San Francisco, CA - Smoking and high blood pressure are responsible for the most "preventable" deaths in the US, according to a study looking at 12 modifiable risk factors [1]. Writing in the April 2009 issue of PLoS Medicine, Dr Goodarz Danaei (Harvard School of Public Health, Boston, MA) and colleagues looked at lifestyle, diet, and metabolic risk factors associated with all preventive, chronic diseases and determined that smoking accounted for one in five deaths and was particularly problematic in men, while high blood pressure, more common in women, accounted for roughly one in six deaths.

In an interview with heartwire, Danaei emphasized that his group had not set out to look specifically at CV deaths.

"We started out with not necessarily CV disease risk factors, but chronic disease risk factors, so that included cancers, diabetes, respiratory disease, and even injuries," he said. "And what we found in this study was that most of the deaths that we could prevent by so-called risk factors for chronic disease were things like hypertension, obesity, etc. . . . In the US and many other Western countries, heart disease is not only the number-one cause of death, it is the number-one preventable cause of death-that's what our results show."

The study drew data on disease-specific mortality for 2005 from the National Center for Health Statistics, then used previously published studies to estimate how much individual risk factors increased the risk of death from each disease. In all, 12 modifiable risk factors were addressed in the analysis: smoking, physical inactivity, heavy alcohol use, high blood glucose, low LDL, high blood pressure, overweight/obesity, high dietary trans-fatty acids, high salt intake, low dietary polyunsaturated fatty acids (PUFAs), low omega-3 fatty-acid intake, and low fruit and vegetable consumption.

For 2005, tobacco smoking was the leading cause of death—roughly 467 000 in all, and the number-one cause of death in men. This was followed by high blood pressure, which caused 395 000 deaths in total and was the number-one cause of death in women. "We think, based on these results, that the approach we take for preventing premature mortality in men and women may be quite different," Danaei said.

While blood pressure and smoking emerged as the two major culprits, other factors were also significant. Being overweight or obese, being physically inactive, or having high blood glucose was responsible for roughly one in 10 deaths. Less important, however, were high dietary salt, high trans-fatty acid consumption, and low omega-3 fatty-acid consumption. Perhaps most strikingly, high LDL cholesterol was not a major cause of death at the population level.

"For us, what was a bit surprising was the low effect of LDL cholesterol," Danaei said, particularly given the prominence of cholesterol in risk-prediction scores, such as Framingham. "We think of cholesterol as being sort of on par with BP, but at a population level, looking at this from a public-health perspective, LDL cholesterol in the US is not one of the major factors for mortality."

Investigators also looked specifically at adults younger than 70 and found that, in this group, smoking was far and away the leading modifiable cause of death, while overweight/obesity emerged as causing more deaths than high blood pressure in this younger group.

The findings are important, Danaei and colleagues write, since they can help inform and prioritize policy decisions and provide a rationale for focusing on the most lethal risk factors. "The results of our analysis of dietary, lifestyle, and metabolic risk factors show that targeting a handful of risk factors has large potential to reduce mortality in the US, substantially more than the currently estimated 18 000 deaths averted annually by providing universal health insurance," they write.

But speaking with heartwire, Danaei emphasized that their study did not take into account the costs of more targeted interventions—something that should be the focus of future research. He also pointed out that interventions for different risk factors have proved to have both different degrees of efficacy and different levels of success at a population level. "We know that for smoking we have relatively good interventions, and we have very cheap drugs that reduce blood pressure effectively. But [for] obesity we don't really have effective interventions, and the same for physical activity," he said.

Even for the top two risk factors, there are important differences, Danaei continued. "If you compare the results from trials of smoking cessation and trials of blood pressure [control], the latter is much more effective, and with drugs being off patent and relative cheaply available across the world, blood pressure seems to be a more manageable story. . . . For smoking, the highest success rates for long-term cessation are not in any way comparable to the level of control that we get from blood pressure."