European Journal of Epidemiology

, Volume 31, Issue 8, pp 747–761 | Cite as

Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women

  • Yunsheng MaEmail author
  • Gioia M. Persuitte
  • Christopher Andrews
  • Kathleen M. Hovey
  • Michael J. LaMonte
  • Annie L. Culver
  • JoAnn E. Manson
  • Lawrence S. Phillips
  • Simin Liu
  • Charles Eaton
  • Lisa W. Martin
  • Barbara V. Howard
  • Raji Balasubramanian
  • Chloe E. Bird
  • Ira S. Ockene
  • Susan R. Sturgeon
  • Judith K. Ockene
  • Lesley Tinker
  • Rami Nassir
  • Jacques Rossouw


To compare impact of incident diabetes on atherosclerotic cardiovascular disease (ASCVD) risk among postmenopausal women according to statin use. Prospective data from 120,499 postmenopausal women without prevalent diabetes or cardiovascular disease at baseline from the Women’s Health Initiative were used. Incident diabetes was self-reported annually and defined as treatment with pills or injectable medication for diabetes. Current statin use was determined at enrollment and years 1, 3, 6, 9 and 13.5 in the three clinical trial arms, and at baseline, year 3, and 13.5 for the observational study. The primary outcome was incident ASCVD events, self-reported annually and adjudicated by blinded local and central physicians. Incident diabetes and statin use status were fitted as time-varying covariates in Cox regression models to assess ASCVD risk during an average follow-up of 13.6 years. For those not on statins at the time of diabetes diagnosis, there was a 42 % increased risk of ASCVD [hazard ratio (HR) 1.42, 95 % CI 1.28–1.58] among women with incident diabetes versus those without diabetes. Among women on statins, there was a 39 % increased risk of ASCVD (HR 1.39, 95 % CI 1.12–1.74) in women with incident diabetes versus those without diabetes. The increased ASCVD risk due to diabetes was similar between women before or after initiating statins (P = 0.89). Whether diabetes was diagnosed before or after statin use did not alter the increased risk of ASCVD associated with diabetes. Mitigating the increased incidence of diabetes in statin users could increase the ASCVD benefit-to-risk ratio of statins.


Epidemiology Diabetes Drug-related problem Cardiovascular disease 



Y.M. and G.M.P wrote the manuscript and researched data. A.L.C., J.E.M., L.S.P., S.L., C.E., M.L., L.W.M, B.V.H, R.B., C.E.B., I.S.O., S.R.S., J.K.O., L.T, R.N., and J.R. contributed to the discussion and reviewed and edited the manuscript. C.A. and K. H performed data analyses and reviewed and edited the manuscript. The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. Our investigation also was supported in part by 5R01HL122241-02. A list of WHI investigators is available in Supplementary Data online. The authors thank the principal investigators of all WHI clinical centers and the data coordinating center for their contribution to the study. They are also indebted to the dedicated and committed participants of the WHI.


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Yunsheng Ma
    • 1
    Email author
  • Gioia M. Persuitte
    • 2
  • Christopher Andrews
    • 3
  • Kathleen M. Hovey
    • 4
  • Michael J. LaMonte
    • 4
  • Annie L. Culver
    • 1
  • JoAnn E. Manson
    • 5
  • Lawrence S. Phillips
    • 6
  • Simin Liu
    • 7
  • Charles Eaton
    • 8
  • Lisa W. Martin
    • 9
  • Barbara V. Howard
    • 10
  • Raji Balasubramanian
    • 11
  • Chloe E. Bird
    • 12
  • Ira S. Ockene
    • 13
  • Susan R. Sturgeon
    • 11
  • Judith K. Ockene
    • 1
  • Lesley Tinker
    • 14
  • Rami Nassir
    • 15
  • Jacques Rossouw
    • 16
  1. 1.Division of Preventive and Behavioral Medicine, Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Corrona LLCSouthboroughUSA
  3. 3.Department of Ophthalmology and Visual SciencesUniversity of MichiganAnn ArborUSA
  4. 4.Department of Epidemiology and Environmental HealthState University of New York at BuffaloBuffaloUSA
  5. 5.Division of Preventive Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  6. 6.Division of EndocrinologyEmory UniversityAtlantaUSA
  7. 7.School of Public HealthBrown UniversityProvidenceUSA
  8. 8.Department of Family Medicine, School of MedicineBrown UniversityProvidenceUSA
  9. 9.Division of Cardiology, School of Medicine and Health SciencesGeorge Washington UniversityWashingtonUSA
  10. 10.MedStar Research InstituteHyattsvilleUSA
  11. 11.Department of Biostatistics and EpidemiologyUniversity of Massachusetts AmherstAmherstUSA
  12. 12.RAND CorporationSanta MonicaUSA
  13. 13.Division of Cardiovascular Medicine, Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  14. 14.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  15. 15.Department of Biochemistry and Molecular MedicineUniversity of California DavisDavisUSA
  16. 16.Women’s Health Initiative Branch, National Heart, Lung, and Blood InstituteBethesdaUSA

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