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New trial on exercise and plaque
A brand new clinical trial just came out looking at the effect of exercise on artery plaque, and the results are super interesting. They took patients with a lot of plaque and angina, all on lipid-lowering treatment such as statins and antiplatelet drugs, so these are high-risk patients. Then they split them randomly. Half got the standard advice from the guidelines: eat a healthy diet, don't smoke, exercise regularly, and manage their blood pressure and their glycated hemoglobin levels. That was the control group, which got the standard of care. The other half were the intervention group, and they started a supervised exercise program.
The exercise program
Specifically, it was an HIIT program. HIIT stands for high-intensity interval training, and it's a pretty popular workout where you have bursts of high-intensity activity interspersed with intervals of recovery, all of this cycled over and over. It can be a pretty intense workout. In this study they used mainly a treadmill or stationary bike, and the workout consisted of an initial warm-up period of 10 minutes at 60 to 70% of peak heart rate. Then they started the workout proper: first a 4-minute period of high intensity at 85 to 95% of peak heart rate, then a recovery period, and this would just cycle over and over, the 4 minutes of high intensity and the 3 minutes of recovery, four times through this cycle, and finally 5 minutes of cool-down. They did this whole workout twice a week, supervised by professional trainers. Outside of that, they were also encouraged to do more exercise at home, including more HIIT.
The Results
After 6 months of this workout program, they measured the plaque in their arteries and compared the values with the measurements before the trial. In the control group, which was doing the standard of care, there was no significant difference in plaque dimensions: no significant increase or decrease. On the other hand, the group doing the HIIT program saw a significant reduction of plaque size. The largest lesion the patients had, the largest segment of plaque, filled on average 49.5% of the artery lumen. The lumen is the hole through the tube, through the artery. That was the value before the trial, and after 6 months of HIIT that number came down to 48.3%. So that was a 1.2% drop. Now, is this a meaningful reduction? Does 1.2% make a difference? If we look at trials with lipid-lowering treatment as a reference, meaning trials using statins or other cholesterol-lowering medications, because we have a lot of those, for each 1% reduction in average plaque size we see about a 20 to 25% reduction in the risk of events like heart attacks or strokes. Grain of salt: this is a different intervention and a different stimulus, so we don't know if the same would apply here. But as a reference, a 1% reduction in plaque size can reflect a very substantial reduction in risk.
Plaque size vs structure
At the end of the day, what we really want to see is outcomes: the risk of actual events like heart attacks, strokes, revascularization, death, etc. This trial doesn't report that. For that type of outcome you normally need longer follow-ups and more people. It's just harder to quantify than surrogates like biomarkers or plaque size, for example. But the results of this trial are definitely really encouraging, and I'm looking forward to seeing more. The other thing that's really good to bear in mind is that when we talk about plaque size and a reduction, this is the thickness of the plaque, and that's meaningful, but what's even more critical is the composition, the structure of the plaque. The structure of a plaque can change in a way that makes it more stable and less likely to rupture without it getting any smaller. That's entirely possible; it can even get a little bit bigger while getting more stable and less of a problem overall. So these are just things that are good to bear in mind, so we have a more nuanced and more educated perspective on all of this.
BMI, HbA1c and cholesterol
Another open question is how different types of exercise affect plaque and eventually outcomes: cardio versus weights versus all kinds of sports. Here they only used this HIIT protocol, so we can't compare, and this is all to be determined. Now, if this effect is real, if exercise, or at least HIIT, ends up shrinking plaque meaningfully and reproducibly, how does that work? The group doing the HIIT program also saw a statistically significant reduction of their BMI and their waist circumference, so they got a little bit leaner, which is not that surprising since they were exercising more. One possibility is that it's the weight loss causing the reduction in plaque, which is possible. On the other hand, and this is really interesting, the HbA1c, the glycated hemoglobin of the participants, as well as their LDL cholesterol and ApoB levels, were not significantly different between the controls and the group doing HIIT. This is very relevant because, as we said, lipid-lowering treatment significantly shrinks plaque; that has been shown many times. But in the context of this trial, we're seeing this significant reduction with constant LDL cholesterol and ApoB. Remember, we said at the beginning that everybody in this trial is on lipid-lowering treatment. Everybody is on a statin or a similar drug and has their LDL cholesterol and ApoB pushed lower, everybody in the control group and everybody in the HIIT group, because they're all high-risk patients. So their average LDL cholesterol at baseline, before the trial, was about 80 milligrams per deciliter, which matches the range where we see plaque stop growing in the lipid-lowering drug trials. Above that range we see plaque grow, and the higher the LDL cholesterol, the faster the growth. Around 80, give or take 70 to 80, is the cutoff where we see growth stop, and under that range, with LDL cholesterol below 70 to 80, we start to see reversal, or regression as it's called: we start to see plaque get smaller. So here we're seeing a similar outcome. This regression, this reduction of plaque size, comes from bringing lipids down to about 80 milligrams per deciliter LDL cholesterol, the range where we normally stop plaque growth. Then, instead of bringing them down even further, we're adding this exercise program on top, and we're seeing regression with that combination. This is very important to understand: the range where we are operating. We might just hear a headline or look at the title of the paper and think, oh, exercise shrinks plaque, so I'll just leave my lipids in the stratospheric range and go for a run, and that should melt my plaque right off. But that is not what this study showed at all.
What the results mean
These observations raise all kinds of interesting questions. For example, what if we have both? What if we bring our lipids lower to the range where we normally see regression with lipid-lowering alone, and we add exercise on top? Maybe the plaque shrinks twice as fast. Maybe there's an additive effect. Or maybe it's not additive, and the two interventions are operating through a common mechanism, so having both is not better than having either one. These are all questions for future research, and we'll definitely keep an eye on this type of data going forward. For more on how to lower ApoB with lifestyle, we have an entire video all about that, and here's the best workout to lower blood pressure. Check those out, and I'll see you next time.