The future of heart-disease treatment, research and prevention was discussed during a 90-minute seminar at Sanford Burnham Prebys Medical Discovery Institute (SBP) on Feb. 7 — just in time to make the Light’s Valentine’s Day issue.
The biggest current breakthrough is a new class of drugs for artherosclerosis (hardening and narrowing of the arteries) called proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitors. Right now, there are two that are FDA-approved, alirocumab (Praluent) and evolocumab (Repatha), both delivered by injection only.
“There’s a study going on right now where these PCSK9-inhibitors get injected once a month, or at most twice, and you get profound lipid-lowering,” said Dr. Anthony DeMaria, professor of medicine and founding director of UCSD Health’s Sulpizio Cardiovascular Center.
DeMaria said that PCSK9s reduced heart events by 22.4 percent and that, with continued research, “I think it’s possible that the next generation may not know the ravages of artherosclerosis.”
For now, DeMaria said, the state of the art is still statins, which DeMaria called “the most amazing drugs ever introduced in our society.” Despite the conspiracy theories you might read about them on the internet, he said, they still reduce mortality by 20 percent.
“That’s the hardest end point,” DeMaria said. “There’s no debating death. If you’re dead, you’re dead. You’re not a little bit dead.”
Another heart frontier with new weaponry is aortic-valve failure. (More than a quarter of everyone over age 65 has some aortic stenosis.) DeMaria explained a new process called transcatheter aortic valve replacement (TAVR).
In the past, he said, surgeons would “filet your chest.” But now, with a prosthetic aortic valve, a catheter inserts a balloon.
“You blow up the balloon and you replace the valve,” DeMaria said, “you push the old one away and have a brand new one.” DeMaria added that “maybe in the next couple of years, we won’t do surgery at all.”
In the far future, DeMaria said, using stem cells to regrow the myocardium is a strong possibility, but he ran out of time to explore it.
Karen Ocorr, assistant professor in SBP’s aging and regeneration program, explained how fruit flies are helping her investigate the genes that might cause atrial fibrillation (AFib), an irregular heartbeat that can lead to deadly blood clots, stroke and heart failure. (It affects 9 percent of people over age 65.)
Ocorr said that fruit flies are ideal because they age quickly. (In fruit flies, one week is the equivalent of a human decade.) They have all the same ion channels (proteins that make heart muscles contract) as humans, which makes them a good model for understanding what happens when human hearts malfunction. And — contrary to what most non-biology majors assume, Ocorr said — “they do have a heart.”
Ocorr showed a high-speed video showing strikingly similar atrial fibrillation in old (8-week-old) fruit flies and elderly humans.
“We are looking for genes to manipulate to try and fix this,” she said. “We are taking genes that can be identified as being aberrant in patients with AFib.”
In partnership with Scripps Health, Ocorr explained, she plans to do that by taking samples from Scripps patients with AFib, and comparing their genetic signatures to samples from patients hospitalized for different reasons. The hope is to build a genetic network that identifies different targets for future drugs.
“Our plan is to take these pieces of tissue that would normally be thrown away and come up with signatures,” she said. “Those will be the genes we will focus on in our fly model. We’ll start knocking them down or expressing them to look for genes. Then we’ll take those same genes from the fly model and test them in human sites.”
Same old prevention
Of course, all 100 attendees knew they would be warned at some point to exercise more, eat less and never smoke. But DeMaria was mercifully entertaining in delivering this inevitable advice.
He showed a slide describing the 1,420-calorie Monster Thickburger from Hardee’s — consisting of 2.3 pounds of beef, four strips of bacon, three slices of cheese and mayo on a buttered bun. Then he showed an escalator arriving at a top floor of a convention center full, alongside an empty flight of stairs. When he explained that the photo was taken at an American Heart Association conference, the audience erupted with laughter.
During a Q&A after the presentations — which also included an address by Donna Marie Robinson, a former Bank of America employee coping with heart failure — DeMaria was asked about different diets. He admitted that some evidence supports the ketogenic diet.
“This is an extreme version of the Atkins diet and in many people, they get favorable effects and it’s very fashionable now,” he said. “Eat this diet so that you feel anorexic and terrible and your body is acidotic and you may live 27 days more.”
But, DeMaria said, the best data in the world at the moment supports the Mediterranean diet.“Fruits, vegetables, proteins and a lot of olive oils,” he said. “We should all move to Italy for a lot of reasons. People put on that diet have had fewer events.“Another proven heart-disease prevention method, DeMaria said, is “any amount of exercise.”
“The latest thinking is that if you do any exercise in moderation,” he said, “you’re still going to get significant benefits.”
In other words, exercise more, eat less and never smoke.