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A nested case–control study of the association between melatonin secretion and incident myocardial infarction
  1. Ciaran J McMullan1,2,
  2. Eric B Rimm2,3,4,
  3. Eva S Schernhammer2,3,
  4. John P Forman1,2
  1. 1Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  2. 2Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  4. 4Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  1. Correspondence to Dr Ciaran J McMullan, 41 Avenue Louis Pasteur, Suite 121, Boston, MA 02115, USA; cmcmullan1{at}


Objectives Low nocturnal melatonin secretion is associated with cardiovascular risk factors, diabetes and hypertension, while individuals with prevalent cardiovascular disease have lower nocturnal melatonin levels. However, the prospective association of melatonin secretion with myocardial infarction (MI) has not been studied. We aimed to study the association between melatonin secretion and the risk of developing MI.

Methods We performed a prospective nested case–control study of participants from the Nurses' Health Study cohorts I and II. A total of 209 incident cases of fatal and non-fatal MI were identified among women who provided first morning voided urine specimens at baseline and were matched to 209 controls. Nocturnal melatonin secretion was assessed using 6-sulfatoxymelatonin concentrations in morning urines normalised to the urines' creatinine concentration. Multivariable conditional logistic regression was used to analyse associations independent of important risk factors.

Results Lower melatonin secretion was significantly associated with a higher risk of MI. After conditioning on matching variables, the OR for every one unit lower log-transformed sulfatoxymelatonin/creatinine ratio was 1.51 (95% CI 1.16 to 1.96). In multivariable models controlling for factors included in the American Heart Association Cardiovascular Risk Score plus circadian factors, every one unit lower in the ratio was associated with a significantly increased risk of MI (OR, 1.40; 95% CI 1.02 to 1.93). Women in the highest category had an estimated absolute risk of MI of 84 cases per 100 000 person-years compared with 197 cases per 100 000 person-years in the lowest category. The association was strongly modified by body mass index (BMI) (p value for interaction=0.02).

Conclusions Lower melatonin secretion was significantly associated with a greater risk of incident MI in women with increased BMI. Melatonin may be a novel and modifiable risk factor for MI among such women.

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  • ESS and JPF contributed equally.

  • Contributors CJM contributed to the design of the study and was responsible for completing the analysis. He also drafted the manuscript, which was reviewed by all the authors. JPF and ESS were also responsible for conceiving the study, design and review of the manuscript. EBR was involved in the manuscript review and revision.

  • Funding This study was funded by several grants from the National Institutes of Health (NIH) in the USA: DK58845, HL103607, UM1 CA186107, R01 CA49449, R01 HL034594, UM1 CA176726 and R01 CA67262. The NIH had no role in the design, conduct or reporting of the study described.

  • Competing interests None declared.

  • Ethics approval Partners Institution Review Board. This study was approved by the institutional review board at the Brigham and Women's Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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