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Three of the most common human diseases are cardiovascular disease, cancer, and Alzheimer's disease. The most significant drivers of cardiac disease are smoking, hypertension and elevated APOB, a biomarker of LDL particle number. However, less is known about Alzheimer's disease, whose incidence is rising year after year. In this clip, Dr. Peter Attia outlines the relative risk and biomarkers associated with some of the leading human diseases.
Rhonda: But, yes, Alzheimer's disease is one of the neurodegenerative diseases that are up in the top four or five, like you mentioned, cause...
Peter: Well, it's the top. It's the only neurodegenerative disease that's on the top 10 list of death.
Rhonda: Top 10, yeah. So cardiovascular disease...
Peter: So cardiovascular is far and away number one. It's not even...I mean, cancer in an aggregate is number two, but as an oncologist I, sort of, take an issue with that because cancer's a completely heterogeneic form of diseases. So to put this in perspective, right...so breast cancer, who's not afraid of breast cancer if you're a woman? Breast cancer accounts for 3% of deaths in women. I was shocked to learn that, very low. I would have thought much, much higher.
Now, cancer in women, all cancers, 20%, 21%. Cardiac disease, 22% 23%. So if you're woman, if you ask any woman in the street, "Are you more afraid of heart disease or breast cancer?" I think most women would understandably say breast cancer. And yet, it's dwarfed by cardiac disease by a factor of seven and a half to one.
Rhonda: And we definitely know that diet and lifestyle play a major role in your risk for cardiovascular disease.
Peter: Yeah. I mean, I think there's no place where that's more obvious than actually in Alzheimer's disease for other reasons, which is...
Rhonda: Really? Alzheimer's?
Peter: Yeah. I think so.
Rhonda: More than cardiovascular?
Peter: Well, I mean I say that just based on what I called the existence principle, right? So cardiac disease, I mean I think that's entirely true. I think cardiac disease is inevitable. Right? And, while we've had a deterioration in our lifestyle over the past 40 years, a pretty precipitated and accelerated, sort of, move in the wrong direction on that, it's been largely offset by pretty amazing medical advances. So the three things that have, I think, allowed cardiac disease to remain...in fact, it's actually come down. If you look at the death rate from cardiac disease, it's come down. So it's still the number one killer but it's actually on a downward slope, I mean it's sort of plateauing. But when you look at what, sort of, the three biggest drivers are of cardiac disease, the first one is not disputed. It's smoking. So the data are really clear that if you could only make one behavioral change to reduce your risk of heart disease, it's don't smoke.
The next two are actually, because they are so cross-correlated you can't actually distinguish which one is more important, are hypertension and elevated ApoB or LDL particle number. And, again, ApoB is the single best biomarker or LDL-P to distinguish your risk of cardiac disease. It trumps LDL cholesterol, it trumps non-HDL cholesterol, it trumps triglycerides, HDL cholesterol. Those things don't hold a candle to LDL particle number ApoB. Well, think about it. Think about the advances we've made in the last 40 years on all of those, right? So smoking has gone from 45% of the population to 18% of the population. So we reduced smoking.
Rhonda: In the U.S.?
Peter: In the U.S. that's right. Obviously, we haven't done the same in the developing world. Think of the litany of drugs we have for controlling hypertension and think about the litany of drugs we have to bring down ApoB. So despite enormous improvements in the three big picture drivers, it's still the number one killer. So it's got to be lifestyle-driven but we're blunting the effect of that. Whereas in Alzheimer's disease, we don't really have any pharmacotherapy plays. Like, we're still arguing about what the environmental trigger is. Is it all diet-driven, is it sleep-driven, is it stress-driven, what's the combination of factors? Is it is a virus? Is it prions? I mean I've heard every argument under the sun, right?
But here's what we do know. We know that in the last 50 years, the prevalence of Alzheimer's disease has gone up about 2.5%...per year, by the way. I'm sorry. That's per year. Whereas we know that our longevity has increased at about 0.6% per year over that same period of time. Now, over a 50-year period, a 2% spread per year of prevalence. Actually, I think that might be incidence, now when I think about it. I think it's incidence. And longevity suggests that Alzheimer's disease isn't just the natural response of getting old. There's something driving it.
And even if you accept that part of that increase in incidence is a greater appreciation for the diagnosis, it's hard to argue that makes up the full 2% spread. And to me, that's the most convincing case for why there is something in our environment that's triggering Alzheimer's disease and it is not just the natural consequence of aging.
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
The primary apolipoprotein of chylomicrons, VLDL, IDL, and LDL particles. Apolipoprotein B is produced in the small intestine and the liver. It transports fat molecules (such as cholesterol) to all the body's cells and tissues. High levels of ApoB, especially when LDL particle concentrations are also high, are the primary driver of the formation of plaques that cause vascular disease.
A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.
A waxy lipid produced primarily in the liver and intestines. Cholesterol can be synthesized endogenously and is present in all the body's cells, where it participates in many physiological functions, including fat metabolism, hormone production, vitamin D synthesis, and cell membrane integrity. Dietary sources of cholesterol include egg yolks, meat, and cheese.
High blood pressure. Hypertension, defined as a systolic pressure of 130 mm Hg or higher, or a diastolic pressure of 80 mm Hg or higher, is a robust predictor of future incidence of stroke, coronary heart disease, heart attack, heart failure, and cardiovascular-related death. Central to the pathophysiology of hypertension is the loss of arterial compliance, which can have far-reaching effects on multiple organ systems, including the brain and kidneys.
A measure of the number of small LDL particles in a person’s blood. LDL-P is thought to be a better predictor of heart attack risk than total LDL cholesterol. Apolipoprotein B (ApoB) is used as a marker for LDL-P since there is one ApoB molecule per LDL particle.
A broad range of disorders caused by the progressive death of neurons in the central and peripheral nervous systems. Common neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington’s disease, and multiple sclerosis. Although treatments are available for some neurodegenerative diseases, there are currently no cures.
An infectious agent thought to be the cause of the transmissible spongiform encephalopathies (TSEs). Prions were initially identified as the causative agent in animal TSEs such as bovine spongiform encephalopathy (BSE)-- known popularly as "mad cow disease"-- and scrapie in sheep. Human prion diseases include Creutzfeldt-Jakob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome, Fatal Familial Insomnia, and kuru.
A molecule composed of a glycerol molecule bound to three fatty acids. Triglycerides are the primary component of very-low-density lipoproteins (VLDL). They serve as a source of energy. Triglycerides are metabolized in the intestine, absorbed by intestinal cells, and combined with cholesterol and proteins to form chylomicrons, which are transported in lymph to the bloodstream.
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