 It is well accepted that coronary atherosclerosis is a chronic progressive disease that begins early in life and slowly progresses over several decades before symptoms arise. However, the average age in cholesterol-lowering drug trials is 63, and therefore people had already been exposed to a lifetime of circulating LDL cholesterol. So no wonder pharmaceutical therapies typically reduce cardiovascular disease risk by only 20 to 30%. We know LDL, so-called bad cholesterol, plays a central role in the initiation, development, and progression of our number one killer. Over 100 prospective studies involving more than a million people have demonstrated that those with higher LDL levels are at higher risk. It seems reasonable to assume that if lowering cholesterol later in life can help, then keeping LDL levels low early in life may prevent arteries from getting clogged in the first place. But let's not just assume. It would be considered unethical to set up a controlled clinical trial in which young adults with elevated serum cholesterol levels were treated or not treated over their lifetime, just like you couldn't ethically set up a study in which half the kids are made to start smoking to see if smoking really does cause lung cancer. That's where observational studies come in. You can follow people who already smoke and compare their disease rates to those that don't. It's like 40 years ago when the President of the American Heart Association tried to argue that we should all stop smoking even though there were no randomized controlled trials. Look, those who smoke have a higher risk of heart attack, the more we smoke the higher the risk, and after we stop our risk drops. The same can be said for high cholesterol. If you look at young men aged 18 through 39 and follow them for up to 34 years, cholesterol levels, even when you're young, predicts long-term risk of heart disease and death. Men in their 20s and 30s who have a total cholesterol, even just under 200, have a substantially longer estimated life expectancy, around 4 to 9 years longer than those over 240. Evidence from observational studies, however, is vulnerable to so-called confounding factors. Eating a diet plant-based enough to lower cholesterol below average may add years to our lives regardless of what our cholesterol is. Ideally, we'd have a long-term randomized controlled trial, and nature may have actually set one up for us. Each of us, at conception, gets a random assortment of genes from our mother and our father, and some of those genes may affect our cholesterol levels, just like there's rare genetic mutations that result in unusually high cholesterol. There are rare genetic mutations that lead to unusually low cholesterol, providing an ideal system to assess the consequences of low LDL cholesterol levels independent of confounding diet and lifestyle factors. Let me show you what I mean. About 1 in 40 African Americans have a mutation that drops their LDL cholesterol from up around 130 down towards more optimal levels. Now this group didn't eat healthy to get there, it's just in their genes. More than half had high blood pressure, there were lots of smokers and diabetics, yet those with genetically low LDL levels still had a significant reduction in the incidence of coronary heart disease even in the presence of all these other risk factors. How significant? How much less heart disease? How about 88% of heart disease gone? The astounding finding was that the heart disease risk in these individuals was reduced by more than 80% whereas the same 20 to 40 point decrease in LDL from drugs only reduces risk like 30%. Makes sense, though, right? The folks with the mutation had low levels like that their whole life. They didn't just start taking some pill when they were 60 years old. The magnitude of the effect of long-term exposure to lower LDL cholesterol concentrations observed in each of these studies represents threefold greater reduction in the risk of heart disease compared to drug treatment started later in life. For you fellow research nerds out there, check out that p-value. You'd have to do like a quintillion studies to get that kind of result by chance. Therefore, a primary prevention strategy that promotes keeping LDL cholesterol levels as low as possible beginning as early in life as possible and sustaining those low levels of LDL throughout the whole of one's lifetime has the potential to dramatically reduce the risk of coronary heart disease. And that's just what a healthy diet can do.