Aspirin slows blood clotting, and blood coagulation plays a role in vascular disease, so the thinking is that some heart attacks and strokes can be prevented with regular use of aspirin, and indeed there is empirical support for this. As with many drug therapies, it was the side effects of aspirin use for something else, in this case rheumatoid arthritis (RA), that first suggested it could play a role in CVD prevention -- a 1978 study reported that aspirin use lowered the risk of myocardial infarction, angina pectoris, sudden death, and cerebral infarction in RA patients (study cited in an editorial by Freek Verheugt accompanying the Hira paper), a result that kick-started its use for CVD prevention.
The new Hira et al. study included about 68,000 patients in 119 different practices taking aspirin for prevention of a first heart attack or stroke, not recurrence. The authors looked at clinical records in a network of cardiology practices to assess the proportion of patients in each practice that was taking aspirin, and whether they met the 10-year risk criteria for 'appropriate use' as determined by the Framingham risk calculator. The calculator uses an algorithm based on age, sex, total cholesterol, HDL cholesterol, smoking status, blood pressure and whether the patient is taking medication to control blood pressure.
Appropriate use, according to Hira et al., is a 10-year risk of greater than 6%. According to the calculator itself, 6% risk means that 6 of 100 people with whichever set of factors yields this risk will have a heart attack within the next 10 years. The reason this even has to be thought about is because there is some risk to taking aspirin because it's an anticoagulant and can cause major bleeding, so maximizing the cost/benefit ratio, preventing CVD as well as major bleeds, is what's at issue here. If the benefit is a long-shot because an aspirin user isn't likely to have CVD anyway, the potential cost can outweigh the pluses.
As Verheugt explains:
Major coronary events (coronary heart disease mortality and nonfatal MI) are reduced by 18% with aspirin but at the cost of an increase of 54% in major extracranial bleeding. For every 2 major coronary events shown to be prevented by prophylactic aspirin, they occur at the cost of 1 major extracranial bleed. Primary prevention with aspirin is widely applied, however. This regimen is used not only because of its cardioprotection but also because there is increasing evidence of chemoprotection of aspirin against cancer.Hira et al. found that 11.6% of the population of patients visiting a cardiology practice were taking aspirin inappropriately, having a risk less than 6% as calculated by the Framingham calculator. That is, their risk of bleeding outweighs the potential preventive effect of aspirin.
But, about this 6% risk. Does it sound high to you? Would you change your behavior based on a 6% risk, or would you figure the risk is low enough that you can continue to eat those cheese steaks? Or maybe you'd just start popping aspirin, figuring that made it really safe to continue to eat those cheese steaks?
And why the 6% threshold? So precise. Indeed, a 2011 study suggested different risk thresholds for different age categories, increasing with age. And, different calculators (such as this one from the University of Edinburgh) return different risk estimates, varying by several percentage points given the same data, so so much for precision.
Risk is, of course, estimated from population data, based on the many studies that have found an association between cholesterol, blood pressure, smoking status, and heart attack, particularly in older men. A distribution of risk factors and outcomes would thus show that for a given set of cholesterol and blood pressure values, on average x% will have a heart attack or stroke. These are group averages, and using them to make predictions for individuals cannot be done with precision that we know to be true. Indeed, one of the strongest risk factors known to epidemiology, smoking, causes lung cancer in 'only' 10% of smokers, and it's impossible to predict who. But that's why these CVD risk calculators never estimate 100% risk. The highest risk I could force them to estimate was "greater than 30%".
Hard to know what that actually means for any individual. At least, I have a hard time knowing what to make of these figures. If 6 of 100 people in the threshold risk risk category will have an MI in the next 10 years, this means that 94 will not. So, another way to think about this is that the risk for 94 people is in fact 0, while risk for the unlucky 6 is 100%. For everyone over the 6% threshold, the cost -- possible major bleed -- is assumed to be outweighed by the benefit -- prevention of MI -- even when that's in fact only true for 6 out of 100 people in this particular risk category. But, since it's impossible to predict which 6 are at 100% risk, the whole group is treated as though it's at 100% risk, and put on preventive baby aspirin, and perhaps statins as well, and counseled on lifestyle changes and so on, all of which can greatly affect the outcome, and alter our understanding of risk factors -- or the effectiveness of preventive aspirin. And what if it's true that a drink a day lowers heart failure risk? How do we factor that in?
Further, a lot of more or less well-established risk factors for CVD are not included in the calculation. After decades of cardiovascular disease research, it seems to be well-established that obesity is a risk factor, as well as diabetes, and certainly family history. Why aren't these pieces of information included? Tens if not hundreds of genes have been identified to have at least a weak effect on risk (and even this number only account for a fraction of the genetic risk as estimated from heritability studies), and these aren't included in the calculation either. And, we all know people who seemed totally fit, who had a heart attack on the running trail, or the bike trail, so at least some people are in fact at risk even with none of the accepted risk factors.
So, 11.6% of baby aspirin takers shouldn't be taking aspirin. But, when risk estimation is as imprecise as it is, and as hard to understand, this seems like a number that we should be taking with a grain of salt, if not a baby aspirin. Well, except that salt is a risk factor for hypertension which is a risk factor for heart disease....or is it?
*Or something like that. It turns out that the Hira paper cited a 2007 paper, which cited a 2006 paper, which cited the Behavioral Risk Factor Surveillance System 2003 estimate of 36% of the American population taking a baby aspirin a day. But this is a 12 year old figure, and I couldn't find anything more recent.