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

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA

    Yunsheng Ma, Annie L. Culver & Judith K. Ockene

  2. Corrona LLC, 352 Boston Turnpike, Southborough, MA, 01772, USA

    Gioia M. Persuitte

  3. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA

    Christopher Andrews

  4. Department of Epidemiology and Environmental Health, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    Kathleen M. Hovey & Michael J. LaMonte

  5. Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    JoAnn E. Manson

  6. Division of Endocrinology, Emory University, Atlanta, GA, 30322, USA

    Lawrence S. Phillips

  7. School of Public Health, Brown University, Providence, RI, 02903, USA

    Simin Liu

  8. Department of Family Medicine, School of Medicine, Brown University, Providence, RI, 02912, USA

    Charles Eaton

  9. Division of Cardiology, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA

    Lisa W. Martin

  10. MedStar Research Institute, Hyattsville, MD, 20782, USA

    Barbara V. Howard

  11. Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, 01003, USA

    Raji Balasubramanian & Susan R. Sturgeon

  12. RAND Corporation, Santa Monica, CA, 90407, USA

    Chloe E. Bird

  13. Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01655, USA

    Ira S. Ockene

  14. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Lesley Tinker

  15. Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, 95616, USA

    Rami Nassir

  16. Women’s Health Initiative Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, 20892, USA

    Jacques Rossouw

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  1. Yunsheng Ma
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  2. Gioia M. Persuitte
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  3. Christopher Andrews
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  10. Charles Eaton
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  11. Lisa W. Martin
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  14. Chloe E. Bird
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  15. Ira S. Ockene
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  16. Susan R. Sturgeon
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  17. Judith K. Ockene
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  18. Lesley Tinker
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  19. Rami Nassir
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  20. Jacques Rossouw
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Corresponding author

Correspondence to Yunsheng Ma.

Appendix

Appendix

See Tables 3, 4, 5, 6, 7 and 8.

Post hoc test of comparisons

Comparison

Wald Chi-square

df

P value

Across 3 diabetes groups

3.4597

2

0.177

Pairwise tests

   

Diabetes before statin (if any) and diabetes after statin (low potency)

1.9568

1

0.162

Diabetes before statin (if any)and diabetes after statin (high potency)

1.2013

1

0.273

Diabetes after statin (low potency) and diabetes after statin (high potency)

3.4592

1

0.063

  1. There is no statistical difference between these diabetes groups and risk of ASCVD, after adjustment for multiple comparisons alpha level = 0.017

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Ma, Y., Persuitte, G.M., Andrews, C. et al. Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women. Eur J Epidemiol 31, 747–761 (2016). https://doi.org/10.1007/s10654-016-0153-7

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  • DOI: https://doi.org/10.1007/s10654-016-0153-7

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