Robert O. Bergelin

Prospective Study of Atherosclerotic Disease Progression in the Renal Artery

BACKGROUND The aim of this study was to determine the incidence of and the risk factors associated with progression of renal artery disease in individuals with atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS Subjects with >/=1 ARAS were monitored with serial renal artery duplex scans. A total of 295 kidneys in 170 patients were monitored for a mean of 33 months. Overall, the cumulative incidence of ARAS progression was 35% at 3 years and 51% at 5 years. The 3-year cumulative incidence of renal artery disease progression stratified by baseline disease classification was 18%, 28%, and 49% for renal arteries initially classified as normal, <60% stenosis, and >/=60% stenosis, respectively (P=0.03, log-rank test). There were only 9 renal artery occlusions during the study, all of which occurred in renal arteries having >/=60% stenosis at the examination before the detection of occlusion. A stepwise Cox proportional hazards model included 4 baseline factors that were significantly associated with the risk of renal artery disease progression during follow-up: systolic blood pressure >/=160 mm Hg (relative risk [RR]=2.1; 95% CI, 1.2 to 3.5), diabetes mellitus (RR=2.0; 95% CI, 1.2 to 3.3), and high-grade (>60% stenosis or occlusion) disease in either the ipsilateral (RR=1.9; 95% CI, 1.2 to 3.0) or contralateral (RR=1.7; 95% CI, 1.0 to 2.8) renal artery. CONCLUSIONS Although renal artery disease progression is a frequent occurrence, progression to total renal artery occlusion is not. The risk of renal artery disease progression is highest among individuals with preexisting high-grade stenosis in either renal artery, elevated systolic blood pressure, and diabetes mellitus.

Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: A one- to six-year follow-up

PURPOSE This study investigated changes in the deep venous system and the development of the postthrombotic syndrome (PTS) after an episode of acute deep vein thrombosis (DVT). METHODS Seventy-eight patients (41 male patients, 37 female patients) with acute DVT in 83 legs (31 right, 42 left, five bilateral) underwent annual follow-up examinations for 1 to 6 years (median, 3 years) for symptoms and signs of the PTS. A venous duplex scan was performed at each visit to detect obstruction and reflux in the veins, both of which may contribute to the development of the PTS. DVT was primary in 69 limbs and recurrent in 14 limbs. RESULTS When last examined 49 limbs were free of symptoms, and 34 had the PTS (23 edema only, 11 hyperpigmentation). Only two patients had ulcers during the follow-up period; both patients had the ulcers in areas of hyperpigmentation in limbs with recurrent DVT. The extent of disease was similar in limbs with the PTS (79% multisegment, 18% single segment) and those without the PTS (69% multisegment, 12% single segment). In limbs with the PTS the deep veins were normal in only one (3%), six (18%) showed reflux only, five (15%) obstruction only, and 22 had features of both obstruction and reflux (65%). In limbs without the PTS the deep veins showed no abnormality in nine (18%), reflux only in 17 (35%), obstruction only in six (12%), and reflux with obstruction in 17 (35%). In the 11 limbs with hyperpigmentation nine had obstruction and reflux noted, one had obstruction only, and one had reflux alone. CONCLUSIONS After an episode of acute DVT 12% of the limbs returned to normal by duplex criteria. Although only 13% developed skin complications, 41% had features of the PTS. Limbs with the PTS had more than three times the odds of having combined reflux and obstruction than did limbs without the PTS (odds ratio = 3.5, 0.95 confidence intervals = 1.4, 8.6). Continued study of these patients will determine the course of those limbs with venous abnormalities that have not yet developed symptoms and signs of the PTS.

Deep venous insufficiency: The relationship between lysis and subsequent reflux

PURPOSE Although venous valvular insufficiency is well recognized as the most important etiologic mechanism in the development of the postthrombotic syndrome, the factors contributing to valve incompetence after deep venous thrombosis remain obscure. METHODS To establish the relationship between recanalization and valve competence, 113 patients with acute deep venous thrombosis were studied with serial duplex ultrasonography. RESULTS Median lysis times for segments developing reflux (214 to 474 days) were 2.3 to 7.3 times longer than for corresponding segments not developing reflux (65 to 130 days) for all except the posterior tibial vein. In the posterior tibial vein, median lysis times for those with and without reflux were nearly identical (72 vs 80 days). The median time to onset of reflux was significantly less than the median lysis time in the mid and distal superficial femoral veins and was simultaneous with recanalization in all other segments. CONCLUSIONS Early recanalization is important in preserving valve integrity for all but the posterior tibial segment. However, the small number of patients with reflux despite early lysis (< 1 month) or without reflux despite relatively late lysis (> 9 to 12 months) suggests that other factors may also contribute to the development of valvular incompetence. These factors may be particularly important in the posterior tibial vein, in which lysis time has little relationship to the ultimate development of reflux.

Natural history of atherosclerotic renal artery stenosis: A prospective study with duplex ultrasonography

PURPOSE Although the prevalence of renal artery stenosis in patients with peripheral arterial disease is in the range of 30% to 40%, the role of renal revascularization in patients without severe hypertension or kidney failure is controversial. Duplex scanning is a noninvasive technique that is ideally suited for screening and follow-up of renal artery disease. The purpose of this study was to document the natural history of renal artery stenosis in patients who were not candidates for immediate renal revascularization. METHODS Eighty-four patients with at least one abnormal renal artery detected by duplex scanning were recruited from patients being screened for renal artery stenosis. Of the 168 renal artery/kidney sides, 29 were excluded (15 prior interventions, 6 nondiagnostic duplex scans, 8 presumed nonatherosclerotic lesions), leaving 80 patients with 139 sides for the follow-up protocol. Renal arteries were classified as normal, less than 60% stenosis, 60% or greater stenosis, or occluded by use of previously validated criteria. RESULTS The study group included 36 men and 44 women with a mean age of 66 years who were monitored for a mean interval of 12.7 months. The initial status of the 139 renal arteries was normal in 36, less than 60% stenosis in 35, 60% or greater stenosis in 63, and occluded in 5. Although none of the initially normal renal arteries showed disease progression, the cumulative incidence of progression from less than 60% to 60% or greater renal artery stenosis was 23% +/- 9% at 1 year and 42% +/- 14% at 2 years. All four renal arteries that progressed to occlusion had 60% or greater stenoses at the initial visit, and for those sides with a 60% or greater stenosis, the cumulative incidence of progression to occlusion was 5% +/- 3% at 1 year and 11% +/- 6% at 2 years. The mean decrease in kidney length associated with progression of renal artery stenosis to occlusion was 1.8 cm. CONCLUSIONS Progression of renal artery stenosis, as defined in this study, occurs at a rate of approximately 20% per year. Progression to occlusion is associated with a marked decrease in kidney length. Whether this natural history can be improved by earlier intervention for renal artery stenosis remains to be determined.

Noninvasive diagnosis of renal artery stenosis by ultrasonic duplex scanning.

We retrospectively studied the results of duplex scanning for evaluation of renal artery disease in 158 patients. Satisfactory examinations were achieved in 144 patients (90%). Arteriograms were available for 43 renal arteries. We used the ratio of the peak velocities in the renal artery and the aorta (RAR) to separate nonstenotic arteries (less than 60% diameter reduction) from stenotic arteries (greater than 60% diameter reduction). With an RAR of greater than 3.5 to indicate stenotic lesions, duplex scanning had a sensitivity of 91% (20 of 22 diseased arteries correctly identified) and specificity of 95% (20 of 21 normal or insignificantly diseased arteries correctly identified). One of four occluded arteries was incorrectly interpreted as patent because of misidentification of a collateral vessel. Prospective studies will be necessary to validate this test and establish other criteria for a more detailed classification of renal artery stenosis. The ratio of the end-diastolic to peak systolic velocities in the renal artery (EDR) tended to decrease with increasing serum creatinine levels, presumably because renal vascular resistance increases with end-stage parenchymal disease. EDR may prove useful in the detection of advanced parenchymal disease before renal artery revascularization is attempted.

Valvular reflux after deep vein thrombosis: Incidence and time of occurrence

From December 1986 to December 1990, 268 patients with acute deep vein thrombosis were studied in our laboratory. From this group 107 patients (123 legs with deep vein thrombosis) were placed in our long-term follow-up program. The documentation of valvular reflux and its site was demonstrated by duplex scanning. The duplex studies were done at intervals of 1 and 7 days, 1 month, every 3 months for the first year, and then yearly thereafter. The mean follow-up time for these patients was 341 days. In addition, reflux was evaluated in 502 patients with negative duplex study results and no previous history of deep vein thrombosis or chronic venous insufficiency. In the patients with acute deep vein thrombosis, valvular incompetence was noted in 17 limbs (14%) at the time of the initial study. Reflux was absent in 106 limbs (86%). In this last group reflux developed in 17% of the limbs by day 7. By the end of the first month, 37% demonstrated reflux. By the end of the first year, more than two thirds of the involved limbs had developed valvular incompetence. The distribution of reflux at the end of the first year of follow-up was the following: (1) popliteal vein, 58%; (2) superficial femoral vein, 37%; (3) greater saphenous vein, 25%; and (4) posterior tibial vein, 18%. Reflux seems to be more frequent in the segments previously affected with deep vein thrombosis. Among cases where segments were initially affected with thrombi, after 1 year the incidence of reflux was 53%, 44%, 59%, and 33% for the common femoral vein, superficial femoral, popliteal vein, and posterior tibial vein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study of disease progression in patients with atherosclerotic renal artery stenosis

The natural history of renal artery stenosis (RAS) has been difficult to document because serial arteriography is rarely justified. Duplex scanning is a noninvasive technique that is ideally suited for both screening and follow-up of RAS. In this approach, renal arteries are classified as normal, < 60% stenosis, > or = 60% stenosis, or occluded, and disease progression is defined as a change in the duplex classification. The purpose of this study was to determine the rate of disease progression in atherosclerotic RAS by serial duplex scanning. At least one abnormal renal artery was identified in each of 76 patients being screened for RAS. Of the 152 renal arteries, 20 were excluded (14 prior interventions, 5 occlusions, 1 technically inadequate duplex scan), leaving 132 for the natural history follow-up protocol. The patient group included 36 men and 40 women, with a mean age of 67 years, who were followed for a mean of 32 months (maximum 55 months). The initial status of the 132 renal arteries was normal in 36, < 60% stenosis in 35, and > or = 60% stenosis in 61. The cumulative incidence of progression from normal to > or = 60% RAS was 0% at 1 year, 0% at 2 years, and 8% at 3 years. The cumulative incidence of progression from < 60% to > or = 60% RAS was 30% at 1 year, 44% at 2 years, and 48% at 3 years. All 4 renal arteries that progressed to occlusion had > or = 60% stenoses at the initial visit, and for those arteries with a > or = 60% stenosis, the cumulative incidence of progression to occlusion was 4% at 1 year, 4% at 2 years, and 7% at 3 years. Progression of RAS occurred at an average rate of 7% per year for all categories of baseline disease combined. Progression of atherosclerotic RAS is relatively common, particularly from < 60% to > or = 60% stenosis.

Long-term follow-up and clinical outcome of carotid restenosis******

The efficacy of carotid endarterectomy is dependent on the inherent ability of the operation to prevent stroke as well as the incidence of restenosis and associated symptoms. To examine the long-term effects of restenosis, 301 patients having carotid endarterectomy were followed by serial duplex scanning for an average of 4 years. Carotid restenosis, defined as 50% or greater diameter reduction by duplex scanning, occurred after 78 of the endarterectomies; regression of recurrent stenosis occurred in 20 arteries. By life-table analysis the cumulative incidence of restenosis at 7 years was 31%, and the cumulative incidence of regression was 10%. Thus the prevalence of recurrent stenosis at 7 years was 21%. Restenosis developed in women more frequently than men (p = 0.01). Transient ischemic attack occurred in 12% of patients with restenosis, and stroke occurred in 3%; however, the cumulative incidence of stroke or transient ischemic attack was not statistically different in those patients with and without restenosis. Similarly, cumulative survival at 7 years was no different. Carotid restenosis usually occurs early in the postoperative period and tends to regress or remain stable during long-term follow-up. A conservative approach to treatment appears justified, since transient ischemic attacks and stroke were rarely associated with restenosis.

Determinants of chronic venous disease after acute deep venous thrombosis

PURPOSE The purpose of this investigation was to evaluate the relationship between the presenting features of an acute deep venous thrombosis (DVT), the subsequent natural history of the thrombus, and the ultimate outcome as defined according to the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery reporting standards in venous disease. METHODS Patients with an acute DVT were followed with serial clinical and ultrasound examinations. Thrombus extent within 7 venous segments was scored retrospectively according to the reporting standards (scores ranged from 0 to 3), and segmental reflux was scored as present (1) or not present (0). The initial and final thrombus scores, the rates of recanalization and rethrombosis, and the total reflux scores were then calculated from these grading scales and related to ultimate chronic venous disease (CVD) classification. RESULTS Sixty-eight patients with an acute DVT in 73 limbs were followed for 18 to 110 months (mean, 55 +/- 26 months). At the completion of the follow-up period, 20 extremities (27%) were asymptomatic (class 0), 13 (18%) had pain or prominent superficial veins (class 1), 25 (34%) had manifested edema (class 3), 13 (18%) had developed hyperpigmentation (class 4), and 2 (3%) had developed ulceration (class 5). In a univariate analysis, CVD classification was correlated with the reflux score (P =.003) but not with the initial or final thrombus score or with the rate of recanalization or rethrombosis. In a multivariate model of features documented at presentation, only the tibial thrombosis score was a significant predictor of CVD classification (R2 =.06). Outcome was better predicted (R2 =.29) with a model that included variables defined during follow-up the final reflux score, the final popliteal score, and the rate of recanalization. CONCLUSION The ability to predict the severity of CVD after an acute DVT is currently limited, although the natural history appears more important than the presenting features of the event. The extent of reflux, the presence of persistent popliteal obstruction, and the rate of recanalization are related to ultimate CVD classification, but other determinants remain to be identified.

Renal atrophy and arterial stenosis. A prospective study with duplex ultrasound.

Renal artery disease is an important cause of both renal failure and hypertension. Duplex ultrasound is a reliable noninvasive method for classifying the severity of renal artery lesions and can be repeated to follow the course of the disease over time. The purpose of this study was to determine the changes in kidney size associated with various degrees of renal artery disease. Serial kidney lengths were measured as part of a prospective duplex ultrasound study of patients with renal artery narrowing. Fifty-four patients (22 men, 32 women; mean age, 65.8 years) with 101 renal artery and kidney sides eligible for follow-up were evaluated at 6-month intervals for an average of 14.4 months (range, 4 to 24 months). No kidneys with renal arteries classified as normal or less than 60% diameter stenosis by duplex criteria were found to have a decrease in length of greater than 1 cm during follow-up. In kidneys with a high-grade renal artery stenosis (> or = 60% diameter reduction), 26% (13 of 49 sides) were found to have a decrease in length of greater than 1 cm. The average decrease in length was 1.9 cm (range, 1.2 to 3.4 cm). By life table analysis, the estimated risk of a decrease in length of greater than 1 cm for kidneys with 60% stenosis or greater was 19% at 1 year. Loss of renal mass, as documented by ultrasound measurement of kidney length, is an important consequence of high-grade renal artery stenosis.