Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative.
BACKGROUND
Vitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.


RESULTS
Analyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.


CONCLUSIONS
CaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.


BACKGROUND
http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.). mdonneyong@partners.org.
Macarius M
MM
Donneyong
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Carlton A
CA
Hornung
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Kira C
KC
Taylor
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Richard N
RN
Baumgartner
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
John A
JA
Myers
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Charles B
CB
Eaton
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Eiran Z
EZ
Gorodeski
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Liviu
L
Klein
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Lisa W
LW
Martin
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
James M
JM
Shikany
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Yiqing
Y
Song
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
Wenjun
W
Li
From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).
JoAnn E
JE
Manson
D000368:Aged; D002136:Calcium, Dietary / Q000008:administration & dosage*; D019587:Dietary Supplements; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage; D016387:Women's Health
D002136:Calcium, Dietary; D014815:Vitamins; D014807:Vitamin D
calcium; clinical trial; heart failure; vitamin D; women