Friday, March 28, 2014

The ever-changing list of cardiovascular disease risk factors

The stories on obesity and heart disease are coming fast and furious.  This is strange because while trends or fads do change, they don't change as fast as the recommendations and findings we get daily from our 'experts'.

This month, obesity is caused by sugar (here's a fine BBC radio program on whether fructose is toxic or not), or antibiotics, and now, according to a piece on the CNN website, food allergies.  Or rather, the public thinks it's caused by food allergies because their friends who went gluten-free lost weight, but it turns out it isn't.  So that one is an urban myth.  But it's an interesting one because it indicates that despite the scorn with which many people hold nutrition advice, given that it changes every week, a lot of people are still looking for simple answers.

Source: Wikipedia

And then there's the question of whether saturated fat -- those fats that are solid at room temperature, like butter, cheese, or fats in meat -- long accepted to be a dietary demon, is actually bad for us.  That is, whether it raises our risk of stroke or heart disease.  The latest news is that it does not.

The BBC sums up the new news this way: "Contrary to guidance, there is no evidence that changing the type of fat you eat from "bad" saturated to "healthier" polyunsaturated cuts heart risk."  But the story is a beautiful example of the role of both faith and evidence in nutritional 'science' because, before describing the study, the reporter hastens to add that researchers still say we should not eat saturated fat.
Heart experts stressed the findings did not mean it was fine to eat lots of cheese, pies and cakes. 
Too much saturated fat can increase the amount of cholesterol in the blood, which can increase the risk of developing coronary heart disease. 
Most of us eat too much of it - men should eat no more than 30g a day and women no more than 20g a day. 
There has been a big health drive to get more people eating unsaturated fats such as olive and sunflower oils and other non-animal fats - instead.
"A big health drive" -- this should mean that unsaturated fats have been clearly demonstrated to protect against heart disease because any expensive public health drive should be based on solid evidence.  As Gary Taubes wrote 13 years ago now in Science, and has been saying ever since, dietary fats have been demonized for decades -- 60 years now -- based on the idea that they raise blood cholesterol levels.

But, as Taubes wrote,
The proposition, now 50 years old, that dietary fat is a bane to health is based on the fact that fat, specifically the hard saturated fat found primarily in meat and dairy products, elevates blood cholesterol levels. This is turn raises the likelihood that cholesterol will clog arteries, a condition known as atherosclerosis, which then increases risk of coronary artery disease, heart attack, and untimely death By the 1970s, each individual step of this chain from fat to cholesterol to heart disease had been demonstrated beyond reasonable doubt, but the veracity of the chain as a whole has never been proven. In other words, despite decades of research it is still a debatable proposition whether the consumption of saturated fats above recommended levels (step one in the chain) will increase the likelihood of untimely death (outcome three).
Taubes goes on to say that in the 1960's, when some scientists were still questioning the role of dietary fat in heart disease, politicians stepped in and "initiated the process of turning the dietary fat hypothesis into dogma."  That is, the nutritional advice we've been given for 60 years, public health policy, was driven by politics, not science.  So Taubes must have been gratified to see the recent report about saturated fat.  (Taubes actually has a dog in this fight, as he has written a lot about sugar as the culprit, e.g. here, believing that replacing fats with carbohydrates has been a mistake.)

The study described in the BBC piece was done by British Heart Association researchers who performed a meta-analysis, looking at 72 studies of the effects of saturated fat, including more than 600,000 participants in total.  The results are published in the Annals of Internal Medicine ("Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis," Chowdhury et al.).  Down the line, no blood lipid measure has a significant effect on risk.
In observational studies, relative risks for coronary disease were 1.03 (95% CI, 0.98 to 1.07) for saturated, 1.00 (CI, 0.91 to 1.10) for monounsaturated, 0.87 (CI, 0.78 to 0.97) for long-chain ω-3 polyunsaturated, 0.98 (CI, 0.90 to 1.06) for ω-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty acids when the top and bottom thirds of baseline dietary fatty acid intake were compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86 to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to 1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the associations among individual circulating fatty acids and coronary disease. In randomized, controlled trials, relative risks for coronary disease were 0.97 (CI, 0.69 to 1.36) for α-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain ω-3 polyunsaturated, and 0.86 (CI, 0.69 to 1.07) for ω-6 polyunsaturated fatty acid supplementations.
And they conclude, "...the pattern of findings from this analysis did not yield clearly supportive evidence for current cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of saturated fats. Nutritional guidelines on fatty acids and cardiovascular guidelines may require reappraisal to reflect the current evidence."

Source: Wikipedia

It will be interesting to see whether this changes nutritional guidelines.  We're betting it won't, since there is so much belief, and vested interest in current policy.  It's true that if policy were changed to reflect every new finding, there would be no consistent policy, but if Taubes is correct (he's written a lot on fats and heart disease, in addition to the Science piece), the evidence has been inconclusive for a long time, and nutritional recommendations about saturated fats have still not changed.

Is obesity a risk factor?
And then there's the question of whether obesity is a risk factor for stroke and heart disease.   Some studies say yes and some studies say no.  Perhaps that's because sometimes it is and sometimes it isn't; stroke and heart disease happen to people who aren't obese, and obese people don't all have strokes or heart attacks.

A recent study reviewed in a recent issue of The Lancet reports on
... a large collaborative study on the role of overweight and obesity on risk of coronary heart disease and stroke, and on the contributions of blood pressure, dyslipidaemia, and glucose concentration both singly and in combination. The study, which included nearly 2 million individuals of different ethnicity from around the world, increases our understanding of coronary heart disease and stroke. The three major risk factors—often associated with overweight and obesity—explain roughly 50% of the cardiovascular outcomes recorded.
That is, high blood pressure, cholesterol and glucose, associated with obesity, were found to be responsible for 50% of the cardiovascular disease among study subjects, while 50% was unexplained.  The Lancet suggests that, "Therefore, future research should examine other mechanisms linking obesity to cardiovascular disease, including inflammation, cytokine excess and oxidative stress, and cardiorespiratory fitness."

Well, yes, heart disease is yet another complex trait.  Just as with other complex traits, there are multiple paths to cardiovascular disease, and large heterogenous study samples will include many of them, but the analysis won't.  And to complicate things further, if inflammation, cytokine excess and oxidative stress, for example, are found to be linked to cardiorespiratory fitness, they will be in non-obese people as well.

Another bob of the yo-yo
After all these years of work, why do we still have to see such results?  Do these count as actual 'results' or is this just another bob of the yo-yo?  When can we get results we can trust, and then stop re-studying the same thing again and again?  Why are we in this situation?

Culture changes, but if the world follows natural laws, the molecular effects of cholesterol or salt or sugar etc. should not change.  That is, by now, or long before now, we ought to have a sense of the per-dose effects and that should not change, even if our habits do.  But the fact seems to be that we do not, even by now after decades of heavy investment, have such knowledge.  Or, perhaps more cogently, the effects are not acting on their own, and depend on our habits.  Does that mean an endless boon for schools of public health and their epidemiological research projects, that seem to get uncritically ever longer and costlier without more definitive results?  Where, as the old ads said, is the beef?

Or is the truth that this whole field reflects the problem with reductionist science?  When the assumption is that the culprit is a single food, or a single gene, it's impossible to elucidate a more complex interplay of risk factors. It is not new to suggest that this is simply not a very good way to do this sort of science!  Context-dependency at the very least depends on combinations of exposures, not single-factor (including single-gene) causation, even if each individual factor has its own molecular interactions.

But more worrisome is our feeling that even highly technical multivariate statistical slicing and dicing of very large datasets is not a good or effective approach, even if at present we really have no better one.   Ever more sophisticated statistical analysis applied to ever-larger studies do not seem to be generating answers.  As we say many times, it serves perhaps most as a stalling action to keep these research operations in business, rather than a way to stimulate better science.

We know that moderation is a generally good thing, for reasons that range from philosophical to evolutionary.  We also know that small subsets of people are severely affected by some of these factors like sugar (diabetics) or cholesterol (LDL Receptor mutations) and so on.  If we removed the overdosing by our McCulture, we would perhaps be left with these subsets that really might be amenable to simple-cause analysis, and there the application of technological solutions might be feasible -- there is where the research effort should go, not to just more studies of minor statistical effects, in our view.

But our system, though fully aware of the situation, cannot slow itself down to think more critically, is bureaucratized and entrenched so it cannot adequately train new students to be innovative and creative, and cannot forthrightly fess up to the problem.  Instead, whether or not the scientists are just yo-yo's, the science certainly seems to be just that.

No comments: