This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jialal, I. Articles by Devaraj, S. Search for Related Content PubMed PubMed Citation Articles by Jialal, I. Articles by Devaraj, S. Related Collections Lipid and lipoprotein metabolism

(Circulation. 2001;103:1933.)
© 2001 American Heart Association, Inc.

Brief Rapid Communication

Effect of Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitor Therapy on High Sensitive C-Reactive Protein Levels

Presented in part at the 73rd Scientific Sessions of the American Heart Association, New Orleans, La, November 12–15, 2000, and published in abstract form (Circulation. 2000;102[suppl II]:II-833).

I. Jialal, MD, PhD; D. Stein, MD; D. Balis, MD; S. M. Grundy, MD, PhD; B. Adams-Huet, MS; S. Devaraj, PhD

From the University of Texas Southwestern Medical Center at Dallas, Tex (I.J., D.B., S.M.G., B.A.H. S.D.), and Albert Einstein College of Medicine, Bronx, NY (D.S.).

Correspondence to I. Jialal, MD, PhD, Director, Division of Clinical Biochemistry and Human Metabolism, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9073. E-mail jialal.i{at}pathology.swmed.edu

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background—Prospective studies indicate that baseline levels of C-reactive protein (CRP), the prototypic marker of inflammation, are associated with an increased risk for cardiovascular events. Limited studies have examined therapies that influence high-sensitive CRP (hs-CRP) levels, especially in hyperlipidemic patients. Thus, we tested the effects of 3 hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins), simvastatin (20 mg/d), pravastatin (40 mg/d), and atorvastatin (10 mg/d), on levels of hs-CRP in a randomized, double-blind, crossover trial of 22 patients with combined hyperlipidemia (LDL cholesterol >130 mg/dL and triglycerides of 200 to 600 mg/dL).

Methods and Results—After 6 weeks of an American Heart Association Step 1 diet, fasting blood samples were drawn at baseline and after 6 weeks of therapy with each drug. hs-CRP levels were significantly decreased after treatment with all 3 statins compared with baseline (median values: baseline, 2.6 mg/L; atorvastatin, 1.7 mg/L; simvastatin, 1.7 mg/L; and pravastatin, 1.9 mg/L; P<0.025). The reductions obtained with the 3 statins were similar. In addition, there was no significant effect on either plasma interleukin-6 or interleukin-6 soluble receptor levels. There was no relationship between reductions in hs-CRP and LDL cholesterol.

Conclusions—Pravastatin, simvastatin, and atorvastatin significantly decreased levels of hs-CRP. These data support an anti-inflammatory effect of these drugs.

Key Words: statins • inflammation • C-reactive protein

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Recently, numerous trials with the hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) demonstrated a significant reduction in cardiovascular events.¹ Although the majority of the effect could be ascribed to a beneficial effect on the lipid profile, the statins might have additional effects that could confer benefit. Inflammation seems to be a pivotal final step in acute coronary syndromes.^{2 3} The advent of a highly sensitive assay for C-reactive protein (CRP) has led to a greater understanding of the role of inflammation in coronary artery disease. CRP, a prototypic marker of inflammation, is driven by the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor-, and IL-6.⁴ Numerous prospective epidemiological studies have clearly demonstrated an increased risk with increasing CRP levels.^{2 3} In addition, studies have demonstrated that CRP confers risk above that of an abnormal lipid profile.^{2 5} Thus, modalities targeting inflammation and reducing proinflammatory cytokines and CRP levels could be a potential additional strategy in the prevention of cardiovascular disease.

Regarding the statins, one study to date demonstrated that patients who have increased CRP levels (increased inflammation) have a greater benefit from pravastatin therapy⁶ and that median CRP levels were reduced 17.4% in the group that received pravastatin.⁷ Thus, it is important to determine whether this reduction in CRP is specific for pravastatin or if it also occurs with other commonly prescribed statins. The aim of the present study was to test if simvastatin and atorvastatin, at LDL-lowering doses similar to those of pravastatin (as determined by the CURVES study⁸ ), resulted in a significant reduction in high-sensitive CRP levels (hs-CRP).

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
Patients were recruited from the Lipid Clinics at the University of Texas Southwestern Medical Center in Dallas. This protocol was approved by the Institutional Review Board, and all patients gave informed consent. Inclusion criteria for the subjects included an age of 18 to 70 years, a triglyceride level between 200 to 600 mg/dL, and an LDL cholesterol level 130 mg/dL.

Exclusion criteria were as follows: use of lipid-lowering drugs or drugs known to affect lipid metabolism, use of antioxidant supplements, use of warfarin or heparin for the past 4 weeks, liver or renal dysfunction, diabetes, hypothyroidism, infection, cancer, and/or recent major surgery or illness.

Study Design
This was a randomized, double-blind, crossover study design. A total of 22 patients were enrolled. There was a 6-week lead-in dietary phase when the patients were instructed by the dietitian to follow an American Heart Association Step 1 diet for the study duration, followed by a 6-week drug therapy phase with a 3-week washout period between drugs. The statins used included simvastatin (20 mg/d), atorvastatin (10 mg/d), and pravastatin (40 mg/d).⁸

Three fasting blood samples were obtained at baseline (7 days apart), and 2 fasting blood samples were obtained during therapy with each drug (5.5 and 6 weeks). Levels of total cholesterol, total triglycerides, and LDL and HDL cholesterol were assayed by routine laboratory techniques, as reported previously.⁹ If plasma triglycerides were >400 mg/dL, LDL cholesterol was assessed by a direct method.⁹ Levels of CRP were measured by a highly sensitive nephelometric assay using a monoclonal antibody to CRP coated on polystyrene beads (Dade Behring). This assay is referenced to the World Health Organization standard and is sensitive in the range of 0.175 to 60 mg/L. Both interassay and intra-assay coefficients of variation were <5%. IL-6 and IL-6 soluble receptor levels in serum were measured using a highly sensitive immunoassay (R&D Systems). The intra-assay coefficient of variation was <4%.

Statistical Analyses
All statistical analyses were performed using SAS version 8.0. Because some variables were skewed (triglycerides, hs-CRP), nonparametric tests were used for these data. The number of replicates needed to achieve the validity coefficient of cholesterol (0.91) with CRP was 2.¹⁰ Treatment order for this crossover study was assessed with repeated measures ANOVA models using log transformations for skewed data.

The 3 statin drugs were compared with Friedman’s test and Wilcoxon signed rank test for pairwise comparisons: the means of the 3 baseline levels were compared with the 2 levels obtained on therapy. Weighted correlation coefficients were computed to assess associations between variables of interest.¹¹ The level of significance was set at P<0.05 (2-sided).

	Results

Top Abstract Introduction Methods Results Discussion References

 
The salient characteristics of the participants in this study are as follows: age, 47.2±9.7 years; male/female ratio, 10/12; and body mass index, 24.5±4.9 kg/m². As is evident in the Table, there was a significant reduction in total and LDL cholesterol with all 3 statins; a significant reduction in plasma triglycerides was only seen with simvastatin and atorvastatin. None of the drugs had a significant effect on HDL cholesterol levels in these patients. As shown in the Figure, all 3 drugs resulted in a significant reduction in CRP levels. The percentage of patients showing a reduction of CRP with pravastatin, simvastatin, and atorvastatin was 72.7%, 81.8%, and 81.8%. A total of 54.6% of patients responded to all 3 statins. There were no significant differences in the median percent reduction in hs-CRP levels with pravastatin, simvastatin, and atorvastatin (20.3%, 22.8%, and 28.3%, respectively). Of the responders, 40% of the reduction in CRP was seen in 31.3%, 38.8%, and 44.4% of patients receiving pravastatin, simvastatin, and atorvastatin, respectively.

View this table: [in this window] [in a new window]   Table 1. Effect of Statin Therapy on Lipid and Lipoprotein Levels

View larger version (13K): [in this window] [in a new window]   Figure 1. Effect of statin therapy on hs-CRP levels. Data are presented as 25th percentile, median, and 75th percentile. P indicates pravastatin; S, simvastatin; and A, atorvastatin. *P<0.025 compared with baseline.

Neither plasma IL-6 nor IL-6 soluble receptor levels were significantly reduced with any of the drugs (IL-6: baseline, 2.5±0.4 pg/mL; pravastatin, 2.6±0.5 pg/mL; simvastatin, 2.4±0.4 pg/mL; and atorvastatin, 2.8±0.5 pg/mL; P>0.4; IL-6 soluble receptor: baseline, 21.5±8.1 ng/mL; pravastatin, 21.0±7.5 ng/mL; simvastatin, 21.3±9.0 ng/mL; atorvastatin, 21.7±8.4 ng/mL; P>0.4). Although no significant correlation was found between changes in CRP levels and changes in LDL cholesterol (r=-0.1, P=0.7) or HDL cholesterol (r=0.04, P=0.9), the correlation with triglycerides was significant (r=0.59, P=0.005). Furthermore, while in the washout phase, LDL-cholesterol increased significantly (P<0.001) but, compared with the drug phase, there was no significant increase in CRP levels (P=0.21).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Whether CRP is a risk marker or risk factor will only be settled by future studies. To date, CRP has been localized to foam cells in atherosclerotic lesions, it colocalizes with activated complement fragments, and it induces adhesion molecule expression from the endothelium and tissue factor secretion from monocytes.^{3 12 13}

Previously, Ridker et al⁶ showed that patients with hs-CRP levels in the upper quartile had a greater benefit (54% relative risk reduction) compared with those in the lowest quartile. Furthermore, they showed a significant reduction in hs-CRP with pravastatin therapy. In the present report, we confirm that pravastatin therapy results in a significant reduction in CRP levels. Furthermore, we show that simvastatin and atorvastatin also result in a significant reduction in CRP levels. There was no significant difference between the 3 statins regarding reductions in hs-CRP. Like the Cholesterol And Recurrent Events (CARE) study, we showed no significant correlations between total cholesterol, LDL cholesterol, or HDL cholesterol and hs-CRP levels. The increase in LDL-cholesterol but not CRP in the washout phase further underscores a divergence of statins on these 2 effects. However, we found a significant correlation between a reduction in triglycerides and hs-CRP levels. Because our sample size is small and pravastatin reduced CRP without having a significant effect on triglycerides, these findings need to be viewed with caution, and confirmation must await future studies.

This study explored a potential mechanism by which statins may result in a significant reduction in hs-CRP levels. IL-6 levels were measured, but statin drugs had no effect on IL-6 levels. Because there is a great circadian variation in IL-6 levels and our sample size is small, this finding needs to be viewed with caution. Plasma IL-6 may not be the best reflection of the IL-6 levels that bathe the liver. More meaningful data would have been obtained if IL-6 levels were measured after activation, because statin therapy resulted in a significant reduction in IL-6 in lipopolysaccharide-activated whole blood.¹⁴ Because IL-6 soluble receptor levels did not change, a decrease in IL-6 soluble receptor levels cannot explain the reduction in CRP.¹⁵ Another potential reason for a failure to see a reduction in IL-6 levels despite a reduction in CRP could be that statins are acting through IL-6–independent mechanisms.¹⁶

In conclusion, the present study makes the novel observation that pravastatin, atorvastatin, and simvastatin therapy result in a significant reduction in hs-CRP levels. Furthermore, all 3 statins reduced hs-CRP levels to a similar extent.

Recently, the present investigators showed that high-dose RRR- tocopherol (1200 IU/d) resulted in a reduction in plasma hs-CRP levels and monocyte IL-6 levels in both controls and type 2 diabetic patients.¹⁷ In the Physician’s Health Study, patients with the highest CRP levels received the greatest benefit from aspirin therapy.¹⁸ Although studies with aspirin therapy are conflicting,^{19 20} the benefit of statins in reducing hs-CRP levels is supported by at least 2 studies to date. Further studies need to be directed toward elucidating the mechanism of reduction in CRP.

	Acknowledgments

 
Supported by Merck, Warner-Lambert, and the National Institutes of Health (grants K24 AT00596 and MO1-RR-00633).

Received January 16, 2001; revision received February 15, 2001; accepted February 16, 2001.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Maron DJ, Fazio S, MacRae FL. Current perspectives on statins. Circulation. 2000;101:207–213.[Abstract/Free Full Text]
   
2. Morrow DA, Ridker PM. C-reactive protein, inflammation, and coronary risk. Med Clin North Am. 2000;84:149–161.[Medline] [Order article via Infotrieve]
   
3. Tracy RP. Inflammation markers and coronary heart disease. Curr Opin Lipidol. 1999;10:435–551.[Medline] [Order article via Infotrieve]
   
4. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–351.[Free Full Text]
   
5. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;432:836–843.
   
6. Ridker PM, Rifai N, Pfeffer M, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation. 1998;98:839–844.[Abstract/Free Full Text]
   
7. Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999;100:230–235.[Abstract/Free Full Text]
   
8. Jones P, Kafonek S, Laurora I, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81:582–587.[Medline] [Order article via Infotrieve]
   
9. Maitra A, Hirany S, Jialal I. A comparison of two assays for the measurement of LDL cholesterol. Clin Chem. 1997;43:1040–1047.[Abstract/Free Full Text]
   
10. Sakkinen P, Macy EM, Callas PW, et al. Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology. Am J Epidemiol. 1999;149:261–267.[Abstract/Free Full Text]
    
11. Bland JM, Altman DG. Calculating correlation coefficients with repeated observations, part 2: correlation between subjects. BMJ. 1995;310:633.[Free Full Text]
    
12. Pasceri V, Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102:2165–2168.[Abstract/Free Full Text]
    
13. Torzewski M, Rist C, Mortensen RF, et al. C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol. 2000;20:2094–2099.[Abstract/Free Full Text]
    
14. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet. 1999;353:983–984.[Medline] [Order article via Infotrieve]
    
15. Mackiewicz A, Schooltink H, Heinrich PC. Complex of soluble human Il-6-Receptor/Il-6 up-regulates expression of acute-phase proteins. J Immunol. 1992;149:2021–2027.[Abstract]
    
16. Weinhold B, Rüther U. Interleukin-6-dependent and -independent regulation of the human C-reactive protein gene. Biochem J. 1997;327:425–429.
    
17. Devaraj S, Jialal I. Alpha tocopherol supplementation decreases C-reactive protein and monocyte interleukin-6 levels in type 2 diabetic patients. Free Radic Biol Med,. 2000;29:790–792.[Medline] [Order article via Infotrieve]
    
18. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and risks of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–979.[Abstract/Free Full Text]
    
19. Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation. 1999;100:793–798.[Abstract/Free Full Text]
    
20. Feng D-L, Tracy RP, Lipinska I, et al. Effect of short-term aspirin use on C-reactive protein. J Thromb Thrombolysis. 2000;9:37–41.[Medline] [Order article via Infotrieve]
    

This article has been cited by other articles:

				A. Z. LaCroix, S. L. Gray, A. Aragaki, B. B. Cochrane, A. B. Newman, C. L. Kooperberg, H. Black, J. D. Curb, P. Greenland, and N. F. Woods Statin Use and Incident Frailty in Women Aged 65 Years or Older: Prospective Findings From the Women's Health Initiative Observational Study J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2008; 63(4): 369 - 375. [Abstract] [Full Text] [PDF]

				E. M. Mortensen, M. J. Pugh, L. A. Copeland, M. I. Restrepo, J. E. Cornell, A. Anzueto, and J. A. Pugh Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia Eur. Respir. J., March 1, 2008; 31(3): 611 - 617. [Abstract] [Full Text] [PDF]

				K. Lertsburapa, C. M. White, J. Kluger, O. Faheem, J. Hammond, and C. I. Coleman Preoperative statins for the prevention of atrial fibrillation after cardiothoracic surgery. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 405 - 411. [Abstract] [Full Text] [PDF]

				H. Shao, Y. Shen, H. Liu, G. Dong, J. Qiang, and H. Jing Simvastatin Suppresses Lung Inflammatory Response in a Rat Cardiopulmonary Bypass Model Ann. Thorac. Surg., December 1, 2007; 84(6): 2011 - 2018. [Abstract] [Full Text] [PDF]

				J. S. Gortney and R. M. Sanders Impact of C-reactive protein on treatment of patients with cardiovascular disease Am. J. Health Syst. Pharm., October 1, 2007; 64(19): 2009 - 2016. [Abstract] [Full Text] [PDF]

				K. Groschel, U. Ernemann, J. Larsen, M. Knauth, F. Schmidt, J. Artschwager, and A. Kastrup Preprocedural C-Reactive Protein Levels Predict Stroke and Death in Patients Undergoing Carotid Stenting AJNR Am. J. Neuroradiol., October 1, 2007; 28(9): 1743 - 1746. [Abstract] [Full Text] [PDF]

				A. M. Andrei, R. Fraguas Jr., R. M.S. Telles, T. C.T.F. Alves, C. M.C. Strunz, A. Nussbacher, J. Rays, D. V. Iosifescu, and M. Wajngarten Major Depressive Disorder and Inflammatory Markers in Elderly Patients With Heart Failure Psychosomatics, August 1, 2007; 48(4): 319 - 324. [Abstract] [Full Text] [PDF]

				A. Momin, N. Melikian, S. B. Wheatcroft, D. Grieve, L. C. John, A. El Gamel, M. T. Marrinan, J. B. Desai, C. Driver, R. Sherwood, et al. The association between saphenous vein endothelial function, systemic inflammation, and statin therapy in patients undergoing coronary artery bypass surgery J. Thorac. Cardiovasc. Surg., August 1, 2007; 134(2): 335 - 341. [Abstract] [Full Text] [PDF]

				I. Jialal, E. Miguelino, S. C. Griffen, and S. Devaraj Concomitant Reduction of Low-Density Lipoprotein-Cholesterol and Biomarkers of Inflammation with Low-Dose Simvastatin Therapy in Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3136 - 3140. [Abstract] [Full Text] [PDF]

				M. H. Olsen, T. W. Hansen, M. K. Christensen, F. Gustafsson, S. Rasmussen, K. Wachtell, H. Ibsen, C. Torp-Pedersen, and P. R. Hildebrandt N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population Eur. Heart J., June 1, 2007; 28(11): 1374 - 1381. [Abstract] [Full Text] [PDF]

				P. M. Ridker C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk: Moving an Inflammatory Hypothesis Toward Consensus J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2129 - 2138. [Abstract] [Full Text] [PDF]

				S. Kinlay Low-Density Lipoprotein-Dependent and -Independent Effects of Cholesterol-Lowering Therapies on C-Reactive Protein: A Meta-Analysis J. Am. Coll. Cardiol., May 22, 2007; 49(20): 2003 - 2009. [Abstract] [Full Text] [PDF]

				H. Kamishirado, T. Inoue, M. Sakuma, T. Tsuda, T. Hayashi, K. Takayanagi, and K. Node Effects of Statins on Restenosis After Coronary Stent Implantation Angiology, February 1, 2007; 58(1): 55 - 60. [Abstract] [PDF]

				C. G. Koch, L. Li, D. R. Van Wagoner, A. I. Duncan, A. M. Gillinov, and E. H. Blackstone Red Cell Transfusion is Associated With an Increased Risk for Postoperative Atrial Fibrillation Ann. Thorac. Surg., November 1, 2006; 82(5): 1747 - 1756. [Abstract] [Full Text] [PDF]

				S. Devaraj, E. Chan, and I. Jialal Direct Demonstration of an Antiinflammatory Effect of Simvastatin in Subjects with the Metabolic Syndrome J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4489 - 4496. [Abstract] [Full Text] [PDF]

				R. Topakian, H.-P. Haring, and F. T. Aichner Admission C-Reactive Protein as a Predictor for Stroke Outcome Among Candidates for Thrombolysis: Decision Adjourned Stroke, October 1, 2006; 37(10): 2454 - 2454. [Full Text] [PDF]

				D. A. Morrow, J. A. de Lemos, M. S. Sabatine, S. D. Wiviott, M. A. Blazing, A. Shui, N. Rifai, R. M. Califf, and E. Braunwald Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial Circulation, July 25, 2006; 114(4): 281 - 288. [Abstract] [Full Text] [PDF]

				M. Suzuki, M. Saito, T. Nagai, H. Saeki, and Y. Kazatani Prevention of Positive Coronary Artery Remodeling with Statin Therapy in Patients with Coronary Artery Diseases Angiology, May 1, 2006; 57(3): 259 - 265. [Abstract] [PDF]

				S. Tsimikas, J. T. Willerson, and P. M. Ridker C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J. Am. Coll. Cardiol., April 18, 2006; 47(8 Suppl): C19 - C31. [Abstract] [Full Text] [PDF]

				S. E Kasim-Karakas, A. Tsodikov, U. Singh, and I. Jialal Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 774 - 779. [Abstract] [Full Text] [PDF]

				K. Matsushita, H. Yatsuya, K. Tamakoshi, K. Wada, R. Otsuka, S. Takefuji, K. Sugiura, T. Kondo, T. Murohara, and H. Toyoshima Comparison of Circulating Adiponectin and Proinflammatory Markers Regarding Their Association With Metabolic Syndrome in Japanese Men Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 871 - 876. [Abstract] [Full Text] [PDF]

				S. Desroches, W. R. Archer, M.-E. Paradis, O. Deriaz, P. Couture, J. Bergeron, N. Bergeron, and B. Lamarche Baseline Plasma C-Reactive Protein Concentrations Influence Lipid and Lipoprotein Responses to Low-Fat and High Monounsaturated Fatty Acid Diets in Healthy Men J. Nutr., April 1, 2006; 136(4): 1005 - 1011. [Abstract] [Full Text] [PDF]

				K. Iwakura, H. Ito, S. Kawano, A. Okamura, T. Kurotobi, M. Date, K. Inoue, and K. Fujii Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction Eur. Heart J., March 1, 2006; 27(5): 534 - 539. [Abstract] [Full Text] [PDF]

				U. Singh, J. Tabibian, S. K. Venugopal, S. Devaraj, and I. Jialal Development of an In Vitro Screening Assay to Test the Antiinflammatory Properties of Dietary Supplements and Pharmacologic Agents Clin. Chem., December 1, 2005; 51(12): 2252 - 2256. [Abstract] [Full Text] [PDF]

				G. S. Ginsburg, M. P. Donahue, and L. K. Newby Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1615 - 1627. [Abstract] [Full Text] [PDF]

				S. M. Grundy, J. I. Cleeman, S. R. Daniels, K. A. Donato, R. H. Eckel, B. A. Franklin, D. J. Gordon, R. M. Krauss, P. J. Savage, S. C. Smith Jr, et al. Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement Circulation, October 25, 2005; 112(17): 2735 - 2752. [Full Text] [PDF]

				M. D.M. Engelmann and J. H. Svendsen Inflammation in the genesis and perpetuation of atrial fibrillation Eur. Heart J., October 2, 2005; 26(20): 2083 - 2092. [Abstract] [Full Text] [PDF]

				F. Bruni, A. L. Pasqui, M. Pastorelli, G. Bova, M. Cercignani, A. Palazzuoli, T. Sawamura, A. Auteri, and L. Puccetti Different Effect of Statins on Platelet Oxidized-LDLReceptor (CD36 and LOX-1) Expressionin Hypercholesterolemic Subjects Clinical and Applied Thrombosis/Hemostasis, October 1, 2005; 11(4): 417 - 428. [Abstract] [PDF]

				M. B. Clearfield C-Reactive Protein: A New Risk Assessment Tool for Cardiovascular Disease J Am Osteopath Assoc, September 1, 2005; 105(9): 409 - 416. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Inflammation, Atherosclerosis, and Aspects of Insulin Action Diabetes Care, September 1, 2005; 28(9): 2312 - 2319. [Full Text] [PDF]

				R. Tiruvoipati, M. Loubani, M. Lencioni, S. Ghosh, P. W. Jones, and R. L. Patel Coronary Endarterectomy: Impact on Morbidity and Mortality When Combined With Coronary Artery Bypass Surgery Ann. Thorac. Surg., June 1, 2005; 79(6): 1999 - 2003. [Abstract] [Full Text] [PDF]

				P. M. Ridker, D. A. Morrow, L. M. Rose, N. Rifai, C. P. Cannon, and E. Braunwald Relative Efficacy of Atorvastatin 80 mg and Pravastatin 40 mg in Achieving the Dual Goals of Low-Density Lipoprotein Cholesterol <70 mg/dl and C-Reactive Protein <2 mg/l: An Analysis of the PROVE-IT TIMI-22 Trial J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1644 - 1648. [Abstract] [Full Text] [PDF]

				J.P. Empana, D.H. Sykes, G. Luc, I. Juhan-Vague, D. Arveiler, J. Ferrieres, P. Amouyel, A. Bingham, M. Montaye, J.B. Ruidavets, et al. Contributions of Depressive Mood and Circulating Inflammatory Markers to Coronary Heart Disease in Healthy European Men: The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Circulation, May 10, 2005; 111(18): 2299 - 2305. [Abstract] [Full Text] [PDF]

				The Diabetes Prevention Program Research Group Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance Diabetes, May 1, 2005; 54(5): 1566 - 1572. [Abstract] [Full Text] [PDF]

				B. Cohen, D. Singh, P. Greenland, D. M. Lloyd-Jones, A. J. Moss, B. L. Jaber, N. E. Madias, P. M Ridker, C. P. Cannon, and E. Braunwald C-Reactive Protein Levels and Outcomes after Statin Therapy N. Engl. J. Med., April 14, 2005; 352(15): 1603 - 1605. [Full Text] [PDF]

				V. M. Campese, M. K. Nadim, and M. Epstein Are 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors Renoprotective? J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S11 - S17. [Abstract] [Full Text] [PDF]

				P. M Ridker, C. P. Cannon, D. Morrow, N. Rifai, L. M. Rose, C. H. McCabe, M. A. Pfeffer, E. Braunwald, and the Pravastatin or Atorvastatin Evaluation and Inf C-Reactive Protein Levels and Outcomes after Statin Therapy N. Engl. J. Med., January 6, 2005; 352(1): 20 - 28. [Abstract] [Full Text] [PDF]

				M. Ghayour-Mobarhan, D. J. Lamb, N. Vaidya, C. Livingstone, T. Wang, and G. A. A. Ferns Heat Shock Protein Antibody Titers Are Reduced by Statin Therapy in Dyslipidemic Subjects: A Pilot Study Angiology, January 1, 2005; 56(1): 61 - 68. [Abstract] [PDF]

				L. M. Biasucci CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical Use of Inflammatory Markers in Patients With Cardiovascular Diseases: A Background Paper Circulation, December 21, 2004; 110(25): e560 - e567. [Abstract] [Full Text] [PDF]