The "ibuprofen is protective" spiel was the argument that the drug companies tried to use in their trials to get out of their obviously documented malfeaseance (given the number of internal memos which surfaced which clearly demonstrated that company employees were concerned about the theoretical prothrombotic effects of unbalanced COX inhibition), and it was rejected by the courts, appropriately. Plenty of further research has demonstrated the cardiac risks of vioxx, the most selective cox-II, and less clear results for celebrex, which is not as selective. While ibuprofen may have some mild cardioprotective benefit (not substantiated), subsequent work has made it much less likely that the robust cardiotoxic effects of vioxx were due to this improper comparator.
Vioxx perhaps (especially given the early event risk),Celebrex no. Have you looked at the Cardiovascular RR with regard to some of our old-school NSAIDs? Indomethacin, ketorolac, and diclofenac, are comparable to the Cox-2's or actually riskier from a cards perspective. Meloxicam isn't much better than celebrex from that perspective.
Also at the rate of adverse events we are looking at, the protective effect of ibuprofen could be rather small and still be the thing making the difference. NNT of 125 I think.
The courts will make any decision regardless of science. They've proven it 10,000 times.
And I'd still argue that unless a head-to-head trial of Cox-2s+Aspirin versus Cox-1s+Aspirin, or even a Cox2+ibuprofen versus ibuprofen alone trial, were done, we can't say for sure just how dangerous these drugs are from a cardiovascular perspective. If indeed these drugs are prothrombotic (which admittedly there are good arguments for, as based on the basic science it's easy to see hw selective cox-2 inhibition would lead to increased TXA expression), we should STILL see a difference in cardiovascular event risk.
As for BMI, we use proxies in research all the time. While the value is clearly problematic, its value in epidemiologic research has been well substantiated. Most people with high BMIs are too fat, and most people normal BMIs are not. So while it's obviously problematic, throwing out "any obesity study that uses BMI" leaves us hardly better off than abandoning a flawed instrument.
Proxies are indeed used in research all the time. It's a sore point for a lot of people. I have had to use proxies in my own research and I'm not very pleased about it. One thing that most will agree on, though, is that a good proxy (if there is such a thing) should be causally linked to the thing in question. Body weight is a function of a number different factors from organ weight, to bone weight (highly underemphasized in my opinion), to muscle, and of course fat. Because of the multifactorial nature of bodyweight, and by consequence, BMI, the proxy has a rather weak relationship to the value in question.
Mayo recently took a look at the normal weight population and found that over half of them at unhealthy levels of bodyfat (over 20% in men and over 30% in women--which is a little higher in women than I would personally use, but that's ok, it's a good start). OVER HALF. Which means that in fact, most people with a normal BMI do NOT have healthy levels of body fat.
I can't find a citation right now, but some studies have shown that up to 30% of the overweight population have normal, healthy percentages of body fat. which means that there is significant overlap in body fat between the two groups.
Such massive overlap completely invalidates just about any study that has used BMI as a proxy for the role of body fat in health.
As an example, a few years ago we learned that elderly with higher BMIs tend to have lower mortalities than the elderly with lower BMIs. Similar results were found for Alzheimer's as well. This lead the pro-fat crusaders to scream that 'hey look! fat is good!' Of course, more recent studies that actually measured bodyfat have shown that it wasn't overall weight, but in fact lean muscle mass that was correlated to these things.
the 7-site skinfold test takes a minute or two and is accurate to within 2%. The BMI can never claim that.
Waist/hip measurements, or even better, chest/waist/hip measurements, are also relatively sensitive. Unlike the BMI.
At the end of the day with 50% or more of your 'normal' population being actually unhealthily fat, and up to 30% of your overweight population actually being rather healthy, you lose a whole heck of a lot of resolution in studying the effects of body fat on health. And more concerning from my meathead exercise phys perspective, you never even have a chance of looking at the effects of lean mass on health.
Thanks for that post MoM, really fascinating stuff
