Tag: Inflammation

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Gout flares associated with subsequent cardiovascular events

Gout flares associated with subsequent cardiovascular events

Experts at the University of Nottingham, in collaboration with experts at Keele University, have found that the risk of heart attacks and strokes temporarily increases in the four months after a gout flare.

The research showed that gout patients who suffered from a heart attack or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the 61-120 days prior.

The results of the study, led by Professor Abhishek in the School of Medicine at the University of Nottingham, are published in the journal JAMA.

Gout is a common form of arthritis that affects one in 40 adults in the UK. It is caused by high levels of uric acid, a chemical produced by breakdown of tissues in the body and present in certain foods and drinks.

At high levels, uric acid is deposited in and around joints as needle shaped urate crystals. Once released from their deposits, these crystals cause severe inflammation manifesting as joint pain, swelling, redness, and tenderness that often lasts for 1-2 weeks. These episodes, called gout flares, often recur. Inflammation is also a risk factor for heart attack and stroke.

People with gout tend to have more cardiovascular risk factors, although there have been no previous studies about whether gout flares are linked with an increased risk of heart attack and stroke. In this study, the experts examined whether there was a temporary increase in risk of heart attack or stroke after a gout flare.

The team used anonymized data from 62,574 patients with gout treated in the National Health Service in the UK. Of these, 10,475 experienced heart attack or stroke after the diagnosis of gout, while others of similar age, sex, and duration of gout, did not experience such events. They evaluated the association between heart attacks or strokes and recent gout flares and adjusted these results for comorbidities, socioeconomic deprivation, lifestyle factors and prescribed medications among other things. They found that gout patients who suffered a heart attack or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the preceding 61-120 days.

They found a similar high rate of heart attack or stroke in the 0-60 and 61-120 days after gout flares compared with other time periods, when they used information from only patients who consulted for a gout flare and also experienced either heart attack or stroke. This further strengthened the finding that gout flares are associated with a transient increase in cardiovascular events following flares. The increased odds and rates persisted when people with pre-existing heart disease or stroke before their gout diagnosis were excluded, and when shorter exposure periods such as 0-15 and 16-30 days prior to heart attack or stroke, were considered.

Gout patients who died from a heart attack or stroke had over four times the odds of experiencing a gout flare in the preceding 0-60 days and over twice the odds of gout flare in the preceding 61-120 days.

This is the first study of its kind to examine whether there is an association between recent gout flares and heart attacks and strokes.


The results show that among patients with gout, patients who experienced a heart attack or stroke had significantly increased odds of a gout flare during the preceding 120-days compared with patients who did not experience such events. These findings suggest that gout flares are associated with a transient increase in cardiovascular events following flares.


People with recurrent gout flares should be considered for long-term treatment with urate lowering treatments such as allopurinol. This is a reliable way of removing urate crystal deposits and providing freedom from gout flares. Patients should also be considered for concurrent treatment with anti-inflammatory medicines such as colchicine for the first few months because urate lowering treatments may trigger gout flares in the short term.


People with gout should be encouraged to adopt a healthy lifestyle with appropriate treatment of conditions such as high blood pressure, high cholesterol, obesity and diabetes to minimise their background risk of heart attack and stroke”


Professor Abhishek, lead author on the study

Source:

Journal reference:

Cipolletta, E., et al. (2022) Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout. JAMA. doi.org/10.1001/jama.2022.11390.

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Study identifies an epigenetic regulator that suppresses pathogenic events in rheumatoid arthritis

Study identifies an epigenetic regulator that suppresses pathogenic events in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by chronic inflammation of synovium, eventually leading to joint destruction. Epigenetic alteration (the mechanism of gene expression regulation without DNA sequence changes), such as low levels of DNA methylation, is one of the factors which worsens the RA state. However the mechanism by which the alterations occur remains largely unknown.

In the present study, we identified an epigenetic regulator UHRF1 that was remarkably up-regulated in synovial fibroblasts (SF) from arthritis model mice and RA patients. Previous study showed that UHRF1 is a key player in the maintenance of DNA methylation, although the function for RA is unknown. To understand UHRF1 function for arthritis, we generated mice with SF-specific UHRF1 conditional knockout (cKO) and experimental arthritis was induced.

cKO mice exhibited more severe arthritic phenotypes than the littermate control. Next, to reveal UHRF1 function in SF, RNA-seq and MBD-seq were performed using SF obtained from the control and cKO mice. Integrative genome-wide analyses of the transcriptome and methylome showed that expression of several cytokines was up-regulated in UHRF1-deficient SF accompanied by reduced DNA methylation signatures.

Also, UHRF1 expression in synovium was negatively correlated with several pathogenesis in RA patients. These data suggested that RA pathogenesis is exacerbated when UHRF1 levels are low in SF. Finally, we assessed whether UHRF1 stabilization contributes to improvement of arthritis pathogenesis. Ryuvidine, which was identified as a candidate chemical compound to the stabilize UHRF1 protein, was administrated in arthritis model mice.

The results showed that arthritis pathogenesis was ameliorated by treatment with Ryuvidine. Also, the development of organoids derived from RA-SF was suppressed by Ryuvidine.

This study demonstrated that UHRF1 expressed in SF with RA has a protective role in suppressing multiple pathogenic events in arthritis, suggesting that targeting UHRF1 could be a therapeutic strategy for RA.

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Corticosteroid exposure associated with hospitalization for severe pain event among patients with sickle cell disease

Corticosteroid exposure associated with hospitalization for severe pain event among patients with sickle cell disease

People with sickle cell disease (SCD) who were recently prescribed a corticosteroid – a medicine frequently used to treat asthma or inflammation – were found to be significantly more likely to be hospitalized for a severe pain event, according to a paper published today in the journal Blood. The research also found that older adults, women, and people who were not taking the drug hydroxyurea to manage their underlying SCD symptoms were the most likely to be hospitalized.

SCD is the most common inherited red blood cell disorder in the United States, affecting an estimated 100,000 people. According to the Centers for Disease Control and Prevention (CDC), SCD affects one out of every 365 Black or African American births and one out of every 16,300 Hispanic American births. Pain events, also known as vaso-occlusive episodes (VOE), are the most common complications of SCD and can result in intense pain and potentially irreversible organ damage.

Apart from case reports, researchers say this is the first study to systematically evaluate the association between corticosteroid exposure and hospitalization for VOE.

Individuals living with SCD often suffer crippling episodes of pain, which can greatly impair their quality of life. Based on our data, corticosteroids are commonly prescribed for conditions unrelated to their underlying SCD. Vaso-occlusive events and related hospitalization appear to follow corticosteroid prescription fairly quickly. This evidence suggests corticosteroids may be contributing to the events and should be avoided as much as possible in these patients.”


Ondine Walter, MD, Study Author, Toulouse University Hospital in France

Notably, the median time between filling a prescription for a corticosteroid and hospitalization was just five days. Also striking was the fact that nearly half (46%) of patients with SCD had been prescribed at least one systemic corticosteroid during the study period. Dr. Walter said the results underscore the need for widespread education of clinicians and patients alike about the potential risks of using corticosteroids, especially when there isn’t a clear indication to use them.

“Corticosteroids are mostly easy to avoid, and in circumstances when they are necessary, it’s important to start them in collaboration with an SCD expert and to take all appropriate precautionary measures to administer them safely,” said Dr. Walter.

The study used data from a total of 5,151 patients with SCD drawn from the French National Health Insurance Database between 2010 and 2018. Patients had to have at least one hospitalization for VOE to be included, and corticosteroid exposure was identified using outpatient prescribing records.

The study found that those who had exposure to a corticosteroid – defined in the month leading up to the event – were significantly more likely to be hospitalized for VOE. People who were also taking hydroxyurea seem to have less risk of hospitalization compared with those not taking the drug, which may signal a potential protective effect of hydroxyurea on the occurrence of VOE, Dr. Walter explained. Hydroxyurea is often prescribed to reduce the number of pain events caused by SCD as well as the need for blood transfusions. The risk of admission was also lower in men compared to women and in children compared to adults.

“Some factors such as hydroxyurea use, male gender, and younger age were associated with a lower risk of hospitalization for VOE after corticosteroid exposure in our study. Still, based on these results, we still need to think twice about using corticosteroids when treating patients with SCD,” said Dr. Walter.

This study is limited in that it can only show an association between corticosteroids and VOE-related hospitalizations and not prove causation. Because corticosteroid exposure was based on dispensing data, it is also not possible to confirm that patients took the medicine, only that the prescription was filled.

With future research, investigators aim to understand how corticosteroids may prompt VOE. Studies have shown that the cessation of corticosteroids, in particular, has been associated with rebound pain. ASH’s Clinical Practice Guidelines on SCD recommend against using corticosteroids for acute pain management in patients with SCD. This study adds important data about the association of corticosteroid use with subsequent VOE to a growing body of evidence that suggests corticosteroids should be used only when needed, and under the guidance of an SCD expert.

Source:

American Society of Hematology

Journal reference:

Walter, O., et al. (2022) Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease. Blood. doi.org/10.1182/blood.2021014473.