Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXI. Disease activity, damage accrual, and vascular events in pre‐ and postmenopausal women

Fernández, Mónica; Calvo‐Alén, Jaime; Alarcón, Graciela S.; Roseman, Jeffrey M.; Bastian, Holly M.; Fessler, Barri J.; McGwin, Gerald; Vilá, Luis M.; Sanchez, Martha L.; Reveille, John D.

doi:10.1002/art.21048

Cited by 41 publications

(22 citation statements)

References 48 publications

(50 reference statements)

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“…Gender differences were observed in the univariable analyses with women experiencing a slower decline in disease activity than men; however, gender was not retained in the multivariable analysis. A state of hypoestrogenemia has been suggested to be associated with reduced disease flares (29, 30); however, we did not find menopausal status to be a significant predictor of the slope in our analyses, a finding that is consistent with previous reports in which disease duration rather than menopause contributed to the amelioration of disease activity (11, 31). We have previously shown that African Americans and Texan Hispanics tend to have higher levels of disease activity over time (6).…”

Section: Discussionsupporting

confidence: 89%

Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX

Zhang

González

Roseman

et al. 2010

Lupus

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The objectives of the present study were (1) to clarify and quantify the relationship between age and disease duration with the rate of change in disease activity over time in patients with systemic lupus erythematosus (SLE) and (2) to explore other possible factors associated with this rate of change. To this end, SLE patients from LUMINA were studied if they had ≥3 visits in which disease activity (Systemic Lupus Activity Measure-Revised or SLAM-R) had been ascertained. Variables associated with the rate (slope) of change in disease activity (obtained by regressing the SLAM-R scores against the length of time from diagnosis to last visit) were examined by univariable and multivariable analyses. Five-hundred forty-two of the 632 patients had ≥3 SLAM-R scores. In multivariable analyses Caucasians exhibited the fastest decline in disease activity; Texan Hispanics exhibited the slowest, trailed by the African Americans. Longer disease duration and HLA-DRB1*1503 positivity were associated with a slower decline whereas a greater number of ACR criteria and abnormal laboratory parameters (white blood cell and platelet counts, hematocrit and serum creatinine) were associated with a faster decline. These findings complement existing knowledge on SLE disease activity and are potentially useful to clinicians managing these patients.

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Section: Discussionsupporting

confidence: 89%

Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX

Zhang

González

Roseman

et al. 2010

Lupus

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“…Several longitudinal studies following female subjects through the menopausal transition have noted decreased frequency of flares after menopause, modestly decreased SLE Disease Activity Index (SLEDAI), but greater damage accrual in affected organs from individual flares in the postmenopausal period [87–90]. Cohort studies comparing pre- and post-menopausal subjects yielded similar findings [89].…”

Section: Menopause and Changes In Endocrine And Immune Functionmentioning

confidence: 89%

Autoimmune diseases and reproductive aging

Bove

2013

Clinical Immunology

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As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation.

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“…Similarly, in the LUMINA study hormone therapy was not associated with vascular arterial events (47), and Fernández et al . even speculated that hormone therapy may be a protective factor against the development of arterial vascular events in women with SLE (48). Our data are consistent with these studies suggesting a potential cardioprotective role for estrogens in adulthood during SLE.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol Protects Against the Progression of Hypertension During Adulthood in a Mouse Model of Systemic Lupus Erythematosus

2014

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Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a high prevalence of hypertension and cardiovascular disease. Because SLE predominantly affects women, estrogen is commonly implicated as a contributor to SLE disease progression. Utilizing an established mouse model of SLE (female NZBWF1) we tested whether estrogen has a causal role in the development of hypertension in adulthood. Thirty-week-old SLE and control mice (NZW/LacJ) underwent either a sham or ovariectomy (OVX) procedure. 17β-estradiol (E2; 5μg/mouse, twice/week, s.c.) was administered to a subset of OVX mice. Mean arterial pressure (in mmHg) was increased in SLE mice (134±4 versus 119±3 in controls). Contrary to our hypothesis, OVX exacerbated the hypertension in female SLE mice (153±3; p<0.05 vs. SLE sham), and repletion of E2 prevented the OVX induced increase in blood pressure (132±2). The prevalence of albuminuria was increased in SLE mice in comparison to controls (37% vs. 0%). OVX increased the prevalence in SLE mice (70% versus 37% in SLE shams). Repletion of E2 completely prevented albuminuria in OVX SLE mice. Renal cortical TNF-α was increased in SLE mice compared to controls and was further increased in OVX SLE. The OVX induced increase in renal TNF-α expression was prevented by repletion of E2. Treatment of OVX SLE mice with the TNF-α inhibitor, etanercept, blunted the OVX induced increase in blood pressure (140±2) and prevalence of albuminuria (22%). These data suggest that 17β-estradiol protects against the progression of hypertension during adulthood in SLE, in part, by reducing TNF-α.

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Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXI. Disease activity, damage accrual, and vascular events in pre‐ and postmenopausal women

Cited by 41 publications

References 48 publications

Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX

Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX

Autoimmune diseases and reproductive aging

17β-Estradiol Protects Against the Progression of Hypertension During Adulthood in a Mouse Model of Systemic Lupus Erythematosus

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