Risk of treatment of peripheral arterial disease is related to inflammation-sensitive plasma proteins: a prospective cohort study

BACKGROUND: Studies in patients with peripheral arterial disease (PAD) have reported an association between inflammatory markers and severity of disease or worsening of symptoms. However, few have studied the prognostic significance of inflammatory markers in asymptomatic subjects, measured many years before the onset of symptomatic PAD requiring treatment (trPAD).

MATERIAL AND METHODS: Five inflammation-sensitive plasma proteins (ISPs), including fibrinogen, alpha 1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid, were determined in 5619 healthy men (mean age, 46.8 +/- 3.7 years) without walking-induced calf pain. Data for men who subsequently underwent a revascularization procedure because of trPAD (intermittent claudication or critical ischemia) were retrieved from hospital-based registers. Future trPAD was studied in relation to the number of ISPs in the top quartile at the baseline examination.

RESULTS: Seventy men (1.2%) underwent revascularization because of trPAD at a mean of 16.5 years after the baseline examination. The proportion with future trPAD was 0.4%, 1.0%, 1.5%, and 3.2%, respectively, for men with 0, 1, 2, and 3 or more ISPs in the top quartile (trend, P < .0001). After adjustment for age, screening year, systolic blood pressure, blood pressure medication, cholesterol concentration, diabetes, smoking, and tobacco consumption the corresponding odds ratios (95% confidence interval [CI]) were 1.00 (reference), 1.5 (CI, 0.7-3.6), 1.9 (CI, 0.8-4.6), and 2.9 (CI, 1.3-6.4), respectively, in these groups (trend, P = .003).

CONCLUSION: Elevated ISPs, measured 16 years earlier in apparently healthy men without walking-induced calf pain, were associated with increased risk for development of PAD requiring revascularization.