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Medical News Today: Heart attack: New protein therapy may improve recovery

New preclinical research in animal models finds that infusing a specific protein into scar tissue after a heart attack improves and speeds up the recovery of the heart.

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Researchers are soon to test a new therapy for improving heart function and recovery after a heart attack.

According to the American Heart Association (AHA), around 605,000 people in the United States have a new heart attack each year, and approximately 200,000 experience a recurrent attack.

Reperfusion, which is a technique that frees up the flow of oxygen to the heart's tissue, is a common form of treatment after a heart attack. However, up to one-quarter of people who undergo reperfusion develop heart failure within a year.

So, researchers led by James Chong — an associate professor at the University of Sydney in Australia — have explored an alternative treatment that targets the scar tissue that forms after a heart attack.

Chong and colleagues evaluated the therapeutic potential of a protein therapy called recombinant human platelet-derived growth factor-AB (rhPDGF-AB).

As its name suggests, rhPDGF-AB is a recombinant growth factor-AB derived from human platelets. Platelets are small blood cells that rush to an injury site when they are needed to help the blood clot and start the healing process.

The researchers tested the new treatment in a porcine model of heart attack, and their promising results suggest that the therapy may soon help humans recover from heart attack.

The findings appear in the journal Science Translational Medicine.

How rhPDGF-AB improves heart function

The study was a randomized trial. Chong and team assigned 36 pigs to one of three groups:

  • one that received a sham procedure (these five pigs did not have a heart attack)
  • one that received a balloon occlusion of the coronary artery to mimic a heart attack and took a placebo as "treatment" (11 pigs)
  • one that received balloon occlusion and 7 days of intravenous infusion of rhPDGF-AB (11 pigs)

Nine of the pigs who experienced a heart attack died before having the chance to receive any treatment.

A month after the intervention, the researchers used cardiac MRI and other methods to show that their treatment caused more new blood vessels to form, decreased abnormal heart rhythm, and boosted overall heart function.

Specifically, 28 days after the heart attack, the new procedure improved survival by 40% compared with placebo and improved the heart's ejection fraction in the left ventricle — where the heart attack had taken place — by 11.5%.

"By improving cardiac function and scar formation following a heart attack, treatment with rhPDGF-AB led to an overall increase in survival rate in our study," explains Chong.

"While the treatment did not affect overall scar size, importantly, we found that rhPDGF-AB led to increased scar collagen fiber alignment and strength. This improved heart function after a heart attack."

"This is an entirely new approach with no current treatments able to change scar in this way."

James Chong

Clinical trials in humans to follow very soon

Chong explains how these findings build on the team's previous work, saying, "Our collaborator Prof. Richard Harvey, from the Victor Chang Cardiac Research Institute [in Darlinghurst, Australia], had previously shown that the protein can improve heart function in mouse models following heart attack."

"This project has been developed over more than 10 years, and we now have compelling data in two species for the effectiveness of this treatment."

Chong places the findings in the larger context of the rise of heart disease as a leading cause of death:

"While we have treatment protocols in place, it's clear that there is an urgent, unmet need for additional treatments to improve patient outcomes, particularly after large heart attacks."

"Some further animal studies are required to clarify safety and dosing. Then we can start looking toward clinical trials in humans very soon," says Chong.

"RhPDGF-AB is clearly a promising therapeutic option and could potentially be used alongside existing treatments to improve heart attack patient outcomes and survival rates."

In the future, says Chong, "We […] hope to further investigate the treatment, including whether it could be used in other organ systems impacted by scar tissue, such as the kidneys."

Original Article

Medical News Today: Cholesterol levels in young adults can predict heart disease risk

A recent study investigates the relationship between cholesterol levels in young adulthood and cardiovascular risk in later life — with interesting recommendations for further research.

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A recent study looks at the long term impact of high cholesterol levels.

Research has already well documented that high cholesterol levels can lead to heart disease, the leading cause of death in the United States, and stroke, the fifth leading cause of death.

Cholesterol is a fatty substance that the liver and foods we eat, such as eggs, cheese, and certain meat products produce.

Cholesterol is necessary for the body to function. However, too much "bad" cholesterol, which is also called low-density lipoprotein (LDL), can clog the arteries with a fatty buildup, increasing the risk of heart attack, stroke, or peripheral artery disease.
Scientists have also linked high total cholesterol to overweight, lack of exercise, smoking, and alcohol consumption.

More than 12% of adults in the U.S. aged 20 years and over have total cholesterol levels above 240 milligrams per deciliter (mg/dl), which doctors consider high. Of children and adolescents aged 6–19 years, some 7% have high total cholesterol.

High-density lipoprotein (HDL) is "good" cholesterol and helps to sweep LDL from the arteries back to the liver, which removes it from the body.

A long look at lipids

A new, comprehensive study, appearing in The Lancet, follows almost 400,000 people in 19 countries for up to 43.5 years (1970–2013). The findings shine a spotlight on the link between bad cholesterol (non-HDL) levels in people under 45 years of age and the long-term risk of heart disease and stroke.

Set apart from previous studies, this observational and modeling study, which looked at individual level data, suggests that elevated non-HDL cholesterol levels at a younger age can predict cardiovascular risk at 75 years of age.

The study used data from 38 studies carried out in the U.S., Europe, and Australia.

Of the nearly 400,000 individuals that the study followed, none had cardiovascular disease at the start. The scientists tracked the participants over decades and took details of any heart disease event, fatal or otherwise, or stroke.

In total, there were 54,542 incidents of heart disease, fatal or non-fatal, and stroke.

When researchers analyzed the data for all age groups and both sexes, they saw that the risk of heart disease or stroke dropped continuously as non-HDL levels dropped. In fact, those with the lowest non-HDL levels, — which the scientists defined as 2.6 millimoles (mmol) non-HDL cholesterol per liter — had the least risk.

The highest long-term risks of heart and artery disease were in those younger than 45 years old.

"This increased risk in younger people could be due to the longer exposure to harmful lipids in the blood," says Prof. Barbara Thorand, of the German Research Center for Environmental Health in Neuherberg.

Study suggests early intervention vital

The study confirmed that the level of non-HDL and HDL cholesterol in the blood played a significant part in predicting the risk of cardiovascular disease over time.

Researchers used data to create a model for people aged 35–70 years that could estimate the chances of a heart event by age 75 years. It factored in sex, age, non-HDL levels, and cardiovascular risk factors, such as blood pressure, BMI, diabetes, and smoking status.

It also examined how much one could lower risk if non-HDL cholesterol levels were a hypothetical 50% lower. Using this approach, the researchers saw the most significant reduction in risk in the youngest age group.

As an example, a male under 45 years of age has starting levels of non-HDL cholesterol of between 3.7–4.8 mmol per liter and at least two risk factors for cardiovascular disease; if the individual was to halve their levels of non-HDL cholesterol, they could reduce the risk from 16% to 4%.

A female with the same factors could reduce their risk from around 29% to 6%.

Using the same levels of non-HDL cholesterol in individuals of 60 years or more, males could reduce risk from 21% to 10%, and females from 12% to 6%.

The researchers suggest that intensive efforts to lower non-HDL cholesterol levels could reverse early signs of blocked arteries, which is known as atherosclerosis.

However, there was no clarity on how much slightly increased or seemingly normal cholesterol levels affected cardiovascular risk over a person's lifetime or at what level treatment recommendations should occur, especially in younger adults.

"Our estimates suggest that halving non-HDL cholesterol levels may be associated with reduced risk of cardiovascular events by the age of 75 years and that this reduction in risk is larger the sooner cholesterol levels are reduced."

Co-author Prof. Stefan Blankenberg

"The risk scores currently used in the clinic to decide whether a person should have lipid-lowering treatment only assess the risk of cardiovascular disease over 10 years, and so may underestimate lifetime risk, particularly in young people," notes the study's co-author, Prof. Stefan Blankenberg.

The authors say future research is needed to understand whether early intervention in younger people with low 10-year risk but high lifetime risk would have more benefits than later intervention.

A limitation of the study is that it may not apply to all regions or ethnic groups because its focus was on high income countries.

High cholesterol has no symptoms, and many people are unaware that they have high levels; however, doctors can check levels with a simple blood test.

Original Article