Sudden Cardiac Death in Young People: More Answers

When tragedy strikes, physicians are often asked to answer two questions.  The first is the how question. How did this happen? Long illnesses provide time for patients and family members alike to come to terms with a diagnosis and prognosis. Not always, and not easily, but the time is there.  In the case of sudden cardiac death in a young person, there is no time. Sudden cardiac death is a condition that feels out of place in 2016. That a healthy person can be alive and then, simply, not, feels wrong to modern sensibilities. Nevertheless, the incidence of sudden cardiac death, about 1 per 100,000 young people per year is similar across multiple countries and cultures. Now a manuscript appearing in the New England Journal of Medicine attempts to shed light on how sudden cardiac death can happen. For the video version of this post, click here.

The researchers examined literally every case of sudden cardiac death occurring in individuals less than age 35 in Australia and New Zealand from 2010 to 2012 in a prospective fashion. With each of the 490 cases, they examined autopsy and toxicology reports to determine how the death occurred. While 60% of the cases were explainable by conditions like coronary artery disease and hypertrophic cardiomyopathy, a disturbing 40% had no revealing findings.

So they expanded the search, in a subset of that 40%, the researchers performed advanced genetic sequencing to look for gene mutations that could predispose to sudden death. They found mutations of that type in 27% of the otherwise unexplained cases. While the gap of understanding was narrowed a bit, the how question remained unanswered for many individuals.

Now I should mention that identifying disease-causing mutations is not as easy as it sounds. Most of the mutations identified were classified as “probably pathogenic”. Basically, that means that the mutations are predicted to do harmful things to the protein they affect, but we don’t know for sure at this time.

To take the analysis a step farther, the researchers examined family members of the deceased to screen for the presence of heritable cardiac conditions. In 12 of 91 families screened, such a condition – like long QT syndrome – was found.

So what we have here is a great example of a well-conducted, methodical, and meticulous study that has moved us incrementally towards greater understanding. For some of the families who suddenly lost a loved one – the answer to “how did this happen” is now clear.

Of course that’s only one of the two questions we get asked.  The other is “why did this happen”? And that’s a question that no methodology, no matter how advanced, can answer.

Peanuts, Peanut Avoidance, and the Development of Allergy

I love a nice clinical trial that answers an important question and one of my favorites from the recent past was the “Learning Early About Peanut allergy” or LEAP trial, published in February of 2015 in the New England Journal.  I probably don’t need to reiterate the results of this truly landmark study, but basically, it upended about two decades worth of advice to parents to avoid exposing their infants to food containing potential allergens, such as peanuts.

For the video version of this post, click here.

The trial, which enrolled infants at high risk of peanut allergy, found that the rate of peanut allergy at 5 years was 18.8% among those randomized to peanut avoidance, but only 3.6% among those randomized to peanut consumption.  That’s a number needed to treat of around 7 making eating peanut products in the first five years of life about 7 times more efficacious than taking aspirin for an ST-Elevation MI. OK apples and oranges, or peanuts, but still.

But lingering questions remained.  Would these kids be protected in the long-term? Did the study just kick the peanut allergy ball down the field?

To answer the question, the LEAP researchers conducted the LEAP-ON study, in which individuals in the initial study were instructed to avoid all peanut products for 12 months. Without exposure to peanuts, would allergy come roaring back? Would these kids be doomed to eat peanuts three times a week for the rest of their lives?

Well, around 90% of the original trial participants signed on to the no-peanuts-for-12-months pledge. Overall, adherence was OK. As you might expect, those who had originally been randomized to avoid peanuts had an easier time staying off the sauce – 80% of them reported complete peanut avoidance. Only 40% of those who had been randomized to eat peanuts originally were able to stay away for the year. No shame there, peanuts are delicious.

Bottom line, after 12 months of avoidance there were 6 new cases of peanut allergy, but three from each group. In other words, you didn’t see a “rebound” in peanut allergy among those kids initially randomized to eating peanuts.  By the end of this study, 18.6% of those who had initially avoided peanuts and 5% of those who had eaten peanuts from a young age had confirmed allergy.

The point here is that the protection from allergy conferred from early exposure to peanuts persisted even through a year of not eating peanuts. This is a very good thing for the rare kid out there who doesn’t like peanuts – it seems like the protection you gained in infancy will stick around.

Now, I should mention that there was no control group here. I’m curious what might have happened to kids instructed to keep right on eating lots of peanuts. We also don’t know if avoidance for more than a year might let allergy recrudesce.

But taking this study with the results of the original trial, it’s not exactly a leap to say that early exposure to peanuts might dramatically curb the rising tide of peanut allergy in the developed world.

Huge Chinese Study Suggests 20% of Heart Disease due to Low Fruit Consumption

A 柚子 a day keeps the doctor away? Appearing in the New England Journal this week is a juicy study  that suggests that consuming fresh fruit once daily can substantially lower your risk of cardiovascular disease. In fact, the study suggests that 16% of cardiovascular death can be attributed to low fruit consumption. For those of you keeping score, that's pretty similar to the 17% of cardiovascular deaths that could be prevented if older people stopped smoking.

For the video version of this post, click here.

What we're dealing with here is a prospective, observational cohort of over 500,000 Chinese adults without a history of cardiovascular disease.  At baseline, they were asked how often they consumed a variety of foods, and gave a qualitative answer. Most of the analyses compare people eating fruit "daily" to those who ate fruit "rarely or never".

Those fruit-eaters were substantially different from the non-fruit eaters, but not, perhaps, in the way you might expect.  For example, waist circumference and BMI were higher in the fruit-eaters and fruit-eaters were much more likely to live in urban rather than rural areas. Fruit-eaters also ate more meat, all suggesting that, in China at least, eating more fruit might be a marker of better nutrition overall. Reporting the cardiovascular effects of more frequent eating of other foods would reveal whether this is the case, but that data was not shown.

More in line with our Western expectations, fruit-eaters had a substantially higher income, more education, and were less likely to smoke or drink alcohol.

After more than 3 million person-years of follow-up, there were 5,173 cardiovascular deaths. If you followed a group of 1000 fruit-eaters for a year, you'd expect less than 1 cardiovascular death. Following a similar-sized group of never-fruit eaters, you'd expect 3.7 deaths.

These observations withstood adjustment for socioeconomic factors, smoking, physical activity, BMI and consumption of other types of food, though unmeasured confounding always plays a role in dietary studies.

Why does it work? We don't know.  Though the frequent fruit-eaters had lower blood pressure and lower blood sugar, these factors did not explain the protective effects of the fruit.

Indeed, maybe it's not something in fruit that is beneficial at all, but something that isn't. Like sodium.  Fresh fruit isn't salty and salt-intake was not captured in this study. Missing data like that makes it hard to trust that the observed relationship is truly causal.

Still, there isn't much harm in advising patients to eat fresh fruit more regularly, which is I suppose, what makes studies like these so appealing.