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Certain HRT tablets linked to increased heart disease and blood clot risk

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A study has found that certain hormone replacement therapy (HRT) tablets containing both oestrogen and progestogen are associated with a higher risk of heart disease and rare but serious blood clots known as venous thromboembolism (VTE) in women around the age of menopause.

Another HRT tablet called tibolone was associated with an increased risk of heart disease, heart attack and stroke, but not blood clots, “highlighting the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease,” say the researchers.

HRT is used to relieve menopausal symptoms such as hot flushes and night sweats and different treatments are available depending on symptoms.

Some previous trials have suggested a link between menopausal hormone therapy and an increased risk of cardiovascular disease, but information on risks linked to different types of therapy during menopausal transition age is lacking.

To address this, researchers set out to assess the effect of contemporary menopausal hormone therapy on the risk of cardiovascular disease according to the route of administration and combination of hormones.

Their findings are based on data from 138 emulated trials (observational studies that mimic clinical trials), involving 919,614 healthy women in Sweden aged 50-58 between 2007 and 2020 who had not used hormone therapy in the previous two years. They excluded women with a history of heart disease, stroke, narrowed arteries, or cancer, and who had undergone surgery to remove their ovaries, a hysterectomy, or sterilisation.

Using monthly prescription records, the women were assigned to one of eight menopausal hormone treatment groups: oral combined continuous, oral combined sequential, oral unopposed oestrogen, oral oestrogen with local progestin, tibolone, transdermal combined, transdermal unopposed oestrogen, or no menopausal hormone therapy.

Hospital records were then used to track cardiovascular events over two years, and other potentially influential factors such as age, education level, region of residence, high blood pressure and diabetes were taken into account.

During this monitoring period, 24,089 cardiovascular events were recorded among the 919,614 women in the study.

Compared with not starting menopausal hormone therapy, starting oral combined continuous therapy or tibolone was associated with an increased risk of ischemic heart disease. This translates to approximately 11 new cases of ischaemic heart disease per 1,000 women who start treatment with oral combined continuous therapy or tibolone over one year.

No increased risk of cardiovascular disease was found for transdermal treatments, which include skin patches, gels and creams.

An increased risk of blood clots was also found for oral combined continuous, oral combined sequential, oral unopposed oestrogen, and transdermal combined therapy.

“If 1,000 women started each of these treatments and were observed for a year, we would expect to see seven new cases of venous thromboembolism across all groups,” say the authors.

Tibolone was also linked to an increased risk of stroke and heart attack, but not blood clots.

These are observational findings, so no firm conclusions can be drawn about causality, and the authors point to limitations including a lack of data on menopausal status and the possibility that other unmeasured factors, such as smoking and body mass index, may have affected their results.

However, by using an emulated target trial design they reduced the bias common to observational studies and use of registry data allowed them to distinguish between different types of hormone therapies, including differences in administration, regimens, and combinations of hormones.

The authors say: “These findings highlight the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease.”

Future research should investigate the potential various effects on the risk of cardiovascular disease based on different progestogens used in menopausal hormone therapy.

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ATW’s research round-up: new Alzheimer trigger identified, UK university targets longevity. fibre not protein?…and more

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A UK university will become one of the first in the country to make improving the health and well-being of the elderly one of its six ‘mission-led’ research priorities.

Bournemouth University’s choice to focus on pensioners is partly the result of the Labour Government’s wish for universities to specialise, whilst also reflecting the area’s demographics – the south-coast city has one of the one of the oldest populations in the world.

“Our demographics are much older than other places – about 10 years older on average compared to the rest of the UK,” explained Tom Wainwright, professor of orthopaedics at Bournemouth.

Vary your exercise

The university’s Orthopaedic Research Institute is already heavily involved in work with the surrounding area and its recently published study, in The Lancet, showed that over-65s with osteoarthritis who undertook group-based cycle classes enjoyed much better outcomes than those receiving one-to-one physiotherapy.

Research published in leading British doctors’ publication the BMJ Journal, which tracked 100,000 people over the last 30 years, has shown that mixed exercise routines can have a significant impact on overall health and longevity.

The study tracked the cohorts exercise habits over three decades and found that participants who engaged in the highest variety of exercises had a 19% lower risk of death, compared to those who engaged in the lowest variety.

Benefits were even bigger when looking at specific causes like heart disease, cancer, and respiratory illness, with risk reductions ranging from 13 to 41 percent.

“People naturally choose different activities over time based on their preferences and health conditions,” says Yang Hu, corresponding author and research scientist in the Harvard TH Chan Department of Nutrition.

“When deciding how to exercise, keep in mind that there may be extra health benefits to engaging in multiple types of physical activity, rather than relying on a single type alone.”

US researchers have identified over five dozen new potential blood-based metabolites which could predict a Type 2 diabetes risk, years in advance.

Key Alzheimer trigger identified

Scientists at Mass General Brigham and Albert Einstein College of Medicine, followed 23,634 participants for up to 26 years and over that time analysed 469 metabolites in blood samples, alongside additional genetic, diet and lifestyle data.

In doing so they identified 235 metabolites associated with higher or lower diabetes risk, including 67 new molecules previously unreported.

The researchers say their work supports a shift toward precision prevention strategies which are more reliable than current indicators such as BMI or family history.

Further research into the Alzheimer’s predicting APOE (apolipoprotein E) gene has left UK researchers with renewed conviction of their ability to develop preventive measures, earlier in life.

Researchers at University College London analysed nearly 470,000 people across four major studies, focusing on participants aged 60 and older with confirmed Alzheimer’s diagnoses and genetic data.

Whilst previous studies had identified the ε4 allele of APOE as the one most predictive of Alzheimer’s development the UCL researchers also highlighted how allele ε3 may also carry a significant risk

Dr Dylan Williams, the study’s lead author, explained that the APOE gene’s contribution to the prevalence of Alzheimer’s has been significantly underestimated for a long time, and that the ε3 allele has historically been misunderstood as having a neutral effect on risk.

He said: “Intervening on the APOE gene, or the molecular pathway between the gene and Alzheimer’s, could have huge potential for preventing or treating a large majority of cases.”

Fibre first

Researchers say that fibre – found in beans, lentils, chia seeds, oats, bran, and certain fruits – is emerging as the ‘new hero’ of nutrition science.

Longevity expert Dr Vassily Eliopoulos, MD, who trained at Cornell, highlights how protein has ruled diet trends for years, but says fibre is now stepping into the spotlight.

“Everyone’s chasing protein, but the next big longevity macro is fibre. And fibre might be the most under-appreciated longevity nutrient that you’re missing daily.”

Explaining why fibre plays such a crucial role, he highlights the connection between gut health and overall well-being.

“Here’s the secret, your gut microbes eat what you don’t digest. These microbes convert fibre into powerful compounds that protect the body. They turn fibre into short-chain fatty acids, which act as your body’s natural anti-inflammatory molecules,”

Dr Eliopoulos highlights how chronic inflammation is closely linked to ageing and disease and he recommends aiming for 30 to 40 grams of fibre a day.

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Assisted dying should be ‘gradually’ extended to dementia, author Ian McEwan says

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Author Ian McEwan said legalised assisted dying should be gradually extended to people with dementia.

Speaking at a public book event in London on 28 January, he criticised attempts to block the UK’s assisted dying bill, citing more than 1,000 amendments.

Supporters believe it is near impossible for it to pass the House of Lords before the end of the session in May due to alleged filibustering.

If passed, the bill would legalise assisted dying in England and Wales for adults with less than six months to live.

“I like it when some bishop says on the radio: ‘It’s the thin end of the wedge,’ and I think yes, it is the thin end of the wedge,” said McEwan, who is a patron of Dignity in Dying.

“Certain groups are missing from it, such as those with dementia. It has to be physical pain.

“My guess is that if we pushed it through with all the protections around it – of doctors and dispassionate people making judgements – we’ll look back on this and think, ‘Why did we ever let people die in agony?'”

Asked if he would add an amendment to extend assisted dying to dementia sufferers, McEwan said: “Gradually, yeah, I would. But I think it does require a lot more thought and the idea of living wills.”

“My mother used to say to me: ‘If I ever become really terrible, I’d like you to finish me off.’ But of course, that’s to commit murder as things stand. Imagine standing up in court and saying: ‘Well, she did say when we were on the beach 20 years ago…'”

McEwan spoke about dementia’s impact on his family.

His mother Rose had dementia, as well as his brother-in-law and another close family member.

“By the time my mother was well advanced and could not recognise anyone, she was dead. She was alive and dead all at once.

“It was a terrible thing. And the burden on those closest is also part of the radioactive damage of it all.”

McEwan was speaking at St Martin-in-the-Fields church in central London, as part of its Conversation series, discussing his latest book, What We Can Know, in which dementia is a major theme.

He has also written about dementia in previous novels, Lessons and Saturday.

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Study confirms gut inflammation link to Alzheimer’s

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New research links gut inflammation to Alzheimer’s, with higher levels associated with more amyloid plaque in the brain.

Animal studies have shown Alzheimer’s can be passed to young mice through gut microbe transfer, strengthening the link between the gut and the brain.

A 2023 study adds support to inflammation as a possible mechanism.

Barbara Bendlin, psychologist at the University of Wisconsin, said: “We showed people with Alzheimer’s disease have more gut inflammation, and among people with Alzheimer’s, when we looked at brain imaging, those with higher gut inflammation had higher levels of amyloid plaque accumulation in their brains.”

Margo Heston, pathologist at the University of Wisconsin, and an international team tested faecal calprotectin, a marker of gut inflammation, in stool samples from 125 individuals in two Alzheimer’s prevention cohorts.

Participants completed cognitive tests at enrolment, family history interviews and testing for a high-risk Alzheimer’s gene. Amyloid plaques are abnormal protein clumps in the brain that signal disease processes.

A subset of participants took clinical tests for signs of amyloid protein clumps.

Whilst calprotectin levels were generally higher in older participants, they were even more pronounced in those with Alzheimer’s-characteristic amyloid plaques.

Levels of other Alzheimer’s biomarkers also rose with inflammation, and memory scores fell as calprotectin increased. Even participants without an Alzheimer’s diagnosis recorded poorer memory with higher calprotectin.

Heston said: “We can’t infer causality from this study; for that, we need to do animal studies.”

Laboratory analyses have shown gut-bacteria chemicals can stimulate inflammatory signals in the brain. Other studies have reported increased gut inflammation in patients with Alzheimer’s compared with controls.

The researchers suspect microbiome shifts trigger gut changes that lead to mild but chronic, system-wide inflammation, gradually weakening the body’s protective barriers.

Federico Rey, bacteriologist at the University of Wisconsin, said: “Increased gut permeability could result in higher blood levels of inflammatory molecules and toxins derived from gut lumen, leading to systemic inflammation, which in turn may impair the blood-brain barrier and may promote neuroinflammation, and potentially neural injury and neurodegeneration.”

The team is now testing whether diet-induced inflammation in mice can trigger the rodent version of Alzheimer’s.

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