(Circulation. 1999;100:713-716.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Division of Preventive Medicine (P.M.R., C.H.H., J.E.B., J.E.M.) and Cardiovascular Diseases (P.M.R.), Brigham and Women's Hospital; the Department of Ambulatory Care and Prevention (J.E.B., C.H.H.); and the Childrens' Hospital Medical Center (N.R.), Harvard Medical School, Boston, Mass.
Correspondence to Paul M. Ridker, MD, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail pmridker{at}bics.bwh.harvard.edu
BackgroundIt has been hypothesized that postmenopausal hormone replacement therapy (HRT) may increase levels of C-reactive protein (CRP), a marker of inflammation associated with increased risk of future cardiovascular events. However, data evaluating this hypothesis are sparse and limited to older women.
Methods and ResultsCRP levels were evaluated in a cross-sectional survey of 493 healthy postmenopausal women; mean age was 51 years. Overall, median CRP levels were 2 times higher among women taking HRT than among women not taking HRT (0.27 versus 0.14 mg/dL; P=0.001). This difference was present in all subgroups evaluated, including those with no history of hypertension, hyperlipidemia, obesity, diabetes, or cigarette consumption or a family history of premature coronary artery disease (all P< 0.01). Compared with nonusers of HRT, median CRP levels were higher among women using estrogen alone (P=0.003) and women using estrogen plus progesterone (P=0.03); however, there was no significant difference in CRP levels between users of different HRT preparations. In multivariate analysis, the relationship between HRT use and CRP remained significant after control for body mass index, age, diabetes, hypertension, hyperlipidemia, alcohol use, and cigarette consumption (P=0.001).
ConclusionsIn this cross-sectional survey, CRP levels were increased among apparently healthy postmenopausal women taking HRT. The potential impact of HRT on inflammatory parameters should be investigated in ongoing clinical trials.
Key Words: inflammation hormones C-reactive protein risk factors
This article has been cited by other articles:
![]() |
J. L. Shifren, N. Rifai, S. Desindes, M. McIlwain, G. Doros, and N. A. Mazer A Comparison of the Short-Term Effects of Oral Conjugated Equine Estrogens Versus Transdermal Estradiol on C-Reactive Protein, Other Serum Markers of Inflammation, and Other Hepatic Proteins in Naturally Menopausal Women J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1702 - 1710. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Cauci, M. Di Santolo, J. F. Culhane, G. Stel, F. Gonano, and S. Guaschino Effects of Third-Generation Oral Contraceptives on High-Sensitivity C-reactive Protein and Homocysteine in Young Women Obstet. Gynecol., April 1, 2008; 111(4): 857 - 864. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Ulucay, R. Demirbag, R. Yilmaz, D. Unlu, M. Gur, S. Selek, and H. Celik The Relationship Between Plasma C-Reactive Protein Levels and Presence and Severity of Coronary Stenosis in Patients With Stable Angina Angiology, January 1, 2008; 58(6): 657 - 662. [Abstract] [PDF] |
||||
![]() |
E. A. Booth and B. R. Lucchesi Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory effects of 17beta-estradiol in an in vivo model of myocardial ischemia and reperfusion Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1408 - H1415. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Everett, T. Kurth, J. E. Buring, and P. M. Ridker The Relative Strength of C-Reactive Protein and Lipid Levels as Determinants of Ischemic Stroke Compared With Coronary Heart Disease in Women J. Am. Coll. Cardiol., November 9, 2006; (2006) j.jacc.2006.09.030v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Albert and P. M Ridker C-Reactive Protein as a Risk Predictor: Do Race/Ethnicity and Gender Make a Difference? Circulation, August 1, 2006; 114(5): e67 - e74. [Full Text] [PDF] |
||||
![]() |
P. Geraldes, S. Gagnon, S. Hadjadj, Y. Merhi, M. G. Sirois, I. Cloutier, and J.-F. Tanguay Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells and prevents neutrophil adhesion: An ER{alpha}-mediated pathway Cardiovasc Res, August 1, 2006; 71(3): 566 - 573. [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] |
||||
![]() |
B. L McVeigh, B. L Dillingham, J. W Lampe, and A. M Duncan Effect of soy protein varying in isoflavone content on serum lipids in healthy young men Am. J. Clinical Nutrition, February 1, 2006; 83(2): 244 - 251. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. S Kornman Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging Am. J. Clinical Nutrition, February 1, 2006; 83(2): 475S - 483S. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Miller, M. Zhan, and S. Havas High Attributable Risk of Elevated C-Reactive Protein Level to Conventional Coronary Heart Disease Risk Factors: The Third National Health and Nutrition Examination Survey Arch Intern Med, October 10, 2005; 165(18): 2063 - 2068. [Abstract] [Full Text] [PDF] |
||||
![]() |
the Diabetes Prevention Program Research Group Lipid, Lipoproteins, C-Reactive Protein, and Hemostatic Factors at Baseline in the Diabetes Prevention Program Diabetes Care, October 1, 2005; 28(10): 2472 - 2479. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. G. Best, Y. Zhang, E. T. Lee, J.-L. Yeh, L. Cowan, V. Palmieri, M. Roman, R. B. Devereux, R. R. Fabsitz, R. P. Tracy, et al. C-Reactive Protein as a Predictor of Cardiovascular Risk in a Population With a High Prevalence of Diabetes: The Strong Heart Study Circulation, August 30, 2005; 112(9): 1289 - 1295. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. T. van der Schouw and D. E. Grobbee Menopausal complaints, oestrogens, and heart disease risk: an explanation for discrepant findings on the benefits of post-menopausal hormone therapy Eur. Heart J., July 2, 2005; 26(14): 1358 - 1361. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. F. Hilpert, P. M. Kris-Etherton, and S. G. West Lipid Response to a Low-Fat Diet with or without Soy Is Modified by C-Reactive Protein Status in Moderately Hypercholesterolemic Adults J. Nutr., May 1, 2005; 135(5): 1075 - 1079. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. Zhang, J. E. Buring, I-M. Lee, N. R. Cook, and P. M. Ridker C-Reactive Protein Levels Are Not Associated with Increased Risk for Colorectal Cancer in Women Ann Intern Med, March 15, 2005; 142(6): 425 - 432. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Ropponen, K. Aittomaki, M. J. Tikkanen, and O. Ylikorkala Levels of Serum C-Reactive Protein during Oral and Transdermal Estradiol in Postmenopausal Women with and without a History of Intrahepatic Cholestasis of Pregnancy J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 142 - 146. [Abstract] [Full Text] [PDF] |
||||
![]() |
E.-G. V. Giardina, H. J. Chen, R. R. Sciacca, and L. E. Rabbani Dynamic Variability of Hemostatic and Fibrinolytic Factors in Young Women J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6179 - 6184. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. K. Koh, M.-S. Shin, I. Sakuma, J. Y. Ahn, D. K. Jin, H. S. Kim, D. S. Kim, S. H. Han, W.-J. Chung, and E. K. Shin Effects of Conventional or Lower Doses of Hormone Replacement Therapy in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1516 - 1521. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Kluft Identifying patients at risk of coronary vascular disease: the potential role of inflammatory markers Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C21 - C27. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J Teede, F. S Dalais, and B. P McGrath Dietary soy containing phytoestrogens does not have detectable estrogenic effects on hepatic protein synthesis in postmenopausal women Am. J. Clinical Nutrition, March 1, 2004; 79(3): 396 - 401. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Wakatsuki, N. Ikenoue, K. Shinohara, K. Watanabe, and T. Fukaya Effect of Lower Dosage of Oral Conjugated Equine Estrogen on Inflammatory Markers and Endothelial Function in Healthy Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 571 - 576. [Abstract] [Full Text] |
||||
![]() |
E. S. Ford, W. H. Giles, A. H. Mokdad, and G. L. Myers Distribution and Correlates of C-Reactive Protein Concentrations among Adult US Women Clin. Chem., March 1, 2004; 50(3): 574 - 581. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. G. Barr, C. C. Wentowski, F. Grodstein, S. C. Somers, M. J. Stampfer, J. Schwartz, F. E. Speizer, and C. A. Camargo Jr Prospective Study of Postmenopausal Hormone Use and Newly Diagnosed Asthma and Chronic Obstructive Pulmonary Disease Arch Intern Med, February 23, 2004; 164(4): 379 - 386. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Elsaesser and C. W. Hamm Acute Coronary Syndrome: The Risk of Being Female Circulation, February 10, 2004; 109(5): 565 - 567. [Full Text] [PDF] |
||||
![]() |
B. L. Stauffer, G. L. Hoetzer, D. T. Smith, and C. A. DeSouza Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy J Appl Physiol, January 1, 2004; 96(1): 143 - 148. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M Backes, P. A Howard, and P. M Moriarty Role of C-Reactive Protein in Cardiovascular Disease Ann. Pharmacother., January 1, 2004; 38(1): 110 - 118. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. D. Sesso, J. E. Buring, N. Rifai, G. J. Blake, J. M. Gaziano, and P. M. Ridker C-Reactive Protein and the Risk of Developing Hypertension JAMA, December 10, 2003; 290(22): 2945 - 2951. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M.C. ROSANO, C. VITALE, A. SILVESTRI, and M. FINI Hormone Replacement Therapy and Cardioprotection: The End of the Tale? Ann. N.Y. Acad. Sci., November 1, 2003; 997(1): 351 - 357. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Muller, Y. T. van der Schouw, J. H. H. Thijssen, and D. E. Grobbee Endogenous Sex Hormones and Cardiovascular Disease in Men J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5076 - 5086. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.M. Hirschfield and M.B. Pepys C-reactive protein and cardiovascular disease: new insights from an old molecule QJM, November 1, 2003; 96(11): 793 - 807. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Morin-Papunen, K. Rautio, A. Ruokonen, P. Hedberg, M. Puukka, and J. S. Tapanainen Metformin Reduces Serum C-Reactive Protein Levels in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4649 - 4654. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Wakatsuki, N. Ikenoue, K. Shinohara, K. Watanabe, and T. Fukaya Different Effects of Oral and Transdermal Estrogen Replacement Therapy on Matrix Metalloproteinase and Their Inhibitor in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1948 - 1949. [Full Text] [PDF] |
||||
![]() |
M. Di Napoli Editorial Comment--C-Reactive Protein and Vascular Risk in Stroke Patients: Potential Use for the Future Stroke, October 1, 2003; 34(10): 2468 - 2470. [Full Text] [PDF] |
||||
![]() |
T. B. Ledue and N. Rifai Preanalytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment Clin. Chem., August 1, 2003; 49(8): 1258 - 1271. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Albert, R. J. Glynn, and P. M Ridker Plasma Concentration of C-Reactive Protein and the Calculated Framingham Coronary Heart Disease Risk Score Circulation, July 15, 2003; 108(2): 161 - 165. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Roldan, F. Marin, A. D Blann, A. Garcia, P. Marco, F. Sogorb, and G. Y.H Lip Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation Eur. Heart J., July 2, 2003; 24(14): 1373 - 1380. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Yilmazer, V. Fenkci, S. Fenkci, O. Aktepe, M. Sonmezer, and G. Kurtay Association of serum complement (C3, C4) and immunoglobulin (IgG, IgM) levels with hormone replacement therapy in healthy post-menopausal women Hum. Reprod., July 1, 2003; 18(7): 1531 - 1535. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Silvestri, O. Gebara, C. Vitale, M. Wajngarten, F. Leonardo, J. A.F. Ramires, M. Fini, G. Mercuro, and G. M.C. Rosano Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response Circulation, July 1, 2003; 107(25): 3165 - 3169. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Vongpatanasin, M. Tuncel, Z. Wang, D. Arbique, B. Mehrad, and I. Jialal Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1358 - 1363. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Fenkci, V. Fenkci, M. Yilmazer, M. Serteser, and T. Koken Effects of short-term transdermal hormone replacement therapy on glycaemic control, lipid metabolism, C-reactive protein and proteinuria in postmenopausal women with type 2 diabetes or hypertension Hum. Reprod., April 1, 2003; 18(4): 866 - 870. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Rifai and P. M. Ridker Population Distributions of C-reactive Protein in Apparently Healthy Men and Women in the United States: Implication for Clinical Interpretation Clin. Chem., April 1, 2003; 49(4): 666 - 669. [Full Text] [PDF] |
||||
![]() |
A. Imhof, M. Frohlich, H. Loewel, N. Helbecque, M. Woodward, P. Amouyel, G. D.O. Lowe, and W. Koenig Distributions of C-reactive Protein Measured by High-Sensitivity Assays in Apparently Healthy Men and Women from Different Populations in Europe Clin. Chem., April 1, 2003; 49(4): 669 - 672. [Full Text] [PDF] |
||||
![]() |
C. R. Isasi, R. J. Deckelbaum, R. P. Tracy, T. J. Starc, L. Berglund, and S. Shea Physical Fitness and C-Reactive Protein Level in Children and Young Adults: The Columbia University BioMarkers Study Pediatrics, February 1, 2003; 111(2): 332 - 338. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M Ridker Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention Circulation, January 28, 2003; 107(3): 363 - 369. [Full Text] [PDF] |
||||
![]() |
T. A. Pearson, G. A. Mensah, R. W. Alexander, J. L. Anderson, R. O. Cannon III, M. Criqui, Y. Y. Fadl, S. P. Fortmann, Y. Hong, G. L. Myers, et al. Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association Circulation, January 28, 2003; 107(3): 499 - 511. [Full Text] [PDF] |
||||
![]() |
M. A. Albert, R. J. Glynn, and P. M Ridker Alcohol Consumption and Plasma Concentration of C-Reactive Protein Circulation, January 28, 2003; 107(3): 443 - 447. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Herrington Hormone Replacement Therapy and Heart Disease: Replacing Dogma With Data Circulation, January 7, 2003; 107(1): 2 - 4. [Full Text] [PDF] |
||||
![]() |
L. E. Rabbani, N. A. Seminario, R. R. Sciacca, H. J. Chen, and E.-G. V. Giardina Oral conjugated equine estrogen increases plasma von Willebrand factor in postmenopausal women J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1991 - 1999. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Schachinger and A. M. Zeiher Atherogenesis--recent insights into basic mechanisms and their clinical impact Nephrol. Dial. Transplant., December 1, 2002; 17(12): 2055 - 2064. [Full Text] [PDF] |
||||
![]() |
P. M. Ridker, N. Rifai, L. Rose, J. E. Buring, and N. R. Cook Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular Events N. Engl. J. Med., November 14, 2002; 347(20): 1557 - 1565. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Stangl, G. Baumann, and K. Stangl Coronary atherogenic risk factors in women Eur. Heart J., November 2, 2002; 23(22): 1738 - 1752. [Full Text] [PDF] |
||||
![]() |
P. Garnero, C. Jamin, C.-L. Benhamou, C. Pelissier, and C. Roux Effects of tibolone and combined 17{beta}-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial Hum. Reprod., October 1, 2002; 17(10): 2748 - 2753. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Wang, B.-H. Nam, P. W.F. Wilson, P. A. Wolf, D. Levy, J. F. Polak, R. B. D'Agostino, and C. J. O'Donnell Association of C-Reactive Protein With Carotid Atherosclerosis in Men and Women: The Framingham Heart Study Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1662 - 1667. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. A. Bermudez, N. Rifai, J. Buring, J. E. Manson, and P. M. Ridker Interrelationships Among Circulating Interleukin-6, C-Reactive Protein, and Traditional Cardiovascular Risk Factors in Women Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1668 - 1673. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, M.-S. Shin, J. W. Son, I. S. Choi, and E. K. Shin Effects of Continuous Combined Hormone Replacement Therapy on Inflammation in Hypertensive and/or Overweight Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1459 - 1464. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. K. Koh Effects of estrogen on the vascular wall: vasomotor function and inflammation Cardiovasc Res, September 1, 2002; 55(4): 714 - 726. [Full Text] [PDF] |
||||