Relation of levels of hemostatic factors and inflammatory markers to the ankle brachial index

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Abstract

Associations between hemostatic and inflammatory markers relative to the ankle brachial index (ABI), an indicator of the presence and severity of peripheral arterial disease (PAD), are not fully understood. We studied relations among selected hemostatic factors, inflammatory markers, and the ankle brachial index (ABI) in patients with and without peripheral arterial disease (PAD). Participants were 370 men and women with ABI <0.90 and 231 patients with ABI 0.90 to 1.50 identified from noninvasive vascular laboratories and general medicine practice. Blood factors were d-dimer, prothrombin 1.2, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), and inflammatory markers (high-sensitivity C-reactive protein [CRP], fibrinogen, and serum amyloid A [SAA]). Among patients without a history of cardiac or cerebrovascular disease, the ABI was significantly inversely associated with log d-dimer (p <0.001), log prothrombin 1.2 (p = 0.001), log CRP (p <0.001), and log fibrinogen (p = 0.005) in unadjusted analyses. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, d-dimer was associated independently with ABI in participants with a history of cardiac or cerebrovascular disease (p = 0.003) and in participants without a history of cardiac or cerebrovascular disease (p = 0.017). In these analyses, CRP was associated independently with ABI among participants with a history of cardiac or cerebrovascular disease (p = 0.026). CRP was not associated independently with ABI in participants without a history of cardiac or cerebrovascular disease. We conclude that d-dimer levels may be more sensitive than other blood markers for measuring the extent of atherosclerosis in lower extremity arteries.

Section snippets

Participant identification

This study was performed in patients participating in the Walking and Leg Circulation Study, an observational study assessing the natural history of lower extremity functioning in patients with and without PAD.9, 10 The study was approved by the institutional review board of Northwestern University’s Feinberg School of Medicine and Catholic Health Partners Hospital. All participants gave informed consent. Participants were ≥55 years old.

PAD was defined as ABI <0.90. Absence of PAD was defined

Results

Of 2,662 potential participants identified from the noninvasive vascular laboratories, 220 were deceased, 464 could not be located, 375 were ineligible, and 597 agreed to participate. Of 467 potential participants identified from the general medicine practice, 7 were deceased, 63 could not be located, 22 were ineligible, and 143 participated. Of 740 patients enrolled, 601 (81.2%) had sufficient blood drawn for testing of all blood factor levels and are included in these analyses.

Table 1 lists

Discussion

Our results show that d-dimer levels are significantly associated with the extent of lower extremity arterial obstruction as measured by the ABI. Of the blood factors studied, d-dimer was associated significantly and independently with the ABI among patients with cardiac or cerebrovascular disease and among patients without cardiac or cerebrovascular disease, adjusting for CRP, fibrinogen, SAA, t-PA/PAI-1 ratio, prothrombin 1.2, total cholesterol, high-density lipoprotein, and other known and

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This study was supported by grants #R01-HL58099 and R01-HL64739 from the National Heart Lung and Blood Institute, Bethesda, Maryland, and by grant #RR-00048 from the National Center for Research Resources, National Institutes of Health, Bethesda, Maryland. Dr. McDermott is a recipient of an Established Investigator Award from the American Heart Association, Dallas, Texas.

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