Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial

OBJECTIVES: The UK Prospective Diabetes Study (UKPDS) showed that treatment with metformin decreases macrovascular morbidity and mortality independent of glycaemic control. We hypothesized that metformin may achieve this by improving endothelial function and chronic, low-grade inflammation. Data on this issue are scarce and we therefore tested, in the setting of a randomized, placebo-controlled trial, whether metformin can affect endothelial function and low-grade inflammation. DESIGN: The Hyperinsulinaemia the Outcome of its Metabolic Effects (HOME) trial is a double-blind trial, in which all patients were randomized to receive either metformin or placebo in addition to insulin therapy. At the beginning and the end of a 16-week treatment period fasting blood samples were drawn and a physical examination was carried out. SETTING: The trial was conducted in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden; the Netherlands). SUBJECTS: Patients were included if they were between 30 and 80 years of age; had received a diagnosis of diabetes after the age of 25; had never had an episode of ketoacidosis; and their blood glucose-lowering treatment previously consisted of oral agents but now only consisted of either insulin (n = 345) or insulin and metformin (n = 45). We excluded pregnant women and women trying to become pregnant, patients with a Cockroft-Gault-estimated creatinine clearance <50 mL min(-1), or low plasma cholinesterase (reference value <3.5 units L(-1)), patients with congestive heart failure (New York Heart Association class III/IV), or patients with other serious medical or psychiatric disease. A total of 745 eligible patients were approached; 390 gave informed consent and were randomized (196 metformin, 194 placebo). About 353 patients completed 16 weeks of treatment (171 metformin, 182 placebo). MAIN OUTCOME MEASURES: The HOME trial was designed to study the metabolic and cardiovascular effects of metformin during a follow-up of 4 years. Presented here are the results of an interim analysis after 16 weeks of treatment. RESULTS: When compared with placebo, metformin treatment was associated with an increase in urinary albumin excretion of 21% (-1 to +48; P = 0.06); a decrease in plasma von Willebrand factor of 6% (-10 to -2; P = 0.0007); a decrease in soluble vascular cell adhesion molecule-1 of 4% (-7 to -2; P = 0.0002); a decrease in soluble E-selectin of 6% (-10 to -2; P = 0.008); a decrease in tissue-type plasminogen activator of 16% (-20 to -12; P < 0.0001); and a decrease in plasminogen activator inhibitor-1 of 20% (-27 to -10; P = 0.0001). These changes could not be explained by metformin-associated changes in glycaemic control, body weight or insulin dose. Markers of inflammation, i.e. C-reactive protein and soluble intercellular adhesion molecule-1, did not change with metformin treatment. CONCLUSIONS: In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation.     

Maturation-induces endothelial dysfunction via vascular inflammation in diabetic mice

We hypothesized that maturation-induced vascular inflammation produces endothelial dysfunction in type II diabetes and TNFalpha plays a key role in triggering inflammation in the development of diabetes. In control (Db/db) mice aged 6, 12, 18 and 24 weeks, sodium nitroprusside (SNP) and acetylcholine (ACh) induced dose-dependent vasodilation, and dilation to ACh was blocked by the NO synthase inhibitor N (G)-monomethyl-L: -arginine. In type II diabetic (db/db) mice at age of 12, 18 and 24 weeks, ACh or flow-induced dilation was blunted compared to Db/db; endothelial function is normal at 6 weeks of age in db/db Vs. control mice, but SNP produced comparable dilation at age of 6, 12, 18 and 24 weeks. Decrements in endothelial function in db/db mice progressively increased from 6-12 to 18-24 weeks. Administration of neutralizing antibodies to TNFalpha ameliorated endothelial dysfunction in db/db mice aged 12, 18 and 24 weeks. The effect was most prominent in the younger animals. Plasma concentration, expression of TNFalpha and TNFalpha receptor 1 (TNFR1) were elevated in coronary arterioles, even at the age of 6 weeks before the development of diabetes in db/db mice compared to control mice. Superoxide production was lower in Db/db mice compared to db/db mice and increments in superoxide production in db/db mice progressively increased from 6-12 to 18-24 weeks. NAD(P)H oxidase inhibitor apocynin attenuated superoxide production in db/db mice at 12 weeks of age, mitochondria respiratory chain inhibitor rotenone attenuated superoxide production at 24 weeks in db/db and Db/db mice, but the combination of apocynin and rotenone reduced superoxide production at 18 weeks for db/db and Db/db mice. The expression of TNFalpha and its receptors increase progressively with maturation in concert with the development of diabetes. Incremental increases in TNFalpha/TNFR1 expression induces activation and production of superoxide via NAD(P)H oxidase and/or mitochondria respiratory chain, leading to endothelial dysfunction progressing to the development of type II diabetes.     

Oral fat load effects on inflammation and endothelial stress markers in healthy subjects

The aim was to study the effect of a standardized oral fat load (OFL) on different inflammatory parameters in a large sample of adult healthy subjects (n = 286) of both sexes. The fat load was given between 08:00 and 09:00 h after a 12-h fast. Blood samples were drawn before and 3, 6, 9, and 12 h after the OFL. All patients underwent a measurement of body mass index (BMI), blood glucose (BG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-α (TNF-α). Fasting plasma glucose (FPG) increase was +3.26% at 3 h, +4.35% at 6 h, +1.09% at 9 h while FPG decrease was −1.09% at 12 h. High-density lipoprotein cholesterol increase was +2.08% at 3 h, and at 12 h during OFL study; a significant HDL-C decrease was present in subjects after 6 h (−4.17%; P < 0.05 vs 0). A significant Tg change was observed after 6 h (+70.37%; P < 0.01 vs 0) and 9 h (+58.33%; P < 0.05 vs 0) respectively, and the increase was +22.22% at 3 h and +18.52% at 12 h. Total cholesterol increase was +0.52% after 3 h, +1.04% after 6 h, while after 12 h the decrease was −0.52%. Low-density lipoprotein cholesterol increase was +1.64% after 6 h with a decrease of −0.82% at 9 and 12 h. A significant sICAM-1, hsCRP, and sE-selectin variation was observed after 6 and 9 h, while a significant sVCAM-1 change occurred after 3, 6, and 9 h. Soluble ICAM-1 increase was +20.58% at 3 h, +34.10% at 6 h (P < 0.05 vs 0) +25.94% at 9 h (P < 0.01 vs 0), and +19.14% at 12 h; sVCAM-1 increase was +13.97% (P < 0.05 vs 0) at 3 h, +18.55% at 6 h (P < 0.01 vs 0), +12.02% at 9 h (P < 0.05 vs 0), and +8.70% at 12 h. High-sensitivity CRP increase was +36.36% at 3 h, +90.91% at 6 h (P < 0.01 vs 0), +63.64% at 9 h (P < 0.05 vs 0), and +36.36% at 12 h. Soluble E-selectin increase was +27.11% at 3 h, +51.90% at 6 h (P < 0.05 vs 0), +45.19% at 9 h (P < 0.01 vs 0), and +20.12% at 12 h. Interleukin-6 increase was +61.11% at 3 h (P < 0.05 vs 0), +83.33% at 6 h (P < 0.001 vs 0), +55.56% at 9 h (P < 0.01 vs 0), and +22.22% at 12 h. Tumor necrosis factor-α increase was +42.86% at 3 h (P < 0.05 vs 0), +71.43% at 6 h (P < 0.01 vs 0), (+50.00% at 9 h (P < 0.05 vs 0), and +28.57% at 12 h. We observed that the OFL induces a complex and massive systemic inflammatory response that includes IL-6, TNF-α, hsCRP, and cell adhesion molecules, even before Tg significantly rises.     

The influence of age, gender and ABO blood group on soluble endothelial cell markers and adhesion molecules

The influence of age, gender and ABO blood group on soluble adhesion molecules and markers of endothelial function were tested by measurement of levels of von Willebrand factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), P-selectin, E-selectin and thrombomodulin in venous blood from healthy subjects. Only VCAM-1 showed a significant multivariate correlation with age ( r  = 0.2, P  = 0.019), and thrombomodulin ( P  = 0.0001) and E-selectin ( P  = 0.026) were lower in the women. Significant differences between ABO blood groups were found for von Willebrand factor ( P  = 0.024), E-selectin ( P  < 0.001) and thrombomodulin ( P  < 0.001). As these three are all specific endothelial products, our findings may have implications for vascular biology.     

Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy

Objectives

Antiretroviral therapy (ART) in HIV‐infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART.

Methods

In 115 HIV‐positive treatment‐naïve patients, plasma lipids, E‐selectin, soluble intercellular adhesion molecule 1 (sICAM‐1), soluble vascular cell adhesion molecule 1 (sVCAM‐1), tissue‐type plasminogen activator inhibitor 1 (tPAI‐1) and high‐sensitivity C‐reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean±standard error of the mean.

Results

Prior to treatment, HIV‐infected patients had elevated levels of sICAM‐1 (296±24 vs. 144±12 ng/mL), tPAI‐1 (18 473±1399 vs. 5490±576 pg/mL) and hsCRP (28 060±5530 vs. 6665±2063 ng/mL) compared with controls (P<0.001). In contrast, sVCAM‐1 and E‐selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E‐selectin (15.1±0.8; P<0.01), sICAM‐1 (248±12 ng/mL; P<0.05), sVCAM‐1 (766±33 ng/mL; P<0.001) and hsCRP (14 708±2358 ng/mL; P<0.001) after 2 months, which remained reduced at 14 months. tPAI‐1 was not influenced by initiation of ART.

Conclusions

Markers of endothelial dysfunction were elevated in treatment‐naïve HIV‐infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.     

Simvastatin inhibits Staphylococcus aureus alpha toxin mediated polymorphonuclear leukocyte-induced vasocontraction and endothelial dysfunction

Zusammenfassung Simvastatin, ein HMG-CoA-Reduktase-Inhibitor, wird im klinischen Alltag zur Senkung des Cholesterin-Spiegels eingesetzt. Darüber hinaus berichteten aktuelle Studien über protektive Eigenschaften von Statinen unter inflammatorischen Bedingungen. In dieser Studie wurden die Effekte von Simvastatin auf die Leukozyten-vermittelte Schädigung nach Stimulation mit Staphylococcus aureus alpha-Toxin untersucht. Aortale Gefäßsegmente von Ratten, vorbehandelt mit NaCl oder Simvastatin (100 g/kg) intraperitoneal appliziert, wurden isoliert. Die Gefäßsegmente wurden mit Staphylococcus aureus alpha-Toxin (0,1–1 g/ml) aktiviert und die PMN-Adhäsion quantifiziert. Zusätzlich wurde in der Organbadanlage die PMN-induzierte Vasokontraktion und endotheliale Dysfunktion untersucht. Die Adhäsion von PMN an das vaskuläre Endothel wurde durch die Stimulation mit alpha-Toxin signifikant gesteigert. Die Vorbehandlung mit Simvastatin führte zu einer signifikant geringeren Adhäsion nach alpha-Toxin Stimulation (p<0,05). Im Organbad führte die Inkubation von PMN mit Gefäßringen zu keiner Vasokontraktion bzw. endothelialen Dysfunktion. Nach Stimulation der Gefäßringe im Organbad mit alpha-Toxin 0,5 g/ml und anschließender Koinkubation mit PMN (10⁶ Zellen/ml) zeigte sich eine signifikante Vasokontraktion (119±8 mg, p<0,05). Dies führte gleichzeitig zur deutlichen Einschränkung der endothelialen Relaxation in diesen Gefäßringen nach Acetylcholingabe (21±4% Relaxation, p<0,01). Die endotheliale Dysfunktion konnte in Gefäßringen von mit Simvastatin vorbehandelten Tieren in einem geringeren Ausmaß beobachtet werden (75±5% Relaxation, p<0,05). Auch die PMN-vermittelte Vasokontraktion zeigte sich in den Gefäßringen von Simvastatin vorbehandelten Tieren ebenfalls in einem deutlich geringeren Ausmaß. Die Ergebnisse dieser Untersuchung zeigen, dass Simvastatin die durch alpha-Toxin induzierten PMN-Endothel-Interaktionen an der Gefäßwand signifikant reduziert. Dadurch kommt es zu einer geringeren vaskulären Schädigung welche bei Patienten mit Sepsis oder Endokarditis von Bedeutung sein könnte. Die Zukunft wird zeigen, ob Statine eine therapeutische Anwendung auch zur Reduktion vaskulärer Schädigungen durch bakterielle Toxine finden. Summary Aims Simvastatin, a HMG-CoA reductase inhibitor (statins), has been shown to have vascular protective effects besides its lowering effect on serum cholesterol. Moreover, statins are able to reduce leukocyte endothelium interaction in the microcirculation following inflammatory activation. These effects also play a critical role in inflammatory states like bacterial induced sepsis or systemic infectious diseases. The aim of the study was to determine if treatment with simvastatin attenuates staphylococcus aureus--toxin mediated PMN-induced vasocontraction and endothelial dysfunction. Methods and results Adherence of human PMNs to rat aortic endothelium increased significantly following stimulation of the endothelium with -toxin (0.1, 0.5, and 1 g/mL). This effect could be significantly attenuated when the vascular endothelium of simvastatin pretreated rats was tested. Simvastatin (50 or 100 g/KG) was administered 18 h before the study. Unstimulated human PMNs (10⁶ cells/mL) were added to organ chambers containing rat aortic rings stimulated with -toxin (0.5 g/mL). PMNs elicited a significant vasocontraction in -toxin-stimulated but not in control aortic rings (119±8 mg, p<0.05). This PMN-induced vasocontraction was virtually blunted in aortic rings of rats pretreated with simvastatin (p<0.05). Endothelial function as assessed by endothelium-dependent vasorelaxation to acetylcholine was substantially inhibited after induction of PMN-induced vasocontraction in -toxin-stimulated aortic rings. This endothelial dysfunction was significantly reduced in aortic rings of simvastatin pretreated animals. In contrast, endothelium-independent relaxation to sodium nitrite was not altered by PMN incubation, indicating that vascular smooth muscle function was unaffected. Conclusions PMN-endothelial interaction following Staphylococcus aureus alpha toxin activation with vascular injury and endothelial dysfunction could be preserved with simvastatin pretreatment.

Supported in part by a grant Bu 819/5-2 and Si 560/4-2 of Deutsche Forschungsgemeinschaft, Roux Program, and Robert Müller Foundation, Germany. U. B. was supported by a state grand of Saxony-Anhalt     

Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.

AIMS: To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications. METHODS: Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls. RESULTS: Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control. CONCLUSIONS: These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.     

Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria.

AIMS: To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers. METHODS: In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured. RESULTS: During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively). CONCLUSIONS: In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.     

Fecal markers of inflammation used as surrogate markers for treatment outcome in relapsing inflammatory bowel disease

AIM： To evaluate fecal calprotectin （FC） as a surrogate marker of treatment outcome of relapse of inflammatory bowel disease （IBD） and, to compare FC with fecal myeloperoxidase （MPO） and fecal eosinophil protein X （EPX）.
METHODS： Thirty eight patients with IBD, comprising of 27 with ulcerative colitis （UC） and 11 with Crohn＇s disease （CD） were investigated before treatment （inclusion）, and after 4 and 8 wk of treatment. Treatment outcomes were evaluated by clinical features of disease activity and endoscopy in UC patients, and disease activity in CD patients. In addition, fecal samples were analyzed for FC by enzyme-linked immunosorbent assay （ELISA）, and for MPO and EPX with radioimmunoassay （RIA）.
RESULTS： At inclusion 37 of 38 （97%） patients had elevated FC levels （〉 94.7 μg/g）. At the end of the study, 31 of 38 （82%） patients fulfilled predefined criteria of a complete response IUC 21/27 （78%）; CD 10/11 （91%）]. Overall, a normalised FC level at the end of the study predicted a complete response in 100% patients, whereas elevated FC level predicted incomplete response in 30%. Normalised MPO or EPX levels predicted a complete response in 100% and 90% of the patients, respectively. However, elevated MPO or EPX levels predicted incomplete response in 23% and 22%, respectively.
CONCLUSION： A normalised FC level has the potential to be used as a surrogate marker for successful treatment outcome in IBD patients. However, patients with persistent elevation of FC levels need further evaluation. FC and MPO provide superior discrimination than EPX in IBD treatment outcome.     

Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.     

Effect of preexisting statin use on expression of C-reactive protein, adhesion molecules, interleukin-6, and antioxidized low-density lipoprotein antibody in patients with unstable angina undergoing coronary stenting

BACKGROUND: Statins are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol lowering effect. HYPOTHESIS: We studied the effect of statins on expression of C-reactive protein (CRP), interleukin-6 (IL-6), adhesion molecules, and antioxidized low-density lipoprotein antibody (anti-oxLDL Ab) in patients with unstable angina (Braunwald class IIb or IIIb) undergoing coronary stenting. METHODS: Consecutive 50 patients with unstable angina were included in the study. We classified the study subjects as patients using statins (Group A, n=20, men 10, mean age 62 years) and patients not using statins (Group B, n=30, men 15, mean age 60 years). RESULTS: Baseline levels of inflammatory markers were similar in the two groups. However, 24 h after coronary stenting, serum levels of CRP (2.00 vs. 4.63 mg/l, p < 0.05), intercellular adhesion molecule-1 (ICAM-1) (217 vs. 261 ng/ml, p < 0.01), and anti-oxLDL Ab (8.97 vs. 12.96 U/ml, p < 0.05) were significantly higher in Group B than in Group A. Furthermore, 72 h after coronary stenting, serum levels of CRP (3.00 vs. 5.50 mg/l, p < 0.01) and ICAM-1 (222 vs. 277 ng/ml, p < 0.05) were significantly higher in Group B than in Group A. CONCLUSIONS: Preexisting statin therapy plays a role in reducing the serum levels of CRP, ICAM-1, and anti-oxLDL Ab after coronary stenting in patients with unstable angina. These data support an anti-inflammatory or plaque-stabilizing effect of statin therapy.     

Effect of statin and fibrate treatment on inflammation in type 2 diabetes. A randomized, cross-over study

A randomized, crossover study compared the effects of atorvastatin, gemfibrozil and their combination on inflammatory markers in type 2 diabetes. C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), secretory phospholipase A2 (sPLA2), interleukin 8 (IL8), monocyte chemotactic protein 1 (MCP1) and tumor necrosis factor α (TNFα) were measured. Both lipid-lowering drugs had positive, complementary and additive effects on inflammatory markers, which were closely related to baseline inflammatory status.