Coronary artery disease
Comparison of Usefulness of Inflammatory Markers in Patients With Versus Without Peripheral Arterial Disease in Predicting Adverse Cardiovascular Outcomes (Myocardial Infarction, Stroke, and Death)

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We tested the hypothesis that a combination of measurements of different aspects of atherosclerosis, including burden of atherosclerosis and levels of inflammation, would contain more predictive information than either alone in an outpatient population. We enrolled 110 patients (62 ± 15 years of age) who were referred to the noninvasive vascular laboratory for sequential Doppler pressure measurements of the lower extremities. We measured ankle-brachial index (ABI) and serum markers of inflammation and followed subjects for a mean of 2.25 years. Fifty subjects did not have peripheral arterial disease (PAD; ABI ≥0.9), whereas 60 did (ABI <0.9). Markers of inflammation, including C-reactive protein (3.83 ± 0.9 vs 2.11 ± 1.1, p = 0.019), were higher in subjects who had PAD. During follow-up, 42% developed an event (myocardial infarction, stroke, unplanned coronary or lower extremity revascularization, or death). Decreasing ABI (chi-square 7.3, p = 0.026) and increasing C-reactive protein (chi-square 22.1, p <0.001) increased the risk of an event. Risk increased sixfold between the lowest and highest groups for all events and fourfold for hard events (myocardial infarction, stroke, and death) using both C-reactive protein and ABI. In conclusion, patients who have PAD and increased inflammation are at highest risk for adverse cardiovascular outcomes. Characterizing atherosclerosis on the basis of these parameters provides important prognostic information.

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Patient selection

All men and women who were ≥18 years of age and were referred to the Brigham and Women’s Noninvasive Vascular Laboratory (Boston, Massachusetts) for ABI and segmental Doppler pressure measurement were offered participation between March 1, 1999 and January 31, 2002. Subjects were excluded if they had nonskin cancer, hepatic disease, renal disease (creatinine >1.4 mg/dl), infectious disease, planned revascularization or critical limb ischemia, or myocardial infarction, stroke, or gangrene within

Results

We approached 126 subjects and enrolled 110 during the enrollment phase; 50 subjects had no evidence of significant lower extremity vascular disease and 60 met the criteria for PAD (Table 1). No enrolled subject was later excluded. The physician referral pattern to the vascular laboratory was as expected: 45% by vascular surgeons, 38% by primary care physicians, and 16% by cardiovascular physicians. Subjects who had PAD were older, more likely to have vascular disease risk factors, more likely

Discussion

In this prospective evaluation of patients who presented to a vascular laboratory, our data show a significant relation between severity of PAD and levels of systemic inflammation. Further, patients who have PAD are medically undertreated, despite recommendations that advocate aggressive decreases in risk factors. Most importantly, in addition to demonstrating independent relations between inflammation and outcomes and between extent of atherosclerosis and outcomes, we have shown a graded

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This study was supported by Grant K23 HL-04169 from the National Institutes of Health, Bethesda, Maryland.

Dr. Ridker has been named as a co-inventor on patents filed by the Brigham and Women’s Hospital that relate to the use of inflammatory markers in cardiovascular disease.

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