Tag: cardiovascular disease

Categories : Cardiovascular Disease Lab Tests and ImagingTags :

Comprehensive Bloodstream Lipid Level Test Can Predict CVD Decades Early

On By ModernMedia
Source: Pixabay CC0

Lipidomics, measuring many different bloodstream lipid levels, can predict the risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD) years in the future, according to a new study in PLOS Biology. Such early prediction through lipidomic profiling may provide the basis for recommending diet and lifestyle interventions before disease develops.

At present, patient history and current risk behaviours are the main predictors for T2D and CVD, along with high- and low-density cholesterol ratios and levels. But there are over one hundred other types of lipids in the blood, which are thought to at least partially reflect aspects of metabolism and homeostasis throughout the body.

Nowadays, it is possible to measure thousands of individual lipids that make up the lipidome. Nuclear magnetic resonance spectrometry (NMR) metabolomics is also being increasingly used in large cohort studies to report on total levels of selected lipid classes, and relative levels of fatty acid saturation.

To find out if detailed lipid profiles could be better predictors, the authors drew on data and blood samples from a longitudinal health study of over 4000 middle-aged participants, first assessed from 1991 to 1994, with follow-up to 2015. Using baseline blood samples, the concentrations of 184 lipids were assessed. During the follow-up period, 13.8% of participants developed T2D, and 22% developed CVD.

The authors performed repeated training and testing on the data to create a risk model. Once the model was developed, individuals were clustered into one of six subgroups based on their lipidomics profile.

Compared to the group averages, the risk for T2D in the highest-risk group was 37%, an increase in risk of 168%. The risk for CVD in the highest-risk group was 40.5%, an increase in risk of 84%. Significant reductions in risk compared to the averages were also seen in the lowest-risk groups. The increased risk for either disease was independent of known genetic risk factors, and independent of the number of years until disease onset.

Rsk could be individually defined decades before disease onset, possibly in time to take steps to avert disease. Lipidomics could be combined with genetics and patient history to provide new insights into the beginnings of the disease. Additionally, new drug candidates could be identified from the lipids  contributing the greatest risk.

“The lipidomic risk, which is derived from only one single mass-spectrometric measurement that is cheap and fast, could extend traditional risk assessment based on clinical assay,” said lead researcher Chris Lauber of Lipotype. “In addition, individual lipids in blood may be the consequences of or contribute to a wide variety of metabolic processes, which may be individually significant as markers of those processes. If that is true, Lauber said, “the lipidome may provide insights much beyond diabetes and cardiovascular disease risk.”

Lauber added: “Strengthening disease prevention is a global joint effort with many facets. We show how lipidomics can expand our toolkit for early detection of individuals at high risk of developing diabetes and cardiovascular diseases.”

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

High CAC and Lipoprotein(a) Scores Greatly Worsen CVD Risk

On By ModernMedia
Healthy red blood cells. Source: NIH

Having both a high lipoprotein(a) and high coronary artery calcium score (CAC) results in a 22% risk of heart attack or stroke over the following 10 years, nearly double the risk of having either condition alone. These are the findings are from a study published in the Journal of the American College of Cardiology (JACC).

Two decades ago, it was recognised that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However Lp(a) was not yet proven to be important due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent research has added to the evidence 

“We are hopeful that by making the connection between Lp(a) and CAC as dual risk drivers, we can raise awareness in the medical community and improve earlier heart attack prevention for these patients,” said cardiologist Parag Joshi, MD, Associate Professor of Internal Medicine at UT Southwestern. “Our data may also expedite the development of treatments designed specifically for this high-risk population.”

About one sixth of people in the U.S. have high Lp(a), driven largely by genetics. Coronary artery calcium (CAC) is a marker of plaque deposits around the heart. 

Cardiology researchers confirmed the Lp(a) and CAC connection by comparing data from two landmark cardiovascular trials, the Dallas Heart Study, an ongoing comprehensive study of 6000 diverse and heart-healthy patients conducted from 2000 to present, and the Multi-Ethnic Study of Atherosclerosis (MESA) 6000-participant study investigating early-stage atherosclerosis.

The researchers found that participants with combined high Lp(a) and high CAC had a 22% 10-year risk of heart attack or stroke, compared with a 10-15% 10-year risk in patients who had either risk factor alone.

The team identified three distinct risk-related trends:

  • High Lp(a), high CAC: These individuals face the highest 10-year risk of heart attack or stroke.
  • High Lp(a), zero CAC: 10-year heart attack and stroke risk is low when there is no CAC, even if Lp(a) is high.
  • Low Lp(a), high CAC: 10-year heart attack or stroke risk is higher than average but lower than with high LP(a) and high CAC combined.

“Establishing the connection between Lp(a) and CAC means we can move to the important next phase of research, which will be defining and personalizing early screening protocols to identify patients at high risk of heart attack,” said Dr Joshi. “With further research, this could mean selectively scanning patients with high Lp(a) for their CAC score, and studying therapies specifically designed to reduce Lp(a) among patients with high CAC.”

Source: UT Southwestern Medical Center

Categories : Cardiovascular DiseaseTags :

CVD Risk Warning for Paracetamol That Contains Sodium

On By ModernMedia
Graphical abstract from European Heart Journal editorial: sodium hidden in medication warrants warning labels by drug companies

Clinicians have recommended avoiding effervescent, soluble paracetamol that contains sodium, following findings from a large study that shows a link with a significantly increased risk of cardiovascular disease (CVD) and mortality in people who have hypertension and even in people with normal blood pressure.

The study of nearly 300 000 patients registered with UK GPs was published in the European Heart Journal.

Sodium is often used to help drugs such as paracetamol dissolve and disintegrate in water. However, effervescent and soluble formulations of 0.5g tablets of paracetamol can contain 0.44 and 0.39g of sodium respectively. If a person took the maximum daily dose of two 0.5g tablets every six hours, they would consume 3.5 and 3.1g of sodium respectively – a dose that exceeds the WHO-recommended total daily intake of 2g a day. In 2018, 170 people per 10 000 of the population in the UK were using sodium-containing medications, with a higher proportion among women. There are alternative formulations that contain little or no sodium.

Excessive salt in the diet remains a major public health problem and is associated with an increased risk of cardiovascular disease (CVD) and death among patients with hypertension. However, there is inconsistent evidence showing an increased risk in normotensive individuals.

Professor Chao Zeng led a team which analysed data from a medical database of UK GPs’ records. They looked at 4532 hypertensive patients who had been prescribed sodium-containing paracetamol and compared them with 146 866 hypertensive patients who had been prescribed sodium-free paracetamol. They also compared 5351 normotensive patients who were prescribed sodium-containing paracetamol with 141 948 normotensive patients prescribed sodium-free paracetamol. The patients were aged 60-90 years and followed up for one year.

The researchers found the risk of heart attack, stroke or heart failure after one year for patients with high blood pressure taking sodium-containing paracetamol was 5.6% (122 cases of CVD), while it was 4.6% (3051 CVD cases) among those taking sodium-free paracetamol. Mortality risk was also higher; the one-year risk was 7.6% (404 deaths) and 6.1% (5510 deaths), respectively.

A similar increased risk was seen among normotensive patients. Among those taking sodium-containing paracetamol, the one-year CVD risk was 4.4% (105 cases of CVD) and 3.7% (2079 cases of CVD) among those taking sodium-free containing paracetamol. The risk of dying was 7.3% (517 deaths) and 5.9% (5190 deaths), respectively.

Prof Zeng said: “We also found that the risk of cardiovascular disease and death increased as the duration of sodium-containing paracetamol intake increased. The risk of cardiovascular disease increased by a quarter for patients with high blood pressure who had one prescription of sodium-containing paracetamol, and it increased by nearly a half for patients who had five or more prescriptions of sodium-containing paracetamol. We saw similar increases in people without high blood pressure. The risk of death also increased with increasing doses of sodium-containing paracetamol in both patients with and without high blood pressure.”

Prof. Zeng said that clinicians and patients should be aware of the risks associated with sodium-containing paracetamol and avoid unnecessary consumption, especially when the medication is taken for a long period of time.

“Given that the pain relief effect of non-sodium-containing paracetamol is similar to that of sodium-containing paracetamol, clinicians may prescribe non-sodium-containing paracetamol to their patients to minimise the risk of cardiovascular disease and death. People should pay attention not only to salt intake in their food but also not overlook hidden salt intake from the medication in their cabinet,” he said.

“Although the US Food and Drug Administration requires that all over-the-counter medications should label the sodium content, no warning has been issued about the potentially detrimental effect of sodium-containing paracetamol on the risks of hypertension, cardiovascular disease and death. Our results suggest re-visiting the safety profile of effervescent and soluble paracetamol.”

Being an observational study it can only show only that there is an association between salt in paracetamol and CVD and deaths, rather than that salt causes these events. Other limitations include a lack of data on dietary intake of salt and excretion of salt from urinary samples. The use of over-the-counter paracetamol was not also recorded, however by restricting the study to those over 60 who qualify for free prescriptions in the UK, the risk of this is minimised.

Source: EurekAlert!

Categories : Cardiovascular Disease GenderTags :

Hypertension Risk for Women After Sexual Assault or Harassment

On By ModernMedia
Photo by Sydney Sims on Unsplash

A new study has found that women who have experienced sexual assault or harassment are at higher long-term risk of developing hypertension than women who have not.

The study appears in the Journal of the American Heart Association.

In the US, nearly 43% of women aged 20 and older have hypertension. Defined as a blood pressure of 130/80mmHg or higher, hypertension is a major risk factor for cardiovascular disease – the number one killer of women, causing one in three deaths each year.

“We know that experiences of sexual violence in the form of sexual assault and workplace sexual harassment are common, and that women are disproportionately victims of such violence, with 13–44% of women reporting sexual assault and up to 80% of women reporting workplace sexual harassment,” said study author Rebecca B. Lawn, PhD. “However, exposure to sexual violence is not widely recognized as a contributor to women’s cardiovascular health. We felt it was important to investigate the relationship among common forms of sexual violence with the risk of developing hypertension. These links could help in the early identification of factors that influence women’s long-term cardiovascular health.”

In this study, researchers analysed data over the course of seven years beginning with a 2008 follow-up of the Nurses’ Health Study II, an ongoing cohort study of US women. The 2008 follow-up measured the incidence of sexual violence and other trauma exposure, as well as post-traumatic stress disorder (PTSD) and symptoms of depression, among a subset of 54 703 of the study’s original participants.

From that subset, Lawn and colleagues analysed data for 33 127 women (95% non-Hispanic white women; average age of 53 years at the beginning of the 2008 follow-up) who had no history of hypertension or had not taken medication for high blood pressure as of the start of the 2008 follow-up.

The analyses found:

  • At the seven-year follow-up in 2015, about 1 in 5 (nearly 7100) of the women self-reported they had developed hypertension, validated with medical records.
  • Sexual assault and workplace sexual harassment were common, with lifetime prevalence of 23% for sexual assault and 12% for workplace sexual harassment; 6% of women reported experiencing both.

Compared to women with no history of sexual assault or harassment, women who reported having experienced both had the greatest increased hypertension risk (21%), followed women who reported experiencing workplace sexual harassment (15%) and an women who reported experiencing sexual assault (11%).

“We did not find any association of increased risk for hypertension among women who had a history of other types of trauma and who did not experience sexual violence, suggesting that increased hypertension risk does not appear to be associated with all trauma exposure,” Dr Lawn said. “Our finding that experiencing both sexual assault and workplace sexual harassment had the highest risk of hypertension underscores the potential compounding effects of multiple sexual violence exposures on women’s long-term cardiovascular health.”

Dr Lawn observed screening for partner violence by primary care clinicians is becoming more common, sexual violence overall is not recognised as a risk factor among women for developing cardiovascular disease.

“These results suggest that screening for a broader range of experiences of sexual violence in routine health care, including sexual harassment in the workplace, as well as verbal harassment or assault, and being aware of and treating potential cardiovascular health consequences may be beneficial for women’s long-term health,” she said. “Reducing sexual violence against women, which is important in its own right, may also provide a strategy for improving women’s lifetime cardiovascular health.”

There are several limitations to the study, including memory biases in recall of sexual violence. The sexual assault and harassment had no measures of severity or timing. Most of the women in the study were white women in the nursing field, limiting generalisability.

“We hope future studies will examine these questions with more detailed information on sexual and other forms of violence. These questions need to be investigated in more diverse groups of people of various ages, races and ethnic backgrounds and gender,” Dr Lawn said. “Although women are disproportionately victims of sexual violence, men are also victims and the physical health implications of experiences of sexual violence against men warrants further investigation.”

Source: American Heart Association

Categories : Cardiovascular Disease Diet and NutritionTags :

Vegetable Intake Does Not Reduce Cardiovascular Risk, Study Finds

On By ModernMedia
Photo by Daria Shevtsova from Pexels

A long-term study on almost 400 000 people in the UK finds little or no evidence that differences in the amount of vegetables consumed affects the risk of cardiovascular disease. 

When known socio-economic and lifestyle confounding factors are corrected for, the small apparent positive effect that remains could likely also be explained away by further confounders.

Getting enough vegetables is important for maintaining a balanced diet and avoiding a wide range of diseases. But might a diet rich in vegetables also lower the risk of cardiovascular disease (CVD)? Unfortunately, new results from a powerful, large-scale new study study in Frontiers in Nutrition found no evidence for this.

The notion of CVD risk being lowered by vegetable consumption might seem plausible at first, as their ingredients such as carotenoids and alpha-tocopherol (vitamin E) have properties that could protect against CVD. But so far, prior evidence for an overall effect of vegetable consumption on CVD has been inconsistent.

The study, which drew on UK Biobank data, found a higher consumption of cooked or uncooked vegetables is unlikely to affect the risk of CVD. The study authors also explained how confounding factors might explain previous spurious, positive findings.

“The UK Biobank is a large-scale prospective study on how genetics and environment contribute to the development of the most common and life-threatening diseases. Here we make use of the UK Biobank’s large sample size, long-term follow-up, and detailed information on social and lifestyle factors, to assess reliably the association of vegetable intake with the risk of subsequent CVD,” said Prof Naomi Allen, UK Biobank’s chief scientist and co-author on the study.

The UK Biobank, follows the health of half a million adults in the UK by linking to their healthcare records. Upon their enrolment in 2006-2010, these volunteers were  interviewed about their diet, lifestyle, medical and reproductive history, and other factors.

The researchers used the responses at enrolment of 399 586 participants (of whom 4.5% went on to develop CVD) to questions about their daily average consumption of uncooked versus cooked vegetables. They analysed the association with the risk of hospitalization or death from myocardial infarction, stroke, or major CVD. They controlled for a wide range of possible confounding factors, including socio-economic status, physical activity, and other dietary factors.

Crucially, the researchers also assessed the potential role of ‘residual confounding’, that is, whether unknown additional factors or inaccurate measurement of known factors might lead to a spurious statistical association between CVD risk and vegetable consumption.

The mean daily intake of total vegetables, raw vegetables, and cooked vegetables was 5.0, 2.3, and 2.8 heaped tablespoons per person. The risk of dying from CVD was about 15% lower for those with the highest intake compared to the lowest vegetable intake. However, this effect was greatly weakened when possible confounding factors were taken into account. Controlling for factors such as socio-economic status reduced the predictive statistical power of vegetable intake on CVD by over 80%, suggesting that more precise measures of these confounders would have explained away any residual effect of vegetable intake.

Dr Qi Feng, the study’s lead author, said: “Our large study did not find evidence for a protective effect of vegetable intake on the occurrence of CVD. Instead, our analyses show that the seemingly protective effect of vegetable intake against CVD risk is very likely to be accounted for by bias from residual confounding factors, related to differences in socioeconomic situation and lifestyle.”

The researchers suggest that subsequent studies should further assess whether particular types of vegetables or their method of preparation might affect the risk of CVD.

Source: Frontiers

Categories : Cardiovascular DiseaseTags :

Hypertension Warning for Long-term Paracetamol Use

On By ModernMedia
BP cuff for home monitoring, Source: Pixabay

Long-term paracetamol use could increase the risk of heart disease and strokes in people with high blood pressure, according to a randomised clinical trial by the University of Edinburgh.

Researchers recommend that patients with a long term prescription, usually for chronic pain, should rather choose the lowest effective dose for the shortest possible time.

The study, which appears in Circulation, is the first large randomised clinical trial to address the question of paracetamol’s effect on cardiovascular disease, and complements earlier work in observational studies.

Paracetamol was often suggested as a safer alternative to non-steroidal anti-inflammatory drugs (NSAIDs), which are known to increase blood pressure and risk of heart disease.

In the latest study, 110 patients with a history of high blood pressure were prescribed one gram of paracetamol four times a day – a routinely prescribed dose in patients with chronic pain – or a matched placebo for two weeks. All patients received both treatments, with the order randomised and blinded. The paracetamol group saw a significant increase in blood pressure, compared to the placebo group.

This rise was similar to that seen with NSAIDs, and could be expected to increase the risk of heart disease or stroke by around 20%. The findings should lead to a review of long-term paracetamol prescriptions to patients, said the researchers, especially to those with hypertension and an increased risk of heart disease or stroke.

Lead Investigator Dr. Iain MacIntyre said: “This is not about short-term use of paracetamol for headaches or fever, which is, of course, fine—but it does indicate a newly discovered risk for people who take it regularly over the longer term, usually for chronic pain.”

Principal Investigator Professor David Webb said: “We would recommend that clinicians start with a low dose of paracetamol, and increase the dose in stages, going no higher than needed to control pain. Given the substantial rises in blood pressure seen in some of our patients, there may be a benefit for clinicians to keep a closer eye on blood pressure in people with high blood pressure who newly start paracetamol for chronic pain.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, who funded the study, said: “This research shows how quickly regular use of paracetamol can increase blood pressure in people with hypertension who are already at increased risk of heart attacks and strokes. It emphasises why doctors and patients should regularly review whether there is an ongoing need to take any medication, even something that may seem relatively harmless like paracetamol, and always weigh up the benefits and risks. However, if you take paracetamol occasionally to manage an isolated headache or very short bouts of pain, these research findings should not cause unnecessary concern.”

Source: University of Edinburgh

Categories : Cardiovascular DiseaseTags : 1 Comment

Patient Doing Well after World-first Pig Heart Transplant

On By ModernMedia
Photo by Piron Guillaume on Unsplash

David Bennett, a 57 year old US man, is doing well after being the world’s first human transplant of a pig heart, according to the man’s son, David Bennett Jr.

When his father first told him of the pig heart option, his son was incredulous, telling the BBC: “I didn’t believe him, I thought he was suffering from delirium at first.”

However, when he did some research on the work done, he realised it was a reality and that they were “walking into the unknown”.

He added that according to Dr Bartley Griffith, who performed the surgery, his father has a good prognosis of 6–9 months. The experimental seven-hour procedure at the University of Maryland Medical Center in Baltimore was considered the last hope of saving Mr Bennett’s life, though it is currently unclear what his long-term chances of survival are. 

“It was either die or do this transplant,” Mr Bennett explained a day before the surgery, adding that it was his “last choice”.

Dr Griffith said heart failure and an irregular heartbeat made him ineligible for a human heart transplant or a heart pump.

Xenotransplantation, as these inter-species transplants are called, have failed, largely because patients’ bodies quickly rejected the animal organ. Notably, in 1984, Baby Fae, a dying infant, lived 21 days with a baboon heart. 

What makes this attempt different is that the Maryland surgeons used a heart from a pig that had been genetically modified to remove a sugar in its cells that’s responsible for that hyper-fast organ rejection. Many biotech companies are working on adapting pig organs for xenotransplantation.

“I think you can characterise it as a watershed event,” Dr David Klassen, chief medical officer at the United Network for Organ Sharing (UNOS), which oversees the US transplant system.

Dr Klassen nevertheless cautioned that it’s only a first tentative step into exploring whether xenotransplantation might finally work this time.

The Food and Drug Administration, which oversees such experiments, allowed the surgery under what’s called a “compassionate use” emergency authorisation, available when a patient with a life-threatening condition has no other options.

Surgeon Bartley Griffith said the surgery would bring the world “one step closer to solving the organ shortage crisis”. At present, 17 people die every day in the US waiting for a transplant, with more than 100 000 reportedly on the waiting list. A record 3800 heart transplants were done last year, according to the UNOS.

Source: BBC News

Categories : Cardiovascular DiseaseTags :

New Easy Biomarker for Cardiovascular Risk

On By ModernMedia
Image by Landon Arnold on Unsplash

A large study has shown that apolipoproteins apoB and apoA-1 together provide early and reliable cardiovascular risk information as well as levels of low-density lipoprotein (LDL) cholesterol. The researchers advocate introducing new guidelines for detecting cardiac risk and say the results, published in PLOS Medicine, may pave the way for early treatment, which could help lower morbidity and mortality rates.

Cardiovascular disease is the most common cause of death globally and includes a wide range of conditions, such as stroke and myocardial infarction with atherosclerosis in different organs of the body. In many cases the disease can be prevented and arrested with lifestyle changes and lipid-lowering treatments using statins and other methods.

The cardiac risk assessment usually uses reference values for the LDL cholesterol. Other types of fat particles can also be measured along with apolipoproteins, which transport cholesterol in the blood. International guidelines for cardiovascular disease recommend using apolipoprotein apoB, which transports LDL cholesterol, as an alternative risk marker for people with type 2 diabetes, overweight and very high levels of blood lipids.

Recent research has, however, indicated the importance of also factoring in the apolipoprotein apoA-1, which transports the protective and anti-inflammatory HDL cholesterol. Calculating the apoB/apoA-1 ratio gives a risk quotient reflecting the balance between the fat particles that expedite atherosclerosis and the “good” protective apoA-1 particles that arrest the process.

In this present study, the researchers have analysed the link between cardiovascular disease and apoB/apoA-1 values in more than 137 000 Swedish adults between the ages of 25 and 84. The individuals were followed for 30 years, during which time 22 000 suffered some form of cardiovascular event. The analysis methods are simple, inexpensive and safe, and do not require pre-test fasting, as is the case with LDL and non-HDL tests. Basing their study on a large database, the researchers linked the laboratory analyses to several clinical diagnosis registers.

“The results show that the higher the apoB/apoA-1 value, the greater the risk of myocardial infarction, stroke and need for coronary surgery,” says Göran Walldius, senior author and professor emeritus at the Institute of Environmental Medicine, Unit of Epidemiology, Karolinska Institutet. “The study also showed that the risk was amplified in the presence of low protective levels of apoA-1.”

Individuals with the highest apoB/apoA-1 values had a 70% higher risk of severe cardiovascular disease and almost triple the risk of non-fatal myocardial infarction compared with those with the lowest apoB/apoA-1 values. Individuals with the highest risk quotient were also more affected by severe cardiovascular diseases many years earlier than individuals with the lowest apoB/apoA-1 values.

The relationship was observed in both men and women and the elevated levels could be detected as early as 20 years before the onset of cardiovascular disease.

“Early preventive treatment and information about cardiovascular risk is, of course, important in enabling individuals to manage their risk situation,” Walldius says. “Early treatment can also reduce the cost burden on the public health services.”

Taken together, the results suggest that the apoB/apoA-1 ratio is a better marker for identifying at-risk individuals for cardiovascular disease compared to the apoB method alone.

“It should be possible to introduce cut-values for apoB, apoA-1 and the apoB/apoA-1 ratio into new guidelines as a complement to current guidance on the detection and treatment of dyslipidaemia,” said Walldius.

Source: Karolinska Institutet

Categories : Cardiovascular Disease Regenerative MedicineTags :

A Review of Progress Toward Heart Muscle Regeneration

On By ModernMedia
Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Twenty years ago, clinicians first attempted to regenerate a failing human heart by injecting muscle myoblasts into the heart during a bypass operation. Despite high initial hopes and multiple studies since then, attempts to remuscularise an injured heart have met with little, if any, success.

Yet, there is hope that a therapy will be developed, according to experts in a Journal of the American College of Cardiology state-of-the-art review. The challenge is this: A heart attack kills heart muscle cells, leading to a scar that weakens the heart, often causing eventual heart failure. The lack of muscle repair is due to the very limited ability of mammalian heart muscle cells to proliferate, except during a brief period around birth.

In the review, the experts focus on three topics. First are several recent clinical trials with intriguing results. Second is the current trend of using cell-derived products like exosomes rather than muscle cells to treat the injured heart. For the third topic, authors discuss likely future experiments to replace a myocardial scar with heart muscle cells by ‘turning back the clock’ of the existing cardiomyocytes, rather than trying to inject exogenous cells. These efforts try to reverse the inability of mature mammalian heart muscle cells to proliferate.

Clinical trials
One of the clinical trials reviewed involved giving cardiosphere-derived cells to patients with Duchenne muscular dystrophy, which affects both heart and skeletal muscles.

Cardiosphere-derived cells are a type of heart stromal/progenitor cell that has potent immunomodulatory, antifibrotic and regenerative activity in both diseased hearts and skeletal muscle. The HOPE-2 trial gave repeated intravenous doses of cardiosphere-derived cells to patients with advanced Duchenne disease, most of whom were unable to walk. Preliminary results showed safety, as well as major improvements in heart parameters such as left ventricle ejection fraction and reduced left ventricle size.

The HOPE-2 trial evaluated a repeated sequential dosing regimen of cell therapy for any cardiac indication, evaluated intravenous cardiosphere-derived administration, and clinically benefitted Duchenne patients.

Two features of the trial may bode well: a move away from invasive cardiac-targeted cell delivery and toward easily administered intravenous cell delivery, and the use of sequential repeated cell doses.

Cell-derived products
Few cells transplanted into the heart survive, though some functional benefits in heart performance have been seen despite physical clearance of grafted cells. It could be possible that the cells were acting not as replacements but rather boosters of endogenous repair pathways through the release of a wide array of tissue-repairing biomolecules.
This led to investigation of using cell-derived products rather than transplanting cells. Most of these biomolecules – proteins and non-coding nucleic acids – are enclosed in tiny vesicles that cells release naturally. When the vesicles, including exosomes, merge into recipient cells, the biomolecules can modulate signaling pathways. Using vesicles or exosomes involves a simpler manufacturing process compared with live cells, the ability to control quality and potency, and being able to refrigerate the vesicles to make administration simpler.

An alternative approach to the vesicle cell-derived products was the finding that injected stem cells can promote cardiac repair through release of biologically active molecules acting as short-range, paracrine hormones. These molecules are distinct from the biomolecules in vesicles or exosomes.

However, before use of any of these cell-derived products for heart repair in early trials, the reviewers say, more experiments are needed in purification of the products, potential modes of delivery and the suitability of repeated doses.

Proliferation of endogenous heart cells
The final review topic looked ahead toward endogenous generation of cardiomyocytes – in other words, forcing existing native cardiomyocytes to divide, or other cells to become cardiomyocytes.

Pigs can regenerate heart muscle for only a few days after birth. But in one remarkable study, researchers injured the heart by removing part of the apex of the left ventricle one day after birth, and then induced heart attack 28 days after birth. Control pigs without the Day 1 resection showed no repair of heart attack damage at Day 56. In contrast, the pigs that had a resection one day after birth, and then had experimental heart attacks at Day 28, showed heart repair by Day 56 – notably an absence of dead heart muscle, known as an infarction. Furthermore, these pigs had more cardiomyocytes throughout their left ventricles.

This study showed that heart muscle cells in large mammals can be induced to proliferate and regenerate by inducing a heart injury at Day 1 to extend the neonatal regneration window. “If this cardiomyocyte cell-cycle activation can be activated in neonates, the same signaling pathways may be activated in adults as well,” the authors wrote, “which is highly impactful and significant.”

Another possible approach to endogenous generation is the direct programming of cardiac fibroblasts into cardiomyocytes. Inducing proliferation of cardiomyocytes will also need ways to promote growth of heart blood vessels to supply the new cardiomyocytes.

In conclusion, the authors believe that short-term approaches to clinical trials of post heart-attack therapies will use cells like cardiospheres or cell products. The longer-term approach, the reviewers said, will target “a more direct remuscularisation of the injured left ventricle by ‘turning back the clock’ of the cardiomyocyte cell-cycle or generating new cardiomyocytes from other cell types such as fibroblasts.”

“However, the efficiency and safety of these strategies, particularly their ability to generate cardiomyocytes seamlessly coupled with their native counterparts and to allow a regulation of these induced proliferative events preventing an uncontrolled and harmful cardiac growth, still need to be appropriately addressed before moving to clinical applications.”

Source: University of Alabama at Birmingham

Categories : Cardiovascular DiseaseTags :

Heart Failure Risk Further Increased by Aspirin Use

On By ModernMedia
Aspirin may increase heart failure risk in at-risk people
Photo by Stephen Foster on Unsplash

Aspirin use is associated with a 26% higher risk of heart failure in people with at least one risk factor for it, according to a study published today in ESC Heart Failure. Risk factors included smoking, obesity, hypertension, high cholesterol, diabetes, and cardiovascular disease.

“This is the first study to report that among individuals with a least one risk factor for heart failure, those taking aspirin were more likely to subsequently develop the condition than those not using the medication,” said study author Dr. Blerim Mujaj of the University of Freiburg, Germany. “While the findings require confirmation, they do indicate that the potential link between aspirin and heart failure needs to be clarified.”

The influence of aspirin on heart failure is controversial, and so the study sought to investigate its association with heart failure incidence in people with and without heart disease and assess whether it is related to a new heart failure diagnosis in at-risk individuals.

The analysis included 30 827 individuals at risk for developing heart failure who were enrolled from Western Europe and the US into the HOMAGE study. The definition of “at risk” included one or more of the following: smoking, obesity, hypertension, high cholesterol, diabetes and cardiovascular disease. Participants were aged 40 years and older and were free of heart failure at baseline. Aspirin use was recorded at enrolment and participants were classified as users or non-users. Participants were followed-up for the first incidence of fatal or non-fatal heart failure requiring hospitalisation.

Average participant age was 67, 34% were women, and at baseline, a total of 7,698 participants (25%) were taking aspirin. During the 5.3-year follow-up, 1330 participants developed heart failure.

The investigators assessed the association between aspirin use and incident heart failure after adjusting for factors including demographic variables, medical history and medication. Taking aspirin was independently associated with a 26% raised risk of a new heart failure diagnosis.

For consistency, the researchers repeated the analysis after matching aspirin users and non-users for heart failure risk factors. In this matched analysis, aspirin was associated with a 26% raised risk of a new heart failure diagnosis. After excluding patients with a history of cardiovascular disease, in 22 690 participants (74%) without cardiovascular disease, aspirin use was still associated with a 27% increased risk of incident heart failure.

Dr Mujaj noted that “this was the first large study to investigate the relationship between aspirin use and incident heart failure in individuals with and without heart disease and at least one risk factor. Aspirin is commonly used – in our study one in four participants were taking the medication. In this population, aspirin use was associated with incident heart failure, independent of other risk factors.”

He concluded that “large multinational randomised trials in adults at risk for heart failure are needed to verify these results. Until then, our observations suggest that aspirin should be prescribed with caution in those with heart failure or with risk factors for the condition.”

Source: European Society of Cardiology