Four Main Risk Factors for PAD

October 24, 2012

BOSTON — Four risk factors--hypertension, diabetes, smoking, and high cholesterol--account for the vast majority of cases of peripheral arterial disease (PAD), a new study shows [1].

The study, published in the October 24/31, 2012 issue of the Journal of the American Medical Association, was conducted by a team led by Dr Michel Joosten (Beth Israel Deaconess Medical Center, Boston, MA).

Joosten commented to heartwire : "These four risk factors could potentially eliminate as much as 75% of PAD. Preventing people from ever developing these risk factors needs to be a public-health priority."

He said this was particularly true for hypertension and smoking. "For PAD, the risk from smoking persists for as long as we can measure, so it is important not to start. For blood pressure, the risk seems to go up relatively soon after being diagnosed, so again, lifestyle efforts to prevent it are important."

Joosten noted that the four risk factors are independent and multiplicative. "Even if you have one of them, it appears important not to get additional ones, as every additional risk factor counts just as much."

Not Necessary to Look for Other Causes

He added that the results also suggest that it is not necessary to look for other causes. "We needn't worry excessively about undiscovered risk factors or factors like genetics that we don't measure in a clinical setting. We just need to concentrate on the four main risk factors that we have already identified."

For the current study, Joosten and colleagues analyzed data from the Health Professionals Follow-up Study, which followed 51 529 US male health professionals aged 40 to 75 years at baseline in 1986. They completed a questionnaire about disease history, including intermittent claudication and lifestyle factors, every two years. Men with a family history of or diagnosed with cardiovascular disease (MI, stroke, coronary artery bypass graft surgery, coronary angioplasty, and intermittent claudication) were excluded.

During a median follow-up of 24 years, there were 537 cases of PAD. Each of the four conventional cardiovascular risk factors of smoking, hypertension, hypercholesterolemia, and type 2 diabetes was found to be significantly and independently associated with a higher risk of PAD after adjustment for the other three risk factors and confounders.

Incidence of PAD as Related to Number of Risk Factors

Risk factors (n) Age-adjusted incidence rate of PAD (cases/100 000)
0 9
1 23
2 47
3 92
4 186


The multivariable-adjusted hazard ratio for each additional risk factor was 2.06. Men without any of the four risk factors had a hazard ratio of PAD of 0.23 compared with all other men in the cohort. In 96% of PAD cases, at least one of the four risk factors was present at the time of PAD diagnosis. The absolute incidence of PAD among men with all four risk factors was 3.5/1000 person-years. The researchers note that the incidence of PAD may have been somewhat underestimated because the definition of a new PAD diagnosis was quite strict.

They point out that although the four major risk factors are the same as those for other cardiovascular disease, there are some important differences. For example, at least one of these risk factors is present in 80% of patients with coronary heart disease, compared with more than 95% of cases of severe PAD. In addition, active smoking is two or three times more strongly associated with PAD than with CHD, and the risk of PAD does not appear to return to baseline on stopping smoking, which it does for CHD and stroke risk.