Real Truth in Labeling for the new statin replacement

The FDA is about to or just has approve a new cholesterol-fighting drug to supplement or replace statins.  But is it taking all the 'side effects' into account?  Should it?  The new substances (several pharmaceutical outfits apparently have them near to market) inhibit a different genetic pathway from what statins do and can be used to treat high cholesterol in those who can't handle statins, or for whom statins aren't lowering their LDL cholesterol, and may also actually be much more effective even for the current millions who take statins.

These drugs inhibit the action of a gene called PCSK9 and interfere with the liver's detection and response to LDL levels in the body; see the NYT story here from last week for more details about the drugs.  The excited news reports, at least, describe what are truly remarkable reductions in LDL levels without untoward side effects. If these facts stand up to larger or longer term trials and experience, it will be a major pharmaceutical success....in more ways than one.

One immediate issue is the 'usage creep' that almost inevitably seems to follow the appearance of a new drug, and in this case one with fewer side effects and higher efficacy with regard to lowering the most dangerous type of circulating cholesterol (the 'bad', or LDL form). Recommended approval is for use in three groups of patients: those whose high LDL cholesterol can't be lowered sufficiently with statins, those at particularly high risk because of previous heart attack or diabetes and high LDL, and those with high levels of LDL who can't tolerate statins.

But if these agents are as effective as reports suggest, and with less or even no serious side effects, then even if they are initially approved or recommended for just these specific groups, usage will surely expand as the definition of who is 'at risk' expands. Perhaps people whose cholesterol is responding to statins but who don't like the side effects, or someone whose close relative has had heart disease but whose current LDL levels are not high will ask for this treatment as a preventive, or doctors will think 'off label' usage is absolutely proper, assuming no serious side effects. Hell, if the makers are extremely lucky, maybe it will turn out it even treats erectile dysfunction or male-pattern baldness! And then, what about extending to, say, younger ages or even simply to everyone, like putting vitamins in milk or iodine in salt?  This is what we mean by usage creep.

One might reasonably say that this is just what should be done.  Precedent might suggest that eventually we'll find that the agents are less effective than current tests suggest or have some serious long-term but as yet undiscovered downsides.  However, things that can't be known until the drug is used by millions of people for numbers of years.  Making decisions about usage is harder than one might think.

One reason for concern about usage creep is already being mentioned in the blaring news stories about the apparently genuinely major advantages of these compounds.  That is, the obvious issue of the financial mega-bonanza to be reaped by the pharmaceutical firms.  These drugs are going to be very expensive.  The money to be made is certain to encourage usage creep.  Could we expect otherwise?

But worse than just profiteering is that, even with Obamacare available so that presumably even the poor could have access to these beneficial drugs, putting the whole population, so to speak, on these pills for their whole lives, could bankrupt the health-care funding system that is already a heavy burden on society.  It's being suggested that these new pharmaceuticals could simply by themselves eat up any reasonable premium level for health care plans.

But there is another issue, and that relates to truth in advertising and the issue of side effects--and here we don't refer to incomplete data that may be leading to premature approval or anything like that.  Instead, it's more of a philosophical issue:  What does a list of side effects mean, in this case, and what would the whole truth actually be? What should the manufacturer or the FDA tell you so you would be truly better informed when you take the new drugs for the rest of your life, as so many are likely to do, across the developed world?

From the Sanofi website; Sanofi is one of the makers of these statin replacements

What the FDA and medical community doesn't list on the label
The FDA requires that known side effects of drugs be clearly stated on packaging or labeling material, and surely physicians will know about them.  Isn't that right?  It should be, but there is a sleeping tiger here, that apparently nobody has thought about or, if they have, that they've buried so deep you never will realize it.  In fact, there will be huge unstated negative side effects of these new drugs.  Indeed, shouldn't a proper labeling for these new medications include something like the following?:

"WARNING: Use of this product will greatly increase your risk of Alzheimer's Disease and other dementias, arthritis and other muscle and joint diseases, some forms of cancer, diminished vision and hearing, other degenerative disorders, and accidental death."

Of course such truth in labeling won't happen, and the reasons are subtle and if taken seriously would lead us, as a society, to think more deeply about the role of medicine in health, and of the meaning of health, in a real world in which life is finite.  There is no one who can provide 'the' answers to the problems that are raised, and indeed each person would, in principle, provide his/her own answers.

But at least, there should be a societal discussion.  The reason has to do with the concept of 'causation' and the demographic realities in a world of competing causes.  If these drugs lower LDL cholesterol anywhere nearly as much as they seem on present evidence to do, and if the association between LDL cholesterol and heart disease is as linear as is hoped, then that by itself will eliminate or greatly forestall the occurrence of fatal heart disease in those who take them.  But then what?

If people live much longer as a result, they will inevitably get the sorts of diseases that could be included in an empirically correct labeling!  If you don't get heart disease, it is simply obvious that you will get something else, and it is likely to be slower and more progressive than the quick end to life that heart attacks can be.  Note that our warning list did not include some causes, like kidney failure, diabetes, and the like that could be stalled or avoided by lowering LDL cholesterol--so we are being quite conservative here.

The problem is that of what are known as competing causes, and we've written about it before.  It is inevitable that you will die of something.  If not heart disease, something else.  One might say, well, OK, but at least I'll have more years of life before that something-else gets me. This is likely to be true to some extent, but there are two cautions.

First, people with heart disease often have other health issues because by and large heart diseases gets people at older age, and they are more likely to have less healthy lifestyles.  That includes more risky conditions than high cholesterol.  So, these other causes may be lurking just around the corner, so the removal of heart disease may mean that the gain in years might not be very much!

Secondly, other disorders that those saved from heart attacks will eventually get, if they don't have them already, are ones with gradual onset: you become more and more affected over time.  Mental deficiencies, joint and mobility problems, vision and hearing, are clear examples.  And the nature of accelerating risk is that if you slow it down you defer the onset of serious-level symptoms but you also stretch out the decay process at the end: you have more years with more and more serious symptoms before your body finally conks out.

What is 'cause'?
Are we just playing word games here?  Is it accurate to suggest that the new drugs will 'cause' dementia?  Surely the chemical doesn't mess with neurons!  Let's assume that's true and that no such direct molecular effect is ever found. Then the effect of the medication is related to the occurrence of these other traits, but not in a directly causal way.

This raises questions about causation.  It is more than simply saying that correlation is not the same as causation, because while the active mechanisms responsible for, say, Alzheimer's or joint disease, are not affected by the LDL-reducing drugs, they open the way for the former to act because the person lives longer.  Correlations such as the brand of car you drive being associated with some forms of disease arise because both may be the result of income levels and associated dietary habits. The dietary habits, not the type of car, are causes of interest.

But in the case of competing causes of disease, reduction of one is a sort of mechanistic effect, not just a spurious cause.  If a mechanism is changed in a way that allows a different mechanism to proceed for longer times, this is part of the overall mechanism of the related traits.  The chronic late-onset diseases most of us in the rich world die of now are directly the result of so successfully controlling infectious diseases, our previous killers. One definition of cause is that if you remove it, the effect changes, in this case the protective effect, relative to cancer, of dying of a heart attack.

And what if widespread use of these new drugs puts serious pressure on the health care system, so that some treatments will have to be deferred or denied to more people than presently?  Is that so unlikely?  And is that then not a cause of deteriorating health?

And what if it worked miracles and the relative fraction of our population (and the world's population) of wearing-out old people substantially increased?  That puts all sorts of pressures and pinches on everyone else, indeed, even on the normal living needs of the increased elderly segment.

Causation is not so simple and straightforward a notion.

So, what is 'health care'?
The new LDL reducers raise many deep, and deeply important questions.  The point here is to be realistic about disease in our society and have an open consideration of how to deal with the kinds of game-changing environmental or behavioral aspects of our society, and their long shadow of implications.

In a very serious sense, even if indirectly, the new LDL-lowering agents might have disastrous effects for countless numbers of people.  It's a discussion we should be having.  The news media should be leading the way, to force that on the scientists and health system.

Indeed, these issues should force us to consider what, exactly, we even mean by 'medical care' and 'health care'.  How do they relate to each other, and to the idea of 'public health'?

We think these are real, complex, disturbing, serious truths that have no one answer, and that affect individuals as well as society.  This is not a matter of complaining about science, policy or even drug company profits.  It is about profound issues in human life, that should be discussed openly and fully, because they affect everyone's future.

What's a 'healthy diet' anyway?

A nutrition advisory panel is convened by the US Department of Agriculture every five years to review recent research in the field, make sense of it, and offer recommendations about what Americans should be eating for optimal health.  Those food pyramids, MyPlate, decades of advice to limit our cholesterol, saturated fat and salt intake?  All the work of these panels of experts who scoured the data and told us what it meant.  And as a result, from the 1960's onward, good, conscientious people reduced their cholesterol intake, took the salt shaker off the table and the whole milk and butter out of the refrigerator, cattle were bred to be leaner, eggs were banned from breakfast, low-salt and low-fat processed foods appeared on the shelves, and heart disease death rates ... continued to fall.

Deaths due to diseases of the heart (United States: 1900–2006). Circulation.2010; 121: e46-e215

Now, according to numerous news accounts, including here at the Washington Post, after more than 50 years of anti-cholesterol, anti-fat expert advice, the current advisory panel is reportedly poised to recommend that we need no longer need to limit the amount of cholesterol we eat, nor worry about our salt intake.  Bring on the shrimp, the lobster, the eggs, the meat, banish the guilt!

Oh, wait.  Hold on a sec.  Let's go back to those falling heart disease rates.  I remember one of the first lectures I heard as a new grad student at the University of Texas School of Public Health in the late 1970s, given by heart disease epidemiologist Reuel Stallones, Dean of the school.  His point was that rates had been falling since the 1960's and epidemiologists had no idea why.  He systematically destroyed every argument then (and now) current that might explain the rise and fall of heart disease death rates -- changing diet, decreased smoking, de/increased exercise.

In fact, he made the same case in 1980 in Scientific American in an article called "The Rise and Fall of Ischemic Heart Disease".  (The terms ischemic heart disease, coronary heart disease, and arteriosclerotic heart disease are more or less interchangeable, according to Stallones.)

In the U.S. the death rates attributed to heart attack and other results of the obstruction of the arteries that nourish the heart have fallen since the 1960's. Why they have is not understood.

Here's Stallones' graph of heart disease death rates, from 1900 to 1980.  I can't explain why deaths are still rising in the above graph in the 1950's, but falling in this graph; presumably this has to do with differing classifications of deaths due to heart disease.  Anyway, here rates rose rapidly starting in 1920 and then began to fall in the 1950's, steeply in the 1960's.

Stallones, Scientific American 354(5); 53-59

Here's another graph showing the decline more or less in line with Stallones' data, from a 2000 paper in Circulation.

"Death rates for major cardiovascular diseases in the United States from 1900 to 1997. *Rates are age-adjusted to 2000 standard." Source: Circulation, Cooper et al., 2000

As Stallones wrote, "Plainly a sustained decline in the death rate for ischemic heart disease commands attention and calls for explanation." And, he backs up to ask not only why the fall, but why it was that heart disease mortality began to rise so quickly in 1920, particularly among men.  Whatever explains the decrease must also explain the increase.

Smoking began to rise after World War 1, which fits the rise in heart disease mortality, and began to decrease from the mid-1960's or so, which fits the decrease.  But such an explanation would assume no latency period between beginning to smoke and its effects on heart disease.  And, middle-aged men quit smoking at higher rates than women, and this is not, as Stallones said, in concordance with the pattern of decline in heart disease mortality.  Treatment isn't an effective explanation either, because incidence rates -- new cases -- followed the same pattern as mortality.

He concluded,

In summary, four major variables are known to be associated with the risk of ischemic heart disease in individuals. Among the four, hypertension does not fit the trend of the mortality from ische­mic heart disease at all; physical activity fits only the rising curve, serum choles­terol fits only the falling curve and only cigarette smoking fits both. In no case is the fit as precise as one would like. This raises doubt that any of the factors is a fully satisfactory explanation for the variation in mortality.

So, in sum, as of 1980 epidemiology had no explanation for the rise and fall of heart disease mortality rates.

And epidemiology still can't tell us what causes heart disease, or predict who'll get it.  So, apparently we'll soon be told that we no longer have to monitor our cholesterol intake, and there's a lot of talk about fat consumption not being linked with heart disease anymore, and it's not clear whether obesity or hypertension are actually causal.  At least smoking is probably still a problem.

It's clear from the rise and fall of death rates through the 20th century that genes aren't going to be the major explanation because genes can't explain the spike in the 1920's and the fall 40 years later.  That experience also makes it clear that we can't predict environmental changes (or, often, even figure out what they were in hindsight) that might be associated with risk, and thus we aren't going to be able to predict the future, despite the claims of precision medicine advocates.

Stallones suggested that heart disease mortality data might indicate a single environmental cause to explain the rise and fall of death rates, but found reasons to argue against each of the most obvious ones.  Could the cause have been inflammatory?  If so, that would reinforce the idea that predicting future environments and causes is not going to be possible.

And, if there was a single cause, it's curious that our reductionist approaches, with large carefully designed samples and sophisticated statistical analysis, were unable to identify it, because that's what they are widely thought to be best at.  This makes it more likely that heart disease in populations has multiple causes.  And in fact every heart attack is unique, because no two people eat the same things, do the same amount of exercise, suffer the same infectious diseases, and so on. So maybe the very word 'cause', and the very approach (statistical), both of which assume some regular, replicability properties, are not being appropriately conceived.  This is a subject we'll discuss next time.....

"Experts" responding to the coming cholesterol recommendations have said that we still need to eat a healthy diet.  But when we still have no idea what's unhealthy, it's hard to know what is.

When good cholesterol isn't

First we were told to lower our cholesterol.  This was back in the 1960's, when the first results of the then major new epidemiological project, the Framingham Heart Study, were released.  If the Framingham Heart Study taught us anything, it was that high cholesterol was a major risk factor for heart disease.  So we all started eating oat bran and granola and eschewing beef.

And then,  in the 80's we were told that it's not all cholesterol we need to be concerned about, that there's a good and a bad cholesterol, and we should be raising one and lowering the other.  How?  Eat healthy -- no eggs, no butter, no red meat.

Egg in a spiral eggcup; Wikimedia

And then it turned out that the people living on the Mediterranean had known all along what eating healthy is -- everything in moderation, except for olive oil and red wine, two foods that we should all be consuming more of.  From the Mayo Clinic:

Key components of the Mediterranean diet

The Mediterranean diet emphasizes:

• Eating primarily plant-based foods, such as fruits and vegetables, whole grains, legumes and nuts
• Replacing butter with healthy fats, such as olive oil
• Using herbs and spices instead of salt to flavor foods
• Limiting red meat to no more than a few times a month
• Eating fish and poultry at least twice a week
• Drinking red wine in moderation (optional) [not clear which is optional here, the red wine or the moderation]

So, follow these new rules and live as long as the Italians do.  Somewhere along the line, though, eggs were taken off the list of forbidden foods, and the usual American replacement for butter, margarine, turned out to have transfats which are bad for you, and anyway, saturated fats -- the stuff that's hard at room temperature, like margarine -- aren't good for you in any form.

And it turns out it's hard to lower your bad cholesterol with diet.  So, maybe try doing it with drugs.  Statins are good.  Indeed, the more people taking statins the merrier.  But whether statins are lowering all the risky components of LDL is still open to question (e.g., this paper).  Statins are designed to control circulating lipids (fats), which confer heart-disease risk. They inhibit an enzyme called 'HMG-CoA reductase' which is expressed in liver cells as they produce cholesterol from raw ingredients and secrete it into the blood stream. Lower enzyme activity, lower circulating lipids. Whether this is what they are doing is still not entirely clear, however.  There is evidence that statins may be reducing inflammation in irritated arteries and veins, which may be what reduces risk of heart disease rather than any effect on cholesterol.  Perhaps heart disease is an inflammatory process more than one affected by cholesterol levels, after all.

Oh, but then a rather confusing study was published last year, showing that Australian men who switched polyunsaturated fat for the saturated fats in their diet did in fact lower their LDL, but they also were more likely to die of a heart attack than those who hadn't changed their diets.  Indeed, most people who have heart attacks don't have high LDL.

But ok, assuming the cholesterol model of heart disease, along with lowering LDL, it would make sense to also raise your HDL, the good cholesterol.  But now it turns out that it's possible to have too much of a good thing.  A new paper in Nature Medicine (paywall) reports that while HDL normally should keep arteries clear and protect against heart disease, in arterial walls, HDL acts quite differently from circulating HDL, and can lead to arterial blockage and heart attack.

The BBC reports that the authors say people should still "eat healthily".  But, what this means, when the definition of a healthy diet keeps changing, and today's healthy diet can be the cause of ill health, is not at all clear.

Everything in moderation seems good to go with.

Wait, wait! Don't tell me!

Heart disease risk factors
There's an NPR radio program called "Wait, wait.... don't tell me!" that has relevance to science these days, as is easy to see.  We see frequent reports of how to live if we want to stay healthy, such as to keep an eye on our cholesterol if we want to avoid heart disease.....

But wait, should we obsess about our cholesterol numbers or shouldn't we?  And, if we obsess too much, will the stress cause the very heart disease we're trying to prevent? A short piece in Sunday's New York Times refers to new analysis of an old study of Australian men, and effects of various dietary components on blood lipid levels and risk of death. The new analysis was published in the British Medical Journal last month, with an accompanying commentary by Philip Calder. 

We've known for decades, in large part due to the never ending Framingham Heart Study, which began in 1948 and is now looking at third generation subjects from Framingham, Massachusetts, that saturated fats raise the risk of heart disease because they raise cholesterol levels.  And, we've known that polyunsaturated fatty acids (PUFA's) -- safflower, sunflower, corn and soybean oils -- reduce cholesterol, and thus lower heart disease risk. Framingham may have led the way, but many other studies confirmed these findings, and eating more PUFA's and less animal fat has been the basis of heart friendly dietary advice for decades. 

Or not....
But wait! Now researchers have reanalyzed the Australian data, which originally took place between 1966-1973.  In this study, one group of  men with heart disease ate more omega-6-rich polyunsaturated fat, linoleic acid, and the control group, also with heart disease, ate as usual. According to the NYT:

The men were followed for an average of 39 months, and those on the polyunsaturated-rich diet lowered their cholesterol levels by an average of 13 percent. But they also were more likely to die, and in particular to die of a heart attack, than those who stuck with their usual diet, which consisted of about 15 percent saturated fat.

What does this mean?  Yes, polyunsaturated fats do seem to lower cholesterol, but they also raise risk of death from heart disease.  Does this mean we need to question the link between cholesterol levels and heart disease?  Or, maybe there's another pathway -- polyunsaturated oils may decrease cholesterol but at the same time increase inflammation, which has been shown subsequent to these and early Framingham results, to be involved in heart disease, though it's not clear how.  And this may override the supposed positive effects of lowered cholesterol.

Indeed, according to the editorial in the BMJ, proper studies of the effect of replacing saturated fat with PUFA's without other dietary changes have rarely been done, so that it has been impossible to evaluate the effect of linoleic acid alone on cardiovascular disease risk. Until now, with the re-evaluation of the Australian data.

The original analysis showed an increased risk of all cause mortality in the study group, the men who increased their intake of linoleic acid, but the new analysis shows that death from cardiovascular disease also increased.

These findings argue against the “saturated fat bad, omega 6 PUFA good” dogma and suggest that the American Heart Association advisory that includes the statement “higher [than 10% of energy] intakes [of omega-6 PUFAs] appear to be safe and may be even more beneficial” may be misguided. The more cautious UK dietary recommendations on fat and fatty acids, which include the statement, “There is reason to be cautious about high intakes of omega 6 PUFAs,” seem fully justified in the light of the current study’s findings.

Calder suggests, and rightly, that "subtle, and in some cases unsubtle aspects of study design" have effects on results that are too often not considered when results are interpreted, and dietary advice made public.  This of course always pertains, not just in the case of diet and heart disease risk factors.

So, advice is often given on shaky evidence.  A piece in Nature on 26 February -- "Cholesterol limits lose their lustre" -- is another example.  People all over the world are on statins for life to lower their cholesterol to prescribed targets, making pharmaceutical companies very rich, but how valid are those targets? 

Most people who have heart attacks, it turns out, don't have high LDL's ('bad' cholesterol).  A cardiologist at the University of Minnesota Medical School in Minneapolis is quoted in the piece saying, "If your arteries and heart are healthy, I don't care what your LDL or blood pressure is."

So, cholesterol guidelines established by the US National Heart, Lung and Blood Institute may soon be changed, and LDL targets abolished. 

Expected to be released later this year, the fourth set of guidelines, called ATP IV, has been drawn up by an expert panel of 15 cardiologists appointed by the institute. The guidelines will set the tone for clinical practice in the United States and beyond, and will profoundly influence pharmaceutical markets. They will also reflect the growing debate over cholesterol targets, which have never been directly tested in clinical trials.

And, a report last week suggests that processed meats like bacon and sausage are lethal.  But, wait, not if you're Italian and eat a lot of Parma ham!  Does that mean that the Chianti and Valpolicella of the Mediterranean diet compensate? All of this gives 'bringing home the bacon' a suddenly negative connotation! 

From "Processed meat 'early death' link," BBC

But wait, if the new report that post-traumatic stress disorder raises the risk of heart disease is true, mediated by increased insulin resistance, then perhaps attention will be taken off cholesterol and diet entirely, and turned to reducing stress!

How to recognize dangerous warnings and avoid risks....
It isn't just your health that's at risk with all of these confusing never-ending contradictory reports.  Whenever you hear (as you almost always do!) an investigator say "studies show that" or "we need further research," grab hold of your wallet and run for cover!  Because you're about to be pick-pocketed, and that, unlike the epidemiological studies, is something you can rely on!

There are many reasons for resisting the understandable desire of epidemiologists and geneticists to seize on these uncertainties as a rationale for more funding to study the same problems essentially with the same methods but on a bigger, longer scale.  We'll go over them in a forthcoming post.

Will eggs kill you? The truest answer is "It depends"

Dueling conclusions
Headline in The Atlantic:

Study: Eggs Are Nearly as Bad for Your Arteries as Cigarettes

Conclusion from the actual paper in Atherosclerosis:

Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease.  

What's the story?  Other than that journalist gets it wrong again.  Or actually, some right some wrong.  The headline is literally correct, but the story avoids the nuances.  Not surprisingly.  So we'll try to fill in.

Knowing that the effect of dietary cholesterol, particularly eggs, is increasingly considered insignificant -- because the relationship between dietary cholesterol and serum cholesterol levels is not at all a linear one -- a group of Canadian researchers undertook to determine once and for all whether in fact eating eggs does increase serum cholesterol levels.

That was then
Eggs were first shown to increase serum cholesterol way back when we first were being told to watch our cholesterol intake, back when the Framingham Heart Study showed us this something like 40 years ago.  (Indeed, here's your handy heart attack risk calculator, based on data from that study.)  So eggs became one of those guilty pleasures we consumed knowing we were knocking hours off our lives with every bite of that runny cholesterol-laden yolk.  Same with that hunk of marbled steak we couldn't resist.

But then we were told six years ago or so to forget all that -- at least the eggs bit -- when a study by Christine Greene et al. of the effects of eggs on cholesterol showed that "most people's bodies handle the cholesterol from eggs in a way that is least likely to harm the heart" as described in a 2012 piece in ScienceNews. And in fact the more eggs you eat, the bigger the HDL and LDL lipoproteins you make, which is good because large LDLs (the 'bad' cholesterol) are less likely to enter artery walls and contribute to plaque, and large HDLs (the 'good' stuff) are better at transporting plaque-producing cholesterol out of the body. Eat more eggs! That is, if you aren't already at high risk of heart disease, which you've determined with the heart attack risk calculator in the paragraph above. 

This is now

But now we're being told we should go back to an egg free existence -- or the guilty egg indulgence of earlier years.  At least according to The Atlantic.  The Canadian study of 1200 people, based on lifestyle and dietary questionnaires and assessment of arterial plaque build-up, and including recall data on egg consumption and smoking, found that arterial plaque increased linearly after age 40, most in smokers and then second in people who consumed more than 3 eggs per week.  But, they, naturally, recommend further research, including more detailed dietary information (i.e., more reliable dietary information?), but in particular they want to account for the "possible confounders," waist circumference and exercise.  

Possible confounders they call these?  These are all factors that have been shown over and over again to be associated with heart disease risk, and they didn't include them?  Not even exercise?!  "Possible confounders" is the scientific way to say "Even we don't believe this study!"?  Of course, it also diverts attention from what they really mean, which is that their study is of the additional risk, after all the known major causes are accounted for.  Anyway, it's all based on dietary recall, which as we've said numerous times before, is not a greatly accurate way to collect reliable data.  So, really, should we believe any of the conclusions of this study?    

It's complicated

But let's go back to that "most people" part of the sentence about bodies and how they handle cholesterol from eggs. That's the crucial bit here, as Greene's work and others have pointed out -- but The Atlantic did not.  It seems that most bodies can handle the cholesterol from eggs just fine (unless you eat 42 a week, as reported (paywall) in Atherosclerosis this month -- cutting down to 6 a week brought the patient's cholesterol levels down to levels that no longer worried her doctors). People with risk factors like diabetes or existing heart disease tend to have smaller lipoproteins than most other people, which may indicate that they process dietary cholesterol in a way that can lead to arterial plaque, the risky consequence of excess cholesterol levels. Or, it may indicate that these diseases lead the body to process cholesterol differently. And Greene has found that some people are "hyper responders," which means that the pool of study subjects is heterogeneous and should be stratified by how they process cholesterol in any study of the effects of dietary cholesterol.  But then, at least some of Greene's work has been funded by the American Egg Board, and it's not uncommon for industry-supported work to come out in favor of the industry.  So yet more caveats (not proof, but issues to be aware of).

 
As the Canadian study itself points out, many studies have shown that dietary cholesterol, including eggs, had no effect on blood levels, some that it raised some lipoproteins and not others, others that the effect depended on genetic background.  In short, it wasn't possible to issue blanket dietary advice that was true for everyone.  Do we just ignore all of those results now? And indeed, the Canadian researchers themselves acknowledge that the effects of dietary cholesterol are different for different people because they fall short of recommending that we all limit our egg consumption, only suggesting this for people who are already at high risk of heart disease.  

So, we venture to say as with all complex diseases, there's no one-size-fits-all answer here. It wouldn't be at all surprising if the cholesterol in eggs were actually protective against heart disease for some, but risky for others.  Population-level statistics which are the basis of all recommendations about diet are hard to interpret clinically. 

By the way, 50 years on the Framingham study is still going at a nicely funded level....

Should you eat eggs?  The answer is "It depends."