The authors previously demonstrated a significant association between the presence of mitral annulus calcification (MAC) and aortic atheroma, carotid atherosclerotic disease, and coronary artery disease. The present study was designed to determine whether an association exists between MAC and peripheral arterial atherosclerotic disease. Of the 805 patients in whom the diagnosis of MAC was made by transthoracic echocardiography between 1995 and 1997, 77 patients (40 men and 37 women; mean age, 73.1 +/- 11.4 years; range, 44-90 years) underwent peripheral arterial testing for various indications, and comprised the study group. They were compared with 58 age-matched and sex-matched patients without MAC (30 men and 28 women; mean age, 73.2 +/- 11.8 years; range, 31-93 years) who underwent peripheral arterial testing during the same period for the same indications (control group). MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet detected by transthoracic echocardiography. An ankle/brachial systolic pressure index (ABI) was calculated by dividing the higher dorsalis pedis or posterior tibial Doppler-derived pressures by the higher of the 2 upper extremity systolic pressures. ABI was graded as follows: normal > or = 1, abnormal < 1, mild 0.71 to 0.99, moderate 0.41 to 0.7, and severe < or = 0.4. No differences were found between the groups in indications for referral for peripheral arterial testing and in risk factors for atherosclerosis except for hypertension, which was found to be significantly more prevalent in the study group (66% vs 41%, p = 0.004). The study group included 151 limbs, and the control group included 113 limbs. The mean ABI was significantly lower for all limbs in the MAC group (0.56 +/- 0.27 vs 0.87 +/- 0.24, p = 0.0001), abnormal ABI < 1 (94% vs 68%, p = 0.001), moderate peripheral arterial disease (44% vs 25%, p = 0.001), and a severe disease (27% vs 1%, p = 0.001). Of the 77 patients with MAC, 73 (95%) had a disease (right and/or left limbs) compared with 40 of 58 (69%) in the control group (p = 0.001). Bilateral disease (Doppler index < 1 for both right and left limbs), and severe bilateral disease (Doppler index < or = 0.4 for both right and left limb) were also found to be significantly more prevalent in the MAC group (87% vs 60%, p = 0.001; and 12% vs 0%, p = 0.007, respectively). There is a significant association between the presence of MAC and peripheral arterial disease. This information strengthens our hypothesis that MAC may be an important marker for generalized vascular atherosclerotic disease.