Body

Breast cancer medicines may force some cancer cells into 'sleeper mode', allowing them to potentially come back to life years after initial treatment.

These are the early-stage findings from scientists at Imperial College London, who studied human breast cancer cells in the laboratory.

The team, who studied a group of breast cancer drugs called hormone treatments, say their research opens avenues for finding ways of keeping the cancer cells dormant for longer, or even potentially finding a way of awakening the cells so they can then be killed by the treatment.

Dr Luca Magnani, lead author of the study from Imperial's Department of Surgery and Cancer said: "For a long time scientists have debated whether hormone therapies - which are a very effective treatment and save millions of lives - work by killing breast cancer cells or whether the drugs flip them into a dormant 'sleeper' state.

"This is an important question as hormone treatments are used on the majority of breast cancers. Our findings suggest the drugs may actually kill some cells and switch others into this sleeper state. If we can unlock the secrets of these dormant cells, we may be able to find a way of preventing cancer coming back, either by holding the cells in permanent sleep mode, or be waking them up and killing them."

In the study, published in the journal Nature Communications and funded by Cancer Research UK and the NIHR Imperial Biomedical Research Centre, the team studied around 50,000 human breast cancer single cells in the lab, and found that treating them with hormone treatment exposed a small proportion of them as being in a dormant state.

The team say the 'sleeper cells' may also provide clues as to why some breast cancer cells become resistant to treatment, causing a patient's drugs to stop working, and their cancer to return.

Hormone therapies are used to treat a type of breast cancer called oestrogen-receptor positive. These make up over 70 per cent of all breast cancers, and are fuelled by the hormone oestrogen.

These cancers are usually treated with surgery to remove the tumour, followed by a course of targeted hormone therapy - usually either aromatase inhibitors or tamoxifen, which target oestrogen receptors.

However, around 30 per cent of breast cancer patients taking hormone therapies see their cancer eventually return - sometimes as long as 20 years after treatment. This returning cancer is usually metastatic, meaning it has spread around the body, and the tumours are often now resistant to medication.

Previous work by the same team has investigated why breast cancer cells become resistant to hormone treatment, with findings suggesting cells can make their own 'fuel', allowing them to avoid being 'starved' by cancer treatment.

This new research provides another piece in the puzzle, explained Dr Iros Barozzi, co-author of the study, also from the Department of Surgery and Cancer: 'These sleeper cells seem to be an intermediate stage to the cells becoming resistant to the cancer drugs. The findings also suggest the drugs actually trigger the cancer cells to enter this sleeper state."

The research also revealed cells in this dormant sleeper state were more likely to spread around the body, explained Dr Sung Pil Hong, study co-author from Imperial: "Our experiments suggest these sleeper cells are more likely to travel around the body. They could then 'awaken' once in other organs of the body, and cause secondary cancers. However, we still don't know how these cells switch themselves into sleep mode - and what would cause them to wake up. These are questions that need to be addressed with further research."

The team added that hormone therapies remain one of the most effective treatments against breast cancer, and that further patient research will explore whether taking hormone therapies for longer after initial cancer treatment could prevent cancer cells from waking from their sleeping state.

Dr Rachel Shaw from Cancer Research UK, said: "Although treatments for breast cancer are usually successful, cancer returns for some women, often bringing with it a poorer prognosis. Figuring out why breast cancer sometimes comes back is essential to help us develop better treatments and prevent this from happening. This study highlights a key route researchers can now explore to tackle 'sleeping' cancer cells that can wake up years after treatment, which could potentially save the lives of many more women with the disease."

HAMILTON, ON (Sept. 2, 2019) - Concerted effort by friends, family and non-physician health workers can make a dramatic difference in reducing the risk factors for heart problems in patients with hypertension, an international study by Hamilton researchers has found.

People with new or poorly controlled hypertension given an integrated and comprehensive intervention by non-physician health workers along with personal supporters over a year had a reduction in cardiovascular risk of more than 40 per cent compared to usual care.

"There was a doubling in blood pressure control, with reductions in low-density lipoprotein (LDL) cholesterol, and improvements in medication adherence, physical activity, and diet," said lead author Jon-David Schwalm of the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.

The study results are part of a presentation today in Paris, France at the European Society of Cardiology Congress with the World Congress of Cardiology and are also being published in The Lancet. The clinical trial, called Heart Outcomes Prevention and Evaluation 4 or HOPE 4, is led by PHRI.

Hypertension is the leading cause of cardiovascular disease worldwide, with the majority of the burden in low- and middle-income countries. Although there are clear benefits and recommendations for the use of antihypertensive medications and statins in patients with hypertension, control of blood pressure and use of statins in these countries is very low.

The study involved 1,371 people 50 or older from 30 communities in Colombia and Malaysia.

People in sixteen communities received usual care and those in 14 communities had an intervention that included the initiation and monitoring of treatments and controlling risk factors by non-physician health workers using computer tablet-based management algorithms and counselling; the provision of free antihypertensive and statin medicines recommended by non-physician health workers under supervision of physicians, and the involvement of a friend or family member to support adherence to medications and lifestyle advice.

"Previous studies with non-physician health workers led to modest effects on cardiovascular risk factors. We tested whether an intervention involving health workers, general practitioners and family, with provision of evidence-based medications, can safely and substantially reduce individual cardiovascular risk and found it successful," said Schwalm, an associate professor of medicine at McMaster, a scientist at the PHRI and an interventional cardiologist at Hamilton Health Sciences.

Regarding how the intervention was done, computer tablets were used to collect study data, help the health workers make decisions when with the patients using simplified management algorithms to initiate and monitor antihypertensives and statins, and support counselling participants on health behaviours.

The friend or family supporter was encouraged to attend sessions with the health worker or physician, and they were present at three-quarters of the visits. In addition, the supporter's role was to give ongoing help to improve adherence to medications and healthy behaviours between scheduled health worker visits.

The primary outcome was change in Framingham Risk Score, which is an estimate of the ten-year risk of cardiovascular disease. In those who received the intervention, their risk score dropped by 11.2 per cent as compared to 6.4 per cent in the control. This is approximately two fold.

There was an 11.45 mmHg greater reduction in systolic blood pressure, and a 0.41 mmol/L larger reduction in serum LDL cholesterol in the intervention, compared to the control group. Both of these findings are statistically significant and predict large reductions in future cardiovascular disease events. The proportion of patients with controlled hypertension was more than twice as great, 69 per cent in the intervention group compared to 31 per cent in the control group.

In particular, there were important improvements in physical activity and diet.

"All components of the intervention were essential to the benefits observed," Schwalm said. "Our intervention is innovative in how, by taking a systems approach, it is more than the sum of its parts. It was developed after a detailed health system assessment and barrier analysis in each country, using a combination of quantitative and qualitative research, to identify local challenges and tailor the intervention to overcome these."

Salim Yusuf, principal investigator of the study and PHRI executive director, added that the research results will have global impact.

"This strategy is pragmatic, effective, and scalable, and has the potential to substantially reduce cardiovascular disease globally, compared to current methods that are solely physician based," he said.

"Adopting or adapting the HOPE 4 strategy in different countries to better control hypertension and reduce other risk factors could help achieve the United Nations' target for a one-third reduction in premature cardiovascular mortality by 2030."

An extreme case of "fussy" or "picky" eating caused a young patient's blindness, according to a new case report published today [2 Sep 2019] in Annals of Internal Medicine.

The University of Bristol researchers who examined the case recommend clinicians consider nutritional optic neuropathy in any patients with unexplained vision symptoms and poor diet, regardless of BMI, to avoid permanent vision loss.

Nutritional optic neuropathy is a dysfunction of the optic nerve which is important for vision. The condition is reversible, if caught early. But, left untreated, it can lead to permanent structural damage to the optic nerve and blindness.

In developed countries like the UK, the most common causes of nutritional optic neuropathy are bowel problems or drugs that interfere with the absorption of various important nutrients from the stomach. Purely dietary causes are less common because food supply is good, but elsewhere in the world, poverty, war and drought are linked to malnutrition and higher rates of nutritional optic neuropathy.

Clinician scientists from Bristol Medical School and the Bristol Eye Hospital examined the case of a teenage patient who first visited his GP complaining of tiredness. The link between his nutritional status and vision was not picked up until much later, and by then, his visual impairment had become permanent.

Aside from being a "fussy eater," the patient had a normal BMI and height and no visible signs of malnutrition and took no medications. Initial tests showed macrocytic anaemia and low vitamin B12 levels, which were treated with vitamin B12 injections and dietary advice. When the patient visited the GP a year later, hearing loss and vision symptoms had developed, but no cause was found. By age 17, the patient's vision had progressively worsened, to the point of blindness. Further investigation found the patient had vitamin B12 deficiency, low copper and selenium levels, a high zinc level, and markedly reduced vitamin D level and bone mineral density. Since starting secondary school, the patient had consumed a limited diet of chips, crisps, white bread, and some processed pork. By the time the patient's condition was diagnosed, the patient had permanently impaired vision.

The researchers concluded that the patient's 'junk food' diet and limited intake of nutritional vitamins and minerals resulted in the onset of nutritional optic neuropathy. They suggest the condition could become more prevalent in future, given the widespread consumption of 'junk food' at the expense of more nutritious options, and the rising popularity of veganism if the vegan diet is not supplemented appropriately to prevent vitamin B12 deficiency.

Dr Denize Atan, the study's lead author and Consultant Senior Lecturer in Ophthalmology at Bristol Medical School and Clinical Lead for Neuro-ophthalmology at Bristol Eye Hospital, said: "Our vision has such an impact on quality of life, education, employment, social interactions, and mental health. This case highlights the impact of diet on visual and physical health, and the fact that calorie intake and BMI are not reliable indicators of nutritional status."

The team recommend dietary history should be part of any routine clinical examination like asking about smoking and alcohol intake. This may avoid a diagnosis of nutritional optic neuropathy being missed or delayed as some associated visual loss can fully recover if the nutritional deficiencies are treated early enough.

The DNA of Scottish people still contains signs of the country's ancient kingdoms, with many apparently living in the same areas as their ancestors did more than a millennium ago, a study shows.

Experts have constructed Scotland's first comprehensive genetic map, which reveals that the country is divided into six main clusters of genetically similar individuals: the Borders, the south-west, the north-east, the Hebrides, Orkney and Shetland.

These groupings are in similar locations to Dark Age kingdoms such as Strathclyde in the south-west, Pictland in the north-east, and Gododdin in the south-east. The Dark Ages are widely considered to be from the end of the Roman Empire in 476 AD to around 1000 AD.

In addition to showcasing Scotland's genetic continuity, experts believe this type of population analysis could aid the discovery of rare DNA differences that might play major roles in human disease.

The new data from Scotland means this is the first time the genetic map of the United Kingdom and the Republic of Ireland can be seen in its entirety, researchers say.

The study also discovered that some of the founders of Iceland may have originated from north-west Scotland and Ireland and that the Isle of Man is genetically predominantly Scottish.

The study looked at the genetic makeup of more than 2500 people from Britain and Ireland - including almost 1000 from Scotland - whose grandparents or great grandparents were born within 50 miles of each other.

Researchers from the University of Edinburgh and RCSI (Royal College of Surgeons in Ireland) then compared this with the DNA of people who lived thousands of years ago.

Experts found that Orkney and Shetland had the highest levels of Norwegian ancestry outside Scandinavia and that many islands within the archipelagos had their own unique genetic identity.

The islands also contained subtle, but notable genetic differences between people living only a few miles apart, with no obvious physical barriers.

The study was funded by the Medical Research Council, the Chief Scientist Office of the Scottish Executive and Science Foundation Ireland.

It is published in the journal Proceedings of the National Academy of Sciences.

Professor Jim Wilson, from the University of Edinburgh's Usher Institute and MRC Human Genetics Unit, said: "It is remarkable how long the shadows of Scotland's Dark Age kingdoms are, given the massive increase in movement from the industrial revolution to the modern era. We believe this is largely due to the majority of people marrying locally and preserving their genetic identity."

Dr Edmund Gilbert, from RCSI, added: "This work is important not only from the historical perspective, but also for helping understand the role of genetic variation in human disease. Understanding the fine-scale genetic structure of a population helps researchers better separate disease-causing genetic variation from that which occurs naturally in the British and Irish populations, but has little or no impact on disease risk."

Paris, France - 02 Sept 2019: Malaria infection is linked with a 30% raised risk of heart failure, according to a small study presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

The mosquito-borne infection affects more than 219 million people worldwide each year, according to 2018 statistics from the World Health Organization (WHO). (2)

"We have seen an increase in the incidence of malaria cases and what is intriguing is we have seen the same increase in cardiovascular disease in the same regions," said first author Dr Philip Brainin, a postdoctoral research fellow at Herlev-Gentofte University Hospital, Denmark. "Even though we have taken preventive measures to decrease the malaria numbers it remains a major burden."

The researchers used Danish nationwide registries to identify patients with a history of malaria infection between January 1994 and January 2017. The mean age of patients in the study was 34 years old and 58% were male.

A total of 3,989 malaria cases were identified, with 40% having plasmodium falciparum, a parasite transmitted through mosquito bites that is responsible for the majority of severe malaria cases in humans.

The 11-year follow-up of patients revealed 69 cases of heart failure, which was very high as compared to the general population, and 68 cases of cardiovascular death, which was considered within normal range.

"These patients had a 30% increased likelihood of developing heart failure over the follow-up time," Dr Brainin said. "Thirty percent is a high number, but you also have to understand that it is a relatively small study, which is a limitation. As of right now the results of this study are more hypothesis-generating for future studies."

Dr Brainin noted that, while heart failure risk was increased for patients in the study, there was not a link to heart attack or cardiovascular death.

More research will be needed to further validate the findings, but recent studies have found that malaria could be a contributor to functional and structural changes in the myocardium, which is the muscle tissue of the heart.

Experimental studies have also shown that malaria may affect the blood pressure regulatory system causing hypertension, which is a contributor to heart failure.

Malaria can also affect vascular pathways that cause inflammation in the heart, which could lead to fibrosis and then heart failure.

"I think these findings are quite interesting not only from an epidemiological perspective but also from the medical perspective," he added. "If malaria is potentially linked to cardiac disease it could represent a therapeutic target we could use to control and prevent cardiac disease in these regions."

Because it is too early to convert the results into clinical practice, Dr Brainin advised that physicians should continue to focus on traditional and validated risk factors that may lead to heart failure.

According to the European Society of Cardiology (ESC), a combination of high blood pressure, diabetes, obesity, and coronary artery disease are among the most common risk factors for heart failure.

"I think, in light of these findings, there is room for much more research into a potentially overlooked complication to malaria, which could be development of cardiac disease or heart failure. And I hope that these findings will be a catalyst for future research into this field," he concluded.

Dr Brainin's research group, in collaboration with Federal University of Acre in Brazil, will systematically investigate malaria patients and their cardiovascular status by looking at biomarkers, echocardiograms, and following malaria patients for cardiovascular events, beginning in 2020.

BOSTON--Results were released today from the first two clinical studies designed specifically to examine the effects of the heart drug sacubitril/valsartan on the structure and function of the failing heart. Treatment with sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor (ARNI), substantially lowers rates of death and hospitalization in certain types of heart failure patients. However, the mechanisms by which the drug actually affects the heart are poorly understood.

These two new studies suggest a key effect of ARNI is to reverse cardiac remodeling -- a finding that could lead to better management of this condition. One of the studies, called PROVE-HF, was led by James L. Januzzi, MD, a physician in the Division of Cardiology at Massachusetts General Hospital (MGH). The other study, called EVALUATE-HF, was led by Akshay S. Desai, MD, director of Cardiomyopathy and Heart Failure in the Cardiovascular Division at Brigham and Women's Hospital. Both studies were published online this morning in the Journal of the American Medical Association and presented today at the European Society of Cardiology Scientific Sessions in Paris, France. Scott Solomon, MD, director of Noninvasive Cardiology and senior physician at Brigham and Women's Hospital, helped to lead both studies, and is a co-author on both reports.

In heart failure, progressive cardiac remodeling leads to changes in the shape and size of the heart, contributing to weakened heart function and progressive symptoms such as shortness of breath, reduced exercise capacity, and fluid retention. The researchers found that treatment with ARNI was associated with significant improvements in cardiac structure and function and that these changes were strongly associated with reductions in blood levels of the biomarker amino-terminal-pro-B-type natriuretic peptide (NT-proBNP). Levels of NT-proBNP levels are tightly linked to the risk of death and heart failure hospitalization.

"In remodeling, the heart gets larger and stiffer, making it more difficult for it to pump," says Januzzi. "Reversing remodeling can reduce those effects and lead to better function."

The PROVE-HF trial was a prospective, single arm study of nearly 800 patients with heart failure and reduced ejection fraction who were over the age of 65 and had just started on ARNI. Patients were followed for one year and monitored serially with blood tests to measure cardiac biomarkers and echocardiography to assess cardiac structure and function. Treatment with ARNI rapidly and significantly lowered levels of NT-proBNP at one year, and this reduction in levels of the biomarker was strongly associated with improvements in cardiac structure and function at both six months and one year.

Ejection fraction is an important measure of the heart's ability to pump blood. When the study started, the mean ejection fraction among the participants was just 28%: In healthy individuals that number is usually above 50%. After patients started the drug their ejection fraction levels rose by an average of 9.5% per quarter, with 25% patients seeing dramatic increases of 13% or more. "An overwhelming number of patients showed improvement, and some people were all the way back to a normal ejection fraction level by the end of study," says Januzzi.

An important observation of the PROVE-HF study was that ARNI appeared to benefit patients that had not been studied in previous trials of the drug, including those with relatively new-onset heart failure, those with lower concentrations of NT-proBNP, and those who could not tolerate higher doses of the medication. Safety and tolerability of ARNI at one year were also consistent with the findings of the PARADIGM-HF trial, which led to initial FDA approval of the drug. "Our results suggest that ARNI therapy would be expected to benefit a wide range of patients suffering from heart failure with reduced ejection fraction," Januzzi says.

Changes in cardiac structure and function may also be closely related to progressive stiffening of the aorta, which increases the load on the failing heart and may stimulate further cardiac remodeling. The second study, EVALUATE-HF, was designed as a prospective, randomized comparison of the effects of ARNI versus enalapril (a cornerstone of heart failure treatment) on aortic stiffness and cardiac structure and function in patients with heart failure and reduced ejection fraction.

This study randomly allocated 464 patients with chronic heart failure, reduced ejection fraction, and history of high blood pressure to treatment with ARNI or enalapril and followed them for a period of 12 weeks with periodic assessment of arterial stiffness, cardiac structure and function, cardiac biomarkers, and quality of life. At 12 weeks, no difference was noted between the two treatments with regard to change in aortic impedance -- a measure of aortic stiffness. However, consistent with PROVE-HF's findings, significant reductions were seen with ARNI in secondary measures of cardiac structure and function. In this study, improvements in remodeling were also correlated to reductions in NT-proBNP and improvements in quality of life.

Overall, the EVALUATE-HF data suggest that the clinical benefits of ARNI are likely unrelated to changes in central aortic stiffness, but might be related to favorable early effects of neprilysin inhibition (one of the primary effects of ARNI) on myocardial remodeling.

"Significant improvements in cardiac structure and function, biomarkers of cardiac wall stress and injury, and overall quality of life in the patients treated with sacubitril/valsartan, compared to those treated with enalapril after just 12 weeks underscores the potent effect of sacubitril/valsartan on cardiac remodeling in heart failure," said Desai.

"Together, the PROVE-HF and EVALUATE-HF studies present compelling evidence that the established clinical benefits of sacubitril/valsartan in patients with heart failure and reduced ejection fraction may be related to improvements in cardiac structure and function," said Desai. "These trials suggest that sacubitril/valsartan may actually reverse the cardiac remodeling that drives heart failure progression and worsening of clinical outcomes."

Paris, France - 1 Sept 2019: Influenza vaccination in patients with high blood pressure is associated with an 18% reduced risk of death during flu season, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

"Given these results, it is my belief that all patients with high blood pressure should have an annual flu vaccination," said first author Daniel Modin research associate of the University of Copenhagen, Denmark. "Vaccination is safe, cheap, readily available, and decreases influenza infection. On top of that, our study suggests that it could also protect against fatal heart attacks and strokes, and deaths from other causes."

According to previous research, the stress flu infection puts on the body may trigger heart attacks and strokes. Patients with hypertension (high blood pressure) are at raised risk of heart attack and stroke. By stopping flu infection, vaccination could also protect against cardiovascular events, but until now this had not been investigated.

The study used Danish nationwide healthcare registers to identify 608,452 patients aged 18 to 100 years with hypertension during nine consecutive influenza seasons (2007 to 2016). The researchers determined how many patients had received a flu vaccine prior to each season. They then followed patients over each season and tracked how many died. In particular, they recorded death from all causes, death from any cardiovascular cause, and death from heart attack or stroke.

Finally, they analysed the association between receiving a vaccine prior to flu season and the risk of death during flu season. The analysis controlled for patient characteristics that could impact the likelihood of dying such as age, comorbidities, medications, and socioeconomic status.

After adjusting for patient differences, in a given influenza season, vaccination was associated with an 18% relative reduction in the risk of dying from all causes, a 16% relative reduction in the risk of dying from any cardiovascular cause, and a 10% relative reduction in the risk of dying from heart attack or stroke.

Mr Modin said: "We show that influenza vaccination may improve cardiovascular outcomes in patients with hypertension. During the nine flu seasons we studied, vaccine coverage ranged from 26% to 36%, meaning that many patients with high blood pressure were not vaccinated. If you have high blood pressure, it would be worth discussing vaccination with your doctor."

Regarding how flu and cardiovascular disease might be connected, Mr Modin noted that when the influenza virus infects the body it triggers a strong immune reaction and subsequent inflammation. These responses fight the infection and clear the virus from the body but may increase the risk of having a heart attack or stroke.

He said: "Heart attacks and strokes are caused by the rupture of atherosclerotic plaques in the arteries leading to the heart or the brain. After a rupture, a blood clot forms and cuts off the blood supply. It is thought that the high levels of acute inflammation induced by influenza infection reduce the stability of plaques and make them more likely to rupture."

Paris, France - 1 Sept 2019: Less than 4% of relatives of young cardiac arrest victims receive information on family screening that could prevent further deaths, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

"When a patient under 45 dies from sudden cardiac arrest, the probability of an inherited cardiac disease is highly likely and accurately identifying the cause is crucial for relatives," said study author Dr Ardalan Sharifzadehgan of the Paris Sudden Death Expertise Centre (Paris-SDEC), France.

"All first-degree relatives should be advised to undergo family screening and eventually genetic testing if an inherited cardiac disease is suspected," he continued. "This helps clarify the diagnosis of their loved one and can trigger preventive measures such as lifestyle modification, beta-blockers, or an implantable cardioverter-defibrillator (ICD) to avoid deaths in relatives."

The study was conducted in cardiac arrest patients under 45 who were alive when they arrived at the hospital, but subsequently died in the intensive care unit (ICU).

Performance of diagnostic tests in patients was suboptimal. Coronary angiograms were performed in 18%, brain and chest computed tomography (CT) scans in 25%, and transthoracic echocardiography (TTE) in 29%. Only 11% of victims had an autopsy and 1.4% had blood samples collected for further genetic testing after death. Finally, just 3.5% of families were told about screening.

"While doing these examinations in 100% of patients is ideal, it won't always be realistic as some have circulatory issues that prevent accurate testing," said Dr Sharifzadehgan. "Around two-thirds of sudden cardiac arrest patients that are alive at hospital admission die in ICU. Survivors undergo more examinations and relatives receive more information on family screening. This shows that early systematic investigations are fundamental to understanding the underlying cause, and better follow-up of families is needed after fatal events."

A specific cause of death was not identified in more than half of patients in the study (56%). "We believe this is due to the lack of core cardiac testing during hospitalisation, such as CT scans, TTE, and coronary angiogram," he said. "In addition, there was minimal autopsy and genetic testing done after each death, leaving the study void of data to determine a specific cause or cardiac diagnosis and stop future deaths in family members."

A specific cause of death was identified in 44% of patients. The causes were acute coronary syndrome (45%), structural non-ischaemic heart disease (26%), pulmonary embolism (14%), chronic coronary artery disease (10%), and non-structural heart disease (1.8%).

The study was conducted using Paris-SDEC registry data on 18,622 out-of-hospital cardiac arrests in the Paris area between 2011 and 2016. Of those, 3,028 were admitted alive to ICU at 48 hospitals. Of the patients admitted alive to ICU, 2,190 died in ICU, including 367 patients under 45 who were the focus of the current study.

Paris, France - 1 Sept 2019: Genetic high cholesterol is underdiagnosed and undertreated, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1) Screening could identify patients and family members affected by the condition so that lifestyle changes and treatments can be started to prevent heart attack and stroke.

Heterozygous familial hypercholesterolaemia (FH) is a life-threatening genetic condition linked with a high risk of premature cardiovascular disease, including heart attack and stroke. FH is one of the most common potentially fatal family disorders, with a prevalence estimated at 1/250 to 1/200, corresponding to 3.6 to 4.5 million individuals in Europe.

Patients with FH have high levels of "bad" cholesterol (low-density lipoprotein; LDL) due to a mutation in genes that clear cholesterol from the body. LDL particles accumulate in the blood and can ultimately build up in the coronary artery walls. Children of patients with heterozygous FH have a 50% chance of inheriting the disorder.

As LDL cholesterol levels are elevated as early as birth, the risk of heart attack in patients with FH is 10 to 13 times greater than that of the general population. Elevated LDL cholesterol plus family or personal history of early heart disease are key criteria for diagnosis, which may be confirmed by genetic testing. Management of FH includes a healthy lifestyle and medication.

This study examined the frequency of FH in the RICO survey,(2) a large French database of patients hospitalised for a heart attack between 2011 and 2017. The researchers determined whether patients had FH using LDL cholesterol levels and family or personal history of premature coronary artery disease. Treatments, patient characteristics, and severity of coronary artery disease were compared between patients with and without FH.

Among the 11,624 patients with heart attack, FH was not rare (2.1%). When compared to patients without FH, those with FH were 20 years younger (71 versus 51 years) and had more severe coronary lesions.

Senior author Professor Marianne Zeller of the University of Burgundy - Franche-Comté, Dijon, France said: "Taken together, the earlier onset and severe lesions show the aggressive nature of coronary artery disease in patients with familial hypercholesterolaemia."

Regarding lipid-lowering treatments, chronic statin treatment was used in 48% of FH patients and ezetimibe in 8%. "There was a dramatic underuse of drugs to reduce cholesterol levels," said Prof Zeller. "Nearly half had no chronic treatment before they had a heart attack and ended up in hospital. This indicates that at least half of patients with FH were probably unaware of their diagnosis and their heightened risk of heart disease, and also that their family members could unknowingly be affected."

"Systematic FH screening at the time of hospitalisation for a heart attack could identify these high-risk patients," she continued. "Screening is simple, mainly based on high levels of LDL cholesterol and history of early coronary artery disease (personal and/or family). Diagnosis can be confirmed by a genetic test, which is available in most European countries."

Compared to patients without FH, those with FH had a significantly lower rate of hypertension (59% versus 47%), diabetes (25% versus 17%) and prior stroke (8% versus 4%), but a higher prevalence of smoking (23% versus 56%) and a personal (15% versus 20%) or family history (18% versus 78%) of coronary artery disease.

She concluded: "Better identification of patients with FH is needed so that cholesterol lowering treatments can be started as well as recommended lifestyle modifications such as eat a healthy diet, be physically active and quit smoking. Once we know who the patients are, we can then look for relatives with the condition."

Boston, MA -- The number of patients with heart failure with preserved ejection fraction is on the rise, and the search is on for a therapy that can improve health outcomes in this group of patients for whom no approved therapies are available. In a Hot Line Session at the European Society of Cardiology Congress, 2019, investigators from Brigham and Women's Hospital presented the results of Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF), sponsored by Novartis, the largest, randomized clinical trial of heart failure patients with preserved ejection fraction. The team reports that, overall, the drug sacubitril-valsartan did not significantly reduce heart failure hospitalizations and cardiovascular death compared to valsartan alone, but the data suggest benefit for patients in the lower ejection fraction range, for which there currently exists no approved therapies. Results are published simultaneously in The New England Journal of Medicine.

"Overall, we observed fewer hospitalizations for heart failure in patients who were treated with sacubitril/valsartan compared with valsartan alone, but these results were just short of statistical significance. However, we found that response to therapy differed based on patients' ejection fraction. These findings extend our findings with sacubitril/valsartan in patients with frankly reduced ejection fraction to those with ejection fraction that is less reduced, but not normal," said study co-chair Scott Solomon, MD, the Edward D. Frohlich Distinguished Chair and senior physician at the Brigham.

"Heart failure with preserved ejection fraction accounts for about half of all patients with heart failure; there are currently no approved therapies, and so this represents a huge unmet need," said study co-chair John McMurray, MD, of the British Heart Foundation (BHF) Cardiovascular Research Centre, University of Glasgow.

In 2014, this same team presented data as part of the PARADIGM-HF trial showing that the angiotensin-neprilysin inhibitor sacubitril-valsartan significantly reduced heart failure hospitalization and cardiovascular death, compared with standard treatment, in patients with heart failure with reduced ejection fraction. The new trial, PARAGON-HF, examines the same drug's effects but among heart failure patients with preserved ejection fraction (45 percent or higher).

About 5.7 million adults in the U.S. have heart failure, which is estimated to cost the nation $30.7 billion each year. "Ejection fraction" refers to the percentage of blood that gets expelled each time the heart contracts. A normal ejection fraction is 55 percent or greater. Patients with an ejection fraction of 40 percent or less are diagnosed with heart failure with reduced ejection fraction and therapies exist for these patients. In heart failure with preserved ejection fraction, in which the ejection fraction is greater than 40 percent, either the pumping ability of the heart or the filling ability of the heart may be impaired.

In PARAGON-HF, 4,822 patients were randomly assigned to receive sacubitril-valsartan or valsartan. Patients were followed for up to five years. During the study, there were 894 primary events (690 hospitalizations for heart failure and 204 deaths from cardiovascular causes) in 526 patients in the sacubitril-valsartan group. Of the 557 patients in the valsartan group, there were 1,009 primary events (797 hospitalizations for heart failure and 212 cardiovascular deaths). The difference between the groups did not meet the predetermined level of statistical significance.

Safety outcomes between the two groups were similar, with slightly higher rates of low blood pressure among patients taking sacubitril-valsartan, but lower rates in those patients of elevated serum creatinine or potassium -- markers of kidney dysfunction -- compared to those taking valsartan.

Solomon and colleagues analyzed outcomes among several prespecified subgroups, finding evidence of a benefit in women and in those patients with an ejection fraction of 45-57 percent. Women comprise a high proportion of heart failure patients with preserved ejection fraction. Historically, women have been underrepresented in cardiovascular clinical trials, but they comprised over half of the patients in this trial.

"Heart failure with preserved ejection fraction represents an important area of unmet need and limited understanding," said Solomon. "Our findings suggest that there may be an important difference among female patients' response to this therapy, and we'll be working over the next several years to understand why."

Boston, MA -- In late-breaking clinical trial results presented in a Hot Line Session today at the European Society of Cardiology Congress 2019, investigators from Brigham and Women's Hospital and Greater Paris University Hospitals - AP-HP/Université de Paris presented the results from The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), a clinical trial sponsored by AstraZeneca that evaluated whether adding ticagrelor to aspirin improves outcomes for patients with stable coronary artery disease and diabetes mellitus but without a history of heart attack or stroke. Taking ticagrelor in addition to aspirin reduced the risk of a composite of cardiovascular death, heart attack, or stroke. Patients on this dual-antiplatelet therapy also experienced greater risk of major bleeding. In THEMIS-PCI, a study that specifically looked at THEMIS patients with a history of previous percutaneous coronary intervention (PCI) that includes stenting, versus the overall THEMIS population, investigators found even more favorable results for patients taking ticagrelor plus aspirin. Results of THEMIS are published simultaneously in The New England Journal of Medicine and results from THEMIS-PCI are published simultaneously in The Lancet.

"With prolonged dual-antiplatelet therapy, we need to be thoughtful in considering which patients are most suited to taking the regimen -- that is, those at high ischemic risk and low bleeding risk," said THEMIS co-chair Deepak L. Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs at the Brigham and professor of medicine at Harvard Medical School. "Our findings show that the greatest benefit occurred in those patients with diabetes and stable coronary artery disease with a history of prior stenting for whom ticagrelor, when added to aspirin, reduced important cardiovascular events, such as heart attacks, strokes and amputations."

THEMIS co-chair Philippe Gabriel Steg, MD, Chief of Cardiology at Hôpital Bichat, Greater Paris University Hospitals - AP-HP, and professor at Université de Paris, stated, "The THEMIS population is a critically important one in which to understand the potential benefits of taking ticagrelor in addition to aspirin. As the number of people with diabetes continues to rise globally, we need to evaluate ways of improving long-term outcomes and preventing cardiovascular and ischemic events."

In THEMIS, the largest trial of patients with diabetes to date, more than 19,000 patients with stable coronary artery disease and diabetes were randomized to receive either ticagrelor plus aspirin or a placebo plus aspirin. Patients were followed for an average of more than three years. During that time, 736 of 9,619 patients (7.7 percent) taking ticagrelor plus aspirin experienced cardiovascular death, myocardial infarction, or stroke versus 818 of 9,601 patients (8.5 percent) taking placebo plus aspirin - a 10 percent reduction.

As seen with other anti-platelet medications, ticagrelor increased the risk of major bleeding (206 patients versus 100 patients) and intracranial hemorrhage (70 patients versus 46 patients) compared with placebo. The difference in intracranial hemorrhages was driven by an increased number of traumatic bleeds, most of them subdural, and not by spontaneous or procedural bleeding.

Among participants with a history of previous PCI, the risk reductions outweighed the increased bleeding risks. Patients who had received PCI, which commonly uses devices known as stents to widen a coronary blood vessel and keep blood flowing, accounted for the majority (58 percent) of the total THEMIS population. Among these patients in THEMIS-PCI, 404 of 5,558 (7.3 percent) participants taking ticagrelor plus aspirin experienced cardiovascular death, myocardial infarction, or stroke, versus 480 of 5,596 (8.6 percent) participants taking placebo plus aspirin - a 15 percent reduction. Major bleeding occurred in 111 of 5,536 (2.0 percent) patients receiving ticagrelor and 62 of 5,564 (1.1 percent) patients receiving placebo. The risk for intracranial bleeding was similar between ticagrelor and placebo (33 patients versus 31 patients, respectively). Ticagrelor provided a very favorable balance of benefit versus risk -- more than in patients without a history of PCI.

"Our results indicate that among those with diabetes and stable coronary artery disease, we should focus on ticagrelor for patients with a history of prior stenting. This is an easily identifiable, logical sub-group," said Bhatt. "Studies currently support using long-term dual antiplatelet therapy for patients with acute coronary syndrome who are at high ischemic risk but low bleeding risk. Our work suggests that a much broader population of patients with stable coronary artery disease and diabetes stand to benefit substantially."

A study of nearly half a million people has found for the first time that those with heart or blood vessel problems benefit more from having a physically active lifestyle than do healthy people without cardiovascular disease (CVD).

Increased physical activity reduced the risk of dying during a six-year follow-up period for people with and without CVD, but the researchers found the greatest reduction in risk was in people with CVD and this continued to reduce the more exercise they did.

The study, which is published in the European Heart Journal [1] today (Sunday), is also presented at the same time at the European Society of Cardiology (ESC) Congress 2019 together with the World Congress of Cardiology in Paris, France [2].

There is plenty of evidence to show that physical activity reduces the risk of dying from CVD in healthy people; there is less evidence of its effect in people with pre-existing CVD although guidelines recommend it, and, until now, no study has compared the beneficial effect of physical activity between people with and without CVD.

Researchers led by Dr Sang-Woo Jeong, a cardiologist at Seoul National University (Seoul, Korea), looked at data from a total of 441,798 people enrolled in the Korean National Health Insurance Services Health Screening Cohort, who underwent a health screening programme between 2009 and 2015 and completed surveys on physical activity. The participants were aged over 40 years, and the average age was 60. A total of 131,558 had CVD and 310,240 did not; 53.5% were men. The participants were followed for nearly six years, and information on deaths and causes of death were collected from the Korean National Death Index.

The survey on physical activity asked them to remember how much physical activity they had undertaken in the past seven days and this information was converted into units of metabolic equivalent task (MET) minutes per week (MET-mins/week).

Co-author Dr Si-Hyuck Kang, also a cardiologist at Seoul National University, said: "The 2016 ESC guideline for primary prevention recommends healthy adults of all ages should perform at least 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity aerobic physical activity, or an equivalent combination. One way you can achieve 500 MET-minutes a week is to do brisk walking for 30 minutes, five times a week. If you are very busy and have no time to work out during weekdays, the other way to achieve approximately 500 MET-minutes a week is to do vigorous physical activity such as climbing hills with no loads for 75 minutes once a week. You can achieve 1500 MET-minutes a week by doing brisk walking for 30 minutes five times a week plus climbing hills for 2.5 hours once a week."

By the end of the follow-up period, the researchers found that people with CVD benefited more from physical exercise than did those without CVD; for every 500 MET-mins/week the risk of death was reduced by 14% and 7% respectively.

After adjusting for factors that could affect the results, such as age, sex, smoking and other medical conditions, healthy people without CVD benefited the most from doing 0-499 MET-mins/week of exercise. The risk of death among the totally sedentary was 27% higher than among those who performed the most physical activity (1500 MET-mins/week or more). It fell to an 8% increased risk for those doing 0-499 MET-mins/week of exercise and after that the reduction in risk was much smaller and levelled out above 1000 MET-mins/week.

Among people with CVD, although the greatest benefit was seen in those who did 0-499 MET-mins/week, the reduction in the risk of death continued to improve beyond 500 MET-mins/week. Compared to people without CVD who did the most exercise, the increased risk was 87% and 45% for people with CVD who had a totally sedentary lifestyle and for those who did 0-499 MET-mins/week, respectively. Among people with CVD who did 1000 MET-mins/week or more of physical activity, the risk of death fell further to a 14% increased risk.

Dr Jeong: "We found that approximately half of the people in the study did not reach the recommended level of leisure-time physical activity, and a quarter had a totally sedentary lifestyle. People with cardiovascular disease had lower levels of physical activity than those without, but the more exercise people did, the lower their risk of death during the six years of follow-up. The main new finding of this study is that people with cardiovascular disease benefit from a physically active lifestyle to a greater extent than healthy people without cardiovascular disease."

The researchers believe their findings can apply to other people in other countries as the role played by physical activity in CVD is common to all populations.

Dr Kang said: "There may be several plausible explanations for why people with CVD benefited the most from exercise. First, sedentary lifestyle is a well-known risk factor for CVD. Patients with CVD may have had sedentary lifestyles, and thus changing their lifestyle to become more physically active may be more beneficial. Secondly, a number of previous studies have shown that physical activity helps control cardiovascular risk factors such as blood pressure, cholesterol and blood glucose. The benefit of physical activity in secondary prevention may come by better controlling such risk factors. Lastly, patients with CVD usually have higher levels of systemic inflammation than those without CVD, and there is evidence that physical activity lowers systemic inflammatory levels."

As a result of their findings, Dr Kang said: "Doctors should emphasise the importance of a physically active lifestyle for patients with cardiovascular disease. They should be encouraged to maintain as much physical activity as possible. People who are physically active sleep better, feel better and function better. We would like to stress that physical activity is an economic way to live longer, healthier and happier, with little adverse effects."

Limitations of the study include the fact that participants reported their physically activity by answering a questionnaire, and this did not include physical activity that took place as part of normal life, such as occupation, transportation and housework. The questionnaire focused mainly on aerobic exercise and information on muscle and bone-strengthening exercise was limited.

Paris, France - 31 Aug 2019: Two decades of a sedentary lifestyle is associated with a two times risk of premature death compared to being physically active, according to results from the HUNT study presented today at ESC Congress 2019 together with the World Congress of Cardiology. (1)

Study author Dr Trine Moholdt of the Norwegian University of Science and Technology, Trondheim, Norway said: "Our findings imply that to get the maximum health benefits of physical activity in terms of protection against premature all-cause and cardiovascular death, you need to continue being physically active. You can also reduce your risk by taking up physical activity later in life, even if you have not been active before."

The aim of this study was to assess how changes in physical activity over 22 years were related to subsequent death from all causes and from cardiovascular disease. Most studies investigating the relationship between physical activity and longevity have asked participants about their level of physical activity only once, and then followed them for several years. But physical activity is a behaviour that changes in many people, so it is important to investigate how such changes over time relate to the risk of death in the future.

The HUNT study invited all residents of Norway aged 20 and older to participate in 1984-1986, 1995-1997, and 2006-2008. At all three time points, individuals were asked about their frequency and duration of leisure time physical activity. The current study used the data from the first and third surveys.

A total of 23,146 men and women were included in the analysis. Physical activity was categorised as inactive, moderate (less than two hours a week), and high (two or more hours per week). Participants were divided into groups according to their activity levels at each survey.

Physical activity data were linked to information on deaths until the end of 2013 using the Norwegian Cause of Death Registry. The risk of death in each physical activity group was compared to the reference group (those who reported a high level of exercise during both surveys). The analyses were adjusted for factors known to influence prognosis such as body mass index, age, sex, smoking, education level, and blood pressure.

Compared to the reference group, people who were inactive in both 1984-1986 and 2006-2008 had a 2-fold higher likelihood of all-cause death and 2.7-fold greater risk of dying from cardiovascular disease. Those with moderate activity at both time points had 60% and 90% raised risks of all-cause and cardiovascular deaths, respectively, compared to the reference group.

Dr Moholdt noted that there are clear recommendations about the amount of exercise adults should do to optimise their health, which are 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity aerobic physical activity. (2)

But she added: "An important point to make here is that physical activity levels even below the advised levels will give health benefits. Physical fitness is more important than the amount of exercise. Clinicians should individualise their advice and help people do even smaller amounts of activity that will improve fitness - this includes all types of exercise that make you breathe heavily."

"Do activities you like and get more movement into your everyday life," she continued. "For example, walk to the shops instead of driving, get off the metro a stop early, and use stairs instead of the lift. I recommend everyone to get out of breath at least a couple of times each week."

As for those who changed categories between surveys, people who went from inactive to highly active had a mortality risk that was between those who were continually active or continually sedentary. In contrast, those who went from highly active to inactive had a similar risk of dying as those who were inactive at both surveys.

"Our data indicate that you can compensate for a previously inactive lifestyle and the sooner you get active, the sooner you will see positive results," said Dr Moholdt. "My advice is to establish good exercise habits as early in life as possible. The health benefits extend beyond protection against premature death to effects in the body's organs and on cognitive function. Physical activity helps us live longer and better lives."

Paris, France - 31 Aug 2019: The ever-present devices that seem to track all our moves can be annoying, intrusive or worse, but for heart failure patients, tiny wearable cameras could prove life-enhancing, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology. (1)

Minute-by-minute images captured by these little "eyes" provide valuable data on diet, exercise and medication adherence, that can then be used to fine-tune self-management.

"The cameras bring more information to health professionals to really understand the lived experience of heart failure patients and their unique challenges," stated study first author Susie Cartledge, a registered nurse and dean's postdoctoral research fellow at Deakin University's Institute for Physical Activity and Nutrition in Melbourne, Australia. "This is a level of detail and context that will help us tailor their care."

Something as seemingly trivial as drinking too much fluid - which cameras can "see" - can tax an already burdened heart, leading to a potentially deadly hospital stay.

Heart failure is a chronic condition where the heart isn't pumping as well as it should be, so the body isn't getting enough oxygen. There is no cure and limited treatments, meaning that self-care is paramount. Healthcare professionals have traditionally gleaned information on patients' daily activities from self-reports, which can be unreliable. This "life-logging technique" is still in its infancy, but studies have shown that it gleans useful data. (2)

For this feasibility study, Dr Cartledge and her colleagues recruited 30 individuals with advanced (NYHA II-III) heart failure from a Melbourne cardiology practice. Participants' mean age was 73.6, and 60% were male.

Patients attached a wide-angle "narrative clip" to their clothing at about chest height. The cameras, barely two centimetres squared, were worn from morning to night and took still images every 30 seconds.

"You can really just see the context of the patient's world from chest height," explained Dr Cartledge. "We saw their bingo score cards, their families, their friends but we only saw them if they stood in front of a mirror. We felt like we had been with the patient for the day."

The images revealed no "scandalous" behaviour on the part of the participants, said Dr Cartledge, but they did highlight areas for improvement. Patients in general needed to increase their exercise and reduce sedentary behaviour that was typically associated with screen time. Participants could also generally improve their diets, for example there was one participant who could cut back on diet sodas, beers at bingo, and cigarettes.

"We can use this information to have a discussion with the patient. Yesterday, one man's pills sat out on his table for ages before he took them," continued Dr Cartledge, who would counsel this patient to take his medication sooner.

Almost all of the participants (93%) said they were happy wearing the camera (the remaining two were neutral). Some went so far as to report that they were reassured "someone was watching over them" or that the cameras spurred them to engage in "good behaviour." All participants had the option of deleting photos before the research team saw them.

But capturing the images and getting consent from patients was the easy part. By the end of the 30-day study period the authors had a library of more than 600,000 photos which they had to sort through and analyse.

Machine learning techniques grouped the images into four domains: medication management, dietary intake, meal preparation and physical activity. This process had mixed results. It was most successful in identifying diet-related photos (an average of 49% of the time), followed by information on meals (average 40%) and physical activity (average 31%). Drug adherence was the least precise, with an average of only 6%. This may be because prescriptions come in so many different forms - pill strips, bottles, sprays and puffers - making them hard to recognise.

"The sorting is actually extremely difficult," admitted Dr Cartledge. She and her colleagues enlisted the help of artificial intelligence experts at Ireland's Dublin City University to build a more specific platform. Eventually, the team envisions a relatively low-cost venture using a search engine platform and reusable cameras.

The sheer number of images was a limitation, acknowledged the author. And the heart failure findings may not be applicable to other populations, however the study methodology could be implemented for other chronic disease populations. Members of the study group were older, had advanced disease and came from a lower socioeconomic neighbourhood. The author predicted that the system, once refined, will be most helpful for guiding newly diagnosed patients.

"This is the first step," Dr Cartledge said. "Patients are happy to wear it. We can see the context of the challenges they face. The next step is to build an artificial intelligence platform to sort the images out in a quick and meaningful way so healthcare practitioners can use it. We're entering a new frontier."

Paris, France - 31 Aug 2019: Eating nuts at least twice a week is associated with a 17% lower risk of death from cardiovascular disease, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology. (1)

"Nuts are a good source of unsaturated fat and contain little saturated fat," said study author Dr Noushin Mohammadifard of Isfahan Cardiovascular Research Institute, Iran. "They also have protein, minerals, vitamins, fibre, phytosterols, and polyphenols which benefit heart health. European and US studies have related nuts with cardiovascular protection but there is limited evidence from the Eastern Mediterranean Region."

This study examined the association between nut consumption and the risk of cardiovascular disease and death in the Iranian population. A total of 5,432 adults aged 35 and older with no history of cardiovascular disease were randomly selected from urban and rural areas of the Isfahan, Arak and Najafabad counties. Intake of nuts including walnuts, almonds, pistachios, hazelnuts, and seeds was assessed in 2001 with a validated food frequency questionnaire.

Participants or family members were interviewed every two years until 2013 for the occurrence of cardiovascular events and death. The specific outcomes investigated were coronary heart disease, stroke, total cardiovascular disease, death from any cause, and death from cardiovascular disease.

During a median 12-year follow-up, there were 751 cardiovascular events (594 coronary heart disease and 157 stroke), 179 cardiovascular deaths, and 458 all-cause deaths.

Eating nuts two or more times per week was associated with a 17% lower risk of cardiovascular mortality compared to consuming nuts once every two weeks. The connection was robust even after adjusting for factors that could influence the relationship such as age, sex, education, smoking, and physical activity. Nut intake was inversely associated with the other outcomes but lost significance after adjustment.

ESC guidelines list 30 grams of unsalted nuts per day as one of the characteristics of a healthy diet, while noting that the energy density of nuts is high.(2)

"Raw fresh nuts are the healthiest," added Dr Mohammadifard. "Nuts should be fresh because unsaturated fats can become oxidised in stale nuts, making them harmful. You can tell if nuts are rancid by their paint-like smell and bitter or sour taste."