Day: May 27, 2025

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags : Leave a comment

Does Hormone Therapy Improve Heart Health in Menopausal Women?

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Photo by Teona Swift on Unsplash

Deciding whether to start hormone therapy during the menopause transition, the life phase that’s the bookend to puberty and when a woman’s menstrual cycle stops, is a hotly debated topic. While hormone therapy is recommended to manage bothersome symptoms like hot flashes and night sweats, Matthew Nudy, assistant professor of medicine at the Penn State College of Medicine, said there’s confusion about the long-term effects of hormone therapy, especially on cardiovascular health.

However, long-term use of oestrogen-based hormone therapies may have beneficial effects on heart health, according to a new study led by Nudy. A multi-institutional team analysed data from hormone therapy clinical trials that were part of the Women’s Health Initiative (WHI), a long-term national study focused on menopausal women, and found that oestrogen-based hormone therapy improved biomarkers associated with cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attack and stroke.

Their findings were published in the journal Obstetrics & Gynecology.

“The pendulum has been swinging back and forth as to whether hormone therapy is safe for menopausal women, especially from a cardiovascular disease perspective,” Nudy said. “More recently, we’re recognising that hormone therapy is safe in younger menopausal women within 10 years of menopause onset, who are generally healthy and who have no known cardiovascular disease.”

The hormonal changes that accompany menopause come with an increased risk of cardiovascular disease. The decline in the oestrogen can lead to changes in cholesterol, blood pressure and plaque buildup in blood vessels, which increase the risk of heart attack and stroke.

The research team was interested in understanding the long-term effect of hormone therapy on cardiovascular biomarkers, which hasn’t been evaluated over an extended period of time. Prior research in the field primarily looked at short-term effects.

Here, the team analysed biomarkers associated with cardiovascular health over a six-year period from a subset of women who had participated in an oral hormone therapy clinical trial that was part of the WHI. Post-menopausal participants aged 50 to 79 were randomly assigned to one of two groups, an oestrogen-only group and an oestrogen plus progesterone group. They provided blood samples at baseline and at the one-, three- and six-years marks. In total, they analysed samples from 2696 women, approximately 10% of the total trial participants.

The research team found that hormone therapy had a beneficial effect on most biomarkers in both the oestrogen-only and the oestrogen-plus-progesterone groups over time. Levels of LDL cholesterol, the so-called “bad” cholesterol, were reduced by approximately 11% while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% and 7% for the oestrogen-only and oestrogen-and-progesterone groups, respectively.

However, triglycerides and coagulation factors, proteins in the blood that help form blood clots, increased.

The decrease in lipoprotein(a) concentration was more pronounced among participants with American Indian or Alaska Native ancestry or Asian or Pacific Islander ancestry, by 41% and 38%, respectively. The reason why was unclear, Nudy said.

More surprising to the research team, they said, levels of lipoprotein(a), a type of cholesterol molecule, decreased 15% and 20% in the oestrogen-only and the oestrogen-plus-progesterone groups, respectively. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, concentrations of lipoprotein(a) are thought to be determined primarily by genetics, Nudy explained. Patients with a high lipoprotein(a) concentration have an increased risk of heart attack and stroke, especially at a younger age. There’s also an increased risk of aortic stenosis, where calcium builds up on a heart valve.

“As a cardiologist, this finding is the most interesting aspect of this research,” Nudy said. “Currently, there are no medications approved by the Food and Drug Administration (FDA) to lower lipoprotein(a). Here, we essentially found that oral hormone therapy significantly reduced lipoprotein(a) concentrations over the long-term.”

Nudy noted that the oestrogen therapy the women received in the clinical trial was conjugated equine oestrogens, a commonly prescribed form of oral oestrogen therapy. Before being absorbed by the body, oral hormone therapy is processed in the liver, through a process called first-pass metabolism. That process could increase inflammatory markers, which may explain the rise in triglycerides and coagulation factors.

“There are now other common formulations of oestrogen hormone therapy like transdermal oestrogen, which is administered through the skin,” Nudy said. “Newer studies have found that transdermal oestrogen doesn’t increase triglycerides, coagulation factors or inflammatory markers.”

For those considering menopause hormone therapy, Nudy recommended undergoing a cardiovascular disease risk assessment, even if the person hasn’t had a previous heart attack or stroke or hasn’t been diagnosed with cardiovascular disease. It will give health care providers more information when considering the best option to treat menopause symptoms.

“Currently, hormone therapy is not FDA-approved to reduce the risk of coronary artery disease or stroke,” Nudy said. 

Source: Penn State

Categories : Immune SystemTags : Leave a comment

Daytime Gives a Boost to the Immune System, Scientists Find

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Photo by Julian Jagtenberg on Pexels

A breakthrough study, led by scientists at Waipapa Taumata Rau, University of Auckland, has uncovered how daylight can boost the immune system’s ability to fight infections.

The circadian clock is a 2.5-billion-year-old cellular timekeeper that allows organisms to adapt to the rhythms of day and night. Evidence has shown that disruption of our internal body clock through the likes of shift work or jet lag makes people more susceptible to infections, so the researchers wanted to find out what in the body contributed to that susceptibility.

“In earlier studies, we had observed that immune responses to infection peaked in the morning, during the animals’ early active phase,” says lead researcher Associate Professor Christopher Hall, from the Department of Molecular Medicine and Pathology.

“We think this represents an evolutionary response such that during daylight hours the host is more active so more likely to encounter bacterial infections,” says Hall.

However, the scientists wanted to find out how the immune response was being synchronised with daylight.

They focused on ‘neutrophils’ the most abundant immune cells in our bodies. These cells move quickly to the site of an infection and kill invading bacteria.

The scientists used zebrafish, a small freshwater fish, as a model organism, because its genetic make-up is similar to ours and they can be bred to have transparent bodies, making it easy to observe biological processes in real time.

With this new study, published in Science Immunology, neutrophils were found to possess a circadian clock that alerted them to daytime, and boosted their ability to kill bacteria.

Circadian clocks are present in almost every cell and tissue in the body, telling them what is going on in the outside world and coordinating physiological processes like metabolism, hormone release, and sleep-wake cycles.

Light has the biggest influence on resetting these circadian clocks.

“Given that neutrophils are the first immune cells to be recruited to sites of inflammation, our discovery has very broad implications for therapeutic benefit in many inflammatory diseases,” Hall says.

“This finding paves the way for development of drugs that target the circadian clock in neutrophils to boost their ability to fight infections.”

Source: University of Auckland

Categories : Cardiovascular DiseaseTags : Leave a comment

New Factor Linked to Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

People with type 2 diabetes (DM2) are at increased risk of developing heart failure due to the presence of prominent risk factors (hypertension, obesity, coronary heart disease, etc).

Now, a study published in the journal Cellular and Molecular Life Sciences has identified a new factor linked to the development of pathological hypertrophy. The results of the study suggest that increasing the activity of the GADD45A protein could be a promising therapeutic strategy to slow the progression of this clinical condition.

A factor with a prominent role in cardiac function

The GADD45A (growth arrest and DNA damage inducible 45A) protein is a multifunctional factor associated with stress signalling and cell damage. In this study, the team assessed the role of GADD45A in cardiac function using animal models and human cardiac cells.

The main mechanisms involved in pathological hypertrophy include inflammatory processes, fibrosis, mitochondrial dysfunction, dysregulation of calcium-handling proteins, metabolic alterations, cardiomyocyte hypertrophy and cell death. Fibrosis and inflammation are key factors in the progression of this pathological cardiac hypertrophy and subsequent heart failure.

“Fibrosis, in particular, correlates directly with the development of the disease and with adverse clinical outcomes, and has a major impact on the clinical condition of the patient”, says study leader Professor Manuel Vázquez-Carrera.

The results reveal that the lack of GADD45A factor in mice triggers cardiac fibrosis, inflammation and apoptosis. These changes correlate with hyperactivation of the proinflammatory and profibrotic transcription factors AP-1 (activator protein-1), NF-κB (nuclear factor-κB) and STAT3 (signal transducer and activator of transcription 3).

According to the findings, deletion of GADD45A also caused substantial cardiac hypertrophy that negatively affected cardiac morphology and function in mice lacking this protein. Furthermore, overexpression of GADD45A in human AC16 cardiomyocytes partially prevented the inflammatory and fibrotic response induced by tumour necrosis factor-alpha (TNF-α).

“Taken together, the data presented in this study highlight an important role for GADD45A protein in the heart, as it may prevent inflammation, fibrosis and apoptosis and thus preserve cardiac function”, says Associate Professor Xavier Palomer, who also led the study.

This paper expands our knowledge of the action mechanisms of GADD45A in the body. To date, previous studies have identified the role as a tumour suppressor in cancer development, as well as its involvement in the regulation of catabolic and anabolic metabolic pathways and in the prevention of inflammation, fibrosis and oxidative stress in some tissues and organs. Finally, some studies have indicated that the modulation of GADD45A could be a suitable therapeutic strategy to prevent obesity and diabetes.​​​​​

Source: University of Barcelona

Categories : Surgeries & Procedures UrogenitalTags : Leave a comment

Surgeons Perform World-first Bladder Transplant

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A UCLA Health surgical team has performed the first-in-human bladder transplant. 

The surgery was successfully completed at Ronald Reagan UCLA Medical Center on May 4, 2025. The team was led by Dr Nima Nassiri, a urologic transplant surgeon and director of the UCLA Vascularized Composite Bladder Allograft Transplant Program, with assistance from Dr Inderbir Gill, founding executive director of USC Urology.

“Bladder transplantation has been Dr Nassiri’s principal academic focus since we recruited him to the UCLA faculty several years ago,” said Dr Mark Litwin, UCLA Urology Chair, “It is incredibly gratifying to see him take this work from the laboratory to human patients at UCLA, which operates the busiest and most successful solid-organ transplant program in the western United States.”

“This first attempt at bladder transplantation has been over four years in the making,” Nassiri said. “For the appropriately selected patient, it is exciting to be able to offer a new potential option.” 

The patient had lost most of his bladder during a tumour removal, leaving the remainder too small and compromised to work. Both of his kidneys were also subsequently removed due to renal cancer in the setting of pre-existing end-stage kidney disease. As a result, he was on dialysis for seven years. 

The biggest risks of organ transplantation are the body’s potential rejection of the organ and side-effects caused by the mandatory immune suppressing drugs given to prevent organ rejection.

“Because of the need for long-term immunosuppression, the best current candidates are those who are already either on immunosuppression or have an imminent need for it,” Nassiri said. 

Nassiri and Gill collaborated for several years to develop the surgical technique. Numerous pre-clinical procedures were performed at USC and OneLegacy, Southern California’s organ procurement organisation, to prepare for the first human bladder transplant. 

During the complex procedure, the surgeons transplanted the donated kidney, following that with the bladder. The new kidney was then connected to the new bladder using the technique that Nassiri and Gill pioneered. The entire procedure lasted approximately eight hours. 

“The kidney immediately made a large volume of urine, and the patient’s kidney function improved immediately,” Nassiri said. “There was no need for any dialysis after surgery, and the urine drained properly into the new bladder.”

Current treatment for severe terminal cases of bladder dysfunction or a bladder that has been removed due to various conditions includes replacement or augmentation of the urinary reservoir. These surgeries use a portion of a patient’s intestine to create a new bladder or a pathway for the urine to exit the body. 

While these surgeries can be effective, they come with many short-and long-term risks that compromise a patient’s health such as internal bleeding, bacterial infection and digestive issues.

“A bladder transplant, on the other hand, results in a more normal urinary reservoir, and may circumvent some short- and long-term issues associated with using the intestine,” Nassiri said.

As a first-in-human attempt, there are naturally many unknowns associated with the procedure, such as how well the transplanted bladder will function immediately and over time, and how much immunosuppression will ultimately be needed. 

Bladder transplants have not been done previously, in part because of the complicated vascular structure of the pelvic area and the technical complexity of the procedure. As part of the research and development stage, Nassiri and Gill successfully completed numerous practice transplantation surgeries at Keck Medical Center of USC, including the first-ever robotic bladder retrievals and successful robotic transplantations in five recently deceased donors with cardiac function maintained on ventilator support.

The two surgeons also undertook several non-robotic trial runs of bladder recovery at OneLegacy, allowing them to perfect the technique while working closely with multi-disciplinary surgical teams. 

The bladder is strictly within the domain of urologists. At UCLA, kidney transplantation is also housed within the department of urology. This is why the combined kidney and bladder transplant was ultimately performed at UCLA, which has the necessary infrastructure, clinical expertise, and multidisciplinary support to carry out the procedure and manage the patient from pre-transplant evaluation through post-transplant care, all within the one department.

The procedure was performed as part of a UCLA clinical trial. Nassiri hopes to perform more bladder transplants in the near future. 

UCLA Urology has long been at the frontier of urologic transplantation, with pioneering research in kidney transplantation and now, bladder transplantation. 

Source: UCLA Health

Categories : Cardiovascular Disease Metabolic DisordersTags : Leave a comment

Adult-onset Type 1 Diabetes Increases Cardiovascular Risk, Especially in 40s and Older

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Source: Pixabay CC0

A new study in the European Heart Journal shows that people who develop type 1 diabetes in adulthood have an increased risk of cardiovascular disease and death, and that those diagnosed later in life do not have a better prognosis than those diagnosed earlier. The study, conducted by researchers at Karolinska Institutet, points to modifiable factors – smoking, poor glucose control and obesity – as the main risk factors.

Type 1 diabetes used to be called childhood diabetes but can start at any time during life – a situation for which there is limited research. The researchers behind the current study wanted to investigate the risk of cardiovascular disease and death in this group, particularly for those diagnosed after the age of 40.

The registry-based study identified 10 184 people diagnosed with type 1 diabetes in adulthood between 2001 and 2020 and compared them to 509 172 matched people in the control group.

The study shows that these people with adult-onset type 1 diabetes had a higher risk of cardiovascular disease and death from all causes, including cancer and infections, compared to the control group.

“The main reasons for the poor prognosis are smoking, overweight/obesity and poor glucose control. We found that they were less likely to use assistive devices, such as insulin pumps,” says first author Yuxia Wei, postdoctoral fellow at the Institute of Environmental Medicine, Karolinska Institutet.

The prognosis can be improved 

The results emphasise the seriousness of type 1 diabetes, even when it starts later in life, the researchers say. But the prognosis can improved by avoiding smoking and obesity, especially for those diagnosed later in life.

The researchers plan to continue investigating adult-onset type 1 diabetes, including risk factors for developing the disease and the prognosis of other outcomes, such as microvascular complications. Optimal treatment in adult-onset type 1 diabetes, including the effect of pump use and other advanced technologies, also needs to be explored.

Source: Karolinska Institutet