Category: Cardiovascular Disease

Categories : Antibiotics Cardiovascular DiseaseTags :

Antibiotics Reduce the Gastrointestinal Bleeding Risk of Long-term Aspirin

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A major clinical trial found that the risk of gastrointestinal bleeding caused by long-term aspirin use can be reduced with a short course of antibiotics, potentially improving the safety of aspirin when used to prevent heart attacks, strokes and possibly some cancers.

The results of the HEAT (Helicobacter pylori Eradication Aspirin) trial, which was led by Professor Chris Hawkey from the University of Nottingham, are published in The Lancet.

Aspirin in low doses is a very useful preventative drug in people at high risk of strokes or heart attacks. However, on rare occasions, its blood thinning effect can provoke internal ulcer bleeding. These ulcers may be caused by Helicobacter pylori.

The STAR (Simple Trials for Academic Research) team from the University of Nottingham investigated whether a short course of antibiotics to remove these bacteria would reduce the risk of bleeding in aspirin users.

The HEAT trial, conducted in 1208 UK general practices, was a real-life study which used clinical data routinely stored in GP and hospital records, instead of bringing patients back for follow up trial visits.

The researchers recruited 30 166 who were taking aspirin. Those who tested positive for H. pylori were randomised to receive antibiotics or placebos (dummy tablets) and were followed for up to 7 years.

Over the first two and a half years, those who had antibiotic treatment were less likely to be hospitalised for ulcer bleeding than those taking placebo (6 versus 17). Protection occurred rapidly: with the placebo group, the first hospitalisation for ulcer bleeding occurred after 6 days, compared to 525 days following antibiotic treatment.

Over a longer time period, protection appeared to wane. However, the overall rate of hospitalisation for ulcer bleeding was lower than expected and this in line with other evidence that ulcer disease is on the decline. Risks for people already on aspirin are low. Risks are higher when people first start aspirin, when searching for H. pylori and treating it is probably worthwhile.

Aspirin has many benefits in terms of reducing the risk of heart attacks and strokes in people at increased risk. There is also evidence that it is able to slow down certain cancers. The HEAT trial is the largest UK-based study of its kind, and we are pleased that the findings have shown that ulcer bleeding can be significantly reduced following a one-week course of antibiotics. The long-term implications of the results are encouraging in terms of safe prescribing.

Professor Chris Hawkey, University of Nottingham’s School of Medicine and Nottingham Digestive Diseases Centre

Source: University of Nottingham

Categories : Cardiovascular Disease PaediatricsTags :

Oxygen Deficiency in Newborns may Increase Later Cardiovascular Risk

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A population-based observational study has shown that babies suffering oxygen-deficiency complications at birth are almost twice as likely to develop cardiovascular disease in childhood or early adulthood, though such conditions are rare in youth. The findings are published in the journal The Lancet Regional Health – Europe.

According to the Karolinska Institutet researchers, the study could be the first of its kind to examine how complications related to asphyxiation at birth, which affects four million babies annually, affects the risk of cardiovascular disease later in life. Previous research has mostly concentrated on the association between asphyxia in the neonatal period and brain development.

Despite the relatively high risk, the absolute number of babies who suffer from cardiovascular disease despite asphyxiation at birth is very low. After the 30-year follow-up period, only 0.3% of those with asphyxia-related complications had a cardiovascular diagnosis, compared with 0.15% of those without complications.

Since the study was observational, the researchers are unable to establish any causality or propose any underlying mechanisms.

Largest risk increase for stroke and heart failure

The study followed over 2.8 million individuals born in Sweden between 1988 and 2018, of whom 31 419 suffered asphyxia-related complications at birth. A total of 4165 cases of cardiovascular disease were identified during the follow-up period. The increase in risk was particularly salient for stroke and heart failure, as well as for atrial fibrillation. The researchers took into account potential confounders such as birth weight and maternal lifestyle.

“Even if the absolute risk of cardiovascular disease is low at a young age, our study shows that asphyxia-related complications at birth are associated with a higher risk of cardiovascular disease later in life,” says the study’s corresponding author Neda Razaz, assistant professor at the Department of Medicine, Solna, Karolinska Institutet.

Source: Karolinska Institutet

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 :

Apaxiban Has Lowest Gastrointestinal Bleeding Risk of Common DOACs

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A large-scale comparison of direct oral anticoagulants (DOACs), published in Annals of Internal Medicine, one of the two most common direct oral anticoagulants (DOACs), apixaban, has the lowest risk of gastrointestinal bleeding, with similar performance on stroke prevention and other side effects.

DOACs are used to prevent strokes for people with atrial fibrillation, a condition affecting over 33 million people worldwide. They have recently become gained popularity over warfarin, the previous standard treatment, as they do not require as much follow-up monitoring (which was particularly valuable during the COVID pandemic) and have less risk of side-effects.

For the new study, University College London researchers compared the efficacy and risk of side effects for the four most common DOACs. They reviewed data from more than 500 000 new DOAC users in the UK, France, Germany and the US, including 281 320 apixaban users, 61 008 dabigatran users, 12 722 edoxaban users, and 172 176 rivaroxaban users.

They found that all four drugs were comparable on outcomes for ischemic stroke, brain bleeds and all-cause mortality, while they did identify a difference in risk of gastrointestinal bleeding, which is one of the most common and concerning side effects of DOACs.

The study revealed that apixaban stood out as having lower risk of gastrointestinal bleeding, with 19-28% lower risks when compared directly to each of the other three DOACs.

The researchers found that their findings held true when looking at data only from those aged over 80, and those with chronic kidney disease, two groups that are often underrepresented in clinical trials.

Dr Wallis Lau (UCL School of Pharmacy), who jointly led the work along with her colleague Professor Ian Wong, said: “Direct oral anticoagulants have been prescribed with increasing frequency worldwide in recent years, but evidence comparing them directly has been limited. Our results indicate that apixaban may be preferable to other blood thinners because of the lower rate of gastrointestinal bleeding and similar rates of stroke, a finding that we hope will be supported by randomised controlled trials.

“As with all medications, potential risks and benefits can differ between people, so considering the full spectrum of outcomes and side effects will still be necessary for each individual patient.

Source: University College London

Categories : Cardiovascular Disease Diseases, Syndromes and ConditionsTags :

Study Reveals How Shingles Elevates the Risk of Stroke

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Scientists investigating why people who have had shingles have an increased stroke risk now believe the answer lies within, exosomes, lipid vesicles called that shuttle proteins and genetic information between cells. Their study, published The Journal of Infectious Diseases, details the mechanisms behind the link between shingles and strokes.

“Most people know about the painful rash associated with shingles, but they may not know that the risk of stroke is elevated for a year after infection,” said the study’s lead author Andrew Bubak, PhD, assistant research professor in the Department of Neurology at the University of Colorado School of Medicine. “Importantly, the rash is often completely healed and individuals feel normal but nonetheless are walking around with this significant elevation in stroke risk.”

Herpes zoster (HZ) or shingles is caused by the varicella zoster virus which causes chicken pox. The virus lingers in the ganglionic neurons and can reactivate, causing excruciating pain. But researchers have found that shingles can also increase the risk of stroke especially for those under age 40 where the shingles vaccine is not typically recommended.

The risk is greatest in people with the rashes on their faces, perhaps due to the proximity to the brain.

To better understand how this works, Bubak and his team began looking more closely at exosomes.

“Exosomes carry pathogenic cargo that can cause thrombosis and inflammation distant from site of actual infection,” Bubak said. “That could ultimately lead to a stroke in patients.”

Researchers collected plasma samples from 13 patients with shingles and 10 without. The samples were taken at time of infection and at 3-month follow-ups for a subset of patients and exosomes were extracted from the plasma.

The researchers found prothrombotic exosomes which could cause blood clots in those with the infection. They also discovered proinflammatory exosomes that also pose risks for stroke at the 3-month follow-up.

Bubak said the findings suggest that in a subset of people with shingles, the virus may not return to latency or the circulating exosomes that induce a prolonged prothrombotic state may persist even after therapy is done and the rash is gone. He said using antiviral agents longer with the addition of antiplatelet and anti-inflammatory agents could help.

“As well as initiatives to increase HZ vaccine uptake to decrease stroke risk, particularly in individuals with known preexisting stroke risk factors,” said Bubak. “If these findings are confirmed with a larger longitudinal study, then this could change clinical practice.”

Most physicians are unaware of the connection between shingles (which has an effective vaccine) and stroke.

“But it’s really important and so easily mitigated,” Bubak said. “Send them home with antiplatelet agents.”

Source: University of Colorado Anschutz Medical Campus

Categories : Cardiovascular DiseaseTags :

Intensive Blood Pressure Reduction after Ischaemic Stroke Increases Disability

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Credit: American Heart Association

The largest ever randomised controlled trial of intensive blood pressure lowering after thrombectomy in ischaemic stroke patients found that it led to deterioration in surrounding brain tissue and higher rates of disability, compared to less intensive treatment.

The results of the ENCHANTED2/MT trial were presented in a late-breaking session at the World Stroke Congress and simultaneously published in The Lancet. The trial was stopped early due to the significance of the findings.

Professor Craig Anderson, Director of Global Brain Health at The George Institute for Global Health, said the rapid emergence of this effect suggested the more aggressive approach was compromising the return of blood flow to the affected area.

“Our study provides a strong indication that this increasingly common treatment strategy should now be avoided in clinical practice,” he said.

Endovascular thrombectomy is an increasingly used non-surgical treatment for ischaemic stroke, in which x-ray guided microcatheters are inserted into the blood clot to dissolve it.

“A potential downside of this now widely used and effective treatment is that the rapid return of blood supply to an area that has been deprived of oxygen for a while can cause tissue damage known as reperfusion injury,” said Professor Anderson.

“This has resulted in a shift in medical practice towards more intensive lowering of blood pressure after clot removal to try and minimise this damage, but without evidence to support the benefits versus potential harms.”

To this end, researchers recruited 816 adults with acute ischaemic stroke who had elevated blood pressure after clot removal from 44 centres in China between July 2020 and March 2022. They had an average age of 67 and just over a third were female.

Of these, 407 were assigned to more-intensive (target < 120mmHg) and 409 to the less-intensive (target 140–180mmHg) systolic blood pressure control, with the target to be achieved within one hour of entering the study and sustained for 72 hours.

Researchers looked at how well the patients in both groups recovered according to a standard measure of disability, ranging from 0–1 for a good outcome without or with symptoms but no disability, scores of 2–5 reflecting increasing disability levels, and 6 being death.

Patients in the more-intensively treated group had significantly worse scores on the scale compared to those allocated to those treated less intensively.

Compared to the less-intensive group, they had more early brain tissue deterioration and major disability at 90 days but there were no significant differences in brain bleeds, mortality, or serious adverse events.

Patients who had their blood pressure more intensively controlled also rated their quality of life as significantly worse due to limitations on their physical abilities resulting from their stroke.

Prof Anderson said that after scouring the medical literature the research team had been unable to find strong enough evidence to recommend the ideal target for blood pressure control after blood clot removal in patients with acute ischaemic stroke.

“While our study has now shown intensive blood pressure control to a systolic target of less than 120mmHg to be harmful, the optimal level of control is yet to be defined,” he said.

Source: George Institute for Global Health

Categories : Cardiovascular Disease Implants and ProsthesesTags :

A New Pacemaker that Works with Light, not Electricity

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Pacemakers regulate the heartbeats of people with chronic heart diseases like atrial fibrillation and other forms of arrhythmia. However, pacemaker implantation is an invasive procedure, and the lifesaving pacing the devices provide can be extremely painful. Pacemakers also can only be used to treat a few specific types of disease.

In Science Advances, researchers describe their new pacemaker design that uses light and optogenetics that could be implanted with a less invasive procedure, also causing less pain in operation. As well as triggering cardiac neurons with light, the new design can also be powered by light, removing the need for a battery which has to be surgically replaced.

The study was helmed by researchers in the Gutruf Lab, led by biomedical engineering assistant professor and Craig M. Berge Faculty Fellow Philipp Gutruf.

Currently available pacemakers work by implanting one or two leads, or points of contact, into the heart with hooks or screws. If the sensors on these leads detect a dangerous irregularity, they send an electrical shock through the heart to reset the beat.

“All of the cells inside the heart get hit at one time, including the pain receptors, and that’s what makes pacing or defibrillation painful,” Gutruf said. “It affects the heart muscle as a whole.”

The device Gutruf’s team has developed, yet to be tested in humans, would use a digitally created mesh that would send much more targeted signals.

Modifying cardiac neurons to respond to light

Optogenetics modifies cells, usually neurons, to make them responsive to light. This technique only targets cardiomyocytes, the cells of the muscle that trigger contraction and make up the beat of the heart. This precision will not only reduce pain for pacemaker patients by bypassing the heart’s pain receptors, it will also allow the pacemaker to respond to different kinds of irregularities in more appropriate ways. For example, during atrial fibrillation, the upper and lower chambers of the heart beat asynchronously, and a pacemaker’s role is to get the two parts back in line.

“Whereas right now, we have to shock the whole heart to do this, these new devices can do much more precise targeting, making defibrillation both more effective and less painful,” said Igor Efimov, professor of biomedical engineering and medicine at Northwestern University, where the devices were lab-tested. “This technology could make life easier for patients all over the world, while also helping scientists and physicians learn more about how to monitor and treat the disease.”

To ensure the light signals can reach many different parts of the heart, the team created a design that involves encompassing the organ, rather than implanting leads that provide limited points of contact.

The new pacemaker model consists of four petallike structures made of thin, flexible film, which contain light sources and a recording electrode. The petals, specially designed to accommodate the way the heart changes shape as it beats, fold up around the sides of the organ to envelop it, like a flower closing up at night.

“Current pacemakers record basically a simple threshold, and they will tell you, ‘This is going into arrhythmia, now shock!'” Gutruf said. “But this device has a computer on board where you can input different algorithms that allow you to pace in a more sophisticated way. It’s made for research.”

Because the system uses light to affect the heart, rather than electrical signals, the device can continue recording information even when the pacemaker needs to defibrillate. In current pacemakers, the electrical signal from the defibrillation can interfere with recording capabilities, leaving physicians with an incomplete picture of cardiac episodes. Additionally, the device does not require a battery, which could save pacemaker patients from needing to replace the battery in their device every five to seven years, as is currently the norm.

Gutruf’s team collaborated with researchers at Northwestern University on the project. While the current version of the device has been successfully demonstrated in animal models, the researchers look forward to furthering their work, which could improve the quality of life for millions of people.

Source: University of Arizona

Categories : Cardiovascular Disease Metabolic DisordersTags :

High BMI in Adolescent Males Predicts AF Risk

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A recent analysis of Swedish military conscripts found that increased body mass index (BMI) in adolescent men is strongly linked developing early atrial fibrillation (AF) as well as with subsequent worse clinical outcomes after being diagnosed with AF.

The study, published in the Journal of the American Heart Association, included 1 704 467 young men (average age of 18.3 years) enrolled in compulsory military service in Sweden from 1969 through 2005. During a median follow-up of 32 years, 36 693 cases of atrial fibrillation were recorded, at an average age of 52.4 years at diagnosis. Compared with men with a baseline BMI of 18.5–<20.0 kg/m2, men with a BMI of 20.0–<22.5 kg/m2 had a 1.06-times higher risk of developing atrial fibrillation and those with a BMI of 40.0–50.0 kg/ m2 had a 3.72-times higher risk.

In men diagnosed with atrial fibrillation who were followed for a median of approximately 6 years, investigators identified 3767 deaths, 3251 cases of heart failure, and 921 cases of ischaemic stroke. Compared with those with a baseline BMI of <20 kg/m2, those with a baseline BMI of >30 kg/m2 had 2.86-times, 3.42-times, and 2.34-times higher risks of these outcomes, respectively.

“Whether screening for atrial fibrillation in early adulthood among individuals with long-standing obesity and more robust follow-up and initiation of anticoagulants in people with long-standing obesity and atrial fibrillation may improve survival needs to be addressed in future randomised trials” said corresponding author Demir Djekic, MD, PhD, of Sahlgrenska University Hospital/Östra, in Sweden.

Source: Wiley

Categories : Cardiovascular DiseaseTags :

e-Cigarette Chemicals can Cause Heart Arrhythmias

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Researchers have found that exposure to e-cigarette aerosols can cause heart arrhythmias in animal models – both in the form of premature and skipped heart beats. The study findings, published in Nature Communications, suggest that exposure to certain chemicals in e-cigarette liquids (e-liquids) promote arrhythmias and cardiac electrical dysfunction.

“Our findings demonstrate that short-term exposure to e-cigarettes can destabilise heart rhythm through specific chemicals within e-liquids,” said Alex Carll, assistant professor in the UofL Department of Physiology who led the study. “These findings suggest that e-cigarette use involving certain flavors or solvent vehicles may disrupt the heart’s electrical conduction and provoke arrhythmias. These effects could increase the risk for atrial or ventricular fibrillation and sudden cardiac arrest.”

The researchers tested the cardiac impacts of inhaled e-cigarette aerosols solely from the main two ingredients in e-liquids (nicotine-free propylene glycol and vegetable glycerin) or from flavoured retail e-liquids containing nicotine. They found that for all e-cigarette aerosols, the animals’ heart rate slowed during puff exposures and sped up afterwards as heart rate variability declined, indicating fight-or-flight stress responses. In addition, e-cigarette puffs from a menthol-flavoured e-liquid or from propylene glycol alone caused ventricular arrhythmias and other conduction irregularities in the heart.

This work adds to a growing body of research on the potential toxicity and health impacts of e-cigarettes reported by the American Heart Association Tobacco Regulation and Addiction Center, for which UofL serves as the flagship institute.

“The findings of this study are important because they provide fresh evidence that the use of e-cigarettes could interfere with normal heart rhythms – something we did not know before,” said collaborating researcher Professor Aruni Bhatnagar. “This is highly concerning given the rapid growth of e-cigarette use, particularly among young people.”

As e-cigarette use has grown nationwide, the potential advantages and harms of vaping have been debated. Since vaping does not involve combustion, it exposes users and bystanders to little if any carbon monoxide, tar or cancer-causing nitrosamines compared with conventional cigarettes. However, e-cigarettes can deliver aldehydes, particles and nicotine at levels comparable to combustible cigarettes. Vaping might help smokers quit combustible cigarettes, but the appeal and addictiveness of e-cigarettes may encourage youth to vape amidst unknown long-term risks or take up smoking. More than 25% of high schoolers and 10% of middle schoolers in the U.S. reported using e-cigarettes before the pandemic.

“Our team’s findings that specific ingredients in e-cigarette liquids promote arrhythmias indicates there is an urgent need for more research into the cardiac effects of these components in both animals and humans,” A.Prof Carll said.

Source: University of Louisville

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Diet and Exercise for Obese Mothers Lowers Cardiovascular Risk in Infants

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A new study, published in the International Journal of Obesity, found that 3-year-old children were more likely to exhibit risk factors for future heart disease if their mother was clinically obese during pregnancy. A behavioural lifestyle intervention reduced this risk.

There is increasing evidence to suggest that obesity in pregnancy is associated with cardiometabolic dysfunction in children, and that serious cardiovascular disease may begin in the womb.

The UPBEAT trial, conducted at Guy’s and St Thomas’ NHS Foundation Trust, randomised women with obesity (a BMI of over 30 kg/m2) in early pregnancy to a diet and exercise intervention or to standard pregnancy care. The intervention included one-to-one counselling, restricting dietary intake of saturated fat, eating foods with a low glycaemic index such as vegetables and legumes, moderate and monitored physical activity and tools to record exercise. The intervention arm saw improvements in weight gain in pregnancy, physical activity, a healthier diet, and a healthier metabolic profile across pregnancy.

Follow-up of the children at age three showed that children of women with clinical obesity had evidence of cardiac remodelling, a risk factor for future cardiovascular disease. Changes included increased heart muscle thickness, elevated resting heart rate, evidence of early impairment to the heart’s relaxation function and increased sympathetic nerve activity compared to women of normal weight. The children of women who were allocated to the intervention arm were protected from these early changes in heart structure and function.

Study lead Dr Paul Taylor, from King’s College London, said: “Maternal obesity appears to adversely impact the developing foetal nervous system and foetal heart development which is apparent up to 3 years-of-age. A complex lifestyle intervention in pregnancy was associated with protection against cardiac remodelling in infants. We can hypothesise that these changes to the heart and its function will get worse over time, putting the child at increased risk of cardiovascular disease in the future.”

The study suggests that maternal obesity may have a lasting impact on the child’s cardiovascular health. Promoting dietary changes and physical activity during pregnancy may reduce this risk.

Source: King’s College London