Smoking, diabetes predict different forms of peripheral artery disease

May 31, 2006

Cigarette smoking and high cholesterol predict risk for some forms of peripheral artery disease (PAD), while diabetes predicts risk for other forms of the disease, researchers reported in a rapid access issue of Circulation: Journal of the American Heart Association.

Researchers examined risk factors for PAD progression in large blood vessels (LV-PAD) and in small blood vessels (SV-PAD). PAD is characterized by clogged arteries outside the heart or brain - most often in the legs. An estimated 8 million people in the United States have PAD.

When large leg vessels are involved, the classic symptom is painful cramping in the hips, thighs or calves that occurs during exercise and eases after a few minutes of rest. With small vessels, the feet may be cool to the touch, heal slowly when injured, and in extreme cases require amputation.

Researchers identified several risk factors that influence the evolution of LV-PAD. Smoking appeared to be the most powerful predictor that PAD would get worse.

"Smoking cessation is the most efficient way to slow the progression of PAD, along with altering cholesterol levels through diet, exercise and medication," said study lead author Victor Aboyans, M.D., Ph.D. "By highlighting and focusing preventive efforts on the risk factors, we can improve the prognosis."

Aboyans - a cardiologist and epidemiologist at the Dupuytren University Hospital in Limoges, France - conducted this study while a visiting scholar in the Department of Family and Preventive Medicine at the University of California, San Diego.

He and colleagues examined 403 men and women (average age 69) with LV-PAD and 290 with SV-PAD (average age 68) who were previously suspected of having PAD and underwent evaluation. For the current analysis, results from these initial examinations were compared with new tests performed an average of 4.6 years later.

Researchers compared blood pressure readings in the ankles and toes with those in the arms - the ankle-brachial index (ABI) and toe-brachial index (TBI). Blood pressure in the ankle that's less than 90 percent of the arm measurement indicates PAD, while toe blood pressure less than 70 percent of the arm measurement also indicates PAD.

During follow up, patients showed a significant deterioration in ABI and TBI, although some remained stable. Those suffering the steepest declines (the highest 10 percent), with at least a 0.30 decrease in ABI or 0.27 decrease in TBI, were considered to have major PAD progression. Researchers compared risk factors in these patients with those whose arteries did not narrow as significantly during follow up.

Among those with LV-PAD, current smokers were 3.2 times more likely to have major progression. Those with a high ratio of total cholesterol to high-density lipoprotein (HDL) - the good cholesterol - were also more likely to have their PAD substantially progress.

Heavy drinking (more than 21 alcoholic beverages per week) was also associated with worse LV-PAD, but was considered "borderline predictive" of PAD progression. Likewise, higher pulse pressure (the difference between the upper and lower numbers in a blood pressure reading, which indicates stiffening in major blood vessels) was a borderline predictor of progression.

Researchers analyzed several novel cardiovascular risk factors and found that high levels of Lipoprotein a, or Lp(a) - a lipid particle, and high levels of highly sensitive C-reactive protein, or hsCRP - an inflammation marker, were also predictive of greater progression of LV-PAD. However, high levels of homocysteine, previously identified as a risk factor for PAD, did not predict progression.

The only significant predictor of SV-PAD progression was diabetes.

"The most surprising result was the absence of an impact of diabetes in large vessel PAD progression," Aboyans said.

The findings point to the importance of thinking about small and large-vessel PAD separately and looking for both when assessing blood flow in the legs.

"Some patients in this study had progressive artery blockage, but the only initial evidence was in the toe," said co-author Michael H. Criqui, M.D., M.P.H., professor of medicine and professor of family and preventive medicine at the University of California, San Diego School of Medicine. "Particularly in patients with diabetes, doctors may need to measure both ABI and TBI."

The results reinforce new American College of Cardiology/American Heart Association guidelines on the management of PAD, published in Circulation in March, 2006. The guidelines recommended anti-platelet therapy - such as aspirin and cholesterol treatment with statins.

"If you have PAD and are taking low-dose aspirin and a statin, you're doing two things that are very helpful," Criqui said.
Co-authors are: Julie O. Denenberg, M.A.; James Knoke, Ph.D.; Paul M. Ridker, M.D., M.P.H.; and Arnost Fronek, M.D., Ph.D. The study was partly funded by a National Heart, Lung, and Blood grant and an American Heart Association grant.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.

NR06 - 1059 (Circ/Aboyans)

American Heart Association

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