Natural history of claudication: long-term serial follow-up study of 1244 claudicants.

OBJECTIVE: The purpose of this study was to delineate the natural history of claudication and determine risk factors for ischemic rest pain (IRP) and ischemic ulceration (IU) among patients with claudication. METHODS: We prospectively collected data on 1244 men with claudication during a 15-year period, including demographics, clinical risk factors, and ankle-brachial index (ABI). We followed these patients serially with ABIs, self-reported walking distance (WalkDist), and monitoring for IRP and IU. We used Kaplan-Meier and proportional hazards modeling to find independent predictors of IRP and IU. RESULTS: Mean follow-up was 45 months; statistically valid follow-up could be carried out for as long as 12 years. ABI declined an average of 0.014 per year. WalkDist declined at an average rate of 9.2 yards per year. The cumulative 10-year risks of development of IU and IRP were 23% and 30%, respectively. In multivariate analysis using several clinical risk factors, we found that only DM (relative risk [RR], 1.8) and ABI (RR, 2.2 for 0.1 decrease in ABI) predicted the development of IRP. Similarly, only DM (RR, 3.0) and ABI (RR, 1.9 for 0.1 decrease in ABI) were significant predictors of IU. CONCLUSION: This large serial study of claudication is, to our knowledge, the longest of its kind. We documented an average rate of ABI decline of 0.014 per year and a decline in WalkDist of 9.2 yards per year. Two clinical factors, ABI and DM, were found to be associated with the development of IRP and IU. Our findings may be useful in predicting the clinical course of claudication.

Outcome events in patients with claudication: a 15-year study in 2777 patients.

OBJECTIVE: The purpose of this study was to delineate the natural history of claudication and determine risk factors for death. METHODS: We reviewed the key outcomes (death, revascularization, amputation) in 2777 male patients with claudication identified over 15 years at a Veterans Administration hospital with both clinical and noninvasive criteria. Patients with rest pain or ulcers were excluded. Data were analyzed with life-table and Cox hazard models. RESULTS: The mean follow-up was 47 months. The cohort exhibited a mortality rate of 12% per year, which was significantly (P <.05) more than the age-adjusted US male population. Among the deaths in which the cause was known, 66% were due to heart disease. We examined several baseline risk factors in a multivariate Cox model. Four were significant (P <.01) independent predictors of death: older age (relative risk [RR] = 1.3 per decade), lower ankle-brachial index (RR = 1.2 for 0.2 change), diabetes requiring medication (RR = 1.4), and stroke (RR = 1.4). The model can be used to estimate the mortality rate for specific patients. Surprisingly, a history of angina and myocardial infarction was not a significant predictor. Major and minor amputations had a 10-year cumulative rate less than 10%. Revascularization procedures occurred with a 10-year cumulative rate of 18%. CONCLUSIONS: We found a high mortality rate in this large cohort and four independent risk factors that have a large impact on survival. Risk stratification with our model may be useful in determining an overall therapeutic plan for claudicants. A history of angina and myocardial infarction was not a useful predictor of death, suggesting that many patients in our cohort presented with claudication before having coronary artery symptoms. Our data also indicate that claudicants have a low risk of major amputation at 10-year follow-up.

Etiologic factors in progression of carotid stenosis: a 10-year study in 905 patients.

PURPOSE: The purpose of this study was to determine the etiologic factors in the progression of carotid stenosis. METHODS: We performed prospective serial duplex scan surveillance of 1470 carotid arteries in 905 asymptomatic patients during a 10-year period, with an average follow-up interval of 29 months and an average of 3.0 scans per carotid artery. Vascular laboratory and hospital records were used to collect risk factor information. The data were analyzed with proportional hazards modeling. RESULTS: We examined several demographic, clinical, and laboratory risk factors that were chosen because of their potential relevance to atherosclerotic disease. These factors were analyzed with univariate proportional hazards modeling, in which time to progression of stenosis was the outcome variable. The six significant predictors (P <.05) were age, sex, systolic pressure, pulse pressure (systolic pressure - diastolic pressure), total cholesterol, and high-density lipoprotein (HDL). All, except HDL, were positive predictors of time to disease progression. With multivariate modeling, only pulse pressure and HDL remained as significant independent predictors of stenosis progression. The risk ratio for a 10-mm Hg rise in pulse pressure was 1.12, and the risk ratio for a 10-mg/dL decrease in HDL was 1.20. CONCLUSION: In this large cohort of patients who were followed prospectively for carotid stenosis, pulse pressure and HDL were found to be the key risk factors for carotid stenosis progression. The fact that pulse pressure superseded systolic pressure in multivariate modeling may shed light on the biology of carotid plaque progression. Further, our identification of these modifiable risk factors may help in the design of therapeutic trials for the prevention of progression of carotid atherosclerosis.

Progression of asymptomatic carotid stenosis: a natural history study in 1004 patients.

PURPOSE: The purpose of this study was to delineate the natural history of the progression of asymptomatic carotid stenosis. METHODS: In a 10-year period, 1701 carotid arteries in 1004 patients who were asymptomatic were studied with serial duplex scans (mean follow-up period, 28 months; mean number of scans, 2.9/patient). At each visit, stenoses of the internal carotid artery (ICA) and the external carotid artery (ECA) were categorized as none (0 to 14%), mild (15% to 49%), moderate (50% to 79%), severe (80% to 99%), preocclusive, or occluded. Progression was defined as an increase in ICA stenosis to >/=50% for carotid arteries with a baseline of <50% or as an increase to a higher category of stenosis if the baseline stenosis was >/=50%. The Cox proportional hazards model was used for data analysis. RESULTS: The risk of progression of ICA stenosis increased steadily with time (annualized risk of progression, 9.3%). With multivariate modeling, the four most important variables that affected the progression (P <.02) were baseline ipsilateral ICA stenosis >/=50% (relative risk [RR], 3.34), baseline ipsilateral ECA stenosis >/=50% (RR, 1.51), baseline contralateral ICA stenosis >/=50% (RR, 1.41), and systolic pressure more than 160 mm Hg (RR, 1. 37). Ipsilateral neurologic ischemic events (stroke/transient ischemic attack) occurred in association with 14.0% of the carotid arteries that were studied. The progression of ICA stenosis correlated with these events (P <.001), but baseline ICA stenosis was not a significant predictor. CONCLUSION: In contrast to recently published studies, we found that the risk of progression of carotid stenosis is substantial and increases steadily with time. Baseline ICA stenosis was the most important predictor of the progression, but baseline ECA stenosis also was identified as an important independent predictor. Contralateral ICA stenosis and systolic hypertension were additional significant predictors. We found further that the progression of ICA stenosis correlated with ischemic neurologic events but not baseline stenosis. The data provide justification for the use of serial duplex scans to follow carotid stenosis and suggest that different follow-up intervals may be appropriate for different patient subgroups.