ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2887

Post-Menopausal Factors and the Risk of Seropositive and Seronegative Rheumatoid Arthritis Phenotypes: Results from the Nurses’ Health Study

Camilla Bengtsson1, Susan Malspeis2, Jeffrey A. Sparks3, Karen H. Costenbader3 and Elizabeth W. Karlson3, 1The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 3Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Epidemiology and Public Health IV: Rheumatoid Arthritis Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose

Among women, the peak incidence of rheumatoid arthritis (RA) is reported to be 45-74 years of age. In addition, it has been suggested that the post-menopausal transition, especially at younger ages (Pikwer, Ann Rheum Dis, 2012), is related to an increased risk of RA, but the literature is scarce. Whether menopause has different impact on seropositive/seronegative RA phenotypes remains to be elucidated. Our aim was to explore whether age and menopausal factors were independently associated with subsequent development of serologic RA phenotypes in 2 prospective cohorts.

Methods

Data were analyzed from Nurses’ Health Study (NHS, 1976-2010) and NHSII (1989-2011).  In NHS 121,701 female nurses aged 30-55and in NHSII 116,430 female nurses aged 25-42 were followed via biennial questionnaires on lifestyle factors and disease outcomes.  In total, 1,089 incident RA cases were confirmed by questionnaire and chart review. Seropositive RA was defined as +RF or ACPA by chart review or lab measurement. We used Cox proportional hazards models to obtain HR (95% CI) of seropositive or seronegative RA associated with menopausal status, age at menopause, type of menopause, severity of hot flashes and ovulatory years, adjusting for age, income, BMI, smoking, breast-feeding, and parity.  

Results

Women aged 45 or more had an increased risk of seronegative RA in all age-groups, compared with women aged 25-44, with peak HR at ages 55-59. Women aged 50 or more had an increased risk of seropositive RA, with peak HR at ages 55-59, but the risk attenuated after age 60. Post-menopausal women had an increased risk of seronegative RA after adjusting for age and other potential confounders (NHS: HR 1.8, 95% CI 1.1-3.0; NHSII: HR 2.5, 95% CI 1.5-4.2; pooled HR 2.1, 95% CI 1.5-3.1) without marked differences according to type of menopause. Early age at menopause associated with an increased risk of seronegative RA (NHS: HR 2.0, 95% CI 1.2-3.4; NHSII: HR 3.0, 95% CI 1.7-5.1; pooled HR 2.4, 95% CI 1.6-3.5), regardless of type of early menopause. Moderate/severe hot flashes was mainly associated with an elevated risk for seronegative RA (NHS HR=2.4, 95% CI 1.4-4.3; NHSII: 3.7, 95% CI 2.0-6.8; pooled HR 3.0, 95% CI 2.0-4.5).  None of the menopausal factors were significantly associated with seropositive RA.

Conclusion

In these prospective cohorts, women of older ages have an increased risk of both RA phenotypes, but this risk attenuates after age 60 for seropositive RA. Post-menopausal factors are strongly associated with seronegative RA, but not seropositive RA, suggesting potential differences in disease etiology.



Table. Age and menopausal factors and the relative risk of seropositive RA and seronegative RA in the NHS (1976-2010) and NHSII (1989-2011) cohorts 

NHS I

NHS II

Pooled (NHS+NHSII)

Factors

Seropositive RA (n=457)

Seronegative RA (n=267)

Seropositive RA (n=694)

Seronegative RA

(n=395)

Seronegative RA

(n=662)

Age*

HR (95% CI)

HR (95% CI)

HR (95% CI)

HR (95% CI)

HR (95% CI)

   25-44

1.0 (ref)

1.0 (ref)

1.0 (ref)

1.0 (ref)

1.0 (ref)

   45-49

1.2 (0.8-1.8)

2.1 (1.3-3.4)

1.5 (1.0-2.1)

1.9 (1.2-3.0)

2.1 (1.5-3.0)

   50-54

2.1 (1.5-2.9)

1.8 (1.1-2.9)

2.3 (1.6-3.2)

1.8 (1.1-2.9)

2.0 (1.4-3.1)

   55-59

1.9 (1.3-2.6)

1.9 (1.2-3.1)

3.1 (2.1-4.6)

3.3 (1.9-5.5)

3.1 (1.3-7.4)

   60-64

1.5 (1.0-2.1)

2.1 (1.3-3.3)

0.8 (0.2-3.4)

2.4 (0.8-7.8)

2.5 (1.5-4.2)

   ≥65

1.3 (1.0-1.9)

1.9 (1.2-2.9)

N/A

N/A

N/A

Menopausal statusµ

    Pre-menopausal

1.0

1.0

1.0

1.0

1.0

    Post-menopausal

1.3 (0.9-1.9)

1.8 (1.1-3.0)

1.1 (0.7-1.7)

2.5 (1.5-4.2)

2.1 (1.5-3.1)

Type of menopauseµ

    Pre-menopausal

1.0

1.0

1.0

1.0

1.0

    Natural

1.3 (0.9-1.9)

1.8 (1.1-3.0)

1.0 (0.6-1.6)

2.4 (1.3-4.4)

2.0 (1.4-3.0)

    Surgical

1.4 (0.9-2.2)

1.8 (1.0-3.1)

1.2 (0.8-1.9)

2.7 (1.5-4.7)

2.2 (1.5-3.3)

Age at menopauseµ

    Pre-menopausal

1.0

1.0

1.0

1.0

1.0

    ≤ 44 years   

1.4 (0.9-2.1)

2.0 (1.2-3.4)

1.1 (0.7-1.8)

3.0 (1.7-5.1)

2.4 (1.6-3.5)

    45-49 years

1.3 (0.9-2.0)

1.7 (1.0-2.9)

1.2 (0.7-1.9)

1.9 (0.9-4.0)

1.7 (1.1-2.7)

    50-54 years

1.3 (0.9-2.0)

1.7 (1.0-3.0)

1.1 (0.6-1.8)

2.4 (1.1-5.4)

1.9 (1.2-3.0)

    ≥ 55 years

1.6 (0.9-2.9)

1.7 (0.8-3.9)

2.4 (0.9-6.4)

3.5 (0.9-14.0)

2.1 (1.0-4.2)

Type / age at menopauseµ

   Pre-menopausal

1.0

1.0

1.0

1.0

1.0

   Natural ≤ 44

1.6 (1.0-2.5)

2.2 (1.3-4.0)

0.9 (0.4-2.3)

3.0 (1.2-7.2)

2.5 (1.5-4.0)

   Natural ≥ 45

1.3 (0.9-1.9)

1.6 (1.0-2.8)

1.0 (0.6-1.7)

2.1 (1.0-4.3)

1.8 (1.2-2.8)

   Surgical ≤ 44

1.2 (0.7-2.1)

1.6 (0.8-3.2)

1.1 (0.6-2.0)

2.9 (1.6-5.4)

2.2 (1.2-4.0)

   Surgical ≥ 45

1.5 (1.0-2.4)

1.7 (0.9-3.1)

1.4 (0.7-2.5)

2.1 (0.9-5.0)

1.8 (1.1-3.0)

Hot flashesµ

   Pre-menopausal

1.0 (ref)

1.0 (ref)

1.0

1.0

1.0

   Post-menopausal, none

1.1 (0.7-1.7)

1.8 (1.1-3.1)

1.0 (0.5-1.8)

2.6 (1.3-5.3)

2.1 (1.3-3.2)

   Mild, moderate

1.0 (0.6-1.5)

1.7 (0.9-2.9)

1.2 (0.7-1.9)

1.7 (0.8-3.4)

1.7 (1.1-2.6)

   Moderate, severe

1.5 (1.0-2.3)

2.4 (1.4-4.3)

1.2 (0.7-1.9)

3.7 (2.0-6.8)

3.0 (2.0-4.5)

   Severe, 10+ years

1.5 (0.6-3.3)

2.0 (0.7-5.9)

1.4 (0.5-3.9)

5.4 (1.8-15.8)

3.3 (1.2-8.7)

Ovulatory yearsµ

   < 24 years

1.0

1.0

1.0

1.0

1.0

   24-29 years

0.9 (0.7-1.3)

0.9 (0.6-1.4)

0.8 (0.4-1.4)

0.4 (0.2-0.9)

0.7 (0.3-1.3)

   30-34 years

1.1 (0.7-1.5)

0.7 (0.5-1.1)

0.9 (0.5-1.8)

0.5 (0.2-1.0)

0.7 (0.4-1.0)

   ≥ 35 years

0.9 (0.6-1.3)

0.8 (0.5-1.3)

0.8 (0.4-1.7)

0.5 (0.2-1.2)

0.7 (0.5-1.1)

*Crude, unadjusted HR. µCox proportional hazards models adjusted for age, questionnaire cycle, median household income, BMI, smoking pack-years, breast-feeding, parity. Reference category is premenopausal women for menopausal variables

Disclosure:

C. Bengtsson,
None;

S. Malspeis,
None;

J. A. Sparks,
None;

K. H. Costenbader,
None;

E. W. Karlson,
None.

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