Premature coronary heart disease in systemic lupus erythematosus: what risk factors do we understand?

Nikpour, Mandana; Gladman, D. D.; Urowitz, MB

doi:10.1177/0961203313493031

Cited by 44 publications

(28 citation statements)

References 51 publications

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“…CAD occurs in 5-8% in the first decade with SLE, and increases each decade reaching 28% after 4 decades of SLE. SLE patients who develop a myocardial infarct carry a worse prognosis and usually have a longer hospital stay [8]. Late-onset SLE correlates with increased CAD mortality [15].…”

Section: Discussionmentioning

confidence: 99%

“…Possibly, ongoing inflammatory states or co-existent antiphospholipid syndrome in 40% of patients are added culprits [8].…”

Section: Discussionmentioning

confidence: 99%

“…The causes of death within the 5 year period from the diagnosis of lupus remain to be infections and renal disease. The prognosis after 5 years of disease depends on the development of accelerated atherosclerosis and disease damage accrual [8]. The main treat-to-target in SLE is complete remission, since studies have shown that patients in remission have better survival outcomes [9].…”

Section: Introductionmentioning

confidence: 99%

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Good prognosis for hospitalized SLE patients with non-related disease

Zimlichman¹,

Rothschild²,

Shoenfeld³

et al. 2014

Autoimmunity Reviews

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Section: Discussionmentioning

confidence: 99%

“…Possibly, ongoing inflammatory states or co-existent antiphospholipid syndrome in 40% of patients are added culprits [8].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Good prognosis for hospitalized SLE patients with non-related disease

Zimlichman¹,

Rothschild²,

Shoenfeld³

et al. 2014

Autoimmunity Reviews

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“…Most previous studies have focused on rheumatoid arthritis (RA) 20 and systemic lupus erythematosus (SLE) 21,22 . The data regarding spondyloarthropaties, including AS are limited, although CV mortality and morbidity increase is evident 23 .…”

Section: Discussionmentioning

confidence: 99%

Microvascular dysfunction in ankylosing spondylitis is associated with disease activity and is improved by anti-TNF treatment

Batko¹,

Maga

Urbański

et al. 2018

Sci Rep

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Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recent studies indicate that microvascular dysfunction may underlie cardiovascular risk in AS. We hypothesized, that microvascular morphology and dysfunction is linked to AS activity and is modifiable by TNF-α inhibitor (TNFi) treatment. Functional Laser Doppler Flowmetry with post-occlusive reactive hyperemia, and structural nailfold capillaroscopy were performed in 54 patients with AS and 28 matched controls. Active AS was diagnosed based on BASDAI ≥ 4 (n = 37). Effects of 3-month TNFi on microcirculation in active AS were studied. AS was associated with prolonged time to peak hyperemia compared to healthy controls. High disease activity was associated with increased time to peak hyperemia and decreased peak hyperemia when compared to patients with inactive AS. In capillaroscopy, AS was associated with morphological abnormalities indicating increased neoangiogenesis and pericapillary edema compared to controls. Microvascular function improved following 3 months of TNFi in reference to basal flow as well as post-occlusive parameters. TNFi reduced pericapillary edema, while other parameters of capillary morphology remained unchanged. Microvascular dysfunction and capillary neovascular formation are associated with disease activity of AS. Anti-TNF-α treatment may restore microcirculation function and capillary edema but does not modify microvascular structural parameters.

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“…Premature atherosclerosis is a severe complication of SLE leading to appreciable morbidity and mortality from cardiovascular disease (2, 3). Gain-of-function polymorphisms in IRF5 are strongly associated with an increased risk of developing SLE and IRF5 inhibition is being considered as a therapeutic approach in SLE (14).…”

Section: Discussionmentioning

confidence: 99%

IRF5 Deficiency Ameliorates Lupus but Promotes Atherosclerosis and Metabolic Dysfunction in a Mouse Model of Lupus-Associated Atherosclerosis

Watkins

Yasuda

Wilson

et al. 2015

The Journal of Immunology

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Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. Here we addressed this question using the gld.apoE−/− mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and non-immune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients.

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Premature coronary heart disease in systemic lupus erythematosus: what risk factors do we understand?

Cited by 44 publications

References 51 publications

Good prognosis for hospitalized SLE patients with non-related disease

Good prognosis for hospitalized SLE patients with non-related disease

Microvascular dysfunction in ankylosing spondylitis is associated with disease activity and is improved by anti-TNF treatment

IRF5 Deficiency Ameliorates Lupus but Promotes Atherosclerosis and Metabolic Dysfunction in a Mouse Model of Lupus-Associated Atherosclerosis

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