Fast Breaking Comment by JoAnn Manson

JoAnn Manson answers a few questions about this month's fast breaking paper in the field of Clinical Medicine.

From •>>June 2004

Field: Clinical Medicine
Article Title: Estrogen plus progestin and the risk of coronary heart disease
Authors: Manson, JE;Hsia, J;Johnson, KC;Rossouw, JE;Assaf, AR;Lasser, NL;Trevisan, M;Black, HR;Heckbert, SR;Detrano, R;Strickland, OL;Wong, ND;Crouse, JR;Stein, E;Cushman, M;Alving, B;Rossouw, JE;Pottern, L;Ludlam, S;McGowan, JA;Prentice, R;Anderson, G;LaCroix, A;Patterson, R;McTiernan, A;Cochrane, B;Hunt, J;Tinker, L;Kooperberg, C;McIntosh, M;Wang, CY;Chen, C;Bowen, D;Kristal, A;Stanford, J;Urban, N;Weiss, N;White, E;Shumaker, S;Rautaharju, P;Prineas, R;Naughton, M;Stein, E;Laskarzewski, P;Cummings, S;Nevitt, M;Dockrell, M;Harnack, L;Cammarata, F;Lindenfelser, S;Psaty, B;Heckbert, S;Wassertheil-Smoller, S;Frishman, W;Wylie-Rosett, J;Barad, D;Freeman, R;Hays, J;Young, R;Anderson, J;Lithgow, S;Bray, P;Manson, J;Buring, J;Gaziano, JM;Rexrode, K;Chae, C;Assaf, AR;Carleton, R;Wheeler, C;Eaton, C;Cyr, M;Phillips, L;Pedersen, M;Strickland, O;Huber, M;Porter, V;Beresford, SAA;Taylor, VM;Woods, NF;Henderson, M;Kestin, M;Hsia, J;Gaba, N;Ascensao, J;Laowattana, S;Chlebowski, R;Detrano, R;Nelson, A;Heiner, J;Marshall, J;Ritenbaugh, C;Valanis, B;Elmer, P;Stevens, V;Karanja, N;Caan, B;Sidney, S;Bailey, G;Hirata, J;Kotchen, JM;Barnabei, V;Kotchen, TA;Gilligan, MAC;Neuner, J;Howard, BV;Adams-Campbell, L;Passaro, M;Rainford, M;Agurs-Collins, T;Van Horn, L;Greenland, P;Khandekar, J;Liu, K;Rosenberg, C;Black, H;Powell, L;Mason, E;Stefanick, ML;Hlatky, MA;Chen, B;Stafford, RS;Giudice, LC;Lane, D;Granek, I;Lawson, W;San Roman, G;Messina, C;Jackson, R;Harris, R;Frid, D;Mysiw, WJ;Blumenfeld, M;Lewis, CE;Oberman, A;Fouad, MN;Shikany, JM;West, DS;Bassford, T;Mattox, J;Ko, M;Lohman, T;Trevisan, M;Wactawski-Wende, J;Graham, S;Chang, J;Smit, E;Robbins, J;Yasmeen, S;Lindfors, K;Stern, J;Hubbell, A;Frank, G;Wong, N;Greep, N;MoOnk, B;Judd, H;Heber, D;Elashoff, R;Langer, RD;Criqui, MH;Talavera, GT;Garland, CF;Hanson, RE;Gass, M;Wernke, S;Watts, N;Limacher, M;Perri, M;Kaunitz, A;Williams, RS;Brinson, Y;Curb, D;Petrovitch, H;Rodriguez, B;Masaki, K;Sharma, S;Wallace, R;Torner, J;Johnson, S;Snetselaar, L;VanVoorhis, B;Ockene, I;Yood, R;Aronson, P;Lasser, N;Hymowitz, N;Lasser, V;Safford, M;Kostis, J;O'Sullivan, MJ;Parker, L;Estape, R;Fernandez, D;Margolis, KL;Grimm, RH;Hunninghake, DB;LaValleur, J;Hall, KM;Brunner, R;St Jeor, S;Graettinger, W;Oujevolk, V;Heiss, G;Haines, P;Ontjes, D;Sueta, C;Wells, E;Kuller, L;Caggiula, A;Cauley, J;Berga, S;Milas, NC;Johnson, KC;Satterfield, S;Ke, TW;Vile, J;Tylavsky, F;Brzyski, R;Schenken, R;Trabal, J;Rodriguez-Sifuentes, M;Mouton, C;Allen, C;Laube, D;McBride, P;Mares-Perlman, J;Loevinger, B;Burke, G;Crouse, R;Parsons, L;Vitolins, M;Hendrix, S;Simon, M;McNeeley, G;Gordon, P;Makela, P
Journal: N ENGL J MED
Volume: 349
Page: 523-534
Year: AUG 7 2003
* Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02215 USA.
* Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
* George Washington Univ, Dept Med, Washington, DC USA.
* Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
* NHLBI, Program Off, Bethesda, MD 20892 USA.
* Brown Univ, Mem Hosp, Sch Med, Pawtucket, RI USA.
* Univ Med & Dent New Jersey, New Jersey Med Sch, Prevent Cardiol Program, Newark, NJ 07103 USA.
* Univ Buffalo, Dept Social & Prevent Med, Buffalo, NY USA.
* Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA.
* Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
* Univ Calif Los Angeles, Div Cardiol, Harbor Res & Educ Inst, Torrance, CA USA.
* Emory Univ, Woodruff Sch Nursing, Atlanta, GA 30322 USA.
* Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA 92717 USA.
* Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA.
* Med Res Labs Int, Highland Hts, KY USA.
* Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
* Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
* Harvard Univ, Sch Med, Boston, MA USA.

Why do you think your paper is highly cited?

“The Women's Health Initiative (WHI) was the first large-scale primary prevention clinical trial of hormone therapy, so the CHD results were eagerly anticipated. In contrast to the observational studies that suggested cardioprotection, the WHI suggested no heart benefit with estrogen plus progestin (E+P) and even an 81% risk elevation in year 1 of treatment.”

The effect of hormone therapy on coronary risk has been the subject of vigorous debate and controversy. The Women's Health Initiative (WHI) was the first large-scale primary prevention clinical trial of hormone therapy, so the CHD results were eagerly anticipated. In contrast to the observational studies that suggested cardioprotection, the WHI suggested no heart benefit with estrogen plus progestin (E+P) and even an 81% risk elevation in the first year of treatment. An additional goal was to examine whether any clinical characteristics or biomarkers could identify women at particularly high or low risk of CHD with E+P. We found that most variables—including baseline C-reactive protein (CRP) levels—did not significantly modify risk with E+P, but women who had higher baseline levels of LDL cholesterol and those who were at least 20 years past menopause had the greatest CHD risk elevations with E+P. Women who were less than 10 years past menopause did not appear to have an increased risk of CHD with E+P, but statistical power was limited. Although we conclude that hormone therapy should not be initiated or continued for the purpose of preventing CHD, additional research to address the role of estrogen in recently menopausal women and the effect of different formulations and doses of hormone therapy will be of major interest.

Does it describe a new discovery or a new methodology that's useful to others?

It describes the final results of the WHI trial regarding estrogen plus progestin and risk of CHD among generally healthy postmenopausal women. The results have clinical implications for patient management.

How did you become involved in this research?

I have been one of the principal investigators of the WHI since 1993. As an endocrinologist, I've had a long-term interest in the benefits and risks of hormone replacement therapy. I'm also one of the investigators with the Nurses' Health Study, which has assessed the relationship between hormone therapy and the risks of heart disease, stroke, venous thromboembolism, breast cancer, and many other outcomes. I was particularly interested in collaborating on a randomized clinical trial of hormone therapy in a primary prevention setting.

Could you summarize the significance of your paper in layman's terms?

The manuscript provides the final detailed results of the WHI trial of estrogen plus progestin and CHD, which was the primary efficacy outcome of the trial. We documented the absence of cardioprotection with E+P, the significant increase in the first year after initiation, and the role of clinical characteristics and biomarker levels in identifying women at particularly high or low risk of a CHD event while taking E+P (see above response for additional details). We conclude that E+P should not be started or continued for the purpose of preventing CHD.

JoAnn E. Manson, M.D., Dr. P.H.
Chief, Division of Preventive Medicine
Brigham and Women's Hospital
Professor of Medicine and the Elizabeth F. Brigham Professor of Women's Health
Harvard Medical School
Boston, Massachusetts, USA

Read a Hot Paper in Medicine from in-cites: "Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative Randomized Controlled Trial" from the Women's Health Initiative about this subject.

ESI Special Topics, June 2004
Citing URL - http://www.esi-topics.com/fbp/2004/june04-JoAnnManson.html