin levels . Hypothesis : Combination therapy with amlodipine and atorvastatin would increase plasma adiponectin levels . Methods : A total of 25 patients with coronary artery disease and concomitant hypertension and hypercholesterolemia were evaluated . The combination of amlodipine and atorvastatin in 8 different dosage strengths were flexibly titrated over a period of 14 weeks . Lipid profile and plasma adiponectin were measured . Brachial flow-mediated dilation ( FMD ) was determined by vascular ultrasound . Results : As compared with baseline , combination therapy with amlodipine and atorvastatin significantly reduced systolic and diastolic blood pressure , total cholesterol , and low-density lipoprotein cholesterol ( all P < 0.05 ) . Furthermore , there were significant increases in adiponectin levels ( mean [ 95 % confidence interval ( CI ) ] , 12.1 [ 10.7 - 13.7 ] vs 8.1 [ 6.5 - 10.0 ] μg/mL ; P < 0.001 ) and brachial FMD ( 4.4 ± 0.6 % vs 5.6 ± 0.5 % ; P = 0.046 ) over 14 weeks of treatment . The change in adiponectin levels correlated significantly with the changes in diastolic blood pressure ( r = −0.49 ; P = 0.014 ) and FMD ( r = 0.55 ; P = 0.007 ) . Conclusion : The results of this study indicate that along with its antihypertensive and cholesterol-lowering effects , combination therapy with amlodipine and atorvastatin appears to increase plasma adiponectin levels and improve endothelial function Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes , reducing their phagocytic activity , and suppressing the accumulation of modified lipoproteins in the vascular wall . Contradictory data have been reported about the effect of statins on adiponectin plasma levels . In this work , adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration ( ACTFAST ) study , a 12-week , prospect i ve , multi-centre , open-label trial which enrolled subjects with coronary heart disease , coronary heart disease-equivalent or a 10-year coronary heart disease risk > 20 % . Subjects were assigned to atorvastatin ( 10 - 80 mg/day ) based on low-density lipoprotein (LDL)-cholesterol concentration at screening . For comparison , age and gender-matched blood donors ( N=40 ) were used as controls . Control subjects did not present hypertension , hypercholesterolemia , diabetes , metabolic syndrome and history of cardiovascular diseases . Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [ 4166 ( 3661 - 4740 ) vs 5806 ( 4764 - 7075 ) ng/ml respectively ; geometric mean ( 95 % CI ) ; P<0.0001 ] . In the whole population , atorvastatin treatment increased adiponectin levels [ 9.7 (3.2 - 16.7);% Change ( 95 % CI ) ; P=0.003 ] . This increment was in a dose-dependent manner ; maximal effect observed with atorvastatin 80 mg/d [ 24.7 ( 5.7 - 47.1 ) ; P=0.01 ] . Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment . No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment . In conclusion , atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk , revealing a novel anti-inflammatory effect of this drug BACKGROUND Antihypertensive agents differentially influence the plasma adiponectin concentration and the effects of fixed-dose combination regimens remain unclear . The influence of a combination of an angiotensin-converting enzyme inhibitor ( ACEI ) and a thiazide-type diuretic or an ACEI alone on plasma adiponectin concentrations in patients with essential hypertension was evaluated in the present study . METHODS AND RESULTS After a 2-week placebo run-in phase , 30 patients with essential hypertension were r and omized to receive preterax ( 2 mg perindopril/0.625 mg indapamide ) or cilazapril ( 2.5 mg ) once daily for 12 weeks . Plasma adiponectin and insulin concentrations were measured before and after treatment . Insulin resistance was measured by homeostasis assessment index ( HOMA-IR ) . Treatment with preterax ( P=0.003 ) and cilazapril ( P=0.031 ) significantly reduced systolic blood pressure ( BP ) , but only preterax reduced diastolic BP ( P=0.024 ) . Cilazapril treatment significantly increased the plasma adiponectin concentration ( P=0.025 ) and reduced plasma triglycerides ( P=0.041 ) , whereas preterax treatment increased the plasma insulin concentration ( P=0.041 ) and tended to increase HOMA-IR . CONCLUSIONS The combination of an ACEI and indapamide improved BP control , but attenuated the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension . Such a combination may be best reserved for improved BP control rather than for metabolic protection in clinical hypertension Background : In addition to lipid lowering , further pleotropic effects of statins have been postulated . We aim ed to study if the various pleotropic effects are due indirectly to the modulation of adipocytokines . Material s and methods : We studied the effect of atorvastatin on insulin sensitivity and the plasma adiponectin and leptin concentrations . Our r and omized open labeled study had 29 hyperlipidemic Type 2 diabetic patients ( 14 females , 15 males , mean age 60.0±2.2 yr ) . They were r and omized into three 12-week atorvastatin intervention types . Each day patients were given either 10 mg ( no.=10 ) , 20 mg ( no.=10 ) or 40 mg ( no.=9 ) . Evaluations were performed before and after intervention . Results : All baseline characteristics were statistically identical in the 3 groups . Drop in total cholesterol , LDL-cholesterol , and triglyceride levels were measured at the end . With 10 mg the drop was 30 % , 37 % , and 30 % . The 20 mg group was 43 % , 54 % , and 34 % . The 40 mg group was 42 % , 51 % , and 27 % . Groups had no significant change of body mass index , HDL-cholesterol , and glycated hemoglobin levels . Also , levels of insulin , adiponectin , leptin , homeostasis model assessment index ( HOMA ) and Quantitative Insulin Sensitivity Check Index ( QUICKI ) stayed the same . Pooled parameters of all 29 patients showed no difference in levels of insulin , adiponectin , leptin , HOMA , and QUICKI before and after treatment . Conclusions : Atorvstatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes Background Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease ( ESRD ) . Although statins exert pleiotropic effects , it is uncertain whether statin therapy improves insulin resistance in these patients . In this prospect i ve r and omized controlled trial , we aim ed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis ( PD ) . Methods Patients were r and omized into a statin group ( n = 35 ) or a control group ( n = 35 ) . The statin group received 10 mg per day of rosuvastatin for 6 months . We determined insulin resistance by homeostatic model assessment of insulin resistance ( HOMA-IR ) index . Serum concentrations of adipokines such as adiponectin , leptin , and resistin were measured using enzyme-linked immunosorbent ( ELISA ) assay . As inflammatory markers , high sensitive C-reactive protein ( hsCRP ) and interleukin-6 were also measured . Results There were no significant differences in baseline characteristics between the two groups . Compared to baseline value , statin treatment significantly decreased HOMA-IR index from 2.37 ± 1.08 to 2.05 ± 0.82 ( P = 0.014 ) . There was a concordant decrease in hsCRP levels in the statin group ( 2.05 ± 1.57 to 1.21 ± 0.84 mg/L , P < 0.001 ) , but such improvements were not observed in the control group . When between-group differences in these parameters were compared , hsCRP levels were more decreased in the statin group than in the control group ( P = 0.021 for between-group difference ) , whereas HOMA-IR index was not ( P = 0.189 for between-group difference ) . During this period , statin treatment did not result in the improved adipokine profiles . Conclusion This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment . Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients OBJECTIVE Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged . Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin , as well as combined therapy , on fasting plasma glucose , insulin resistance index , adipokines ( leptin , resistin , adiponectin ) and levels of proinflammatory cytokines ( TNF-α , IL-6 ) in patients with impaired fasting glucose ( IFG ) and mixed hyperlipidemia . MATERIAL S AND METHODS 67 patients were r and omly assigned to four treatment arms : monotherapy with atorvastatin , monotherapy with fenofibrate , combined therapy ( fenofibrate and torvastatin ) or therapeutic lifestyle change . The study lasted for 90 days . All participants received counseling regarding proper diet and physical activity . RESULTS Compared to the control subjects , prediabetic patients exhibited elevated plasma levels of leptin , resistin , TNF-α and IL-6 , and a lower plasma level of adiponectin . All therapeutic interventions result ed in significant alterations in the lipid profile . Insulin resistance index ( HOMA-IR ) was reduced after treatment with fenofibrate . The effect of atorvastatin on insulin resistance was comparable to therapeutic lifestyle change alone . Therapy with hypolipidemic drugs caused increases in adiponectin levels and decreases in leptin and resistin . An additive effect of the combined treatment on plasma IL-6 level was also observed . CONCLUSIONS Fenofibrate-based treatment was associated with improved insulin sensitivity . Atorvastatin did not cause a deterioration in insulin sensitivity . Hypolipidemic therapies result ed in significant changes in the proinflammatory cytokine network as well as in adipokine levels . At the end of the study the measured parameters nearly resembled those of the healthy subjects In a framework of multicenter study ATLANTIKA in a group of patients we carried out noninvasive ultrasound test of endothelium dependent vasodilatation ( EDVD ) of brachial artery before and at the background of therapy with atorvastatin . Aim of the study was to assess and compare effects of incremental ( 10 - 80 mg/day ) and stable ( 10 mg/day ) doses of atorvastatin on functional state of endothelium . The group of observation comprised 148 patients A 86 men , 62 women aged 59.5 ( 55;66 ) years , who were included into ATLANTIKA study and r and omized to 3 groups : group A - active therapy with stable dose of atorvastatin ( 10 mg/day ) ( n=52 ) , active therapy with titration of atorvastatin dose from 10 to 80 mg/day ( n=50 ) , group C - common therapy which could include lipid lowering drugs ( n=46 ) . At baseline there were no statistically significant differences between groups in main demographical , laboratory and instrumental parameters . Median EDVD was 5.4 ( 3.5 ; 8.0 ) , 5.1 ( 3.9 ; 7.6 ) and 5.6 ( 3.2 ; 8.1)% in groups A , B , and C , respectively . After 12 and 24 weeks of observation statistically significant increases of brachial artery EDVD occurred only in group B ( by 27.2 and 31.9 % , respectively ) . There was no statistically significant positive dynamics of EDVD in groups A and C. Results of the presented work show that for achievement of statistically significant positive vascular effect it is necessary to titrate dose of atorvastatin until target level of low density lipoprotein cholesterol ( < 2.5 mmol/l ) is achieved . Vascular effect of therapy with atorvastatin in a fixed dose 10 mg/day is inferior to that of aggressive therapy , however it is substantially superior to common treatment AIM To assess changes in circulating incretin levels and body fat compositions with initial combination therapy with α-glucosidase inhibitor and dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes ( T2D ) . METHODS In this multicenter open-label 24-week trial , Japanese over-weight ( BMI ≥ 25 kg/m(2 ) ) patients with T2D not taking medication or taking metformin and /or sulfonylurea  were r and omly assigned to receive either 50 mg of miglitol three times a day ( M , n=14 ) , 50 mg of sitagliptin once a day ( S , n=14 ) , or a combination of both ( M+S , n=13 ) . Changes in plasma incretin levels during a meal tolerance test ( MTT ) and body fat composition with impedance method were evaluated . RESULTS During MTT , postpr and ial plasma glucose levels decreased more after M+S than after M or S , and postpr and ial serum insulin levels decreased significantly after M and M+S whereas they increased after S. After M , active gastric inhibitory polypeptide ( aGIP ) decreased significantly at 30 min despite a significant increase at 120 min . After S , aGIP levels increased significantly throughout the MTT . After M+S , aGIP increased significantly at 0 and 120 min despite of significant decrease at 30 min . M+S further enhanced postpr and ial active glucagon-like peptide-1 levels during MTT than S did . Total body fat mass decreased significantly after M and M+S. Visceral fat mass decreased significantly only after M+S. Serum adiponectin increased significantly only after M+S. CONCLUSIONS In over-weight patients with T2D , M+S may have a beneficial effect on adiposity with relation to these different effects on two incretins Aldosterone production causes vascular injury and may occur despite the long-term administration of angiotensin converting enzyme-inhibitors ( ACE-I ) ( ie , aldosterone breakthrough ) . The angiotensin II receptor blocker ( ARB ) telmisartan can function as a lig and for peroxisome proliferator-activated receptor ( PPAR ) gamma . Stimulation of PPAR gamma has been demonstrated to raise adiponectin production and suppress angiotensin II type 1 receptor expression . Thus , we investigated the effect of the ACE-I perindopril erbumin ( perindopril ) and the ARB telmisartan on plasma levels of aldosterone and adiponectin . Patients with essential hypertension were r and omly assigned to receive 48 weeks of perindopril ( 2 - 8 mg/d ) or telmisartan ( 20 - 80 mg/d ) . We measured adiponectin , aldosterone , angiotensin II , and renin at weeks 0 , 8 , 24 , and 48.A total of 53 subjects were r and omized . Data on 51 subjects ( 25 in the perindopril group and 26 in the telmisartan group ; mean age , 65.1 years ) were available for analyses . Plasma aldosterone decreased significantly in both the telmisartan ( 69.9+/-5.6 to 58.1+/-5.4 pg/mL ) and perindopril ( 74.1+/-4.7 to 64.7+/-5.3 pg/mL ) groups at 8 weeks , but returned toward the baseline in the perindopril group ( 67.9+/-4.1 pg/mL ) at 24 weeks . Plasma glycated hemoglobin levels or urine albumin did not change significantly after the treatment in either group . Telmisartan seemed to be more effective at suppressing aldosterone and raising adiponectin levels than perindopril ; however , improvements in insulin sensitivity and albuminuria were not detected . These results are consistent with the idea that the use of an ARB with PPAR gamma stimulating activity is equivalent to ACE-I for the treatment of hypertension BACKGROUND Statins improve cardiovascular outcome , but less is known on the renal outcome . We , therefore , studied the relationship between the use of statins and urinary albumin excretion ( UAE ) and glomerular filtration rate ( GFR ) in two setting s : a r and omized controlled trial ( RCT ) and an observational cohort study , in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis . METHODS We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial ( PREVEND-IT ) and the PREVEND cohort study . The PREVEND-IT subjects ( 788 with a UAE 15 - 300 mg/day ) received pravastatin 40 mg/day vs placebo and /or fosinopril 20 mg/day vs placebo in a 2x2 factorial- RCT design . Of the 3440 cohort subjects , 469 used statins during the 4-year follow-up period . Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR . RESULTS In the RCT , pravastatin did not change UAE or GFR , neither in fosinopril yes/no subgroups . In the observational cohort , statin use was associated with a rise in UAE ( + 12.1 % ) , compared with statin non-use ( + 3.6 % , P<0.001 ) . This rise was most pronounced in those on statins prior to the first screening [ + 24.8 % ( 95 % CI : 11.9 - 39.2 ) ] , those using statins>3 years [ + 18.5 % ( 7.3 - 30.8 ) ] and those with > 1 or > 2 defined daily doses ( + 15.7 and + 17.3 % , respectively ) . These differences remained significant after adjustment for relevant variables and propensity score . The rise in UAE could not be attributed to a higher dose or a specific statin . GFR fell in 4 years in both statin users and non-users ( 4.6+/-13.5 and 2.4+/-11.2 , respectively ) . The fall in GFR between groups was not different after adjustment ( P=0.11 ) . CONCLUSIONS We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia . In the observational cohort study , the use of statins similarly was not associated with a fall in UAE ; UAE instead increased . Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR Pravastatin increases the plasma adiponectin level . We examined whether this is a statins ' class effect or specific to pravastatin . Of 50 patients undergoing cardiac surgery for coronary artery disease ( CAD , n = 36 ) and valvular heart disease ( VHD , n = 14 ) , 23 with CAD and serum LDL-cholesterol level > 100 mg/dL were r and omized  to pravastatin at 10 mg/day ( PRAVA , n = 12 ) or rosuvastatin at 2.5 mg/day ( ROSUVA , n = 11 ) for 2 months , and the other 13 with CAD and LDL-cholesterol ≤100 mg/dL were not treated with statin ( Non-statin , n = 13 ) . Patients with VHD did not have CAD and were not treated with statin . Blood was sample d at baseline and surgery . Visceral ( VIS ) and subcutaneous ( SC ) adipose tissues were harvested during surgery . At baseline , the plasma adiponectin level was low in patients with CAD compared with that of patients with VHD . At surgery , adiponectin level in PRAVA was increased to the level in VHD , whereas those in ROSUVA and Non-statin were unchanged . VIS contents and gene expressions of adiponectin in PRAVA and VHD were similar to each other and were both higher than those in Non-statin and ROSUVA . SC content and gene expression of adiponectin were similar among 4 groups . Protein carbonyl ( PC ) level , an indicator of oxidative stress , in VIS was lower in PRAVA and VHD than in ROSUVA and Non-statin . There was a negative correlation between the plasma adiponectin and VIS PC levels ( r = -0.41 , P < 0.05 ) . Thus , pravastatin  increases adiponectin generation , whereas rosuvastatin does not BACKGROUND Insulin resistance is thought to play a pathophysiological role in the development of atherosclerosis . Decreased adiponectin levels are associated with hyperinsulinemia , insulin resistance , and coronary artery disease . Patients with familial hypercholesterolemia ( FH ) develop premature atherosclerosis and should be insulin resistant and have low adiponectin levels . METHODS A total of 51 homozygous FH ( HoFH ) and 20 heterozygous FH ( HeFH ) patients were studied before and after statin therapy .  Twenty normocholesterolemic subjects were controls .  Fasting lipograms , glucose , insulin , proinsulin , adiponectin , and high-sensitivity C-reactive protein ( hsCRP )  were measured . Insulin resistance was calculated with the homeostasis model assessment ( HOMA-IR ) formula . Carotid intima media thickness ( CIMT ) was measured as a sub clinical marker of atherosclerosis . RESULTS On multiple regression analysis , the major determinant of insulin resistance measured by HOMA-IR was body mass index ( BMI ) ( r=0.54 ; P=0.004 ) . On simple linear regression , the highest correlation was with BMI ( r=0.39 ; P=0.0002 ) . Log hsCRP correlated with BMI ( r=0.35 ; P<0.002 ) and insulin resistance ( r=0.22 ; P=0.05 ) . Low-density lipoprotein cholesterol ( LDL-C ) and CIMT did not correlate with insulin resistance . Unexpectedly , adiponectin levels were highest in HoFH patients and correlated with LDL-C ( r=0.34 ; P=0.001 ) . No change in the degree of IR was observed with statin therapy . CONCLUSIONS FH patients are not insulin resistant and do not have low adiponectin levels . There was no significant change in insulin resistance with high-dose statin therapy OBJECTIVE We evaluated the long-term effects of rosuvastatin and simvastatin on insulin sensitivity and secretion in patients with well-controlled type 2 diabetes . METHODS After a 3 weeks run-in , 27 eligible patients were r and omly assigned to receive either rosuvastatin 20 mg daily ( Group 1 ) or simvastatin 20 mg daily ( Group 2 ) for 6 months ; thereafter they were switched to the other treatment for additional 6 months . Patients were recruited among individuals attending the outpatient service of the Diabetology Unit of the " Policlinico Tor Vergata " University Hospital , Rome , Italy . Serum lipids , glucose and insulin , glycated hemoglobin , C-reactive protein , TNF-α , leptin , adiponectin , insulin sensitivity by euglycemic-hyperinsulinemic clamp , β-cells function by HOMA-β were assessed at months 0 , 6 and 12 . Additionally , endothelial function was assessed by use of the brachial artery reactivity technique . RESULTS Besides marked reduction in lipid levels , glycated hemoglobin significantly increased from baseline after 12 months in both Group 1 ( + 0.8 ± 0.2 % , p < 0.001 ) and Group 2 ( + 0.9 ± 0.3 % ; p < 0.001 ) . Similar trends were observed for fasting glucose in both groups . No changes in insulin sensitivity were detected throughout the study , whereas HOMA-β significantly decreased from baseline after 12 months in both Group 1 ( -21.9 % , p < 0.01 ) and Group 2 ( -38.9 % ; p < 0.001 ) . In addition , both treatments similarly decreased C-reactive protein and leptin , as well as improved endothelial function . No changes in anthropometric measures were observed . CONCLUSIONS In well-controlled type 2 diabetic patients  both rosuvastatin and simvastatin significantly impaired glycemic control and insulin secretion , without affecting insulin sensitivity Asymmetric  dimethylarginine ( ADMA ) and monomethylarginine ( LMMA ) are endogenous inhibitors of nitric oxide synthase . A high level of ADMA in plasma has shown to be a significant risk factor for acute coronary syndromes and elevated plasma ADMA levels are prevalent in patients with hypercholesterolemia . It was therefore hypothesized that lowering plasma cholesterol levels with statin treatment would also lower ADMA concentrations . This double-blind study addressed the effect of high-dose statin treatment on plasma levels of ADMA and LMMA .  Forty-eight subjects with mild hypercholesterolemia were r and omly assigned to receive simvastatin 80 mg/d , atorvastatin 40 mg/d , or placebo for 8 weeks . Both statins decreased low-density lipoprotein cholesterol effectively ( simvastatin 54 % and atorvastatin 49 % ) . However , concentrations of arginine derivatives remained unchanged during statin treatment and did not correlate with cholesterol levels . This study indicates that statin treatment has no clear influence on plasma ADMA or LMMA concentrations BACKGROUND In a r and omized , controlled , 2 x 2 factorial trial on the effect of long-term changes in diet and exercise , a significant reduction in body weight and fat mass was observed . Alterations in leptin and plasminogen activator inhibitor-1 concentrations were previously reported from this study . OBJECTIVE We examined the separate and combined effects of a 1-y exercise and diet intervention on several adipokines ; adiponectin , interleukin-6 and -8 , tumor necrosis factor-alpha , monocyte chemoattractant protein-1 , hepatocyte growth factor , nerve growth factor , C-reactive protein , and resistin . DESIGN One hundred eighty-eight men with several risk factors for diabetes and cardiovascular disease were r and omly allocated to 4 groups : diet , exercise , combined diet and exercise , and control . RESULTS Plasma adiponectin concentrations remained unchanged , whereas body mass index and fat mass decreased after dietary changes and an increase in physical activity . In the control group , adiponectin concentrations were reduced . Analyzed according to the factorial design , only diet intervention had a significant ( P = 0.03 ) positive effect on plasma adiponectin relative to control , and this effect was largely explained by changes in fat mass . After adjustment for change in percentage body fat , there were significant positive effects on tumor necrosis factor-alpha in all 3 intervention groups ( P = 0.01 for the diet group , 0.03 for the exercise group , and 0.05 for the combined diet and exercise group ) . Minor changes were observed for the other adipokines . Neither baseline concentrations of nor changes in adiponectin and plasminogen activator inhibitor-1 were significantly correlated to the other adipokines , whereas concentrations of and changes in the other adipokines were significantly correlated . CONCLUSION Diet intervention had a significant positive effect on adiponectin concentrations , which is largely explained by a reduction in fat mass AIMS To determine whether early statin therapy in acute myocardial infa rct ion has any effect on ventricular late potentials which are considered as a noninvasive tool for evaluation of arrhythmogenic substrate . METHODS AND RESULTS Study population consisted of prospect ively enrolled 72 patients presenting with acute myocardial infa rct ion ( < 6 h ) . Thirty-four of the patients were r and omized to pravastatin ( 40 mg/day ) on admission irrespective of lipid levels . All patients received thrombolytic therapy .  Signal-averaged ECG recordings were obtained serially prior to thrombolytic therapy , 48 h after and 10 days later . Late potentials were defined as positive if signal-averaged ECG met at least two of Gomes criteria : filtered total QRS duration > 114 ms , root mean square voltage of the last 40 ms of the QRS < 20 mV , or the duration of the terminal low ( < 40 mV ) amplitude signals > 38 ms . Changes observed in signal-averaged ECG recordings after thrombolysis were evaluated statistically with regard to statin usage . There were no significant differences between the clinical characteristics of the two r and omized groups . There was a significant decrease in the rates of late potentials between the first and third signal-averaged ECG recordings after thrombolytic therapy in pravastatin group . Pravastatin group also had lower incidence of ventricular arrhythmias compared with control group ( 26 vs. 63 % , P=0.021 ) . The in-hospital cardiovascular event rates were also lower in statin group . CONCLUSION Early use of pravastatin reduces the incidence of late potentials following thrombolytic therapy in acute myocardial infa rct ion . Statin therapy also seems to be reducing the incidence of in-hospital ventricular arrhythmias . These beneficial effects of statins might be explained through prevention of new myocardial ischemic episodes due to early plaque stabilization or regulation of endothelial and platelet functions Objective : To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion and stroke ) in men with earlier acute coronary syndromes . Design , subjects and measurements : A nested case – control study examined circulating leptin and adiponectin levels in plasma obtained 4–6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) trial . Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events . The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis . Results : Relative risk ( RR ) increased across increasing leptin quartiles ; the highest quartile compared with the lowest quartile was related to the highest risk ( P for trend=0.002 ) ; the increased risk remained after adjustment for risk factors ( P=0.018 ) or for obesity ( P=0.038 ) , but in the final model ( adjusted for r and omized treatment , other drugs , LIPID risk score , age and body mass index ) , the risk was attenuated ( RR=1.61 , 95 % CI : 0.72–3.57 , P for trend=0.34 ) . Adiponectin did not predict cardiovascular events . Subjects r and omly allocated to pravastatin had 6 % lower leptin levels ( P=0.04 ) than those allocated to placebo . Conclusion : Plasma leptin was a significant and independent predictor of recurrent cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion and stroke ) in men with earlier acute coronary syndromes
The meta- analysis showed a significant increase in plasma adiponectin levels following statin therapy .
Although statins are known to increase the risk for new onset diabetes mellitus , our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression
BACKGROUND AND AIMS The effect of statin therapy on plasma adiponectin levels has not been conclusively studied .
Therefore , we aim ed to evaluate this effect through a systematic review and meta- analysis of available r and omized controlled trials ( RCTs ) .