Simvastatin lowers C-reactive protein by 14 days: an effect independent of that on LDL cholesterol

Plenge, Julie K.; Well, Kathleen M.; Grunwald, Gary K.; Forster, Jeri E.; Poirier, Paul; Eckel, Robert H.

doi:10.1016/s0735-1097(02)80986-x

Cited by 110 publications

(140 citation statements)

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“…Changes in inflammatory markers with omega-3 fatty acids plus simvastatin treatment in patients with mixed dyslipidemia Simvastatin were known to lower hsCRP (Madsen et al, 2001;Plenge et al, 2002;Meredith et al, 2007). However, this study showed no significant improvement in hsCRP levels with the use of combination therapy or simvastatin alone.…”

Section: Discussioncontrasting

confidence: 69%

“…However, this study showed no significant improvement in hsCRP levels with the use of combination therapy or simvastatin alone. In this study, in which high-risk patients were excluded, the baseline hsCRP level (0.2 mg per 100 ml) was lower than that (1.1-2.8 mg per 100 ml) of previous studies Omega-3 fatty acid plus simvastatin versus simvastatin Hyo-Soo Kim et al (Madsen et al, 2001;Plenge et al, 2002;Meredith et al, 2007). This difference may explain why there were no changes in the hsCRPs in either group of this study.…”

Section: Discussioncontrasting

confidence: 51%

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Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability

Kim

Lee

et al. 2010

Eur J Clin Nutr

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Background: This study was designed to evaluate the effects of omega-3 fatty acids supplements and simvastatin on lipoproteins and heart rate variability (HRV), a surrogate parameter of cardiac autonomic function, in patients with mixed dyslipidemia. Methods: This study was a prospective, randomized, open-label study. Among the 171 patients screened, 62 who met the inclusion criteria after 6 weeks on a strict diet therapy were randomized into two treatment groups. The inclusion criteria were mixed dyslipidemia with a high triglyceride level (200-499 mg per 100 ml) and a total cholesterol level 4200 mg per 100 ml. After a run-in period of 6 weeks, the patients were randomized into two groups and given a combination treatment with 4 g of omega-3 fatty acids (four 1 g Omacor (eicosapentaenoic acid, 465 mg; docosahexaenoic acid, 375 mg; other omega-3 fatty acids, 60 mg; others 100 mg, Gun-il Pharmacy, Seoul, Korea)) and 20 mg of simvastatin daily or a monotherapy of 20 mg simvastatin for 6 weeks. In the combination therapy group, seven patients dropped out, and in the simvastatin alone therapy group, five patients dropped out during the study period. Results: After 6 weeks of drug treatment, triglyceride levels decreased by 41.0% in the combination treatment group and 13.9% in the simvastatin monotherapy group (from 309.2 ± 95 mg per 100 ml to 177.7 ± 66 versus 294.6 ± 78 mg per 100 ml to 238.3 ± 84 mg per 100 ml, respectively, P ¼ 0.0007). No significant changes in the HRV parameters were observed in either group. Conclusion: The combination of omega-3 fatty acids plus simvastatin, which achieved a significantly greater reduction of triglycerides without adverse reactions, should be considered as an optimal treatment option for patients with mixed dyslipidemia.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussioncontrasting

confidence: 51%

Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability

Kim

Lee

et al. 2010

Eur J Clin Nutr

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“…50 In adults, behavioral and pharmacological interventions including weight loss, exercise training, and therapy with hydroxymethylglutaryl coenzyme A (CoA) reductase inhibitors (statins) lower hsCRP levels. 15,[51][52][53][54][55] This has not been demonstrated in obese children so far. It must be emphasized that this study does not provide the definitive evidence that weight loss can alter impaired vascular function and inflammation in obese children.…”

Section: Discussionmentioning

confidence: 88%

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

Kapiotis

Holzer

Schaller

et al. 2006

ATVB

195

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Background-Obesity is generally accepted as a risk factor for premature atherosclerosis. Subclinical inflammation as quantified by blood levels of C-reactive protein (CRP) contributes to the development and progression of atherosclerosis. We hypothesized that inflammation in obese children is related to functional and early morphological vascular changes. Methods and Results-Blood levels of high sensitivity (hs) CRP, hsIL-6, the soluble intercellular adhesion molecule1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and E-selectin were measured in 145 severely obese (body mass index [BMI], 32.2Ϯ5.8 kg/m 2 ) and 54 lean (BMI, 18.9Ϯ3.2 kg/m 2 ) children 12Ϯ4 years old. Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measured by high-resolution ultrasound as markers of early vascular changes were assessed in 92 (77 obese and 15 lean) and 59 (50 obese and 9 lean) children, respectively. Obese children had significantly higher levels of hsCRP, hsIL-6, and E-selectin than healthy controls (4.1Ϯ4.8 versus 0.9Ϯ1.5 mg/L, PϽ0.001 for hsCRP; 1.99Ϯ1.30 versus 1.42Ϯ1.01 pg/mL, Pϭ0.05 for hsIL-6; and 78Ϯ38 versus 59Ϯ29 ng/mL, Pϭ0.01 for E-selectin). There were no differences in the levels of ICAM-1 and VCAM-1 between groups. Obese children had lower peak FMD response (7.70Ϯ6.14 versus 11.06Ϯ3.07%, Pϭ0.006) and increased IMT (0.37Ϯ0.04 versus 0.34Ϯ0.03 mm, Pϭ0.03) compared with controls. Morbidly obese children (nϭ14, BMI 44.1Ϯ3.9 kg/m 2 ) had highest levels of hsCRP (8.7Ϯ0.7 mg/L), hsIL-6 (3.32Ϯ1.1 pg/mL), and E-selectin (83Ϯ40 ng/mL). Conclusions-A proinflammatory state is detectable in obese children, which is accompanied by impaired vascular endothelial function and early structural changes of arteries, even in young subjects at risk. It remains to be determined whether high hsCRP in obese children predicts cardiovascular events.

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“…On first glance, our finding seems to contradict results of recent clinical studies with pravastatin and simvastatin. 16 -18,32 These results were obtained by post hoc analysis of a large outcome trial and in smaller short-term studies, 16,18,32 and may therefore have been confounded by cotherapies usually given to cardiovascular risk patients such as aspirin. 15 In the primary prevention cohort of the Pravastatin Inflammation CRP Evaluation trial comprising 1702 subjects with no prior history of cardiovascular disease, treatment with 40 mg pravastatin significantly reduced hsCRP by 16.9%, but the absolute decrease in mean hsCRP serum concentration was modest, ie, 0.20 mg/L.…”

Section: Discussionmentioning

confidence: 99%

“…2,9 Results of recently published studies indicated that increased hsCRP serum levels can be lowered by nonpharmacological interventions, eg, weight reduction, as well as pharmacological interventions, eg, use of aspirin and HMGCoA reductase inhibitors (statins). [13][14][15][16][17][18] In this regard, large controlled studies with angiotensin II (Ang II) subtype 1 receptor antagonists are still lacking, despite the well-known proinflammatory properties of Ang II. 19 -21 The present prospective, double-blind, placebo-controlled, multicenter study was undertaken to evaluate the antiinflammatory effect of the Ang II subtype 1 receptor antagonist olmesartan medoxomil in patients with essential hypertension and signs of (vascular) microinflammation (ie, hsCRP Ͼ3 mg/L).…”

mentioning

confidence: 99%

Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation

2004

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Background-Experimental studies revealed proinflammatory properties of angiotensin II. We evaluated antiinflammatory effects of the angiotensin II subtype 1 receptor antagonist olmesartan medoxomil alone and in cotherapy with the HMG-CoA reductase inhibitor pravastatin in patients with essential hypertension and microinflammation. Methods and Results-We measured a panel of vascular inflammation markers, including high-sensitivity C-reactive protein, and lipid levels during 12 weeks of therapy with olmesartan (nϭ100) or placebo (nϭ99) in a prospective double-blind multicenter study. Pravastatin was added to the double-blind therapy at week 6 in both treatment arms. Blood pressure control was achieved with addition of hydrochlorothiazide. Olmesartan treatment had already significantly reduced serum levels of high-sensitivity C-reactive protein (Ϫ15.1%; PϽ0.05), high-sensitivity tumor necrosis factor-␣ (Ϫ8.9%; PϽ0.02), interleukin-6 (Ϫ14.0%; PϽ0.05), and monocyte chemotactic protein-1 (Ϫ6.5%; PϽ0.01) after 6 weeks of therapy, whereas placebo treatment (ie, blood pressure reduction) had no major effect on inflammation markers. After 12 weeks of therapy, high-sensitivity C-reactive protein (Ϫ21.1%; PϽ0.02), highsensitivity tumor necrosis factor-␣ (Ϫ13.6%; PϽ0.01), and interleukin-6 (Ϫ18.0%; PϽ0.01) decreased further with olmesartan and pravastatin cotherapy, but treatment with pravastatin alone (ie, cotherapy with placebo) did not significantly alter inflammation markers. In contrast, addition of pravastatin led to a significant (PϽ0.001) reduction in LDL cholesterol serum concentrations in the olmesartan and placebo treatment groups (Ϫ15.1% and Ϫ12.1%, respectively). Conclusions-Angiotensin II receptor blockade significantly reduces vascular microinflammation in patients with essential hypertension by as early as week 6 of therapy. This antiinflammatory action of angiotensin II receptor antagonists may contribute to their beneficial cardiovascular effects.

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Simvastatin lowers C-reactive protein by 14 days: an effect independent of that on LDL cholesterol

Cited by 110 publications

References 0 publications

Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability

Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation

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