Tag: heart failure

Categories : Diseases, Syndromes and Conditions Injury & TraumaTags :

Autistic Adults Have Higher Risks of Injury and Disease

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A large-scale registry study found that older autistic adults have a significantly higher risk of injury, especially self-inflicted, and physical conditions such as type 2 diabetes, anaemia, heart failure and COPD. The findings were published in The Lancet Healthy Longevity.

“We found an increased disease burden in middle-aged and older autistic adults, both men and women, irrespective of the presence of intellectual disability,” says Shengxin Liu, doctoral student at Karolinska Institutet. “Our findings point up the need to improve the support and care of older autistic adults.”

In the population-based study, the KI researchers linked different national registers and compared the risk for five types of injury and 39 age-related physical conditions in people over the age of 45. Of the four million-plus people born between 1932 and 1967, 1930 women and 3361 men had an autism diagnosis. For each physical condition, they evaluated the 25-year cumulative incidence and the relative risk in autistic people compared with non-autistic people of the same sex and age.

Seven-fold risk of self-harm

Autistic people had a higher risk of four of five studied injures, for which self-harm accounted for the greatest risk increase, followed by poisoning, falls and other physical injuries.

“The risk of self-harm was worryingly high, a full seven times higher than in non-autistic people,” says Liu. “Reasons behind this remain largely unknown. One possible contributing factor could be mental health conditions that commonly co-occur with autism, such as anxiety and depression.”

The researchers also found a risk increase for 15 physical conditions. For example, autistic people had three times the risk of anaemia and glucose dysregulation and almost double the risk of heart failure, type 2 diabetes, and COPD (chronic obstructive pulmonary disease).

Multiple contributory factors

“We now need to find out the cause of these associations and how they are affected by factors such as biology, age when diagnosed with autism, psychotropic treatment and psychosocial environment,” says the study’s last author Mark Taylor, senior researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “But most importantly, researchers, health services and policymakers need to cooperate to make sure that older autistic adults have a better quality of life.”

Since this was an observational study, no causal relationships can be ascertained, and the researchers were not able to take into account variables such as socioeconomic status. Furthermore, given that the study used Swedish registers, it is difficult to make generalisations to other countries.

Source: Karolinska Institutet

Categories : Cardiovascular Disease ExerciseTags :

Strong Legs Reduce Risk of Heart Failure after Heart Attack

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People with strong legs are less likely to develop heart failure after a heart attack, according to new research. Myocardial infarction is the most common cause of heart failure, with around 6–9% of heart attack patients going on to develop the condition. Previous research has shown that having strong quadriceps is associated with a lower risk of death in patients with coronary artery disease.

Presented at Heart Failure 2023, a scientific congress of the European Society of Cardiology (ESC), this study tested the hypothesis that leg strength is associated with a lower risk of developing heart failure after acute myocardial infarction. The study included 932 patients hospitalised in 2007 to 2020 with acute myocardial infarction who did not have heart failure prior to the admission and did not develop heart failure complications during their hospital stay. The median age was 66 years and 753 participants (81%) were men.

Maximal quadriceps strength was measured as an indicator of leg strength. Patients sat on a chair and contracted the quadriceps muscles as hard as possible for five seconds. A handheld dynamometer attached to the ankle recorded the maximum value in kg. The measurement was performed on each leg and the researchers used the average of both values. Strength was expressed relative to body weight, meaning that quadriceps strength in kg was divided by body weight in kg and multiplied by 100 for a % body weight value. Patients were classified as ‘high’ or ‘low’ strength according to whether their value was above or below the median for their se

The median value for women was 33% body weight and the median value for men was 52% body weight. A total of 451 patients had low quadriceps strength and 481 had high strength. During an average follow-up of 4.5 years, 67 patients (7.2%) developed heart failure. The incidence of heart failure was 10.2 per 1000 person-years in patients with high quadriceps strength and 22.9 per 1000 person-years in those with low strength.

The researchers analysed the association between quadriceps strength (low vs. high) and the risk of developing heart failure. The analysis was adjusted for factors known to be associated with the development of heart failure after myocardial infarction including age, sex, body mass index, prior myocardial infarction or angina pectoris, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, peripheral arterial disease and kidney function. Compared with low quadriceps strength, a high strength level was associated with a 41% lower risk of developing heart failure (hazard ratio [HR]: 0.59; 95% confidence interval [CI] 0.35–1.00; p=0.048).

The investigators also analysed the association between quadriceps strength as a continuous variable and the risk of developing heart failure. Each 5% body weight increment in quadriceps strength was associated with an 11% lower likelihood of heart failure (HR 0.89; 95% CI 0.81–0.98; p=0.014).

Study author Mr. Kensuke Ueno, a physical therapist at the Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan said: “Quadriceps strength is easy and simple to measure accurately in clinical practice. Our study indicates that quadriceps strength could help to identify patients at a higher risk of developing heart failure after myocardial infarction who could then receive more intense surveillance. The findings need to be replicated in other studies, but they do suggest that strength training involving the quadriceps muscles should be recommended for patients who have experienced a heart attack to prevent heart failure.”

Source: European Society of Cardiology

Categories : Cancer Cardiovascular DiseaseTags :

Study Reveals Why Cancer Drugs Cause Cardiotoxicity

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While being effective at treating cancer, some cancer treatments can cause cardiotoxicity which can lead to heart failure – a phenomenon unexplained until now. An international study, published in the journal Science Advances, has identified proteins present in the blood that are linked to an increased risk of developing cardiac disease, including heart failure, and which are also affected by drugs used in cancer treatment.

The findings can explain how cancer drugs cause their damaging effects on the heart and could help to identify those at increased risk. In the long run, the researchers believe this will help to improve cancer treatments, with new drugs potentially being developed that can shrink tumours without affecting the identified proteins.

In addition, the study reveals new potential drug targets for treating heart diseases including heart failure. These may work by inhibiting proteins linked to higher disease risk, or activating proteins linked to lower risk.

The researchers first performed a genome-wide association study, searching through the DNA of nearly 37,000 people without heart disease enrolled in the UK Biobank study. This identified genetic variants linked to changes to the structure and function of the pumping chambers of the heart – the ventricles.

The researchers then pinpointed 33 proteins using Mendelian randomisation, coded for by these genetic variants, that are present in the blood and associated with the risk of developing several heart diseases. These included different types of heart failure, and atrial fibrillation (a common abnormal heart rhythm which increases the risk of stroke). Crucially, many of these proteins are the targets of drugs currently used to treat cancer.

Lead author Dr Floriaan Schmidt said: “The proteins identified in our study will help to accelerate future drug development, offering scientists a blueprint for new treatments for both cancer and heart diseases. This can help them to be more confident of the effects of the drugs that they design – whether that’s shrinking tumours without causing damage elsewhere or improving the heart’s pumping action.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said: “While there have been advances in treating cancer, one of the consequences has been a risk of heart damage from these drugs.

“This research points the way towards developing safer and more refined drugs so that, one day, worries about developing heart problems after cancer treatment might be a thing of the past.”

Source: University College London

Categories : Cardiovascular DiseaseTags :

Hunger Hormone Increases Cardiac Function in Heart Failure

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A clinical study published in the European Heart Journal shows that the hunger hormone ghrelin can increase the heart’s pump capacity in patients with heart failure.

Heart failure occurs when the heart muscles are weakened, such as from myocardial infarction, reducing the ability to pump blood. Current treatments can slow disease progression, but none directly increase the heart’s pumping capacity.

Ghrelin is an endogenous hormone that has many receptors distributed in cardiac muscle tissues. It increases the appetite and stimulates the release of growth hormones. The researchers believe that its receptors are a promising target for enhancing the heart’s pumping capacity.

“Heart failure is the most common cause of hospitalisation in older generations and is associated with a poor quality of life and high mortality,” says principal investigator Lars Lund, professor at the Department of Medicine, Solna, Karolinska Institutet, and senior consultant at Karolinska University Hospital. “If we can find ways to increase the heart’s pump function, we can potentially improve life quality and prognosis for these patients.”

In this double-blind study, 30 patients with heart failure at Karolinska University Hospital’s cardiology unit were randomly assigned to two groups, receiving either active treatment with ghrelin or a placebo given intravenously for two hours. The participants were followed up after two to five days.

Pump function up by 28%

After two hours’ treatment, the cardiac output had increased by an average of 28% in the ghrelin group, (4.08 ± 1.15 to 5.23 ± 1.98 L/min) compared to a small reduction in the placebo group (4.26 ± 1.23 to 4.11 ± 1.99 L/min). The increase was from more blood being pumped per beat, as the heart rate remained unchanged or was even slightly slower. At the two- to five-day follow-up, the pump capacity was still 10% higher in the ghrelin group compared to in the placebo group.

No serious adverse reactions were seen, though the ghrelin group had slightly elevated levels of a heart-failure biomarker, which would need to be investigated further. The small size of the group makes limits the generalisability of the results.

Using mouse heart cells, the researchers observed that treatment with ghrelin increased the contractile function of the heart cells, and they identified a novel molecular mechanism for this increase. The researchers now plan to do larger clinical studies.

Source: Karolinska Institutet

Categories : Cardiovascular Disease VaccinesTags :

Flu Vaccine Reduces Early Mortality in HF Patients

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In a study published in The Lancet Global Health, an international team of researchers has found that influenza vaccines greatly reduce both pneumonia and cardiovascular complications in people with heart failure.

“If you have heart failure, you should get your flu shot because it can save your life – that is what we found in this study,” said the study’s principal investigator Mark Loeb. “It is underappreciated that influenza vaccine can save people from cardiovascular death.”

The study showed that over the entire year the influenza vaccine reduced pneumonia by 40% and hospitalisation by 15% in patients with HF. During influenza season in autumn and winter, the influenza vaccine reduced deaths by 20% in these patients.

Data gathered during flu season also showed the vaccine helped protect against cardiovascular complications, such as heart attacks and strokes.

Trial investigators tracked more than 5000 patients with HF in 10 countries across Africa, Asia and the Middle East, where few people have regular influenza vaccination. They received either an influenza vaccine or a placebo annually between June 2015 and November 2021.

While the flu has long been associated with an increased risk of life-threatening cardiovascular events, Loeb said that people with heart failure are already vulnerable to poor health outcomes. Patients with the condition have a 50% chance of dying within five years, while 20% are hospitalised for cardiovascular complications every year.

“Importantly, we looked at low and middle-income countries where 80 per cent of cardiovascular disease occurs and where flu vaccination rates are low.”

Salim Yusuf, executive director of PHRI and an author of the study said: “The flu shot should be part of the standard practise in people with heart failure given how simple, inexpensive and safe it is. Avoiding one sixth of deaths from heart disease and preventing hospitalizations makes it very cost effective and that can have an important public health and clinical impact.”

The study from McMaster University and partners marks the first clinical trial of the flu vaccine’s effectiveness in patients with HF.

Source: McMaster University

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

Smartwatch Equals Treadmill Test in Detecting HF

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A smartwatch ECG can accurately detect heart failure (HF) in nonclinical environments, according to a study published in Nature Medicine. Researchers analysed Apple Watch ECG recordings with AI to identify patients with ventricular dysfunction. Study participants were able to remotely record their smartwatch ECGs at any time, with the data automatically and securely uploaded to their electronic health records via a smartphone app.

“Currently, we diagnose ventricular dysfunction – a weak heart pump – through an echocardiogram, CT scan or an MRI, but these are expensive, time consuming and at times inaccessible. The ability to diagnose a weak heart pump remotely, from an ECG that a person records using a consumer device, such as a smartwatch, allows a timely identification of this potentially life-threatening disease at massive scale,” says senior study author Paul Friedman, MD, chair of the Department of Cardiovascular Medicine at Mayo Clinic.

Ventricular dysfunction might not cause symptoms, but affects about 2% of the population and 9% of people over 60. Symptoms may develop with a low ejection fraction, including shortness of breath, a rapid heart rate and swelling in the legs. Early diagnosis is important because once identified, there are numerous treatments to improve quality of life and decrease the risks of heart failure and death.

Mayo researchers interpreted Apple Watch single-lead ECGs by modifying an earlier algorithm developed for 12-lead ECGs that is proven to detect a low ejection fraction.

While the data are early, the modified AI algorithm using single-lead ECG data had an area under the curve of 0.88 to detect low ejection fraction. By comparison, this measure of accuracy is as good as or slightly better than a medical treadmill diagnostic test.

“These data are encouraging because they show that digital tools allow convenient, inexpensive, scalable screening for important conditions. Through technology, we can remotely gather useful information about a patient’s heart in an accessible way that can meet the needs of people where they are,” says first author Zachi Attia, PhD, the lead AI scientist in the Department of Cardiovascular Medicine at Mayo Clinic.

“Building the capability to ingest data from wearable consumer electronics and provide analytic capabilities to prevent disease or improve health remotely in the manner demonstrated by this study can revolutionize health care. Solutions like this not only enable prediction and prevention of problems, but also will eventually help diminish health disparities and the burden on health systems and clinicians,” says co-author Bradley Leibovich, MD, the medical director for the Mayo Clinic Center for Digital Health.

Approximately 420 of the 2454 participants had an echocardiogram within 30 days of logging an Apple Watch ECG in the app. Of those, 16 patients had low ejection fraction confirmed by the echocardiogram, which provided a comparison for accuracy.

Source: Mayo Clinic

Categories : Cardiovascular DiseaseTags :

Iron Drives Chronic Heart Failure in Myocardial Infarction Survivors

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A multi-institution study has found that iron drives the formation of fatty tissue in the heart and leads to chronic heart failure in about 50% of myocardial infarction (MI) survivors. The discovery, recently published in Nature Communications, paves the way for treatments that have the potential to prevent heart failure.

“For the first time, we have identified a root cause of chronic heart failure following a heart attack,” said study leader Rohan Dharmakumar, PhD, of Indiana University School of Medicine.

“While advances across populations have made survival after a heart attack possible for most, too many survivors suffer long-term complications like heart failure,” said Subha Raman, MD, who is physician director of the Cardiovascular Institute. “Dr. Dharmakumar’s breakthrough science illuminates who is at risk and why and points to an effective way to prevent these complications.”

The study followed large animal models over six months. In MI with bleeding complications, scar tissue is slowly replaced by fat. Fatty tissue can’t push blood from the heart effectively, and this is what leads to heart failure and eventually to death in many survivors of haemorrhagic MI, Dharmakumar said.

“Using noninvasive imaging, histology and molecular biology techniques, and various other technologies, we have shown that iron from red blood cells is what drives this process,” he explained. “When we removed the iron, we reduced the amount of fat in the heart muscle. This finding establishes a pathway for clinical investigations to remedy or mitigate the effects associated with iron in haemorrhagic myocardial infarction patients.”

Dharmakumar’s team is currently testing iron chelation therapy to do just that in a just-launched clinical trial.

“Thanks to a clinical trial underway being led by his team at Indiana University, I’m excited to see this treatment improve the lives of millions of heart attack survivors worldwide,” said Raman.

Source: Indiana University School of Medicine

Categories : Cardiovascular DiseaseTags :

SGLT2 Inhibitors may be Effective for All HF Ejection Fractions

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Researchers presented new evidence that SGLT2 inhibitors may benefit a wide range of patients with heart failure (HF). At the ESC Congress 2022 in Barcelona, and in simultaneous publications in The New England Journal of Medicine and The Lancet, physician-scientists presented late-breaking research from the largest trial to date of heart failure patients with mildly reduced or preserved ejection fraction (EF).

They showed that dapagliflozin, which had previously been shown to benefit patients with heart failure with reduced ejection fraction (HFrEF), is likely to also reduce cardiovascular death and hospitalisation for patients with mildly reduced or preserved EF, for whom therapeutic options are limited. A meta-analysis that included two clinical trials further strengthened the evidence that this class of drugs may provide protection for a wide range of heart failure patients.

Scott Solomon, MD, at the Brigham, presented results from the AstraZeneca-funded DELIVER trial, a randomised, placebo-controlled trial of dapagliflozin among patients with heart failure with mildly reduced or preserved EF.

“In the largest and most inclusive trial of heart failure with mildly reduced or preserved ejection fraction, we found that treatment with the SGLT2 inhibitor dapagliflozin can benefit patients across the full spectrum of heart failure,” explained Dr Solomon. “These findings establish SGLT2 inhibitors as foundational treatment for patients living with heart failure, regardless of ejection fraction, to help prevent hospitalisation and morbidity and to extend meaningful survival and improve health-related quality of life. These are the outcomes that matter most to patients and to clinicians – to keep patients feeling well and living longer.”

Muthiah Vaduganathan, MD MPH, also at the Brigham, presented results from a pre-specified meta-analysis of DELIVER and EMPEROR-Preserved, a large-scale clinical trial of empagliflozin, funded by Boehringer Ingelheim and Eli Lilly.

“Our meta-analysis, encompassing more than 12 000 patients, provides a summary of the totality of the evidence and drives home the message that, when it comes to heart failure, this is a therapy for all,” said Dr Vaduganathan. “These trials included patients across a broad range of ages, race, functional class, sex and medical histories, but regardless of individual characteristics, they benefited consistently from this treatment.”

Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitor, which causes the body to excrete sugar in urine. As well as blood glucose control in diabetes, SGLT-2 inhibitors have been shown to provide significant cardiovascular and kidney disease benefits. The DELIVER trial was designed to determine whether dapagliflozin would decrease cardiovascular morbidity and mortality in patients with heart failure with mildly reduced or preserved EF.

The international trial enrolled patients aged 40 or older and had symptomatic HF with an EF of greater than 40%, including mildly reduced ejection fraction and preserved EF, as well as patients who had previously had reduced EF that had improved to greater than 40%, and in both the outpatient and inpatient setting. More than 6000 participants were randomised to receive dapagliflozin or placebo and followed for a median of 2.3 years. The primary endpoint was a composite of cardiovascular death or worsening heart failure.

Dapagliflozin significantly reduced the primary composite endpoint by 18 percent. In the dapagliflozin group, 11.8% experienced worsening heart failure compared to 14.5% of the placebo group. Cardiovascular death in these groups occurred in 7.4 % and 8.3% of participants, respectively. Key secondary outcomes were also significantly reduced, including total heart failure hospitalisations and total symptom burden.

The meta-analysis used data from DELIVER and EMPEROR-Preserved, with a composite of cardiovascular death or first hospitalisation for heart failure. SGLT2 inhibitors were found to reduce primary outcome risk by 20%. Effects were consistent across subgroups by age, sex, race, body mass index, systolic blood pressure, history of various medical conditions and more.

The team further incorporated data from additional clinical trials with SGLT2 inhibitors, including those performed with dapagliflozin and empagliflozin in patients with HFrEF, and in patients from a clinical trial of the SGLT1/2 inhibitor sotagliflozin. Taken together, the evidence with all these data suggest that patients across the full spectrum of HF benefit from this class of drugs, regardless of EF or care setting.

Limitations were noted by the authors. Black patients made up less than 5% of the patients enrolled in DELIVER; the COVID pandemic limited symptom assessment after March 2020; and subgroups in the trial were underpowered. However, findings were consistent across prespecified subgroups.

“There are more than 64 million people worldwide affected by heart failure, half of whom have mildly reduced or preserved ejection fraction,” said Dr Solomon. “Our goal is to rigorously and scientifically evaluate potential treatments so that we can provide the best evidence-based care to help them lead longer, healthier lives.”

Source: Brigham and Women’s Hospital

Categories : Cardiovascular DiseaseTags :

Salt Restriction May Worsen HF with Preserved Ejection Fraction

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Spilled salt shaker
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Salt restriction has long been held to be a key component of heart failure treatment, but cutting back too much may actually worsen the outcomes for people with preserved ejection fraction, suggests research published in Heart.

The findings indicate that younger people and those of black and other ethnicities seem to be most at risk.

Salt restriction is frequently recommended in heart failure guidelines, but the optimal restriction range (from less than 1.5g to less than 3g daily) and its effect on patients with heart failure with preserved ejection fraction (HFpEF) is less clear as they have often been excluded from relevant studies.

HFpEF, which accounts for half of all heart failure cases, occurs when the lower left chamber of the heart (left ventricle) isn’t able to fill properly with blood (diastolic phase), so reducing the amount of blood pumped out into the body.

In a bid to explore the association with salt intake further, the researchers drew on  secondary analysis of data from 1713 people aged 50 and above with heart failure with preserved ejection fraction who were part of the TOPCAT trial.

A phase III, randomised, double-blind, placebo-controlled study, this trial was designed to find out if the drug spironolactone could effectively treat symptomatic heart failure with preserved ejection fraction.

Participants were asked how much salt they routinely added to the cooking of staples, such as rice, pasta, and potatoes; soup; meat; and vegetables, and this was scored as: 0 points (none); 1 (⅛tsp); 2 (¼tsp); and 3 (½+tsp).

They were followed up for an average of three years for the primary endpoint, a composite of death from cardiovascular disease or admission to hospital for heart failure plus aborted cardiac arrest. Secondary outcomes were all cause mortality and cardiovascular disease mortality plus hospitalisation for heart failure.

Around half the participants (816) had a cooking salt score of zero: more than half of them were men (56%) and most were of white ethnicity (81%). They weighed significantly more and had a lower diastolic blood pressure (70 mm Hg) than those with a cooking salt score above zero (897).

They had also been admitted to hospital more often for heart failure, were more likely to have type 2 diabetes, poorer kidney function, to be taking meds to control their heart failure, and to have a reduced left ventricular ejection fraction (lower cardiac output). 

Participants with a cooking salt score above zero were at significantly lower risk of the primary endpoint than those whose score was zero, mainly driven by the fact that they were less likely to be hospitalised for heart failure. But all-cause mortality or CVD mortality was no higher than those whose cooking salt score was zero.

Those aged 70 or younger were significantly more likely to benefit from adding salt to their cooking than were those older than 70 in terms of the primary endpoint and admission to hospital for heart failure. 

Similarly, those of black and other ethnicities seemed to benefit more from adding salt compared with white participants, although the numbers were small.

Gender, previous hospitalisation for heart failure, and the use of heart failure meds weren’t associated with heightened risks of the measured outcomes and cooking salt score.

This is an observational study, and as such, can’t establish cause. Not all relevant data from the TOPCAT trial were available, while the cooking salt score was self-reported, acknowledge the researchers. And reverse causation, whereby people with poorer health might have been advised to further restrict their salt intake, can’t be ruled out. 

Lower sodium intake is usually associated with lower blood pressure and a reduced risk of cardiovascular disease in the general public and in those with high blood pressure. It is thought that it reduces fluid retention and the triggering of the hormones involved in blood pressure regulation.

But restricting salt intake to control heart failure is less straightforward, say the researchers. It may prompt intravascular volume contraction, which could, in turn, reduce congestion and the requirement for water tablets to ease fluid retention. 

But the researchers pointed out that the that the volume of plasma in the blood, an indicator of congestion, wasn’t significantly associated with cooking salt score – suggesting that low sodium intake didn’t ease fluid retention in people with heart failure with preserved ejection fraction.

“Overstrict dietary salt intake restriction could harm patients with [heart failure with preserved ejection fraction] and is associated with worse prognosis. Physicians should reconsider giving this advice to patients,” they conclude.

Source: EurekAlert!

Categories : Ageing GenderTags :

Losing their Y Chromosome Shortens Men’s Lifespans

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DNA repair
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As many men age, they lose their Y chromosome, which causes heart muscle to scar and can lead to deadly heart failure, new research from the shows. The finding, which appears in Science, may help explain why men die, on average, several years younger than women.

University of Virginia School of Medicine researcher Kenneth Walsh, PhD, says the new discovery suggests that men who suffer Y chromosome loss – estimated to include 40% of 70-year-olds – may particularly benefit from an existing drug that targets dangerous tissue scarring. The drug, he suspects, may help counteract the harmful effects of the chromosome loss – effects that may manifest not just in the heart but in other parts of the body as well.

On average, women live five years longer than men in the United States. The new finding, Prof Walsh estimates, may explain nearly four of the five-year difference.

“Particularly past age 60, men die more rapidly than women. It’s as if they biologically age more quickly,” said Prof Walsh. “There are more than 160 million males in the United States alone. The years of life lost due to the survival disadvantage of maleness is staggering. This new research provides clues as to why men have shorter lifespans than women.”

Many men begin to lose their Y chromosome in a fraction of their cells as they age, especially in smokers. The loss occurs predominantly in cells that undergo rapid turnover, such as blood cells. However, Y chromosome loss does not occur in male reproductive cells, so it is not inherited by the children of men who exhibit Y chromosome loss. It has been observed that men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated maladies such as Alzheimer’s disease. This new research however is believed to be the first hard evidence that the chromosome loss harms men’s health.

Walsh and his team used CRISPR gene-editing technology to develop a special mouse model to better understand the effects of Y chromosome loss in the blood. The loss accelerated age-related diseases, made the mice more prone to heart scarring, leading to earlier death. But more than just the results of inflammation, there was complex series of responses in the immune system, leading to fibrosis throughout the body. This tug-of-war within the immune system, the researchers believe, may accelerate disease development.

The scientists also looked at the effects of Y chromosome loss in human men. They conducted three analyses of data compiled from the UK Biobank, a massive biomedical database, and found that Y chromosome loss was associated with cardiovascular disease and heart failure. As chromosome loss increased, the scientists found, so did the risk of death.

The findings suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives. One treatment option might be a drug, pirfenidone, approved in the US for the treatment of idiopathic pulmonary fibrosis. The drug is also being tested for the treatment of heart failure and chronic kidney disease, two conditions for which tissue scarring is a hallmark. Based on his research, Walsh believes that men with Y chromosome loss could respond particularly well to this drug, and other classes of antifibrotic drugs that are being developed, though more research will be needed to determine that.

At the moment, doctors have no easy way to determine which men suffer Y chromosome loss. Prof Walsh’s collaborator Lars A. Forsberg, of Uppsala University in Sweden, has developed an inexpensive polymerase chain reaction (PCR) test that can detect Y chromosome loss, but the test is largely confined to his and Prof Walsh’s labs. Prof Walsh, however, can foresee that changing: “If interest in this continues and it’s shown to have utility in terms of being prognostic for men’s disease and can lead to personalised therapy, maybe this becomes a routine diagnostic test,” he said.

“The DNA of all our cells inevitably accumulate mutations as we age. This includes the loss of the entire Y chromosome within a subset of cells within men. Understanding that the body is a mosaic of acquired mutations provides clues about age-related diseases and the aging process itself,” said Walsh, a member of UVA’s Department of Biochemistry and Molecular Genetics. “Studies that examine Y chromosome loss and other acquired mutations have great promise for the development of personalised medicines that are tailored to these specific mutations.”

Source: University of Virginia Health System