Category: Cardiovascular Disease

Categories : Cardiovascular Disease Emergency MedicineTags : Leave a comment

Closing the Gap Between Suspecting a Heart Attack and Confirming it

On By ModernMedia

A highly sensitive cardiac test brings traditional lab diagnostics to the field, when it’s most needed

Illustration of a portable cardiac troponin I testing system that wirelessly transmits results to a smartphone.Credit: AI-generated image

A person having a heart attack may be only feet from medical care but miles from the laboratory testing needed to confirm it. That gap matters, especially for rural patients, those in nursing homes, ambulances and other places where access to specialised diagnostics is limited.

In a paper published in Biosensors and Bioelectronics, an international team of researchers details a highly sensitive test designed to bring that molecular evidence closer to the patient.

“A heart attack doesn’t wait for laboratory results,” said lead author Sayantan Tripathy, assistant research scientist in Texas A&M University’s Optical and Bio-Sensing Laboratory in the College of Engineering. “By reducing the time needed to detect heart muscle damage, we’re helping clinicians move more quickly from uncertainty to action, not only in hospitals, but also in ambulatory and resource-constrained settings where rapid diagnostic tools are often unavailable.”

Clinicians may suspect a heart attack based on symptoms or an electrocardiogram, but confirming heart muscle damage has occurred often requires testing for cardiac troponin I, a protein released into the bloodstream when the heart is injured. The most sensitive versions of those tests typically rely on centralised laboratory equipment, creating a potentially dangerous delay between suspicion and certainty.

“Our goal is for emergency medical technicians in an ambulance to be able to take someone’s fingertip sample – just a small finger prick – put that sample into a cartridge that contains all of our components, plug this cartridge into our device, and then be able to run the test in five minutes,” said Dr Samuel Mabbott, associate professor of biomedical engineering and study co-author.

Faster heart attack diagnosis

Many of today’s troponin tests depend on expensive laboratory instruments and trained personnel. As a result, obtaining the information needed to confirm a heart attack can take time, especially when advanced laboratory resources are not immediately available.

“Our vision is to bring affordable and sensitive advanced molecular diagnostics closer to where care is delivered,” said Dr Gerard Coté, professor of biomedical engineering and director of Texas A&M’s Center for Remote Health Technologies and Systems. “The less distance between the patient and the information clinicians need, the faster critical decisions can be made.”

To create the test, the researchers designed a specific structured DNA molecule that remains inactive until it encounters cardiac troponin I. Once it detects the biomarker, it triggers a series of molecular reactions that amplify the signal, making it easier to detect even very small amounts of heart damage. The amplified signal is then measured using portable optical sensing technology.

The researchers say the technology requires additional development before it could be used in clinical practice. The original work takes approximately two hours to complete, but the current version of the technology has reduced the testing time to less than 25 minutes, and further work is underway to shorten it to under 15 minutes, improving its user applicability.

Still, the study points toward a future in which life-saving diagnostic information is no longer tied to a centralized laboratory and can instead move closer to the patients who need it most.

Source: Texas A&M University

Categories : Cardiovascular Disease Diseases, Syndromes and ConditionsTags : Leave a comment

Somatic Mutations Linked to Vascular Damage in Progeria

On By ModernMedia
Angiogenesis. Credit: Scientific Animations CC BY-4.0

In the rare disease progeria, blood vessels deteriorate prematurely. A study from Karolinska Institutet shows how different cell types in the vascular wall undergo progressive changes and accumulate mutations over time. The findings are published in the journal Genome Medicine.

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder that causes remarkable premature ageing. Most patients die during their teenage years from cardiovascular disease, but the precise mechanisms underlying vascular damage remain unclear.

In the new study, researchers analysed cells from the aorta of mice carrying the same genetic mutation found in people with progeria. Using single-cell RNA sequencing, which enables gene activity to be studied in individual cells, they tracked how the vascular wall changes over time. In total, nearly 9000 cells from mice of different ages were analysed.

“This approach allows us to follow, step by step, how different cell types are affected throughout the course of the disease,” says Maria Eriksson, professor at the Department of Medicine, Huddinge, Karolinska Institutet.

Reduced numbers of smooth muscle cells

The researchers focused particularly on vascular smooth muscle cells, which provide blood vessels with strength and elasticity and are essential for normal vascular function. They observed that these cells gradually declined in number.

“Smooth muscle cells are progressively lost both in HGPS and during normal ageing. As these cells die, the vessel wall becomes weaker and more susceptible to disease,” says Lara Garcia Merino, doctoral student at the same department and first author of the study.

The study also showed that smooth muscle cells accumulated higher numbers of so-called somatic mutations, meaning genetic alterations that arise during an individual’s lifetime. The mutation burden was associated with increased cellular stress and activation of genes involved in DNA damage responses.

“This is the first evidence that the accumulation of somatic mutations is a hallmark of vascular disease in HGPS,” says Maria Eriksson.

Reveals a new mechanism

The findings link DNA damage to cellular stress, loss of cellular identity and cell death, thereby revealing a previously unrecognised mechanism driving irreversible vascular injury.

The researchers also found evidence that changes in cell behaviour may be influenced by signalling between different cell types within the vessel wall, suggesting that the process is not driven solely by alterations within individual cells.

“We see that cells undergo multiple changes over time, from stress to identity changes and ultimately cell death. Our results suggest that several different mechanisms interact in the development of vascular damage in progeria,” says Lara Garcia Merino.

The researchers believe that the findings may contribute to a better understanding of how vascular damage develops in progeria and underline the importance of initiating treatment early, before irreversible DNA damage has accumulated.

“New gene-editing approaches can correct the disease-causing mutation in HGPS, but correcting the mutation alone is unlikely to reverse damage in cells that have already accumulated a large number of somatic mutations. Early intervention is therefore essential,” says Maria Eriksson.

The study also provides new insights into the biological processes underlying normal vascular ageing. Several important similarities exist between HGPS and the cardiovascular disease that affects the general population. HGPS is therefore widely used as a model for understanding normal ageing and vascular disease.

The researchers emphasise that further studies are needed to confirm the findings in humans.

The study was conducted in collaboration with researchers from, among others, the Indian Institute of Technology in India and the University of Bergen in Norway. The research was funded by the Swedish Research Council, the European Research Council (ERC), the Swedish Cancer Society and the Center for Innovative Medicine, among others.

Source: Karolinska Institutet

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags : Leave a comment

Premature Menopause Is a High Blood Pressure Risk Factor

On By ModernMedia

Large-scale study results call for earlier cardiovascular screening for women who experience menopause before age 40

Photo by Hush Naidoo on Unsplash

Women who reach menopause before age 40 face a meaningfully higher risk of developing high blood pressure than those who go through menopause after age 45, according to a new study of more than 107 000 women. Risk peaked among women who reached menopause prematurely between the ages of 25 and 35 years. The results of the study are published online today in Menopause, the journal of The Menopause Society.

Hormone shifts during the menopause transition are known to influence a woman’s overall disease risk, and earlier menopause has previously been linked to higher rates of coronary heart disease and stroke. However, evidence connecting the timing of menopause directly to hypertension has been inconsistent, with some prior meta-analyses finding an association and others finding none.

A key challenge has been separating the direct hormone effects of menopause from indirect effects driven by weight gain, metabolic changes, and other cardiovascular risk factors that tend to accompany the menopause transition.

To address this gap, researchers analysed data from 107 836 postmenopausal women enrolled in the UK Biobank between 2006 and 2010, following them for a median of nearly 15 years through the end of 2003. The study classified women by age at menopause – normal (after age 45), early (ages 40 to 45), and premature (before age 40) – as well as by type of menopause (natural vs surgical) and tracked new diagnoses of high blood pressure over time.

Over the follow-up period, 18 508 women (17.2%) were diagnosed with hypertension. The risk climbed steadily as age at menopause dropped: 16.6% of women with normal age at menopause developed hypertension, compared to 18.8% of women with early menopause and 22.6% of women with premature menopause. After adjusting for more than 50 variables – including weight, lifestyle habits, family history, and lab values – women with premature menopause still had a 12.3% higher risk of developing hypertension than women who reached menopause after age 45.

A further analysis modelling age at menopause on a continuous scale found that risk peaks not at the traditional premature-menopause cutoff of age 40 but between the ages 25 and 35, suggesting the cardiovascular risk associated with premature menopause may be concentrated in an even younger group of women than previously defined. Surgical menopause was associated with higher hypertension rates in initial analyses, but that association did not hold once other risk factors were considered.

Based on these findings, the study authors recommend that clinicians treat age at menopause as a distinct cardiovascular risk factor, particularly for women who reach menopause before age 40. In addition to individualised counselling on hormone therapy, they point to earlier identification and management of high blood pressure as an opportunity to help reduce long-term cardiovascular risk in this group of women.

“The results of this study highlight the potential adverse long-term health outcomes associated with premature menopause, and in particular, the need to regularly screen for cardiovascular risk factors such as hypertension. Use of hormone therapy is also routinely recommended in women with premature menopause at least until the natural age of menopause unless contraindications exist,” says Dr Stephanie Faubion, medical director for The Menopause Society.

Source: The Menopause Society

Categories : Cardiovascular DiseaseTags : Leave a comment

Cardiovascular Risk Factors that Drive Rupture-prone Plaques in Coronary Arteries

On By ModernMedia
Source: Wikimedia CC0

Cardiovascular risk factors are linked to higher risk of heart disease, but it has been unknown how they are related to abrupt closure of the coronary arteries leading to heart attack and sudden cardiac death. A new study by Mass General Brigham Heart and Vascular Institute investigators finds that people with higher modifiable risk factors burden such as high blood pressure, high cholesterol, diabetes, smoking and obesity have more widespread buildup of plaques in major coronary arteries. Furthermore, these modifiable factors were associated with more unstable, high-risk plaques that are prone to rupture and cause heart attacks. Results are published in JACC: Advances.

“The higher the number of vulnerable, or rupture-prone plaques, the greater the chance that one of them will trigger an adverse event,” said senior author Ik-Kyung Jang, MD, PhD, at the Mass General Brigham Heart and Vascular Institute. “Our findings highlight the importance of early, intensive and sustained interventions to control the modifiable risk factors and prevent future events.”

To better understand how modifiable risk factors and non-modifiable risk factors (including age, sex and family history of heart disease) influence dangerous plaque buildup, the research team examined plaque burden and plaque characteristics across all three major coronary arteries. They analysed 534 plaques in 131 patients who underwent optical coherence tomography (OCT), an intravascular imaging modality that can visualise plaques at high resolution.

The researchers reported that patients with more risk factors had more plaques across all three coronary arteries. In addition, greater number of modifiable risk factors was associated with fewer stable plaques and more prevalent vulnerable plaque features such as lipid plaques with thin fibrous caps that are susceptible to disruption. In contrast, non-modifiable risk factors were associated with more stable plaque phenotypes.

The authors note that prospective research involving larger cohorts, including patients who have previously been treated for blocked coronary arteries, is needed to generalise their findings.

Source: Mass General Brigham

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Pregnancy Complications Linked to Long-term Risk of Peripheral Artery Disease

On By ModernMedia

Study of over 2 million women finds an association between adverse pregnancy outcomes and an increased risk of PAD up to 46 years after delivery

Image by Scientific Animations, CC4.0

Women who experience pregnancy complications such as gestational diabetes, preeclampsia, or preterm delivery have a significantly increased long-term risk of developing peripheral artery disease (PAD) later in life, according to a new study published July 21st in the open access journal PLOS Medicine by Casey Crump of the University of Texas, US, and colleagues.

PAD, a condition in which narrowed arteries reduce blood flow to the limbs, affects more than 230 million people worldwide and is a strong predictor of future stroke, ischaemic heart disease, and premature mortality. Adverse pregnancy outcomes have been identified as risk factors for other cardiovascular diseases, but their association with long-term PAD risk had not been well established.

In the new study, researchers analysed data from 2 201 446 women who had a singleton delivery in Sweden between 1973 and 2015, following them for PAD diagnoses from nationwide inpatient, outpatient, and primary care records through 2018. Five adverse pregnancy outcomes were examined: preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes.

In 54 million person-years of follow-up, 13 211 women (0.6%) were diagnosed with PAD, at a median age of 62. All five adverse pregnancy outcomes were independently associated with increased PAD risk. At 30–46 years after delivery, adjusted hazard ratios were highest for gestational diabetes (HR 3.83, 95% CI 3.20–4.59), followed by small for gestational age (HR 1.74, 95% CI 1.65–1.83), other hypertensive disorders (HR 1.61, 95% CI 1.21–2.15), preterm delivery (HR 1.58, 95% CI 1.48–1.70), and preeclampsia (HR 1.28, 95% CI 1.20–1.37). Women with multiple adverse pregnancy outcomes had further increases in risk. These findings were largely unexplained by shared familial factors in co-sibling analyses.

“Because this was a relatively young cohort, the risks of PAD following adverse pregnancy outcomes may be even higher as women reach older ages when PAD is more likely to manifest,” the authors write. “Women with pregnancy complications may warrant early cardiovascular risk assessment and long-term clinical follow-up given their higher subsequent risk of PAD.”

The authors add, “Pregnancy is a “natural stress test” that may reveal higher cardiovascular risks in early adulthood. In a population of > 2 million women, we found that all 5 major adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes) are independently linked with higher risks of peripheral artery disease up to 46 years later. Women with pregnancy complications need early and long-term follow-up with their physician to reduce their lifetime risk of peripheral artery disease and other cardiovascular diseases.”

Provided by PLOS

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

New Drug for Chronic Heart Failure Tested in Early Study

On By ModernMedia
Right side heart failure. Credit: Scientific Animations CC4.0

An early clinical study shows that a new oral drug is safe and well-tolerated in patients with chronic heart failure. The study, led by researchers at Karolinska Institutet, has been published in the scientific journal The Lancet.

Heart failure with reduced pumping capacity means that the heart struggles to pump blood effectively around the body. Despite current treatments, many patients’ condition worsens over time, and existing drugs that strengthen the heart’s contractions can cause serious side effects, such as heart rhythm disturbances and changes in blood pressure.

In the study, researchers investigated a new drug, AC01, which targets the body’s ghrelin receptor. Ghrelin is a hormone that influences metabolism and growth hormone release, and its receptor is also found in heart muscle. AC01 is intended to strengthen the heart’s pumping ability through a different biological mechanism from traditional heart‑stimulating drugs, thereby reducing the risk of side effects.

The study was a randomised, placebo‑controlled phase 1b/2a trial involving 58 patients with stable, chronic heart failure with reduced pumping capacity. Participants received different doses of AC01 or placebo for either seven or 28 days. The main aim was to assess safety and tolerability.

The drug was well tolerated

The results show that the drug was well tolerated. No serious side effects linked to AC01 were reported. The researchers also found no signs of harmful effects on heart rhythm or blood pressure. Exploratory analyses additionally indicated signs of improved heart function, such as increased stroke volume and cardiac output.

“This is an early study with a limited number of patients, but the results suggest that AC01 can be administered safely to people with heart failure. The findings now justify further studies to investigate whether the signals of improved heart function that we have observed can lead to clinical benefit in larger and longer studies,” says Lars Lund, first author and professor at the Department of Medicine, Solna, Karolinska Institutet, and senior consultant cardiologist at Karolinska University Hospital.

Source: Karolinska Institutet

Categories : Cardiovascular DiseaseTags :

BP and Cholesterol in Over-40s with Obesity Are Trending to Normal Levels

On By ModernMedia
Credit: Pixabay CC0

Over the last three decades, differences in unhealthy cholesterol levels and blood pressure between older adults with obesity and those with a normal Body Mass Index (BMI) have narrowed or disappeared in several high-income countries, suggests a study published in The Lancet. The authors propose that this trend is due to the greater, and possibly more intensive, use of cholesterol-lowering medication (such as statins) and blood pressure medication in people aged over 40 living with obesity in high-income countries. 

Obesity is known to increase blood pressure and unhealthy cholesterol levels, which can impact cardiovascular health and increase the risk of heart attack, heart failure, and stroke. However, prior to this study, there was little information on blood pressure and cholesterol levels, and how they have changed, for people with obesity compared with people with normal BMI.

Author Prof Majid Ezzati, from the School of Public Health at Imperial College London (UK), says: “Our study suggests that, in high-income countries, taking medication to lower blood pressure and cholesterol has helped middle-age and older adults lower their cardiovascular risk to levels that are similar to people with normal BMI.”

He continues, “At a time that weight-loss medications are becoming more widely used, our results give a picture of the cardiovascular health of people likely to be prescribed them, which allows the healthcare system to understand how blood pressure and cholesterol treatments benefit the population alongside weight-loss medications.”

The study analysed data on blood pressure and cholesterol in people with obesity, overweight, and normal BMI from 110 health datasets including almost one million participants from 1990 to 2024 in seven high-income countries: England, the USA, Japan, South Korea, Taiwan, Thailand and Finland. 

Converging cardiovascular risk markers

The study finds that in the 1990s adults with obesity generally had higher blood pressure and high-density lipoprotein (non-HDL) cholesterol levels [1] than people with a normal BMI.
 
Since 1990, in the majority of the seven countries studied including England and the USA, blood pressure and unhealthy cholesterol fell more steeply among middle-aged and older adults (40–79 years old) with obesity and overweight than among those with normal BMI, narrowing the gap over time. The exceptions were Taiwan and Thailand, which did not see this convergence as universally as other countries.
 
The findings were most striking in older adults (60–79 years old). In England and the USA, older adults with obesity, and especially with severe obesity, had similar or even lower blood pressure and unhealthy cholesterol levels at the end of the study period than older adults with normal BMI.

Heart medication likely driving the convergence

Over the past three decades, people with obesity were more likely to be prescribed cholesterol-lowering medication (such as a statin) and blood pressure medication than those with a normal BMI. 
 
This gap was especially pronounced in older adults. For example, in England and the USA, around 70–72% of older men with severe obesity (BMI ≥35) were taking cholesterol-lowering medication by the early 2020s, compared with 40–48% of older men with a normal BMI.
 
Author Lakshya Jain, from the School of Public Health at Imperial College London (UK), says “This latest analysis suggests that the observed convergence in cholesterol and blood pressure levels between people aged over 40 with obesity and those with a normal BMI is largely due to statins and other widely accessible medications to reduce cardiovascular risk. That is a significant public health success story, and one we should not lose sight of as new weight-loss medications enter the picture.” 

Cardiovascular risks remain for younger adults with obesity

In younger adults (under 40 years old), the study findings suggest little or no narrowing of the gap in blood pressure or cholesterol between those with obesity and those with a normal BMI. The data also suggests that use of cholesterol-lowering and blood pressure medication is low for this age group, adding further evidence that medication is the driver of the gap reduction in older adults. 

Author Ysé d’Ailhaud de Brisis, from the School of Public Health at Imperial College London (UK), says “While good news for older adults with obesity, our results suggest that cardiovascular health risks remain higher for adults under 40 than for their counterparts with a normal BMI. Early lifestyle interventions, screening and, when appropriate, medication in this younger group should be considered to prevent long-term cardiovascular complications linked to obesity.”

The researchers note some limitations of the study, including that their analysis was limited to seven countries which were all high-income, therefore the finding may not be applicable elsewhere, especially for low- and middle-income countries where the use of unhealthy cholesterol and blood pressure lowering medicines is likely to be lower. Additionally, it was not possible to look at the impact of different medication doses, which require data on prescriptions. 

Writing in a linked Comment, Dr Yuan Lu, Yale School of Medicine (USA), who was not involved in the study, says, “This study reframes obesity-related cardiovascular risk as reflecting not only excess adiposity, but also treatment access, health-system engagement, and timing of intervention. Convergence of risk factors should not be equated with elimination of obesity-related risk. Although treatment of high blood pressure and cholesterol might mitigate part of the cardiovascular harm associated with obesity, the persistent burden among younger adults and the broader multisystem consequences of obesity highlight the need for integrated prevention strategies that move beyond isolated risk factor treatment.”

Source: EurekAlert!

Categories : Cardiovascular Disease ExerciseTags :

Irregular Heartbeat Risk Much Lower in Super‑fit People than Previously Thought

On By ModernMedia

Our study shows that atrial fibrillation risk in very fit people is smaller than previously thought. Pexels Photo by Freestocksorg

Axel Carl Carlsson, Karolinska Institutet; Marcel Ballin, Uppsala University, and Peter Nordström, Uppsala University

Exercise is important for your heart and cardiovascular health. But for years, research has suggested that very fit people – particularly young men – have a higher risk of developing atrial fibrillation (an irregular heartbeat) later in life than less athletic people do.

But our new large-scale study of more than one million young Swedish men challenges this long-held concern about fitness and heart health. The study shows that atrial fibrillation risk in very fit people is smaller than previously thought. And, importantly, the benefits of being fit – such as having lower rates of other cardiovascular diseases, such as stroke and heart attack – clearly outweigh the potential downsides.

To conduct our study, we analysed data from over one million Swedish men. Each of these men had completed a military conscription test between 1972 and 1995 when they were around 18 years old. During conscription, fitness was estimated using a maximal ergometer bicycle test.

We followed the participants using national health registries until 2023. Information was collected on diagnoses in specialised outpatient and inpatient care, as well as information on cause of death where relevant.

Nearly half a million of these men were siblings, allowing the team to compare brothers with different fitness levels. This method also helped control for shared genetics and upbringing to better understand risk.

In the population-wide analysis, where all men were compared based on their fitness levels, the fittest men did show a higher risk of atrial fibrillation until age 40. After 45, however, the benefits – fewer other heart problems – started to outweigh the risk.

But the sibling analysis told a different story. When comparing brothers, the link between high fitness and atrial fibrillation weakened significantly. The net positive effect of fitness on overall heart and cardiovascular health, although also weakening in the sibling analysis, was still evident from the start.

These benefits grew larger as the men aged. Across five decades of follow-up – from the age of 18 until the age of 65 – the benefits of being highly fit outweighed the overall risk of developing atrial fibrillation at all ages.

An advantage of our study is that we were able to compare siblings. Photo by Andrea Piacquadio on Pexels

While the higher risk of atrial fibrillation in the fittest men weakened in the sibling analysis, an elevated risk did remain. However, this risk was small overall. The potential risk of developing atrial fibrillation was also far outweighed by the positive benefits that being fit had on reducing risk of other cardiovascular diseases.

There was also some evidence that the increased risk of atrial fibrillation seemed to be driven by typically milder forms of atrial fibrillation.

Cardiovascular benefits of fitness

These findings suggest that earlier studies may have overestimated the risk of developing atrial fibrillation if you’re very fit because they couldn’t fully account for shared familial factors – such as genes and shared environmental factors – that may influence both fitness and heart health.

Because our study was able to account for these shared factors, we were able to show that we should potentially tone down the message that being very fit or engaging in endurance exercise poses a big risk to heart health. The risk of atrial fibrillation isn’t zero, but the benefits to heart health more generally are far greater.

Our results have also been confirmed in previous studies. However, our research builds upon this prior evidence by incorporating the sibling comparisons in the analyses, showing that the atrial fibrillation risk becomes weaker.

Our study also performed a more detailed examination of risk over time by following up with participants over a longer period of time, while also considering the benefits of high fitness. As such, our research has performed a more direct comparison of benefits and harms throughout life.

Overall, our research illustrates just how beneficial physical fitness is for overall cardiovascular health. Although very fit people do have a slightly higher risk of developing atrial fibrillation compared to people who are less fit, this risk of far lower than previously thought.

Plus, we show that the overall net benefits of fitness on cardiovascular health more broadly far outweigh any potential risk.

Axel Carl Carlsson, Researcher, Department of Neurobiology, Karolinska Institutet; Marcel Ballin, Associated Researcher, Department of Public Health and Caring Sciences, Uppsala University, and Peter Nordström, Professor, Department of Public Health and Caring Sciences, Uppsala University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Cardiovascular Disease GeneticsTags :

Gene Therapy Shows Promise for an Inherited Form of Cardiomyopathy

On By ModernMedia
Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014“. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.

A new gene therapy appears to be safe in patients diagnosed with Friedreich ataxia cardiomyopathy, a progressive and fatal inherited cardiac disease, according to a phase 1 clinical trial led by Weill Cornell Medicine researchers. The treatment may also reduce heart damage, although further investigation is needed. 

The results, published June 17 in JAMA Cardiology, indicated that an intravenous infusion of a healthy frataxin (FXN) gene was generally well tolerated and shows early signs of efficacy. These include a decrease in heart wall thickness – enlarged walls are a sign of cardiomyopathy – and reduced levels of troponin I, a marker of heart damage.

“This is a fatal disease, but this is a potential therapy, and our goal is FDA-approval,” said Dr Ronald G. Crystal, the study’s lead author, professor and chair of the Department of Genetic Medicine at Weill Cornell Medicine and a pulmonologist at NewYork-Presbyterian/Weill Cornell Medical Center.

What is Friedreich Ataxia?

Friedreich ataxia is caused by variants in the FXN gene, leading to decreased levels of the FXN protein, which is essential for energy production in cells. “The two most energy consuming organs in the body are your brain and the heart, so the disease is primarily a brain and heart disease,” Dr Crystal said.

It is an autosomal recessive hereditary disorder, meaning a person must inherit a faulty copy of the FXN gene from both parents. As many as one in 50 000 people in the United States are diagnosed with the disease, according to some reports.

Nervous system symptoms typically begin in childhood and include problems with balance, walking and speaking. While neurologic disease is devastating for maintaining quality of life, most people with Friedreich ataxia develop heart disease, which is the cause of death in up to 65 percent of patients, according to reported estimates. Decreased FXN protein levels in the heart mean the heart cells don’t have the energy to beat normally. The muscle cells grow and the heart walls thicken, a condition known as hypertrophic cardiomyopathy, which can cause dangerous irregular heartbeats and heart failure.  

The US Food and Drug Administration has approved only one other drug, omaveloxolone, to treat Friedreich ataxia. It slows the neurological symptom progression but does not address the direct genetic cause of the disease.

A New Gene Therapy

Based on promising preclinical research, Dr Crystal and his colleagues studied the safety and efficacy of the FXN gene therapy in 17 patients with Friedreich ataxia cardiomyopathy.

“We put the healthy FXN gene in a virus, called adeno-associated virus, which is given intravenously and likes to travel to the heart,” he said.

The researchers pooled data from two independent studies: nine patients were from a Weill Cornell Medicine study, funded by National Heart Lung Blood Institute, and eight were treated in a study by Lexeo Therapeutics, a clinical stage genetic medicine company founded by Dr Crystal. Weill Cornell Medicine Enterprise Innovation, which aims to accelerate the translation of scientific discoveries into patient impact, played a crucial role in launching Lexeo in 2020 and later licensed to it additional technology to further support the clinical trial.

In both studies, the patients received a one-hour infusion of the gene therapy and were evaluated from six to 36 months. Three different doses were tested among three groups of patients.

Overall, the drug was safe, causing four serious adverse events, which were all resolved. Three of these were possibly related to prednisone, an immunosuppression drug that patients took so their bodies did not attack the gene therapy.

In the Lexeo study, researchers took biopsies of the heart before therapy and three months after therapy and found that frataxin protein levels increased in cardiac tissue in all eight patients. Researchers also found that the left ventricular mass index, which is an MRI measurement of heart wall thickness, decreased, demonstrating that the treatment was therapeutic for cardiomyopathy. 

Levels of troponin I, a structural protein of the heart that is released into the circulation when the heart is damaged, also decreased. Troponin I levels are typically high in patients with Friedreich ataxia cardiomyopathy. 

Using the modified Friedreich Ataxia Rating Scale (mFARS), which assesses balance, coordination, speech, and limb function in patients, the researchers found that some neurological components of the disease stabilised. “But we’re unsure whether this was related to the gene therapy reaching the skeletal muscle or the brain,” Dr Crystal said. “That remains to be seen.”

Because most of the patients evaluated in this study had early cardiomyopathy, the researchers also hope to study the gene therapy in people who have a wider range of heart disease severity.

Source: Weill Cornell Medicine

Categories : Cardiovascular Disease ExerciseTags :

90-120 Weekly Minutes of Strength Training May Be Optimal for Lowering Death Risk

On By ModernMedia

Specifically tied to significantly lower risks of cardiovascular and neurological disease deaths
Effects amplified by aerobic exercise, but no further risk reduction above 120 minutes

Photo by John Arano on Unsplash

Clocking up 90 to 120 weekly minutes of strength (resistance) training may be the sweet spot for lowering the risk of death, suggests a 30 year study, published online in the British Journal of Sports Medicine.

The effects were amplified by the addition of aerobic exercise, but no further benefit was apparent above 120 minutes a week of strength training – an amount that was specifically associated with, respectively, 19% and 27% lower risks of dying from cardiovascular and neurological diseases.

The benefits of aerobic physical activity on lowering the risk of death are well known, but less clear is the role of muscle strengthening exercise in reducing the risks of death from all and specific causes, solely or jointly with aerobic exercise, say the researchers.

To explore this further, they drew on 30 years of monitoring data from 3 large groups of study participants: the Health Professionals Follow-up Study, 1992–2022; the Nurses’ Health Study, 2002–21; and  the Nurses’ Health Study II, 2003–21, comprising a total of 147,374 participants (31,540 men and 115,834 women).

Participants were quizzed every 2 years on the amount of time they spent on strength training and aerobic exercise every week for up to 30 years. Aerobic exercise included brisk walking, running, jogging, swimming, cycling, tennis, squash, strenuous outdoor work and stair climbing, while strength training included exercises using weights or body weight, such as press ups, squats, and lunges.

The average age of participants at study entry was 54. Those who clocked up more strength training tended to be younger, weigh less, have a healthier lifestyle, and do more aerobic exercise than those who did no strength training.

Three quarters (74%) of participants did more than the recommended 150 minutes/week of moderate intensity aerobic exercise, measured as 7.5 MET hours over the long term. METs express the amount of calories expended per minute of physical activity, relative to calories expended at rest. And nearly half (46%) of participants did some strength training.

During the 30 year monitoring period, 35,798 study participants died. A higher weekly long term level of strength training was associated with a lower risk of death.

After adjusting for potentially influential factors, 90–119 minutes/week of strength training was associated with a 13% lower risk of death from any cause, with no further benefit observed above 120 minutes/week.

And 90-119 weekly minutes of strength training was specifically associated with a 19% lower risk of dying from cardiovascular disease, and a 27% lower risk of dying from neurological disease.

A reduced risk of cancer was seen only at lower levels: 1–29 mins/week (21% lower) and 30–59 mins/week (18% lower).

Compared with those participants with fewer than 7.5 MET hours/week of aerobic exercise and no strength training, those doing 1–59 and 60–119 mins/week of strength training alone had a 7–11% lower risk of death.

Aerobic activity alone at any level above 7.5 MET hours/week was associated with a 26–43% lower risk of death.

And the lowest risk was observed among those with both high aerobic activity and strength training levels every week: 45% lower risk for 30-44 MET hours/week of aerobic exercise plus 60–119 mins/week of strength training, and 53%-58% lower risks among those with 45+ MET hours/week of aerobic activity, irrespective of strength training level.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers acknowledge various limitations to their study.

These include the self reported nature of the data; the exclusion of strength training activities, such as calisthenics and Pilates; no information on the duration of each exercise session or the intensity of strength training, any or all of which might have influenced the findings.

Nevertheless they conclude: “Our findings on different dose-response relationships between long-term resistance training with all-cause and cause-specific mortality suggest that different amounts of resistance training may be needed to optimise benefits across outcomes.

“The observed pattern that adding resistance training further reduced mortality risk across all levels of aerobic activity up to 45 MET hours/week supports current recommendations encouraging both types of activity to maximise mortality benefits.”

Source: The BMJ Group