CholesterolQuestion

(rhythmic music) - I was maybe a couple blocks from my house and all of a sudden I felt something that was stopping me from pedaling. I was just grabbed. - I lost all of power in my body. The next feeling that came over me was the feeling of impending death. - I felt like the walls were closing in a little bit. At the time, I wasn't thinking heart attack. Although that was exactly what was happening. - [Narrator] Heart attacks strikes once every 34 seconds in North America. And the numbers are rising. For decades, doctors have pointed to a prime suspect in the heart attack crime wave, cholesterol. - The higher your cholesterol level, the higher cardio vascular risk. - And so I go into the doctor and he just says, you have really high cholesterol. And you have to start medication right away. And if you don't, you're gonna be dead before you're 40. - [Narrator] But there are nagging questions. - 50% of the people who have a heart attack or a stroke actually have normal cholesterol levels. The question is, what else is going on here? - If it really is a big deal, then I'm a ticking time bomb. - [Narrator] This case is far from open and shut. What role does cholesterol really play in these matters of the heart? This is a detective story. A hunt for the causes of one of our biggest killers. Heart attack. It's a hunt that's gone on for decades. But we have followed some false leads and overlooked crucial clues. It's time to take a fresh look at the heart attack investigation board. Compile more evidence, identify new suspects, and interview the witnesses. Like Aaron Holm, whose personal connection to this story began 20 years ago with an urgent call from his family doctor. - They said, it's a big problem with your blood results. You have to come in as soon as you possibly can. So I'm like, oh wow, okay. You know, what am I HIV positive? Like what's the issue? And so I go into the doctor and it's a very somber, serious conversation, he says, you have really high cholesterol. If you don't change your lifestyle or whatever, you're gonna be dead before you're 40. And I'm like 21 or 22 years old. I'm super healthy. And not quite sure what any of this stuff means. - [Narrator] What it meant was familial hypercholesterolemia. A genetic tendency for high levels of cholesterol in his blood stream. - I don't have the gene where my body's able to understand that it has produced enough cholesterol and it doesn't need to make more. And so as a result, it just keeps making it. Keeps making all this cholesterol. I have never met anybody who has cholesterol levels as high as I do. - [Narrator] Aaron went to a number of specialists who all said the same thing. Medicate. - If you take the medication, who knows what the long term affects are. Who knows what the impact on your liver is over the years, and your kidneys over the years. Who knows? I don't know. I just did everything else to manage the situation except for taking medication. There's a duality to the cholesterol issue. Because you don't feel any problems. You don't feel sick. Yet there's a lot of pressure and fear around it that make you think that you really have to keep an eye on things. - [Narrator] This pressure and fear is because most doctors say the higher the cholesterol numbers, the higher the risk for a heart attack. - I really don't know what's going on inside. It's like all I know is that there's this abstract number which is supposed to have some kind of meaning and value. And if it really is a big deal, then I'm a ticking time bomb. - [Narrator] If Aaron has questions, he might find answers here. This is where everything we now believe about cholesterol and heart disease got started. Like many good detective stories, this one begins in a small New England town. Framingham, Massachusetts. - Around 1940, 1950, very little was known about the causes of cardiovascular diseases or how to treat it. So the government wanted to try to figure out what were the things that caused heart attacks and better predict who would develop cardiovascular disease. - [Narrator] The study began with over 5000 volunteers who were monitored and tested every two years. And the numbers grew. For Ray Reva, it's been a family affair. - my father was one of the originals and over the years, expanded the program and now my sons are in it. And hopefully someday my grandchildren will be in it too. - [Narrator] A decade after the study started, data began to appear on the participants who were experiencing heart problems. There were certain things they had in common. - Cigarette smoking, high blood pressure, obesity, so these are things that we take for granted now. But before the initiation in Framingham, it wasn't really known. - [Narrator] There was one new suspect in this gang of villains that was a complete mystery to most of us. Cholesterol. It's normally a good guy. Our bodies manufacture it and it's in every cell, essential for making sex hormones and vitamin D. But Framinghamers with heart disease tended to have a lot in their blood stream. And plaque deposits in their arteries were loaded with it. One theory said these deposits might be clogging things up and causing heart attacks. So was this good guy really a dangerous serial killer? And where was all this cholesterol coming from in the first place? For a long time, we believed it only came from places like this. - Welcome to the Heart Attack Grill. The most fattening place on earth. - [Narrator] The Heart Attack Grill in Las Vegas says their food is to die for. - It's bad for you. But it's fun trying it. - [Narrator] Patrons wear hospital gowns. And the wait staff dress as nurses. - You're not gonna see any salads because we don't have any lettuce. - [Narrator] Anyone who weighs over 350 pounds eats for free. And for anyone leaving food on their plate, there are consequences. But what about the consequences of downing all the cholesterol in their famous quadruple bypass burger? Is it really heading straight to the heart? Researchers have long been suspicious about a connection between diet and heart disease. In the early 1900s, a Russian scientist fed eggs to rabbits. And he discovered that their arteries quickly built up plaque deposits full of cholesterol. In the 1950s, American scientist Ancel Keys heard that people in Italy lived long lives and had low rates of heart disease. He wanted to find out why. He launched a study comparing the diets of people in Europe, Asia, and North America that revealed a suspicious connection between heart disease rates and dinner plates. His conclusion, some diets were harboring dangerous fugitives. Countries with higher rates of heart disease not only had higher blood cholesterol, but also a higher consumption of dietary cholesterol and saturated fat. In the decades after Keys' study, ads like these started to appear. - What would you recommend? - Something delicious, light, and low in cholesterol. - [Narrator] Slender actors living the good life creating the impression that removing cholesterol could make our favorite foods healthy again. According to this man, the case files held some surprising secrets. - It's a huge disconnect that most people don't understand between the cholesterol in your diet and the cholesterol in your blood. Girls, who wants chicken scratch? - [Narrator] When Dr. Christopher Gardner is not looking after the diet of his chickens, he's investigating the influence of diet on human health. - It seems like you eat cholesterol in your diet, it ends up in your blood, there's plaques full of cholesterol impeding the flow of blood. It must be a direction connection. But they've done studies with eggs and they gave people an egg a day, three eggs a day, six eggs a day, and they measured their blood cholesterol throughout the study, never changed. And eggs are full of cholesterol. And they've been trashed for years and vilified because of all the cholesterol in the egg. The other big sources are shellfish. But in fact, your body adapts quite easily to the cholesterol that you get in your diet from something like an egg or a shellfish. - [Narrator] But look for cholesterol in food, and another familiar villain is rarely far away. - Here's what happens. Cholesterol is only in animal foods. And animal products typically come with saturated fat in them. And saturated fat has also been vilified for years. And so there was a public health movement to get cholesterol and saturated fat out of our diets. - [Narrator] Saturated fat raises LDL. The so called bad cholesterol that can collect in our arteries and cause heart disease. But it also increases HDL, the good cholesterol that helps clear out the bad. Ultimately, the war on fat was undiscriminating and had unintended consequences. - It also led to an obesity epidemic and you can't pin the obesity epidemic on any one thing. But there's certainly a lot of us that believe that it was the interpretation of the food pyramid that led to a trend of more calories. - [Narrator] The food pyramid was a campaign launched in the 90s to promote healthy diet choices. The base was grains. Then fruit and vegetables. Then dairy, then meat and fish. And then sugar. And virtually no fat. - And what we really got out of it was a lot of bread. A lot of processed refined bread. Because grains were low in fat. And so that has confounded everything that the original investigators had intended. Because vegetables are low fat. Beans and legumes are low fat. Fruits are low fat. And that's not what people were picking. - [Narrator] What people were picking were highly processed foods and refined carbohydrates. Which actually lower HDL, the good cholesterol. They also led to obesity, diabetes, and high blood pressure. All heart risk factors. The low fact diet experiment had big problems. And Gardner argues we could be missing an even bigger picture. - There's 20 other things that affect heart disease. But at the end of the day, there's a lot of people with high LDL cholesterol who don't get heart attack. And there are plenty of people who have low LDL cholesterol who get a heart attack. There seems to be a misunderstanding about the proportion of risk that's attributable just to LDL cholesterol. It's really been exaggerated. I think it's partly driven by the fact there's a lot of money there. - [Narrator] Money. In any investigation, you always follow the money. In this case, Gardner's referring to the billions spent annually on statins. First introduced in 1987, statins currently lower LDL cholesterol numbers in the blood more effectively than diet or any other method. They have become the biggest selling and most popular prescription drugs of all time. And the sales continue to rise. - After the most recent statin guidelines came out from the American Heart Association, it was estimated that if these guidelines were followed, about a billion people worldwide would be prescribed statins. - [Narrator] Could a billion users be wrong? Are statins the answer to the cholesterol question? The prime suspect in the heart disease crime wave continues to be cholesterol. Aaron Holm's doctor told him his cholesterol numbers were dangerously high. He was in his 20s then. And he's been on the run ever since. The doctor told me at one point, if you don't take medication, if you don't get your cholesterol level down, you're gonna be dead before you're 40. And so I never allowed myself to think beyond that age. And as that age became closer, and as I had kids, I started to realize that actually I really wanted to be around. And I really wanted them to have a father. And when I turned 40, it was like the epic moment where the sun comes out and the choir sings. And you're like, holy cow, I didn't die. And so all of a sudden the future was this thing that opened up and I'd never thought about it. I might develop a relationship with a doctor now. And just be candid and say look, I don't wanna take medication. And I'd like it if you were to come up with some alternate ideas around how it is that I can manage this, if it is in fact a problem. I just don't know how many doctors are able to have that conversation. 'Cause most of them can't seem to get past the notion of medicating. - [Narrator] The medication Aaron wants to avoid is a group of drugs called statins. A tall order because statins are the most widely prescribed drugs in the world. He's come to see Dr. Beth Abramson, the author of Heart Health for Canadians. - And in terms of risk for future heart disease, we're just gonna go over a few of these. You've never been told you have high blood pressure? - [Aaron] Nope. - No history of diabetes? - No. - You a smoker? - No. - Shake your hand. - [Aaron] Thank you. - All right, so you're feeling well. But you're a young dad and wanna make sure your future risk is okay, is that right? Okay. Well, I'm gonna have a listen to your heart and lungs. When we calculate someone's future risk for heart disease, cholesterol is an important aspect. It's not the only aspect. A patient is not just a cholesterol value. So if you have diabetes, you're smoking, your blood pressure is high, your risk is going to be even higher. So every one of my patients that I see who's come into the hospital with a heart attack, or who's been diagnosed with coronary heart disease, or who's had a stroke, I know their chances of dying or having a recurrent heart attack are lower on the classic cholesterol pills called statins. - [Narrator] There are a number of statins. - Getting the goal is important. Especially if you have high cholesterol. Plus any of these risk factors. - [Narrator] Many of us have seen the ads. Some aimed at our deep fear of heart attacks. Or playing into our desire for easy solutions by equating a pill with a vigorous swim or bike ride. Statins all work by inhibiting cholesterol production in the liver. In randomized trials, they are the only cholesterol medications that have been shown to reduce risk in people with known heart disease. But debate has been raging. Have they been over prescribed? Dr. Barbara Roberts is the author of the Truth About Statins. - Almost without exception, these trials have been paid for by the pharmaceutical company that makes the statin being studied. And we know that industry sponsored trials are four times more likely to be report a positive result than non industry sponsored trials. - [Narrator] As for statin's role in preventing heart disease. - If you're giving statins to healthy but high risk people, healthy people who haven't had a heart attack, the absolute risk reduction in three of the biggest primary prevention trials, in men, is on the order of 1.5%. Even the most fervent statin apologist has to admit that anywhere from 60 to 80% of cardiac events are not prevented by statins. So if you had a vaccine, for example, that didn't prevent 60 to 80% of the cases of flu, how many people do you think would use that vaccine? Very few. - Take a deep breath in. - [Narrator] Dr. Abramson believes that statins do have a role in primary prevention. Along with other therapies. - In patients who have not yet had a problem, there is a role for cholesterol lowering pills. It doesn't mean we put in the drinking water. And it doesn't mean that we use the statin for a substitute for making lifestyle changes. - [Narrator] But would there be any harm in taking statins just in case? - This gets us to the whole area which gets me upset. And that is that the benefits have been vastly exaggerated and the dangers have been vastly underplayed. The only group where we know there is some benefit is middle aged men who've had a heart attack. In fact, in the older age group, higher levels of cholesterol correlate with better survival. Elevations in cholesterol are only a risk factor until about middle age. - [Narrator] Dr. Roberts says there are also questions about benefits for women. - I think that the reason that women have less benefit from statins if they have any benefit at all, which is questionable, is because LDL is not a significant risk factor in women. The other thing is that women are more apt to have side effects to statins. We know that women are more apt to have muscle pain. And muscle damage. Women are more apt to develop diabetes as a result of statins. There are multiple side effects and I really worry about the long term effect on the nervous system of treating people and getting their cholesterols down to very low levels. - [Narrator] Most doctors argue the benefits of reducing risk outweigh the potential side effects in both men and women. - There are a small percentage of my patients who will have a side effect on a statin or cholesterol pill. That often will manifest as either an ache in the muscles or an abnormality in the blood test. Either the liver function or the muscle enzyme. The good news is is that this is usually reversible. This can be reversed by stopping the medication. Initially, when these drugs were tested, they were tested mainly men. There was less data in women over the years. But we have in this day and age conclusive and good clinical trial evidence that statins save lives in women. - [Narrator] In a surprise move, the American Heart Association recently abandoned the cholesterol targets that help doctors decide who should get a prescription. What's even more surprising is the effect this could have on statin use. - After the most recent statin guidelines came out from the American Heart Association, it was estimated that if these guidelines were followed, about a billion people worldwide would be prescribed statins. - What the American guidelines have said is we've tried lifestyle, it hasn't worked. So we're gonna move ahead in society and use a drug that's effective. It is true that statins will save lives if I prescribe them to more Canadians. I still wanna use the art of medicine, take a history, make sure your risk really is high enough to be on the statin. And make sure you're making the right lifestyle changes as well. - [Narrator] While statins remain the drug of choice for lowering cholesterol and reducing risk, there is still something puzzling about a significant number of heart attack victims. - What's interesting is that 50% of people who have a heart attack or a stroke actually have normal cholesterol levels. - [Narrator] Cardiologist Paul Ridker has a tennis partner who fits this description. A few months ago, the man nearly dropped dead from a heart attack while jogging. He was fit, healthy, and had lower than average cholesterol levels. - [Paul] The question has been, what in addition to cholesterol is driving this process? - [Narrator] In the 1990s Ridker and his colleagues began to follow a trail of clues that began at the site of the heart attack itself. It's where scientists had noticed signs of inflammation. - Inflammation broadly is the mechanism by which our bodies fight off foreign substances, fight off infection, help us to deal with cancer, you can't live without inflammation. The problem is, for some of us, that inflammation can be overactive. And we ask the question, is it possible that in currently healthy individuals, was there a measure of inflammation in the blood that we could get a grasp on that would tell us five, 10, 15 years down the road, a-ha, this person is at high risk because they have a pro-inflammatory response. Just like they might be at risk if they had a high cholesterol level. - [Narrator] So Ridker tested blood from heart attack victims. He was looking for markers of inflammation. If he found one of these markers, he would have evidence that inflammation was at the scene. - It turned out something called C-reactive protein or CRP was a very powerful predictor of your risk of having a future heart attack. Even if your cholesterol levels were low. And it was light bulb going off for us. - [Narrator] But could stopping inflammation actually help stop heart attacks? Ridker looked for answers by investigating another mystery. An unexpected statin side effect. - Investigators around the world had noticed that the statin drugs, these cholesterol lowering drugs, also lower the risk of stroke. And that's a little bit unusual because stroke is not really driven by high levels of LDL cholesterol. But it is driven by inflammation. And we already knew the statins lower the risk of stroke. And so we said, why would that be? - [Narrator] Ridker looked closer and discovered that statins also lowered CRP. So he asked a provocative question. Could statins stop heart attacks in seemingly healthy people with low cholesterol, but with signs of inflammation in the form of CRP? - We randomized almost 18,000 patients around the globe. Their cholesterol levels were very low or baseline. But they all had high levels of CRP and we therefore, they were all at high risk for having a future heart attack or stroke. Well, fast forward several years later, there's a 50% reduction in heart attacks, 50% reduction in stroke. And about a 20% reduction in all cause mortality by giving a cholesterol lowering drug that we know lowers inflammation. To people who don't have high cholesterol. That was a real breakthrough. Statin drugs, the drugs that we think of as cholesterol lowering drugs, are sort of twofers. They both lower cholesterol and they lower inflammation. And many of us now think of the reason is these drugs are so effective is because they have beneficial effects on both of these systems which seem to interact with each other to really deal with aggressive heart disease. - [Narrator] The study was funded by the same company that makes the statin, Crestor. And the results and methods were not without controversy. So Ridker is going one step further to prove his theory. He's testing an anti-inflammatory drug that's been used for years to treat another ailment entirely, arthritis. - And it was noticed many years ago that people who took this drug for arthritis seemed to have lower rates of heart disease. We're giving the drug to patients who had a prior heart attack. They don't have arthritis. And we're asking the question, if we lower the inflammation, will we in turn get fewer heart attacks and fewer strokes? It's a very exciting study. And it's up and running right now in the US and Canada. - [Narrator] Billions have been spent in research labs around the world to try to stop the heart attack crime wave. But meanwhile in a tiny isolated village in Italy, a medical mystery, a mutation that not only stops but reverse heart disease. - I thought it was a one in a million chance. And I was absolutely stunned when it worked. - [Narrator] HDL, Italian style. Italy is in the top 10 when it comes to longevity. The mediterranean diet has been given much of the credit. But here in the north, in the tiny resort town of Limone Sul Garda, there is another secret that has been extending lives. It's a secret that was discovered by Dr. Cesare Sirtori. When he encountered a patient who broke all the rules. A man with high LDL or bad cholesterol, and virtually no HDL, the good cholesterol. - Usually, males have a HDL cholesterol about 40. He had seven. So it is something a little bit weird scientifically. Something unexpected. - [Narrator] Put simply, he should've been dead, yet his arteries were clear. Just what was keeping him healthy? Dr. Sirtori and his team spent years looking for an answer until another clue. There's a protein component in HDL that helps it do its job clearing out bad cholesterol. Tests on the man and his family revealed that it had been genetically mutated. On a hunch, Sirtori went searching for more clues in the patient's home town. Limone. - So in Limone in 1981, we screened the whole population. And my major concern, I say, suppose I go there and draw a 1000 samples of blood, I don't find anyone. Miss Elive is a historical figure for me. Because she was the first diagnosed gene carrier in Limone. And after 30 so years, every time I see her, it's sort of shock for me. - [Narrator] Dr. Sirtori screened 1000 people and found 40 with the same genetic mutation. And no heart disease. Even though they had very low HDL. - This is a very peculiar exception. Of course, one could ask questions, say why here? Why here? It was never found anywhere else. - [Narrator] Sirtori suspected that the largely Mediterranean diet eaten in this isolated community was not enough to answer his question. A search through the church records traced the mutation back to a couple who married in 1750. And their descendants were long lived. - So it's a single mating couple. This part of the lake was isolated. There was no involve from Milan or other towns nearby. Which meant this community is inbred. People married to each other, cousins and so forth. And this is why the mutation was saved so well over the centuries. - Salute. - [Narrator] Could the mysterious HDL these people have preserved for generations help unlock the secrets of the good cholesterol? When it comes to heart health, the more HDL, the better. But these people were healthy and astonishingly, they had almost no HDL in their systems. Sirotri had a theory. Somehow the mutated gene had supercharged the HDL. Making it work more efficiently. Human trials with a synthetic version of the mutant HDL were conducted at the Cleveland Clinic by Dr. Steve Nissen, who was skeptical at first. - I thought it was really interesting. But you know, good scientists are always skeptical. And so you know, we don't drink the Kool-aid. And I must tell you, I thought the chances that this confusion in six weeks is all we did was treat these people for six weeks. And they could reverse the build up of plaque that had taken place over many decades. I thought it was a one in a million chance. And I was absolutely stunned when it worked. - [Narrator] The results were so promising that pharmaceutical giant Pfizer bought the rights to develop the treatment for a reported 1.3 billion dollars. They did more research. But ultimately, never released a drug. A number of companies are now working on the Limone story in hopes of cracking the code. But treatments won't be on the shelves any time soon. - The problem was, we had no way to make this stuff. And we still are struggling to find a way to make enough of it to turn it into a drug that can be used for large numbers of people. - [Narrator] The story is further evidence that the heart disease crime wave is more than a cholesterol numbers game. Genetic abnormalities can give heart protection to some. While causing a cholesterol crisis in others. Our fear of cholesterol in the diet is not all it's cracked up to be. Some people on statins continue to have heart attacks. And many heart attack victims have normal cholesterol levels. Back at the Cleveland Clinic. Dr. Stanley Hazen has been searching for answers beyond cholesterol. - We can treat a person's cholesterol level down to a level of what they were when they were a baby. And we still know that there's a significant additional residual risk. So what are the other pathways that are involved beyond cholesterol? - [Narrator] Hazen's search beyond cholesterol led to a study of blood collected from heart disease victims. - We began with studies of thousands of subjects and said, what can we measure in the blood of humans that tracks with cardiac risk? - [Narrator] They did find a compound called TMAO. But where it came from was a mystery. - At finding that there was a hint that it may have come from bacteria, it really was a kind of eureka moment and very exciting. - [Narrator] What excited Hazen was that it seemed to show up first in the gut. When gut bacteria feed on what we eat, waste byproducts are excreted that show up in the blood stream. Hazen thought this explained where the TMAO was coming from. But it took some testing to figure out what we ate to make it. The answer was carnitine. It's found in the same stuff they serve back at the Heart Attack Grill. Red meat. It's long been associated with heart disease. But researchers suspected that cholesterol and fat couldn't fully explain the connection. Sensing new answers, Hazen investigated. - [Stanley] We had a feeding study that involved literally making steaks. And so we bought a George Foreman grill. And started making small steaks and then would do timed feeding studies to look at following ingestion of a steak, which is a rich source of carnitine, did certain metabolites appear in the blood stream. - [Narrator] That certain metabolite did indeed appear. High levels of TMAO. - That was the really exciting moment where we saw that bacteria are having a huge impact on things that appear in our blood stream. That compound will accelerate heart disease. It both enhances cholesterol that get deposited into cells of the artery wall, and it also inhibits the removal of cholesterol. So the net effect is more build up. - [Narrator] Carnitine is found naturally in most meats. Amounts are low in chicken, higher in lamb. And kangaroo meat has 50 times more carnitine than beef. But carnitine has become a popular body building supplement and can even be found in energy drinks. - We're very concerned about the very widespread use of carnitine as a supplement. That's because carnitine is carnitine to the bacteria, it doesn't really matter whether it comes in an energy drink or a piece of steak. And we've now measured this in thousands and thousands of patients. If you ingest excess carnitine, long term, you might be at increased risk for developing heart disease. Decreasing the amount of red meat in the diet is probably a healthy thing to do. A lot of epidemiology data had already argued for this. This is just reinforcing it now with some data that explain yet another reason to cut the red meat from the diet. So I don't eat red meat on a daily basis like I used to. I now eat it less frequently. But I haven't eliminated it. - [Narrator] Aaron Holm doesn't eat a lot of red meat or drink energy supplements. So he is likely safe from TMAO. He's fit, at least on the outside. But his cholesterol levels have always been off the charts. - From a population perspective, your cholesterol is higher than the majority of the population, I'd say over 90% of the population. - [Narrator] Aaron's about to find out what shape he's in on the inside. When Aaron was diagnosed with high cholesterol in his 20s, doctors warned him, he could be dead by the age of 40 if he didn't take statins. He decided not to. Betting that a healthy lifestyle would trump the high cholesterol. Now that he's 40, he's come to see Dr. Beth Abramson to find out if his bet paid off. - When we first sent you to the lab, your bad cholesterol or LDL cholesterol was so high we couldn't calculate it. So we went back and remeasured it. And your LDL cholesterol is 8.44. It's actually quite high. So your total cholesterol is 12.32. So from a population perspective, it's higher than the majority of the population. I'd say over 90% of the population. If I saw junk in your arteries, a build of atherosclerosis or plaque already, I'd say you're on the road to potentially having a stroke or heart attack. But the good news is, I did this measurement of your carotid arteries, and we don't see plaque. So that's good. We are seeing a thickening. And let's talk about what that means. In Aaron's particular case, we saw a thickening in one of the parts of the arteries that we think is a measurement for future risk. It tells us that his arteries have been affected and damaged to some degree. Likely from high cholesterol over the years. - The lady at the restaurant yelled, 200 pizzas, are you crazy? - If Aaron goes on a cholesterol medication, on a statin, which I'm hoping he will. His thickness in his arteries may not go down. It might. But we don't have a lot of clinical trial data to look at that. But being put on the medication will reduce his risk whether or not that measure changes or not. So your body has been exposed to high cholesterol for 20 years now. That's different than someone who just started off with a borderline elevation in cholesterol at 45 or 46. My personal and professional opinion would be that I would favor medical therapy for you. - What would the medical therapy be? - [Beth] I'd put you on a statin. I'd start you on a low dose 'cause you're not keen on the constant of medication. Commonest side effect is no side effect. - But if you haven't had a heart attack, they're not really able to say with certainty that they reduce the risk. - I think there may be a benefit risk ratio where the benefit outweighs any risk for you. So I don't prescribe cholesterol medications to all patients walking in this office. But there are certain patients who've not yet had a heart attack that we think are at higher risk. And the idea is to try and prevent that. Now the catch 22 is, we never see what we're preventing. - [Narrator] Aaron has always known his cholesterol numbers are high. But his thickening arteries is new information. And a new additional risk factor. - I was asking myself on the way in. I was like, what if they find that inside my body, it's having an impact? What'll I do? And I said the only thing they can really recommend is statin. They don't have any other tools in the chest, really. There's not much else that they can do. So if they recommend it, what'll I do? So I thought about it a lot, and I thought, well, if there is something going on in my body that's an indication that the cholesterol is having a negative impact, I'll probably go on the meds. And then monitor and see how low a dosage I can maintain have the result that I want. - [Narrator] After years avoiding statins, Aaron's decision to give them a try is a bit of a surprise. But while he's taking care of all the risk factors he can, you just can't run from your own genes. Or can you? - We have made tremendous progress in our understanding of cardiovascular disease. And in fact, at the population level, we do know that risk factors such as high blood pressure and high cholesterol can explain up to 90% of the risk. However, when it comes to specific patients, it's very difficult to predict which patient will go on to have the disease, and which one won't. - [Narrator] Dr. Guillaume Pare and the team at the population health research institute in Hamilton are on a hunt for genetic clues to unlock the remaining mysteries of heart disease. They're using a forensic facility that rivals any CSI lab. Blood and DNA from hundreds of thousands of people around the world stored in a deep freeze all managed by Dr. Matt McQueen. - There are about three million samples. They are from over 70 countries. Five continents, and five major ethnic groups in the world. These aren't just samples being stored. They are samples are well characterized so we know all the details, person's illness, what the outcome of the study was. What treatment they received. A whole variety of other information. - [Narrator] Investigators can now reopen the oldest case files of all. Human DNA. Genetic variations can have a major affect on how we respond to risk factors like cholesterol, inflammation, and blood pressure. They may also have answers for a high risk group that's increasing rapidly. People with diabetes. One in nine adults now have it. And their heart risk is three times higher than a person without the disease. Specialist Dr. Hertzel Gerstein is on the team. - So there's no broad agreement on why there is an increased risk of cardiovascular disease in people with diabetes. But there are number of candidates. And we at PHRI here are trying to investigate and better characterize what these candidates are and better understand and hopefully solve the puzzle of why people with diabetes are at higher risk for cardiovascular as well other series health problems. - [Narrator] They are now running a DNA study of 5500 diabetic patients. Searching for genes involved in their heart disease risk. Once identified, the genes will become targets for new treatments. It's a big job. - One of the greatest challenge we're facing right now in human genetics is really a big data problem. Right now, we can sequence all human genomes in three days. And generate a considerable amount of data. But what do we do with this data? How do we identify these mutations that could be important to health and disease within the tens of millions of mutations that were identified? It's a bit like trying to find a needle in the hay stack. We have identified about 50 genes involved in heart disease. But we estimate that over 1000 genes are involved. Once we have identified all of these genes, we will be in a great position to identify individuals and families at risk and perhaps to better treat them as well. - [Narrator] Genes and aging are heart disease risk factors we can't control so far. But there is one risk factor we can work on that will have a positive affect on all the others. - We know that for people who exercise daily throughout midlife and to later life, these people very rarely get heart attacks and strokes. Our own research has shown that diet and exercise contribute to keeping inflammation down. They contribute to keeping blood pressure down. They contribute to keeping cholesterol down. And all of these are contributing in a very important way. - [Narrator] Who hasn't been told by their doctor to get out and exercise? But how many of us actually take that advice? - You think about how hard it is to get people to be more active. What could we do? So we proposed a challenge and in class, somebody came up with a seven minute app that has you do 12 30 second workouts with 10 second breaks. And it's got push ups, and squats and lunges. And triceps. - [Woman] This is favorite, to do lunges. - Let's make this the social norm in the class. That it is acceptable to get up and move because honestly, as health professionals, it should be unacceptable to sit still for two hours and listen to me rant on and on. - It's not enough for us to sit at our hospital and talk about this. We need to get into the community and say the biology of this disease tells us that if I can get people in their teens and 20s and 30s in to exercising regularly, we just won't have as much diabetes. We won't have as much heart disease. We'll have fewer need for the angioplasties in surgeries that my cardiovascular colleagues are so good at providing. It's a win win if we do it right. - [Narrator] The search to catch new culprits in the heart disease crime wave continues. Cholesterol is implicated. But there are other suspects still at large. Each one a menace on its own. And together, this gang can be lethal. Be on the look out. (slow mysterious music)