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How long COVID, artificial sweetener elevate risk of death

By Chukwuma Muanya
17 March 2023   |   2:20 am
As the nation anticipates the end of the COVID-19 public health emergency, new research is showing that some groups are still feeling the long-term impacts of the disease. In the year following infection, individuals who experience Long COVID...

•Condition associated with heart attack, lung problems, stroke, gastrointestinal problems
•Black women twice as likely as white counterparts to have uncontrolled high blood pressure
•New treatment that does not require risky open-heart surgery could help fix heart’s ‘forgotten valve’

As the nation anticipates the end of the COVID-19 public health emergency, new research is showing that some groups are still feeling the long-term impacts of the disease. In the year following infection, individuals who experience Long COVID are at high risk for a range of adverse health outcomes, including a doubled risk of death, according to a new study published in JAMA Health Forum.

The study examined insurance claims data for 13,435 adults with Long COVID-19 and 26,870 without COVID-19 during a 12-month follow-up period. Accounting for factors present prior to infection, the Long COVID group experienced increased mortality, with 2.8 per cent individuals with long COVID-19 dying compared to 1.2 per cent of those without Long COVID.

Those with Long COVID were also roughly two times more likely to experience cardiovascular events including arrhythmias, stroke, heart failure and coronary artery disease. Pulmonary conditions were also common. The risk of pulmonary embolism more than tripled, while the risk of Chronic Obstructive Pulmonary Disease (COPD) and moderate or severe asthma nearly doubled for those with Long COVID.

The study found that risks were greatest among individuals hospitalised within a month of a COVID-19 infection.
“We know from published literature that Long COVID can result in fatigue, headache and attention disorder,” said Dr. Andrea DeVries, Staff Vice President for Health Services Research at Elevance Health and the lead author of the study. “While those conditions are concerning, the results from this study point to even more worrisome outcomes that can severely impact quality and length of life for individuals with Long COVID.”

The United States (US) Centres for Disease Control and Prevention defines Long COVID as having new, returning, or ongoing health issues more than four weeks after onset of initial infection. According to research by the CDC, one in five COVID-19 survivors ages 18 to 64 and one in four survivors 65 years or older experience an ongoing health issue that might be attributable to COVID-19 infection.

Long COVID has been associated with more than 200 signs and symptoms and 50 health conditions. Experts say the health consequences can last from months to years.

“We can only measure out as far as the pandemic has been happening, but early evidence suggests that a large portion of people who experienced post-COVID-19 condition are doing so more than two years after their initial infection, which is basically as long as it could be,” said Dr. Mark Czeisler who wrote a related editorial also published in JAMA Health Forum.

Research has shown that COVID-19 reinfection substantially increases an individual’s risk of death, hospitalisation, and health consequences from Long COVID. For example, the risk of cardiovascular disorders increases from 1.6 with one infection, to 3.0 with two infections and 4.8 with three or more infections.

“It’s demonstrating that it’s not like you have COVID-19 once and then if you don’t get acutely ill or you don’t develop Long COVID from that first infection that the coast is clear,” said Czeisler, who was not involved in the study.

Other risk factors for Long COVID include older age, being female, tobacco use, higher body mass index, and experiencing more symptoms during the acute COVID-19 illness. Being vaccinated prior to infection has been associated with a decreased risk of Long COVID, according to previous research.

The study authors say these findings call for continued efforts to prevent COVID-19 infections and enhanced health monitoring of individuals after an infection.

“The biggest takeaway is that Long COVID is a health condition that we need to continue to study and take seriously,” said DeVries.
Also, researchers found that Long COVID patients are more likely to have gastrointestinal problems. The study, which examined patients infected early in the pandemic, found they were significantly more likely than people who didn’t get COVID-19 to experience lingering reflux, constipation and other issues.

Indeed, stomach pain, constipation, diarrhoea, vomiting, bloating — these are symptoms frequently reported by people with Long COVID.

Now, a large new study reports that COVID-19 patients were significantly more likely to experience gastrointestinal problems a year after infection than people who were not infected.

The study, published on Tuesday in the journal Nature Communications, compared medical records of 154,068 COVID-19 patients in the Veterans Health Administration system with about 5.6 million patients of similar age and other characteristics who had not contracted the coronavirus.

COVID-19 patients were 36 percent more likely to have long-term gastrointestinal problems that they did not have before their infection, with 9,605 of them experiencing issues affecting the digestive system, intestines, pancreas or liver.

The most common diagnoses were acid-related disorders, like gastroesophageal reflux disease (known as GERD) and peptic ulcer disease, which were identified in more than 2,600 patients.

“There seems to be some dysregulation that points to a major imbalance in acid production,” said the senior author of the study, Dr. Ziyad Al-Aly, chief of research and development at the V.A. St. Louis Health Care System and a clinical epidemiologist at Washington University in St. Louis.

Serious inflammatory illnesses — like acute pancreatitis and cholangitis, which is inflammation of the bile duct system — affected a much smaller percentage of patients, but they were nonetheless more common among those who had COVID-19 than those who had not.

“With all of these disorders there is an increased odds ratio, meaning that the people who had COVID-19 and survived for 30 days or longer were more at risk of each of these categories,” said Dr. Saurabh Mehandru, a professor of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York who was not involved in the study.

The study, like others drawing on the database of veterans, involves a patient population that is largely white and male with an average age of about 61. Still, the same patterns were seen among the study’s 37,000 post-COVID-19 Black patients and nearly 17,000 post-COVID-19 female patients, Al-Aly said.

The patients became infected during the pandemic’s early waves, testing positive for the coronavirus between March 1, 2020, and January 15, 2021, the overwhelming majority before vaccines were available. Al-Aly and Mehandru noted that the experience might be different for people infected more recently. Newer virus variants might have different effects, they said, and some research suggests that vaccines can reduce the risk of various long COVID-19 symptoms.

There are several reasons coronavirus infections may fuel long-term gastrointestinal problems. Mehandru, who has studied some possible causes, said his team and others had found that a protein the virus attaches to on some cell surfaces, called the ACE2 receptor, was abundant in the lining of the small intestine. Those receptors might provide a way for the virus to directly enter the digestive system, he said. It’s also possible that some viral fragments remained after infections resolved, keeping patients’ immune systems activated and generating inflammation-related symptoms.

Another possibility is the “gut-brain connection,” said Mehandru, explaining that: “When we’re stressed we have intestinal manifestations.” And, he added: “Some of the symptoms could also be because of a generalized state of being unwell or having illness outside of the intestines, which could impact how we move our bowels or mean that we feel bloated or have acid reflux.”

Al-Aly said most Long COVID patients had other symptoms besides gastrointestinal problems, suggesting that the condition was “too complex to have just one mechanism that explains all of it.”

The new study did not identify whether certain previous health conditions, like diabetes or cardiovascular disease, put people at greater risk of post-COVID-19 gastrointestinal problems. Like many other Long COVID studies, it did find that people whose initial infections were severe enough to warrant intensive care or other hospitalization were more prone to long-term symptoms. Still, people with mild initial infections — who make up a majority of COVID-19 patients — were nonetheless at greater risk than people who were not infected.

Underscoring the significance of post-COVID-19 symptoms, the study found that Long COVID patients were at greater risk of gastrointestinal problems than nearly six million people in the veterans’ database before the pandemic. It also found that people hospitalized with a coronavirus infection were more likely to develop long-term gastrointestinal issues than people hospitalized with the flu.

Al-Aly did sound one note of optimism. While some symptoms of Long COVID, like fatigue and brain fog, can be intractable for months despite different therapies, many gastrointestinal symptoms are treatable.

“Obviously, there’s no one treatment for all of this,” he said. “But I think these are diagnoses and signs and symptoms that could be managed.”
Also, New Cleveland Clinic research showed that erythritol, a popular artificial sweetener, is associated with an increased risk of heart attack and stroke. Findings were published in Nature Medicine.

Researchers studied over 4,000 people in the U.S. and Europe and found those with higher blood erythritol levels were at elevated risk of experiencing a major adverse cardiac event such as heart attack, stroke or death. They also examined the effects of adding erythritol to either whole blood or isolated platelets, which are cell fragments that clump together to stop bleeding and contribute to blood clots. Results revealed that erythritol made platelets easier to activate and form a clot. Pre-clinical studies confirmed ingestion of erythritol heightened clot formation.

Senior author, chairman for the Department of Cardiovascular & Metabolic Sciences in Lerner Research Institute and co-section head of Preventive Cardiology at Cleveland Clinic, Dr. Stanley Hazen, said: “Sweeteners like erythritol, have rapidly increased in popularity in recent years but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors.”

Artificial sweeteners, such as erythritol, are common replacements for table sugar in low-calorie, low-carbohydrate and “keto” products. Sugar-free products containing erythritol are often recommended for people who have obesity, diabetes or metabolic syndrome and are looking for options to help manage their sugar or calorie intake. People with these conditions also are at higher risk for adverse cardiovascular events like heart attack and stroke.

Erythritol is about 70 per cent as sweet as sugar and is produced through fermenting corn. After ingestion, erythritol is poorly metabolised by the body. Instead, it goes into the bloodstream and leaves the body mainly through urine. The human body creates low amounts of erythritol naturally, so any additional consumption can accumulate.

Measuring artificial sweeteners is difficult and labeling requirements are minimal and often do not list individual compounds. Erythritol is “Generally Recognised As Safe (GRAS)” by the United States Food and Drug Administration (FDA), which means there is no requirement for long-term safety studies.

The authors note the importance of follow-up studies to confirm their findings in the general population. The study had several limitations, including that clinical observation studies demonstrate association and not causation.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said Hazen. “It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease.”

Authors recommend talking to your doctor or a certified dietician to learn more about healthy food choices and for personalised recommendations.
Also, according to new data from the American Heart Association, black women are twice as likely as white women to have uncontrolled high blood pressure when they are between the ages of 20 and 50 years old.

It is an especially dangerous time in life to have blood pressure problems because it raises the risk of potentially fatal pregnancy complications. One of the top ways to manage blood pressure – through diet changes and healthy eating – isn’t universally accessible to Black women, with 25 per cent facing barriers to getting healthy foods.

“Food insecurity is important when thinking about high blood pressure since sodium levels are higher in many lower-cost food options such as canned, ultra-processed and fast foods,” study author Dr. Lara C. Kovell, said in a statement. “Moreover, food insecurity and a lack of access to healthy foods have been shown in other studies to increase the risk of high blood pressure.”

Published last week in the Journal of the American Heart Association, the analysis was conducted on data from 1,293 women who ranged in age from 20 to 50 years old and had high blood pressure or were taking medication for high blood pressure. The study defined high blood pressure as 140/90 mmHg or higher. (A normal blood pressure is 120/80 mmHg or lower.) The average age of women in the study was 36 years old, and 80 per cent of the women had previously been pregnant.

The study purposely analysed women of childbearing age to better understand why there are differing blood pressure-related health risks during pregnancy based on someone’s race or ethnicity. Those risks had been established in previous research. The authors called high blood pressure “one of the most important and modifiable risk factors for pregnancy- related morbidity and mortality in addition to lifetime cardiovascular disease.”

Results found that 38 per cent of Black women in the study had uncontrolled high blood pressure, which was significantly higher than the 25 per cent of white women in the study who had uncontrolled high blood pressure. The findings align with previous research that shows Black women are at elevated health risks during pregnancy. They are at least six times more likely than white women to die if they develop pregnancy-induced high blood pressure, such as preeclampsia.

Researchers also looked at whether study participants’ likelihood of having uncontrolled high blood pressure was related to other factors such as education level, income, food security, home ownership, language, and access to health insurance and medical care.

“Our findings suggest factors not explored in this analysis, such as experienced racism, social supports, or stress, may drive inequities in [blood pressure] control,” they wrote. The factors like education level and health insurance “do not explain racial inequity in maternal outcomes and addressing structural racism is necessary to achieve health equity.”

Meanwhile, for the first time, patients with damaged tricuspid valves in their hearts might have a safe treatment that actually helps.
More than one million mostly older Americans have seriously leaking tricuspids, a valve on the right side of the heart that lets deoxygenated blood flow between the right atrium and the right ventricle. When the valve leaks, blood flows backward. As a result, fluid accumulates in vital organs while legs and feet get swollen. The eventual outcome is heart failure.

Patients’ symptoms often are severe — fatigue, abdominal distention, swollen legs and general feelings of malaise. Even their eyes can get swollen, said Dr. Gregg Stone, an interventional cardiologist at Icahn School of Medicine at Mount Sinai.

“Imagine a beach ball filled with fluid in your stomach all the time,” said Dr. Joseph Cleveland, Jr., a cardiothoracic surgeon at the University of Colorado School of Medicine.

Medicine to mitigate the injury causes perilous side effects, and surgical repair of the valve has usually been too dangerous to attempt.
Now the medical device company Abbott is reporting results from a clinical trial of a treatment that involves clipping the floppy tricuspid valve to make it smaller and better able to function. The clipping device used is similar to a successful one used to treat patients with damage to another part of the heart, the mitral valve.

The results were published in The New England Journal of Medicine to coincide with a presentation at the yearly meeting of the American College of Cardiology. And patients may soon have a different option for treatment when another company, Edwards Lifesciences, completes a clinical trial of a different approach that is now underway.

For the study financed by Abbott, researchers report that the clip stopped much of the leakage and allowed many patients who had been debilitated by symptoms to get their lives back. “It’s really nice to see quality of life improvement,” said Dr. Cleveland, who was not involved in the Abbott trial. “This gives an option which is great.”

The treatment was also safe, with a less than one percent mortality risk in these very sick patients and, on average, a one-day hospital stay. The price of the procedure is not yet known.

Patients in the Abbott study have now been followed for at least one year. The clip did not extend life but, said Dr. David Adams, cardiac surgeon in chief at Mount Sinai Health System and co-principal investigator for the study, “we would never see a mortality difference — one year was not enough time.”

“This is a huge win,” said Dr. Kendra Grubb, a heart surgeon and director of the structural heart center at Emory University who was not involved in the study. Dr. Grubb, who is on an advisory board for Abbott and is a speaker for Edwards, added that although doctors have been able to keep patients alive with medical therapy, “it’s a miserable way to live.”

The clinical trial by Edwards is testing a different method. It replaces the tricuspid valve by threading a new valve into the heart, pushing aside the old in a manner similar to a method called trans-catheter aortic valve replacement. The aorta controls blood flow from the heart, and the TAVR method has been used to replace the valves of hundreds of thousands of patients.

The developments come after years of inattention to the tricuspid problem. The valve was long known as the forgotten valve. Cardiologists had assumed that if they fixed problems on the left side of the heart — like a leaky mitral or aortic valve — the tricuspid valve would fix itself.

Their assumption was wrong.
Patients and cardiologists have long sought an effective treatment for tricuspid leakage. The only medical treatment today is with drugs called loop diuretics. They flush excess fluid out of patients’ body, but only temporarily. As the diuretic treatment is repeated, patients’ fluid retention gets worse and worse until the kidneys fail and eventually even the tricuspid valve itself gets engorged with fluids.

“Patients get more and more miserable,” said Dr. Paul Sorajja, chairman of the valve science center at the Minneapolis Heart Institute Foundation and co-principal investigator for the Abbott study.

Few attempt surgery, which is used to repair — not replace — the delicate valve. Most patients have so many other medical problems, often stemming from their tricuspid leakage, that an open-heart surgery would be too risky. The death rate from surgery is 10 percent, which is 10 times higher than the rate with aortic valve replacement.

The Abbott study involved 350 patients with an average age of 78 who had debilitating valve leakage, also known as regurgitation, ranging from valve failure classified as severe to what is known as torrential regurgitation. They were randomly assigned to the clip or to medical therapy with a loop diuretic.

A month after having the clip implanted, 87 percent of patients’ tricuspid regurgitation had been downgraded to mild or moderate as compared to 4.8 percent in the group getting loop diuretics.
Patients who got the clip said their disabling symptoms receded and they could enjoy life again.

“I felt better immediately,” said Adelaide Effertz, 86, who lives on a farm in Pine City, Minn., and was one of the first patients treated in the study. “It’s just wonderful.”

She says she no longer has the intense and unrelenting fatigue that forced her to nap a couple of times each afternoon.If the Edwards valve replacement study is successful and both it and the Abbott clip receive regulatory approval, some patients may face a dilemma over which procedure they should have. If they choose the clip they cannot have the replacement later, because it would impede the process of pushing the old valve aside, said Dr. Howard Herrmann, director of interventional cardiology at the University of Pennsylvania, who enrolled patients in the Abbott trial.That, though, is a good dilemma to have for patients who have had almost nothing. “It’s an exciting beginning,” Adams said.

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