Wood Street Clinic Blog

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Gender transition drugs could be bad for the heart

New research now published in the journal Circulation finds that some people who are gender transitioning may be at a higher risk of experiencing cardiovascular conditions due to the hormone therapy they are receiving.
gender fluid person having coffee
Some drugs required for gender transition may increase cardiovascular risk.

Previous studies have revealed that hormone therapy raises cardiovascular risk.

For instance, according to estimates from the National Institutes of Health (NIH), therapy with estrogen and progestin puts menopausal women at:

a 41 percent higher risk of stroke a 29 percent higher risk of a heart attack a 100 percent higher risk of blood clots

Estrogen alone increases stroke risk by 39 percent and blood clot risk by 47 percent, according to the same NIH estimates.

However, how does hormone therapy affect people who are gender transitioning? So far, scientists have not addressed this question fully, so a new study aimed to fill this gap in research.

Dr. Nienke Nota — a researcher in the Department of Endocrinology at the Amsterdam University Medical Center in the Netherlands — and her team examined the medical records of 3,875 Dutch transgender people who had hormone therapy between 1972 and 2015.

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Their study examined 2,517 transgender women and 1,358 transgender men. The women were 30 years old, on average, and they had received estrogen either alone or in combination with androgen suppressors.

The men were 23 years old, on average, and they received testosterone therapy as a part of their gender transition.

Dr. Nota and her colleagues clinically followed the trans women for an average period of 9 years and the trans men for an average of 8 years after they started hormone therapy.

The researchers examined the incidence of cardiovascular problems such as heart attacks, strokes, and blood clots among transgender people and compared it with the incidence of such events in cis men and cis women.

Cis people are those whose gender identity matches the biological sex assigned to them at birth.

The study found that trans women were more than twice as likely to have a stroke as cis women and almost twice as likely to have a stroke as cis men.

Trans women were also five times and 4.5 times more likely to develop blood clots than cis women and cis men, respectively.

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Trans women also had heart attacks more than twice as often as cis women, and trans men were over three times more likely to have a heart attack than cis women.

Dr. Nota comments on the findings, saying, "In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk."

"It may be helpful to reduce risk factors by stopping smoking, exercising, eating a health[ful] diet and losing weight, if needed before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter."

Dr. Nienke Nota

The authors caution that their analysis did not account for modifiable risk factors such as smoking, stress, diet, and exercise.

However, they say that hormone therapy may be largely to blame for the increased cardiovascular risk.

Specifically, estrogen promotes blood clotting, and testosterone could do the same by raising the concentration of red blood cells and increasing the levels of bad cholesterol, they explain.

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Marijuana may be risky for those with heart disease

Although marijuana may have some benefits, its use could cause health issues for older people with cardiovascular disease. One case, in particular, is sparking some questions.
Marijuana in hand
Marijuana in edible form may have cardiovascular risks for people at risk.

In recent years, the legalization of marijuana has become more widespread.

Some people use the drug recreationally, while some use it to relieve chronic pain and the impact of some mental health issues.

However, experts state that there needs to be more research into the effects of marijuana in older people.

Specifically, the scientific community needs to focus on educating the public on aspects such as potential effects and recommended dosages.

A Canadian Journal of Cardiology case report goes some way toward that. It examined a 70-year-old man who had a heart attack after eating a lollipop that was infused with 90 milligrams (mg) of tetrahydrocannabinol (THC) — which is largely responsible for marijuana's psychological effects.

The man lived with stable coronary artery disease, and he was taking cardiac medication. He ate most of the lollipop and did so to help minimize pain and improve sleep.

Dr. Alexandra Saunders — who works in Horizon Health Network's Department of Cardiology in New Brunswick, Canada — described the man's 90-mg dose as "inappropriate."

Smoking a typical joint would expose a person to just 7 mg of THC, while a starting dose of a synthetic THC called dronabinol is only 2.5 mg. People with AIDS or cancer tend to use this version, and it can also combat nausea and encourage appetite.

"Marijuana can be a useful tool for many patients, especially for pain and nausea relief. At the same time, like all other medications, it does carry risk and side effects."

Dr. Alexandra Saunders

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A cardiovascular link

The large amount of THC the man consumed caused him to experience anxiety and hallucinations. The strain that these effects put on his body is what likely caused his heart attack, by triggering a response in the sympathetic nervous sytem.

His cardiac event was demonstrated by a rapid heart rate, an abnormally high blood pressure, and the release of the stress hormone catecholamine. The man's chest pain went away as soon as the effects of the marijuana had worn off.

Previously, there had been reports of similar incidences showing a relationship between cannabis consumption and acute cardiovascular adverse events. These have ranged from an irregular heartbeat to stroke, and even sudden death.

However, Dr. Robert S. Stevenson — who also works at Horizon Health Network's Department of Cardiology — says, "Most previous research on marijuana-induced myocardial ischemia focused mostly on younger patients and did not focus on its different formulations and potencies."

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A word of warning

The doctors examining the most recent case have issued advice, particularly for older people who use marijuana.

They advise people to use the smallest dose possible for their chosen benefit. Anyone who has a cardiovascular condition or is at high risk of developing one should steer clear of THC. Instead, they can try cannabidiol, which is a nonpsychoactive alternative.

They should also take factors such as tolerance and consumption method into consideration. For example, a person who has smoked marijuana over a long period of time is likely to experience fewer distressing side effects than someone who is not used to the drug.

Similarly, eating a THC-infused brownie or lollipop would expose a person to more THC than if they had used a vaporizer.

With further decriminalization, it is hoped that scientists will work on conducting more research into the potential side effects of marijuana. For now, educating the public — especially aging members — should be a priority.

"For better or worse," concludes Dr. Neal L. Benowitz, chief of the Division of Clinical Pharmacology and Experimental Therapeutics at the University of California, "providing advice and care to such patients who are using cannabis is now necessary for the provision of optimal medical care to these patients."

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Exercise boosts well-being by improving gut health

Both bacterial diversity in the gut and regular exercise are important when it comes to health. But how are the two related? A new study uncovers the effect that exercise has on our health by adjusting the balance of the gut microbiome.
women at the gym
New research finds out how exercise could support bacterial diversity in the gut.

Though this may seem strange, human bodies are actually made, according to recent estimates, of about as many bacteria and other microorganisms as regular human cells.

In the colon alone — the tract that contains the largest number of bacterial cells — there are approximately 38 trillion bacteria.

These bacteria have important effects on the state of our health, and loss of bacterial diversity in the gut is linked to a heightened risk of disease.

Now, a new study suggests that the level of a person's physical activity may affect the bacterial diversity in their gut, and thus influence their health.

In a paper that appears in the journal Experimental Physiology, the authors, from Indiana University Bloomington and the University of Alabama at Birmingham, also explain the biological mechanism that makes this possible.

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The link between exercise and the gut

The researchers knew that cardiorespiratory fitness — the efficiency with which the circulatory and respiratory systems deliver oxygen during exercise — was associated with greater bacterial diversity, but it was unclear whether this was due to physical activity or an individual's percentage of body fat.

In order to find out, the team worked with a cohort of 37 participants who had been successfully treated for nonmetastatic breast cancer.

The decision to work with this cohort resulted from the fact that cancer treatment typically has a negative impact on metabolic health, including cardiorespiratory fitness.

The participants agreed to perform graded exercises so that the researchers could assess their peak cardiorespiratory fitness, as well as total energy expenditure. The investigators also collected fecal samples from the volunteers and used them to analyze the participants' gut microbiota.

Following all the assessments and analyses, the researchers established that participants with higher cardiorespiratory fitness also had more diverse bacterial populations in the gut, compared with peers who had low cardiorespiratory fitness.

Moreover, the team confirmed that cardiorespiratory fitness was linked with about a quarter of the variance in bacterial species diversity and that this effect was independent of that produced by an individual's body fat percentage.

The data thus indicate that exercising with an intensity that is adequately high and can boost cardiorespiratory effectiveness will improve overall health by supporting a better-balanced gut.

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New line of research

Still, the researchers warn that their findings are only correlative, and further research should aim to test the potential causational relationships.

Furthermore, the cohort was very restricted — a small group of women treated for breast cancer — so the team advises caution in applying the findings to other populations.

However, going forward, the investigators aim to address these shortcomings and find out how best to apply their findings to improve the health of at-risk individuals.

"Our group is actively pursuing an interventional study to determine how variation in exercise intensity can influence gut microbiota diversity under controlled-feeding conditions," says the study's lead author, Stephen Carter, Ph.D.

"[The aim is] to uncover how exercise may affect functional outcomes of gut microbiota, as well as studying how exercise prescription may be optimized to enhance health outcomes among clinical populations."

Lead author Stephen Carter, Ph.D.

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Diet drinks linked to a higher risk of stroke after the menopause

Fresh research offers further information on the potential for diet drinks — that is, beverages sweetened with artificial sugar substitutes — to harm cardiovascular health.
senior woman drinking coke
Artificially sweetened soft drinks may raise the risk of heart disease and death in postmenopausal women.

A study that followed tens of thousands of postmenopausal women for more than 10 years has linked a higher consumption of diet drinks to an increased risk of stroke, heart disease, and death.

The link between diet drinks and stroke was strongest for strokes that arise from blocked arteries, and from smaller blood vessels in particular.

The journal Stroke has now published a paper about the analysis. The lead author is Dr. Yasmin Mossavar-Rahmani, an associate professor of clinical epidemiology and population health in the Albert Einstein College of Medicine in the Bronx, NY.

Dr. Mossavar-Rahmani and her team point out that the findings do not prove that diet drinks harm the heart and circulation system. That is because the study was an observational one, and the figures on diet drink consumption came from self-reports.

However, Rachel K. Johnson — who chaired the panel that wrote the science advisory from the American Heart Association (AHA) about diet drinks and heart health — comments, "This study adds to the evidence that limiting use of diet beverages is the most prudent thing to do for your health."

Experts commenting in an editorial that accompanies the new study paper also suggest that until there is sufficient evidence regarding who might benefit from consuming diet drinks, the emphasis should be on drinking water as the most healthful no-calorie drink.

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Diet drinks and cardiovascular risks

The data for this study came from a racially diverse group of 81,714 postmenopausal women in the Women's Health Initiative Observational Study.

The women were all aged 50–79 years when they enrolled during 1993–1998. The study then tracked their health with regular evaluations for an average of 11.9 years afterward.

At the 3-year evaluation point, the women answered some questions regarding how often they had consumed diet drinks in the previous 3 months.

The researchers defined diet drinks as any low-calorie colas, soda, and fruit drinks sweetened with artificial sugar substitutes.

They did not ask the women to specify the which artificial sweeteners the drinks contained.

When they analyzed the data, they adjusted the results to eliminate the effect of other factors that influence stroke risk, such as age, smoking, and high blood pressure.

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The researchers found that compared with consuming fewer than one diet drink per week or none at all, consuming two or more per day was associated with:

a 23 percent raised risk of stroke a 31 percent higher risk of a stroke that results from a clot a 29 percent higher risk of heart disease, as in a fatal or nonfatal heart attack a 16 percent raised risk of death from any cause

They also revealed that a high intake of diet drinks among postmenopausal women with no history of heart disease or diabetes was linked to a more than twofold raised risk of strokes arising from blockages in small arteries in the brain.

Postmenopausal women with obesity who drank two or more diet drinks each day also had twice the risk of stroke than those who drank fewer than one per week.

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'Limit prolonged use of diet drinks'

Because they confined the study to postmenopausal women, the researchers cannot say whether the same would be true for men, or for women before the menopause. It is now up to further studies to determine this.

Also, because the data did not specify which artificial sweeteners the women had consumed, Dr. Mossavar-Rahmani says that the scientists could not distinguish the potentially harmful from the potentially harmless.

"Our research and other observational studies have shown that artificially sweetened beverages may not be harmless and high consumption is associated with a higher risk of stroke and heart disease."

Dr. Yasmin Mossavar-Rahmani

While the AHA advise that people drink water as their preferred no-calorie drink, they acknowledge that diet drinks might help them move away from sugar-sweetened beverages.

However, Dr. Johnson cautions, "Since long-term clinical trial data are not available on the effects of low-calorie sweetened drinks and cardiovascular health, given their lack of nutritional value, it may be prudent to limit their prolonged use."

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Study finds new cognitive decline mechanism in Alzheimer's

People with Alzheimer's disease experience poor blood flow to the brain, which affects cognitive function. A new study conducted in a mouse model has finally uncovered the reason behind this reduced blood flow.
elderly woman
Reduced blood flow to the brain contributes to Alzheimer's, but what mechanism leads to this vascular problem in the first place?

For a while now, researchers have been aware that Alzheimer's disease goes hand in hand with vascular dysfunction, and reduced blood flow to the brain, in particular.

However, it is only recently that investigators have begun to focus their efforts on understanding just how and why poor vascular health can contribute to cognitive decline in this type of dementia.

A study published last month in Alzheimer's and Dementia, the journal of the Alzheimer's Association, calls vascular dysfunction "the disregarded partner of Alzheimer's disease." It argues that researchers must first fully understand all the factors involved in the pathology of this type of dementia before they can develop a pluripotent treatment for it.

"Individualized, targeted therapies for [Alzheimer's disease] patients will be successful when the complexity of [this condition's] pathophysiology is fully appreciated," the study authors write.

Now, in a study in mice, a team of investigators from Cornell University in Ithaca, NY has identified a mechanism — tied to poor blood flow to the brain — that directly contributes to cognitive decline.

The study paper detailing the researchers' findings appears in the journal Nature Neuroscience.

In its introduction, the authors explain that "[v]ascular dysfunction is implicated in the pathogenesis of Alzheimer's disease," and that "[b]rain blood flow is also severely compromised; cortical cerebral blood flow reductions of [approximately] 25 percent are evident early in disease development in both patients with Alzheimer's disease, and in mouse models."

"People probably adapt to the decreased blood flow, so that they don't feel dizzy all of the time, but there's clear evidence that it impacts cognitive function," notes study author Chris Schaffer.

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Researchers find cellular mechanism

According to the researchers, the reduction of blood flow to the brain immediately impairs cognitive function — including attention — when it happens in otherwise healthy humans. In their mouse study, the investigators wanted to find out why this poor blood flow occurs in the first place.

In a past study, co-author Nozomi Nishimura had tried to induce clotting in the brain blood vessels of mouse models to see how that would affect their cognitive abilities. However, Nishimura and team soon found that the vascular problems were already present in rodent models of Alzheimer's pathology.

"It turns out that [...] the blockages we were trying to induce were already in there," she said. "It sort of turned the research around — this is a phenomenon that was already happening," says Nishimura.

The new research revealed that white blood cells — called neutrophils — get stuck inside brain capillaries, which are minuscule blood vessels that usually carry oxygenated blood to this organ. Although few capillaries become clogged in this way, this means that blood flow to the brain decreases considerably.

"What we've done is identify the cellular mechanism that causes reduced brain blood flow in Alzheimer's disease models, which is neutrophils [white blood cells] sticking in capillaries," says Schaffer.

"We've shown that when we block the cellular mechanism [that causes the clogging], we get an improved blood flow, and associated with that improved blood flow is immediate restoration of cognitive performance of spatial- and working-memory tasks."

Chris Schaffer

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'A complete game-changer?'

The researchers add that these findings provide a new potential clinical target for Alzheimer's disease. As Schaffer also notes, "Now that we know the cellular mechanism, it's a much narrower path to identify the drug or the therapeutic approach to treat it."

In fact, the researchers have already identified about 20 different drugs — a good number of which the Food and Drug Administration (FDA) have already approved — that they believe could address this new target. Right now, the investigators are testing these drugs in mouse models.

Though the team acknowledges that further research is necessary in order to ascertain that the same cellular mechanism seen in mice is also present in people with Alzheimer's, its members are happy about their current findings.

Schaffer has even gone so far as to declare himself "super-optimistic" that, in the future, research stemming from these findings "could be a complete game-changer for people with Alzheimer's disease."

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