No abstract

Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes.

Context-Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index is an indicator of atherosclerosis and has the potential to improve prediction.Objective-To determine if the ankle brachial index provides information on the risk of cardiovascular events and mortality independently of the Framingham Risk Score and can improve risk prediction.

Because patients with peripheral arterial disease (PAD) may be asymptomatic or may present with atypical symptoms or findings, the true population prevalence of PAD is essentially unknown. We used four highly reliable, sophisticated noninvasive tests (segmental blood pressure, flow velocity by Doppler ultrasound, postocclusive reactive hyperemia, and pulse reappearance halftime) to assess the prevalence of large-vessel PAD and small-vessel PAD in an older (average age 66 years) defined population of 613 men and women. A total of 11. 7% of the population had large-vessel PAD on noninvasive testing, and nearly half of those with large-vessel PAD also had small-vessel PAD (5.2%). An additional 16.0% of the population had isolated small-vessel PAD. Large-vessel PAD increased dramatically with age and was slightly more common in men and in subjects with hyperlipidemia. Isolated small-vessel PAD, by contrast of PAD by the traditional methods, intermittent claudication and pulse palpation. MethodsAll 624 subjects were members of a geographically defined population initially studied under a Lipid Research Clinics (LRC) protocol.20 21 Subjects were recruited for the study with an introductory letter, followed by a telephone call to schedule an appointment. About half of the subjects (5 1.7%) were from a random sample of the LRC cohort and-the others were selected from the same earlier study for hyperlipidemia, defined as being at or above age-and sex-specific 90th percentiles for cholesterol concentration or 95th percentiles for triglyceride concentration or use of lipid-lowering medications. Subjects were from a predominantly white, upper-middle-class community in southern California, and informed consent was obtained after the procedures had been fully explained.Eleven subjects (1.8%) were excluded because of missing data or unreliable results of noninvasive testing. Two hundred seventy-five men and 338 women ranging in age from 38 to 82 years (mean 66) remained. One hundred fifty-eight subjects were 38 to 59 years old, 161 were 60 to 69 years old, and 294 were 70 to 82 years old.Criteria

In a 1994-1998 cross-sectional study of a multiethnic sample of 2,211 men and women in San Diego, California, the authors estimated prevalence of the major manifestations of chronic venous disease: spider veins, varicose veins, trophic changes, and edema by visual inspection; superficial and deep functional disease (reflux or obstruction) by duplex ultrasonography; and venous thrombotic events based on history. Venous disease increased with age, and, compared with Hispanics, African Americans, and Asians, non-Hispanic Whites had more disease. Spider veins, varicose veins, superficial functional disease, and superficial thrombotic events were more common in women than men (odds ratio (OR) = 5.4, OR = 2.2, OR = 1.9, and OR = 1.9, respectively; p < 0.05), but trophic changes and deep functional disease were less common in women (OR = 0.7 for both; p < 0.05). Visible (varicose veins or trophic changes) and functional (superficial or deep) disease were closely linked; 92.0% of legs were concordant and 8.0% discordant. For legs evidencing both trophic changes and deep functional disease, the age-adjusted prevalences of edema, superficial events, and deep events were 48.2%, 11.3%, and 24.6%, respectively, compared with 1.7%, 0.6%, and 1.3% for legs visibly and functionally normal. However, visible disease did not invariably predict functional disease, or vice versa, and venous thrombotic events occurred in the absence of either.

The WHO/Rose questionnaire has served as the epidemiologic and clinical standard in the assessment of leg pain in patients with peripheral arterial disease (PAD) for over three decades. However, the structure of this questionnaire does not allow assessment of leg-specific (i.e. right versus left) symptoms. We studied 508 patients aged 39-95 years (mean 68 years), initially referred for PAD non-invasive testing. A revised questionnaire, the San Diego Claudication Questionnaire, was administered which allowed determination of leg-specific symptoms and evaluated thigh and buttock as well as calf pain. Leg-specific symptoms were categorized into no pain, pain at rest, non-calf claudication, non-Rose calf claudication, and Rose claudication. At the same visit, the ankle brachial index, the toe brachial index, and peak posterior tibial flow velocity were measured by Doppler ultrasound and five categories of non-invasive results by type and severity of PAD were defined. Legs with previous intervention (Rx), surgery or angioplasty, were evaluated separately. Claudication was reported in 42% of no Rx legs and 50% of Rx legs; 40% of claudication was atypical (not Rose); 64% of no Rx and 81% of Rx legs had PAD by non-invasive testing, and 27% of affected legs had severe PAD. The correlation between the severity of symptoms and the severity of ipsilateral PAD in no Rx legs was r = -0.40, p < 0.001. In Rx legs, this correlation was somewhat less (r = 0.27, p < 0.001) due to more symptomatology at lesser degrees of PAD, suggesting reporting bias and/or more residual disease than evident from non-invasive testing. To our knowledge, these results provide the first comparison between a standardized assessment of leg pain and the severity of ipsilateral PAD by non-invasive testing.

Data from the Framingham Study and other population studies indicate that intermittent claudication (IC) sharply increases in late middle age and is somewhat higher among men than women. Noninvasive testing in populations indicates that the true prevalence of peripheral arterial disease (PAD) is at least five times higher than would be expected based on the reported prevalence of IC. Peripheral arterial disease correlates most strongly with cigarette smoking and either diabetes or impaired glucose tolerance. Other risk factors for PAD include hypertension; low levels of high-density lipoprotein cholesterol; and high levels of triglycerides, apolipoprotein B, lipoprotein(a), homocysteine, fibrinogen and blood viscosity. Individuals with PAD are more likely to have coronary heart disease and cerebrovascular disease than those without PAD. Because of the high risk of both nonfatal and fatal cardiovascular disease (CVD) events in PAD patients, individuals with evidence of PAD should undergo both a careful examination of the entire cardiovascular system and aggressive modification of CVD risk factors.

In a companion article we have reported the prevalence, in an older, defined population, of traditional assessments (intermittant claudication and abnormal pulse examination) of peripheral arterial disease (PAD) as compared with the results of highly accurate noninvasive testing. In this article we report the sensitivity, specificity, and positive and negative predictive values for claudication and abnormal pulses for the diagnosis of large-vessel and small-vessel PAD as determined by noninvasive testing. Claudication and abnormal pulses were completely unrelated to isolated small-vessel PAD. In contrast, both claudication and abnormal pulses were significantly correlated with large-vessel PAD. Claudication and an abnormal femoral pulse showed a high specificity and positive predictive value but a low sensitivity for large-vessel PAD. Conversely, an abnormal dorsalis pedis pulse showed a good sensitivity but low specificity and positive predictive value. The best single discriminator was an abnormal posterior tibial pulse, which had high sensitivity, specificity, and positive predictive value. Various combinations of claudication and pulse abnormalities revealed a good sensitivity for broader criteria but at the expense of specificity, whereas stricter criteria had a good specificity and positive predictive value but a poor sensitivity. No combination was superior to an abnormal posterior tibial pulse alone. Additional analyses revealed that atypical leg pain was more common in patients with large-vessel PAD than in those without, that subjects with isolated large-vessel PAD in the posterior tibial artery did not have claudication, that claudication was rare until large-vessel PAD could be detected bilaterally by noninvasive testing, and finally that in the presence of large-vessel PAD concomitant small-vessel PAD was a marker for more severe large-vessel PAD. These results provide a useful guide to the utility and to the limitations of traditional clinical evaluation of PAD. Circulation 71, No. 3, 516-522, 1985. IN A COMPANION ARTICLE, we have outlined the prevalence of peripheral arterial disease (PAD) in a defined population as assessed first by traditional clinical evaluation (intermittent claudication and pulse palpation) and second by highly accurate, recently developed noninvasive testing procedures. This article evaluates the degree of overlap between traditional clinical evaluation and noninvasive testing results to determine the sensitivity, specificity, and predictive value of positive and negative findings of claudication and pulse palpation, both individually and in combination, for noninvasively diagnosed PAD. These results also shed light on the nature and degree of PAD sufficient to cause symptoms. MethodsAll 624 subjects were members of a geographically defined population initially studied under a Lipid Research Clinics (LRC) protocol.2' 3 Subjects were recruited for the study with an introductory letter, followed by a telephone call to schedule an appointment. About half of the subj...