Men develop irregular heartbeat earlier than women; extra weight a factor

16 Oct 2017

1

Men develop a type of irregular heartbeat, known as atrial fibrillation, about a decade earlier than women on average, and being overweight is a major risk factor, according to a large new study published in the American Heart Association's journal Circulation.

In atrial fibrillation, the upper chambers of the heart, or atria, quiver instead of beat to move blood effectively. Untreated atrial fibrillation increases the risk of heart-related death and is linked to a five times increased risk of stroke. In the new research, having the condition more than tripled a person's risk of dying.

"It's crucial to better understand modifiable risk factors of atrial fibrillation," says study author Christina Magnussen, MD, a medical specialist in Internal Medicine and Cardiology at the University Heart Center in Hamburg, Germany. "If prevention strategies succeed in targeting these risk factors, we expect a noticeable decline in new-onset atrial fibrillation."

This would lead to less illness, fewer deaths and lower health-related costs, she said.

Researchers reviewed records of 79,793 people (aged 24 to 97) in four community-based studies in Europe. The participants did not have atrial fibrillation at the outset. Later assessments of their health -- with a median follow-up period of 12.6 to a maximum of 28.2 years -- showed that 4.4 percent of the women and 6.4 percent of the men had been diagnosed with the condition.

Researchers noted atrial fibrillation:

  • diagnosis rates jumped when men were 50 or older and women were 60 or older;
  • developed in about 24 per cent of both men and women by age 90;
  • onset was tied to higher blood levels of C-reactive protein (inflammation marker) in men; and
  • new atrial fibrillation cases increased more in men than women with increases in body mass index (BMI): 31 per cent in men and 18 per cent in women.

"We advise weight reduction for both men and women," Magnussen says. "As elevated body mass index seems to be more detrimental for men, weight control seems to be essential, particularly in overweight and obese men."

Researchers were surprised to find that higher total cholesterol, a risk factor for heart disease, lowered risk for developing atrial fibrillation, especially in women, although exactly why is not clear.

Due to its design, the study could not shed light on pathophysiological factors causing sex differences in atrial fibrillation risk. The authors also note that atrial fibrillation might have been underdiagnosed at the study's start and later records may not reflect all cases. Strengths of the research include that it studied the condition in the general population and noted how individuals fared over long periods.

Since study participants were from both northern and southern Europe, the findings will probably apply to other Caucasian populations but cannot be generalised to other groups, Magnussen said. However, since BMI in the study was such a strong risk factor for atrial fibrillation, it is likely to also be impactful in other groups, she added.

According to American Heart Association statistics, between 2.7 and 6 million Americans are living with atrial fibrillation, and more than 12 million are expected to have the condition in 2030. Risk factors include body mass index, systolic blood pressure, total cholesterol, diabetes, smoking, alcohol consumption, previous heart attack or stroke and presence of heart disease.

Macrophages, a type of white blood cell involved in inflammation, readily take up a newly approved medication for Duchenne muscular dystrophy (DMD) and promote its sustained delivery to regenerating muscle fibers long after the drug has disappeared from circulation, an experimental model study led by Children's National Health System researchers finds.

The study, published online today, 16 October 2017, in Nature Communications, details the cellular mechanisms of morpholino antisense drug delivery to muscles, improving understanding of how these medicines target muscle tissue and suggesting an avenue to improve treatments for DMD, a devastating disease that currently has no cure.

Duchenne is the most common and severe form of muscular dystrophy and affects about 1 in 5,000 boys worldwide.

The disease is caused by mutations in the X-linked DMD gene. DMD is characterised by significant muscle degeneration, regeneration, heightened inflammation and fibrosis, leading to progressive muscle weakness and loss, explains study co-leader James S. Novak, PhD, a principal investigator in Children's Center for Genetic Medicine Research. Mutations in the DMD gene lead to a lack of functional dystrophin, a protein critical to maintaining structural support in healthy muscle.

Most boys with DMD lose the ability to walk by their teens; life expectancy for people with this disease rarely extends past the early 30s.

Until recently, the only pharmaceutical therapies for DMD targeted the symptoms, rather than its root genetic cause. However, in September 2016 the Food and Drug Administration approved the first exon-skipping medicine for DMD to restore dystrophin protein expression in muscle. Eteplirsen, an antisense phosphorodiamidate morpholino oligomer, has shown significant promise in preclinical studies, but clinical trial results have shown variable and sporadic dystrophin production in the muscles of people who receive it.

Because the medication vanishes from the blood circulation within hours after administration, Children's research efforts have focused on the mechanism of delivery to muscle and on ways to increase its cellular uptake - and, by extension, its effectiveness. However, researchers understand little about how this medication actually gets delivered to muscle fibres or how the disease pathology impacts this process, knowledge that could offer new ways of boosting both its delivery and effectiveness, says Terence Partridge, PhD, study co-leader and principal investigator in Children's Center for Genetic Medicine Research.

To investigate this question, Novak, Partridge and colleagues used an experimental model of DMD that carries a version of the faulty DMD gene that, like its human counterparts, destroys dystrophin expression.

To track the route of the phosphorodiamidate morpholino oligomer (PMO) into muscle fibers, they labeled it with a fluorescent tag. The medicine traveled to the muscle but only localized to patches of regenerating muscle where it accumulated within the infiltrating macrophages, immune cells involved in the inflammatory response that accompanies this process.

While PMO is rapidly cleared from the blood, the medication remained in these immune cells for up to one week and later entered muscle stem cells, allowing direct transport into regenerating muscle fibers. By co-administering the PMO with a traceable DNA nucleotide analog, the research team was able to define the stage during the regeneration process that promotes heightened uptake by muscle stem cells and efficient dystrophin expression in muscle fibers.

"These macrophages appear to extend the period of availability of this medication to the satellite cells and muscle fibers at these sites," Partridge explains. "Since the macrophages are acting as long-term storage reservoirs for prolonged delivery to muscle fibers, they could possibly represent new therapeutic targets for improving the uptake and delivery of this medicine to muscle."

Future research for this group will focus on testing whether macrophages might be used as efficient delivery vectors to transport eteplirsen to the muscle, which would avert the rapid clearance currently associated with intravenous delivery.

"Understanding exactly how different classes of exon-skipping drugs are delivered to muscle could open entirely new possibilities for improving future therapeutics and enhancing the clinical benefit for patients," Novak adds.

Business History Videos

History of hovercraft Part 3...

Today I shall talk a bit more about the military plans for ...

By Kiron Kasbekar | Presenter: Kiron Kasbekar

History of hovercraft Part 2...

In this episode of our history of hovercraft, we shall exam...

By Kiron Kasbekar | Presenter: Kiron Kasbekar

History of Hovercraft Part 1...

If you’ve been a James Bond movie fan, you may recall seein...

By Kiron Kasbekar | Presenter: Kiron Kasbekar

History of Trams in India | ...

The video I am presenting to you is based on a script writt...

By Aniket Gupta | Presenter: Sheetal Gaikwad

view more