Month: August 2021

Added Potassium Salt Substitute Greatly Cuts CVD Risk

Source: Pixabay CC0

Replacing table salt with a low-sodium, added potassium ‘salt substitute’ significantly reduces rates of stroke, heart attack and death, one of the largest dietary intervention studies ever conducted.

Presented at the European Society of Cardiology Congress in Paris, and simultaneously published in the New England Journal of Medicine, the results also showed that there were no harmful effects from the salt substitute, such as hyperkalaemia.

High sodium intake and low potassium intake are widespread. Both are linked to hypertension and increased risks of stroke, heart disease and premature death. Using a salt substitute – where part of the sodium chloride is replaced with potassium chloride – addresses both problems at once. Salt substitutes are known to lower blood pressure but their effects on heart disease, stroke, and death were unclear, until now.

Lead researcher, Professor Bruce Neal of The George Institute for Global Health, said that the benefit could prevent millions of early deaths with the widespread adoption of salt substitutes.

“Almost everyone in the world eats more salt than they should.  Switching to a salt substitute is something that everyone could do if salt substitutes were on the supermarket shelves,’’ he said.

“Better still, while salt substitutes are a bit more expensive than regular salt, they’re still very low-cost – just a few dollars a year to make the switch.”

“As well as showing clear benefits for important health outcomes, our study also allays concerns about possible risks.  We saw no indication of any harm from the added potassium in the salt substitute.  Certainly, patients with serious kidney disease should not use salt substitutes, but they need to keep away from regular salt as well,” added Professor Neal.

The Salt Substitute and Stroke Study enrolled 21 000 adults with either a history of stroke or poorly controlled blood pressure from 600 villages in rural areas of China from 2014 to 2015.

Participants in intervention villages were provided enough salt substitute to cover all household cooking and food preservation requirements – a daily amount of 20g per person. Those in the other villages continued using regular salt.

Over five years’ average follow up, more than 3000 participants had a stroke. Use of salt substitute reduced stroke risk by 14 percent, total cardiovascular events (strokes and heart attacks combined) by 13 percent and premature death by 12 percent.

Professor Neal said that as salt substitutes are relatively cheap (US$1.62 per kg vs US$1.08 per kg for regular salt in China), they are likely very cost effective.

“Last year, a modelling study done for China suggested that about 400 000 premature deaths might be prevented each year by national uptake of salt substitute. Our results now confirm this. If salt was switched for salt substitute worldwide, there would be several million premature deaths prevented every year,” he said.    

“This is quite simply the single most worthwhile piece of research I’ve ever been involved with. Switching table salt to salt substitute is a highly feasible and low-cost opportunity to have a massive global health benefit.”

As a result of the study, George Institute researchers are calling for salt manufacturers to embrace salt substitution, the promotion of salt substitutes by governments, and the use of substitute salt by consumers.

Source: George Institute for Global Health

What is The C.1.2 Variant?

Image by Quicknews

A preliminary study recently uploaded on the medRxiv preprint server, researchers detail the detection and characteristics of the C.1.2 variant of SARS-CoV-2, which has not yet been assigned a variant of interest (VOI) status, but which could potentially have increased transmission and immune escape potential.

The researchers describe how they identified a new SARS-CoV-2 variant, C.1.2. The first detection of this variant was during the third wave of infections in South Africa from May 2021 onwards, and has also been detected in seven other countries around the world.

New SARS-CoV-2 variants are commonly associated with new waves of infection. Like several other variants of concern (VOCs), C.1.2 has accumulated a number of substitutions beyond what would be expected from the background SARS-CoV-2 evolutionary rate. This suggests the likelihood that these mutations arose during a period of accelerated evolution in a single individual with prolonged viral infection through virus-host co-evolution. Deletions within the N-terminal domain have been evident in cases of prolonged infection, further supporting this hypothesis.

C.1.2 contains many mutations that have been identified in all four VOCs (Alpha, Beta, Delta and Gamma) and three VOIs (Kappa, Eta and Lambda) as well as additional mutations. Many of the shared mutations have been associated with improved ACE2 binding or furin cleavage, and reduced neutralisation activity, raising concern about the transmission potential of this variant. The next step is determining the functional impact of these mutations and to find out if they give it a replication advantage over the Delta variant.

The C.1.2 lineage is continuing to grow, and as of 20 August 2021, there were 80 C.1.2 sequences in GISAID, and the variant has now been detected in Botswana and in the Northern Cape of South Africa. Note that this study is yet to have the peer review process completed.

Source: MedRxiv

A Glass of Wine Raises Atrial Fibrillation Risk

Photo by <a href="">Apolo Photographer</a> on <a href="">Unsplash</a>
Photo by Apolo Photographer on Unsplash

A single glass of wine can rapidly increase the risk of atrial fibrillation, according to new research published in Annals of Internal Medicine.

The study provides the first evidence that alcohol consumption significantly increases the chance of the heart rhythm condition occurring within a few hours, and is contrary to the notion of a cardioprotective effect of alcohol.

“Contrary to a common belief that atrial fibrillation is associated with heavy alcohol consumption, it appears that even one alcohol drink may be enough to increase the risk,” said Gregory Marcus, MD, MAS, professor of medicine in the Division of Cardiology at UCSF.

“Our results show that the occurrence of atrial fibrillation might be neither random nor unpredictable,” he said. “Instead, there may be identifiable and modifiable ways of preventing an acute heart arrhythmia episode.”

Atrial fibrillation (AF) is the most common heart arrhythmia seen clinically, but until now research has largely focused on risk factors and treatments for the disease, rather than what can trigger episodes. Large studies have established that chronic alcohol consumption can be a predictor for AF, and Marcus and other scientists have demonstrated that it is linked to increased risk for a first diagnosis of atrial arrhythmias.  

The research centered on 100 patients with documented AF who consumed at least one alcoholic drink a month, but without substance use disorders, certain allergies, or changing medications.

Each participant wore an electrocardiogram (ECG) monitor for roughly four weeks, pressing a button whenever they had a standard-size alcoholic drink. They were also all fitted with a continuously recording alcohol sensor. Blood tests reflecting alcohol consumption over the previous weeks were periodically administered. Participants consumed a median of one drink per day throughout the study period.

Researchers found that an AF episode was associated with two-fold higher odds with one alcoholic drink, and three-fold higher odds with two or more drinks within the preceding four hours. Increased blood alcohol concentration was also associated with AF episodes.

Study limitations included patients possibly forgetting to press their monitor buttons or minimising the number of button presses due to embarrassment, although these considerations would not have affected alcohol sensor readings. The study was also limited to those with established AF, not to the general population.

“The effects seem to be fairly linear: the more alcohol consumed, the higher the risk of an acute AF event,” said Prof Marcus. “These observations mirror what has been reported by patients for decades, but this is the first objective, measurable evidence that a modifiable exposure may acutely influence the chance that an AF episode will occur.”

Source: University of California – San Francisco

When Damaged Hearts Struggle to Heal

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

By analysing a certain protein that forms new blood vessels following a heart attack or unstable angina the long term-survival of heart patients could be predicted.

The study, published in PLOS ONE, has shown the presence or absence of a gene variant for the protein (vascular endothelial growth factor [VEGF]-A) can help predict the long-term survival chances in males who have experienced an acute coronary event.

Dr Barry Palmer of the Massey University School of Health Sciences said that the human body’s ability to recover from severe health events such as heart attacks is aided by its capacity for new blood vessel creation.

“Measuring an individual’s ability to restore blood circulation after a serious, life-threatening health event, may be useful in choosing treatment options and timing of specialist or GP visits. It may also have implications for susceptibility to other complex diseases, such as cancer.

“We showed testing for a VEGF-A gene variant from a patient’s blood was a useful predictor of how long these patients survived after their heart disease event. This association was most obvious in non-diabetic patients.”

The study reported on 1927 patients from the Coronary Disease Cohort Study in New Zealand, of which 30 percent had at least one previous episode of serious heart disease.

In a subgroup, the researchers also investigated the utility of measuring VEGF-A protein itself from 550 heart patients.

It has long been known that VEGF-A plays a role in helping cancer tumours to grow by increasing their blood supply, Dr Palmer said.

“In the heart disease field, it’s been suggested that high levels of VEGF-A might be a good thing to help grow new blood vessels around clogging or blocked arteries. The research so far has led to some controversy with some reports showing that more VEGF-A in the bloodstream is associated with better outcome in heart disease.

“While others, including our study, show high levels of VEGF-A after a heart event is linked to worse outcomes. An explanation for this could be that high VEGF-A levels may signal hearts under stress struggling to restore heart function, but not always rescuing function enough to save badly damaged hearts,” Dr Palmer added.

“High levels of VEGF-A in the blood may be being churned out to try and grow new blood vessels in a badly damaged heart, but may not be enough for the patients with the most damaged hearts. About 40 percent more of patients with high VEGF-A are dying within eight years of their original admission to hospital.

“After adjusting for seven other relevant measurements, patients with 10-fold higher levels of VEGF-A, measured shortly after their health event, had approximately twice the risk of death during the follow-up period.”

Source: Massey University

An Oxygen-delivering Hydrogel for Diabetic Foot Ulcers

Photo by Denes Kozma on Unsplash

A quarter of people with diabetes develop foot ulcers, which are slow to heal due to hypoxic conditions in the wound from impaired blood vessels and increased inflammation. These wounds can become chronic, leading to poor quality of life and possibly amputation.

Jianjun Guan, professor of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has developed a hydrogel that delivers oxygen to a wound and decreases inflammation, helps to remodel tissue and speeds up healing. The results are published in Science Advances

Prof Guan’s new hydrogel uses microspheres to gradually release oxygen to interact with the cells by means of an enzyme coating that converts the microsphere’s contents into oxygen. In this way, the hydrogel delivers oxygen over two weeks, reducing inflammation and promoting healing.
“The oxygen has two roles: one, to improve skin cell survival under the low-oxygen condition of the diabetic wound; and two, oxygen can stimulate the skin cells to produce growth factors necessary for wound repair,” Prof Guan said.

Source: Washington University in St. Louis

The Evidence for The Animal Origins of COVID

Photo by Todd Cravens on Unsplash

An article in Science explores the evidence for the animal origin of COVID, which was first detected in December 2019, but inferred to be present in Hubei province, China, for about a month beforehand. 

The current COVID epidemic can be better understood by examining the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak which began in 2002. Investigations later found that horseshoe bats (Rhinolophus) in China harboured related coronaviruses. It was inferred that a sarbecovirus circulating in horseshoe bats seeded the progenitor of SARS-CoV in an intermediate animal host, most probably civet cats Although other possible intermediate hosts for SARS-CoV were identified, it is a population of civet cats within markets that appear to have acted as the conduits of transmission to humans from the horseshoe bat reservoir of SARS-CoV. Presumably a captive civet cat initially became infected by direct contact with bats or was infected before capture.

SARS-CoV-2 first emerged in Wuhan city, over 1500 km from the closest known naturally occurring sarbecovirus collected from horseshoe bats in Yunnan province. Coronaviruses genetically close to SARS-CoV-2 are circulating in horseshoe bats with wide geographic ranges indicate that the singular focus on Yunnan is misplaced. Confirming this assertion, the evolutionarily closest bat sarbecoviruses are estimated to share a common ancestor with SARS-CoV-2 at least 40 years ago, showing that these Yunnan-collected viruses are highly divergent from the SARS-CoV-2 progenitor. 

Though the virus may have jumped to humans from direct horseshoe bat–to–human contact, a known risk for SARSr-CoVs, the first detected SARS-CoV-2 cases in December 2019 are associated with Wuhan wet markets. This is consistent with multiple animal-market–associated spillover events in November and December (9). It is currently not possible to be certain of the animal source of SARS-CoV-2, but it is notable that live animals, including civet cats, foxes, minks, and raccoon dogs, all susceptible to sarbecoviruses, were for sale in Wuhan markets, including the Huanan market (identified as an epicenter of the outbreak in Wuhan) throughout 2019.

Together, this suggests a central role for SARSr-CoV–susceptible live intermediate host animals as the primary source of the SARS-CoV-2 progenitor that humans were exposed to, as was the case with the origin of SARS.

Spillover events are not so rare, indicated by evidence of SARSr-CoV–specific antibodies in people living in rural areas, and even higher rates recorded in people living near bat caves. When exposed a densely packed human population, such as in Wuhan city, these spillover events have a much higher chance of resulting in substantial onward spread 

Interestingly, the proximity of humans to wildlife may have been increased by demand for alternative meat sources caused by reduced availability of pork in 2019. This was caused by the African swine fever virus (ASFV) pandemic, which led to ∼150 million pigs being culled in China, resulting in a pork supply reduction of ∼11.5 million tonnes in 2019, and from which the country is still recovering. Increased use of cold-chain logistics in the wake of the ASFV pandemic means that frozen animal carcasses carrying SARS-CoV-2 may have been brought from much farther afield.

Once crossed over, SARS-CoV-2 readily established itself in humans by being a generalist, as opposed to being specialised for humans. Ironically, since humans are now the largest reservoir of the virus, animals in contact with humans are at risk of virus spillover. The article authors closed by stressing the need for much greater viral surveillance to spot emerging threats, as current coverage is extremely spotty.

Source: Science

‘Every Guideline We Write Is Out of Date’ Quips ESC as New Data Emerges

Image by Marcelo Leal on Unsplash

Just as the European Society of Cardiology (ESC) unveiled their new guidelines for the treatment of heart failure, along came some data that the guideline’s authors hint will cause the work to be revised.

The guidelines, which appear in the European Heart Journal, state that so far, there is no treatment shown to reduce mortality and morbidity in patients with heart failure with preserved ejection fraction, however there are positive results from the EMPEROR-Preserved study showing that treatment with empagliflozin robustly reduced hospitalisation risk.

“Every guideline we write is out of date a few days after it’s published. I’m, of course, exaggerating a little bit, but guidelines are dynamic documents. They represent what we know at the time that they’re written and then new information comes out and they have to be updated, and that takes time,” Milton Packer, MD, of Baylor University Medical Center in Dallas, told MedPage Today.

“It’s a process, and we all understand that process; there is no real concept of finality here. We do the best we can with the data we have. And so these guidelines coming won’t represent the results of the EMPEROR-Preserved trial, but the next one will,” Dr Packer added.

Carlos Aguiar, MD, of Hospital Santa Cruz in Lisbon, agreed: “We also know that these new indications do need to go through the regulatory authorities, so it does take some time for the whole process to be concluded.”

“We do need to wait for those approvals also from the regulatory agencies in their reviews for physicians to be able to implement this in clinical practice,” he told MedPage Today.

However, the writers of the 2021 guideline did tweak the comprehensive algorithm for the treatment of heart failure, the highlights of which include:

  • Right heart catheterisation should be considered in patients in whom heart failure is thought to be due to constrictive pericarditis, restrictive cardiomyopathy, congenital heart disease, and high-output states. It may be considered in selected patients with heart failure with preserved left ventricular ejection fraction (LVEF) to confirm the diagnosis.
  • In patients with chronic heart failure with reduced LVEF, dapagliflozin (Farxiga) or empagliflozin are recommended to reduce hospitalisation and mortality risk. As a Class I recommendation, it is based on evidence gleaned from randomised clinical trials.
  • Vericiguat (Verquvo) may be considered in patients with New York Heart Association (NYHA) class II to IV heart failure after worsening with treatment with an angiotensin inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist, to reduce the risks of cardiovascular mortality or heart failure hospitalisation.
  • For treatment of heart failure with midrange LVEF — a change in term from “mildly reduced” ejection fraction — to reduce hospitalisation and mortality risk, the guidelines suggest a number of treatments including angiotensin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and the combination agent sacubitril/valsartan but none have strong clinical trial evidence (Class IIb)  .
  • For patients with heart failure with preserved ejection fraction, the current guidelines recommend (Class I evidence) screening for and treatment of aetiologies, as well as cardiovascular and non-cardiovascular comorbidities.
  • After hospitalisation for heart failure, the guidelines recommend (Class I evidence) that patients be carefully evaluated to exclude persistent signs of congestion before discharge and to optimise oral treatment, and that evidence-based oral medical treatment be administered before discharge. An early follow-up visit is recommended at 1 to 2 weeks after discharge to assess signs of congestion and drug tolerance, and to start and/or uptitrate evidence-based therapy.
  • The SGLT2 inhibitors canagliflozin (Invokana), dapagliflozin, empagliflozin, ertugliflozin (Steglatro), and sotagliflozin are recommended in patients with heart failure and type 2 diabetes at risk of cardiovascular events to reduce hospitalisations for heart failure, major cardiovascular events, end-stage renal dysfunction, and cardiovascular death. The SGLT2 inhibitors dapagliflozin, empagliflozin, and sotagliflozin are recommended in patients with type 2 diabetes and heart failure with reduced ejection fraction (Class I evidence). The DPP-4 inhibitor saxagliptin (Onglyza) is not recommended in patients with heart failure (Class III evidence).

Source: MedPage Today

Vulnerability Found in Solid Tumours

Source: NCI

Researchers have found a weakness in a key enzyme key for solid tumour cancer cells’ ability to adapt and survive when oxygen levels are low.

The findings, published in Science Advances, will help researchers develop new treatment strategies to limit the progression of solid cancer tumours, which represent the majority of tumour types that arise in the body.

As tumours advance, the blood vessels that they previously relied on become unable to provide oxygen and nutrients to all parts of the tumour, which results in areas of hypoxia. Over time, this hypoxic environment leads to a buildup of acid inside the tumour cells.

To overcome this stress, the tumour cells adapt by releasing enzymes that neutralise the acidic conditions of their environment, enabling the cells to not only survive, but develop into a more aggressive form of tumour capable of spreading to other organs. One of these enzymes is called Carbonic Anhydrase IX (CAIX).

“Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles heel.’ By inhibiting its activity, we can effectively stop the cells from growing,” explained senior author Dr Shoukat Dedhar, professor in UBC faculty of medicine’s department of biochemistry and molecular biology and distinguished scientist at BC Cancer.

Previously, Dr Dedhar and colleagues had identified a unique compound, known as SLC-0111 (which is currently being evaluated in Phase 1 clinical trials) as a powerful CAIX enzyme inhibitor. Though the effectiveness of this compound in suppressing tumour growth and spread has been tested in pre-clinical models, other cellular properties diminish its effectiveness.

In this study, the researchers set out to investiagete these cellular properties and identify other weaknesses of the CAIX enzyme with the help of a powerful tool known as a genome-wide synthetic lethal screen. This tool systematically deletes one gene at a time from a cancer cell’s genome to determine if a cancer cell can be killed by eliminating the CAIX enzyme together with another specific gene.

According to Dr Dedhar, they had surprising results and point to an unexpected role of proteins and processes that control a form of cell death called ferroptosis, a form of cell death that occurs from an iron build up which weakens the tumour’s metabolism and cell membranes.

“We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis,” said Dr Dedhar. “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumour growth.”

The development of drugs to induce ferroptosis is underway around the world, and this study is contributing to their work.

Source: University of British Columbia

Obesity Connection to Commonly-used Pesticide

Photo by Arjun MJ on Unsplash

A commonly-used pesticide could be contributing to the global obesity epidemic, according to a new study.

Researchers discovered that chlorpyrifos slows down the burning of calories in the brown adipose tissue of mice. Reducing this burning of calories, a process known as diet-induced thermogenesis, causes the body to store these extra calories, promoting obesity. Chlorpyrifos is banned for use on foods in Canada, and also now banned in the US and, as of last year, the EU, but widely sprayed on fruits and vegetables in many other parts of the world. In South Africa it is banned for residential use but is still used in agriculture.

Scientists made the discovery after studying 34 commonly used pesticides and herbicides in brown fat cells and testing the effects of chlorpyrifos in mice fed high calorie diets. Their findings were published in Nature Communications and could have important implications for public health.

“Brown fat is the metabolic furnace in our body, burning calories, unlike normal fat that is used to store them. This generates heat and prevents calories from being deposited on our bodies as normal white fat. We know brown fat is activated during cold and when we eat,” said senior author Gregory Steinberg, professor of medicine and co-director of the Centre for Metabolism, Obesity, and Diabetes Research at McMaster.

“Lifestyle changes around diet and exercise rarely lead to sustained weight loss. We think part of the problem may be this intrinsic dialling back of the metabolic furnace by chlorpyrifos.”

Steinberg said chlorpyrifos would only need to inhibit energy use in brown fat by 40 calories every day to trigger obesity in adults, which would translate to an extra 2kg of weight gain per year.

He said that while several environmental toxins including chlorpyrifos have been associated with increasing obesity rates in both humans and animals, these studies have mostly attributed weight gain to increases in food intake and not calorie burning.

“Although the findings have yet to be confirmed in humans, an important consideration, is that whenever possible consume fruits and vegetables from local Canadian sources and if consuming imported produce, make sure it is thoroughly washed,” said Steinberg.

Source: Medical Xpress

Screening for AF in the Elderly Using Thumb ECGs Reduces Stroke Risk

Screening for atrial fibrillation in 75- and 76-year-olds using thumb ECGS could reduce the risk of stroke, severe bleeding and death, according to a large-scale Swedish study.

Atrial fibrillation (AF) is associated with a five-fold increased risk of stroke, and the symptoms are often deleterious since large blood clots can form in the heart, breaking free and posing a stroke risk. Still, countries do not screen the general population for atrial fibrillation, but rather treat those patients who are discovered during routine care. This study by the Karolinska Institutet in Sweden and published in The Lancet, investigated the effectiveness of screening for AF.

“There has never really been a study that examines if it would be beneficial to screen for atrial fibrillation, which is why we wanted to investigate it,” said Emma Svennberg, cardiologist at the Karolinska University Hospital, Huddinge, and researcher at the Department of Medicine, Huddinge, Karolinska Institutet.

The study included almost 28 000 participants aged 75 or 76, randomised to be invited either to screening or to a control group, who received standard care. Of those invited to screening, more than half choose to participate. They completed a health questionnaire and performed a so-called thumb ECG (electrocardiogram), which involves placing one’s thumbs on an ECG device that measures the heart’s electrical activity.

Those without atrial fibrillation were asked to record their heart rhythm twice daily for two weeks using the ECG device which they took home. If the device registered irregular heart rhythms, the participants were referred to a cardiologist for a standardised work-up and, if there were no contra-indications, initiation of oral anticoagulant therapy.

The study’s 28 000 participants were then followed for at least five years. More detections of atrial fibrillation were recorded in the screening group, which also had a slightly lower incidence of death, stroke and severe bleeding than the control group.

“In total, 31.9 percent of those in the screening group experienced a negative event compared to 33 percent in the control group,” said Johan Engdahl, adjunct lecturer at the Department of Clinical Sciences, Danderyds Hospital, at Karolinska Institutet. “Now, that may sound like a small difference, but you must bear in mind that only about half of those invited to screening participated and it’s possible we would have seen a more pronounced difference had more people turned up for screening. Those who participated in the screening had significantly fewer negative events.”

Based on the findings, the researchers estimated that at least 2300 cases of stroke or death could be avoided per year in Sweden if a national screening of atrial fibrillation in the elderly was introduced.

Source: Karolinska Institute