New research reveals that the level of muscle adiposity (fat content) may indicate a person’s likelihood of experiencing cognitive decline as they age. In the study published in the Journal of the American Geriatrics Society, a five-year increase in fat stored in the thigh muscle was a risk factor for cognitive decline.
This risk was independent of total weight, other fat deposits, and muscle characteristics (such as muscle strength or mass) and also independent of traditional dementia risk factors.
Investigators assessed muscle fat in 1634 adults 69–79 years of age at years 1 and 6 and evaluated their cognitive function at years 1, 3, 5, 8, and 10. Increases in muscle adiposity from year 1 to year 6 were associated with faster and more cognitive decline over time. The findings were similar for Black and White men and women.
“Our data suggest that muscle adiposity plays a unique role in cognitive decline, distinct from that of other types of fat or other muscle characteristics,” said corresponding author Caterina Rosano, MD, MPH, of the University of Pittsburgh’s School of Public Health. “If that is the case, then the next step is to understand how muscle fat and the brain ‘talk’ to each other, and whether reducing muscle adiposity can also reduce dementia risk.”
Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/
In a 12-month trial involving patients with “preclinical” rheumatoid arthritis, treatment with the immunomodulator abatacept (Orencia) kept the condition from becoming clinical, according to findings presented at the European Alliance of Associations for Rheumatology (EULAR) annual meeting.
Rheumatologists have long sought to nip rheumatoid arthritis (RA) in the bud, with many studies supporting early aggressive treatment on RA diagnosis. This has never been recommended for biologic therapies however.
Nevertheless, some patients show up at arthritis clinics with a few painful joints and other features such as RA-related serum biomarkers that suggest progression to full-blown RA is likely. Would aggressive treatment help slow their decline into RA?
In a phase IIb randomised trial involving patients in the UK and Netherlands who were at high risk for developing RA, only seven of the 110 assigned to abatacept had gone on to develop clinical arthritis after 1 year, compared with 30 of 103 in a placebo group.
The effect waned after abatacept was stopped at the one-year mark, and in the following year, 20 more patients in the abatacept group developed clinical arthritis, as did another eight in the placebo group.
Though the abatacept regimen held the edge for a full two years, projections showed that it was likely that the abatacept group would catch up with additional follow-up. At the same time, abatacept had no particular safety issues and thus could likely be continued.
A decade ago, Andrew Cope, MD, MBBS, of King’s College London colleagues thought about aggressive prevention, registering the current trial, Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA), in 2014. In a 2019 description of the protocol, they explained the selection of abatacept because “it targets immune reactions early in the chain of events leading to inflammation in RA. It functions by interrupting the interaction between T cells and antigen-presenting cells, attenuating the co-stimulatory signals required for T-cell activation, differentiation and effector responses,” thereby resulting “in downstream immunomodulatory effects on other inflammatory cells of the immune system.”
Participants had to show joint pain but no synovitis, plus either test positive for anti-citrullinated protein antigen (ACPA) antibodies and for rheumatoid factor (RF), or show high levels of ACPA antibodies without RF. The primary endpoint was development of clinically apparent arthritis in at least three joints or diagnosis of RA according to standard criteria.
While the preventive effect seen in the primary analysis did not hold up across the whole sample, Cope noted that it appeared more so in one very-high-risk subgroup: 49 patients who had some level of IgG ACPA antibodies and who were also positive for a series of other biomarkers, including RF, IgA ACPA antibodies, anti-carbamylated protein antibodies, and anti-acetylated peptide antibodies. For this subgroup, only about 10% of those who had taken abatacept progressed to clinical arthritis after two years, versus 50% of those assigned to placebo.
Women ages 45 years and older taking oral oestrogen pills were more likely to develop hypertension than those using transdermal or vaginal formulations, according to new research published in Hypertension.
Hormone therapy may be prescribed to relieve symptoms of menopause, in gender-affirming care and in contraception. Previous studies have found that some hormone therapies may reduce cardiovascular disease risk in menopausal women under 60 years of age or for whom it has been fewer than 10 years since menopause. The authors of this study noted that while hypertension is a modifiable risk factor for cardiovascular disease, the potential effects of different types of hormone therapy on blood pressure in menopausal women remain uncertain.
“We know oestrogens ingested orally are metabolised through the liver, and this is associated with an increase in factors that can lead to higher blood pressure,” said lead study author Cindy Kalenga, an MD/PhD-candidate at the University of Calgary.
“We know that post-menopausal women have increased risk of high blood pressure when compared to pre-menopausal women, furthermore, previous studies have shown that specific types of hormone therapy have been associated with higher rates of heart disease,” Kalenga said. “We chose to dive deeper into factors associated with hormone therapy, such as the route of administration (oral vs non-oral) and type of oestrogen, and how they may affect blood pressure.”
This study involved a large group of over 112 000 women, ages 45 years and older, who filled at least two consecutive prescriptions (a six-month cycle) for oestrogen-only hormone therapy, as identified from health administrative data in Alberta, Canada between 2008 and 2019. The main outcome of high blood pressure (hypertension) was identified via health records.
First, researchers investigated the relationship between route of oestrogen-only hormone therapy administration and risk of developing high blood pressure at least one year after starting the treatment. The 3 different routes of hormone therapy administration were oral (by mouth), transdermal and vaginal application. Additionally, researchers evaluated the formulation of oestrogen used and the risk of developing high blood pressure. For this study, the researchers reviewed medical records of individuals taking oestrogen-only hormone therapy. The two most common forms of oestrogen used by study participants were oestradiol – a synthetic form of oestrogen closest to the naturally produced form – and conjugated equine oestrogen, an animal-derived form of oestrogen and the oldest type of oestrogen therapy.
The analysis found:
Women taking oral oestrogen therapy had a 14% higher risk of developing high blood pressure compared to those using transdermal oestrogen and a 19% higher risk of developing high blood pressure compared to those using vaginal oestrogen creams or suppositories. After accounting for age, a stronger association was seen among women younger than 70 years of age compared to women older than 70.
Compared to estradiol, conjugated equine estrogen was associated with an 8% increased risk of developing high blood pressure.
Taking oestrogen for a longer period of time or taking a higher dose was associated with greater risk of high blood pressure, the authors noted. According to Kalenga, the study’s findings suggest that if menopausal woman take hormone therapy, there are different types of oestrogen that may have lower cardiovascular risks.
“These may include low-dose, non-oral oestrogen – like oestradiol, in transdermal or vaginal forms – for the shortest possible time period, based on individual symptoms and the risk–benefit ratio, Kalenga said. “These may also be associated with the lowest risk of hypertension. Of course, this must be balanced with the important benefits of hormone therapy, which include treatment of common menopausal symptoms.”
The average age of natural menopause among women worldwide is about 50 years of age. Current evidence supports that initiating menopausal hormone therapy in the early stages may have cardiovascular benefits, though not in the late stages of menopause, according to the American Heart Association’s 2020 Statement on Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention. Previous studies have found that menopausal hormone therapy may help relieve symptoms of menopause, including hot flashes, night sweats, mood changes or sleep disturbances.
Limitations included being based only on medical records, not including women younger than the age of 45 and not collecting data about hysterectomies or menopausal status (which was inferred by taking oestrogen after 45).
The authors will be conducting more research investigating combined oestrogen and progestin, as well as progestin-only formulations of hormone therapy and their impact on heart and kidney diseases.
Participants taking a daily 50mg dose of oral semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, lost more weight than those taking placebo, according to results announced by the manufacturer, Norvo Nordisk.
Novo Nordisk announced headline results from phase 3a trial in a statement. The OASIS 1 trial is a 68-week, efficacy and safety trial comparing once-daily oral semaglutide 50mg for weight management to placebo in 667 adults with obesity or overweight with one or more comorbidities. Participants also undertook lifestyle interventions.
When evaluating the effects of treatment if all people adhered to treatment from a mean baseline body weight of 105.4 kg, people treated with oral semaglutide 50mg achieved a statistically significant weight loss of 17.4% after 68 weeks compared to a 1.8% reduction with placebo. In addition, 89.2% of those who received oral semaglutide 50mg, reached a weight loss of 5% or more after 68 weeks, compared to 24.5% with placebo.
When applying the treatment policy estimand, people treated with oral semaglutide 50 mg achieved a superior weight loss of 15.1% compared to a reduction of 2.4% with placebo and 84.9% achieved a weight loss of 5% or more, compared to 25.8% with placebo.
“We are very pleased with the weight loss demonstrated by the once-daily oral formulation of semaglutide in obesity. The results show comparable weight loss as in the STEP 1 trial with injectable semaglutide 2.4mg in obesity branded as Wegovy®”, said Martin Holst Lange, executive vice president for Development at Novo Nordisk. ”The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences”.
Oral semaglutide 50 mg also appeared be safe and was well tolerated, with the most common adverse events being mostly mild to moderate gastrointestinal ones consistent with the GLP-1 receptor agonist class. Gastrointestinal adverse events were most prominent during dose escalation.
Novo Nordisk expects to file for regulatory approval in the US and the EU in 2023. The global launch of oral semaglutide 50mg is contingent on portfolio prioritisations and manufacturing capacity.
