Print this pageProgression of Atherosclerotic Renovascular Disease: A Prospective Population-Based Study
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Jeffrey D. Pearce, MD, Brandon L. Craven, BS, Kenneth L. Piercy, MD, Timothy E. Craven, MSPH, Juan Ayerdi, MD, Matthew S. Edwards, MD MSPH, Kimberley J. Hansen, M.D..
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Background: There are no prospective, population-based data that define the natural history of atherosclerotic renovascular disease (RVD). Available information regarding RVD is extrapolated from case series, angiographic and ultrasound examinations from retrospective reviews or from prospective studies of selected hypertensive patients. The quality of these studies and the interpretation of their data vary widely. Most commonly, authors consider anatomic progression of RVD a certainty and one that is associated with inevitable decline in kidney size and kidney function. This view is used to support intervention for RVD whenever it is discovered. In contrast to previous studies, this prospective, population-based study estimates the incidence of new RVD and the progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS).
Methods: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women over the age of 65 years. As part of an ancillary study, 876 CHS participants in the Forsyth County cohort underwent renal duplex sonography (RDS) between January of 1995 and February of 1997 to define the presence of RVD. Between 2002 and 2005, a second RDS examination was performed in 119 CHS ancillary study participants (mean study interval 8.0 + 0.8 years). Duplex sonography was performed with an Ultramark-9 HDI Ultrasound System using previously described techniques. RVD was defined as present with a main renal artery peak systolic velocity >1.8 m/s (renal artery stenosis), or if duplex failed to demonstrate a Doppler shifted signal from the renal artery (renal artery occlusion). Renal artery incident disease was defined as new stenosis or occlusion on follow-up RDS exam. Significant change of RVD was defined as a change in peak systolic velocity of greater that two times the standard deviation of the expected change over time or progression to renal artery occlusion.
Statistical Analysis: Variability of the expected longitudinal change in PSV was estimated using serial RDS data collected in the Vascular Laboratory on an independent, age-matched group of 435 patients with two or more RDS exams performed between 1997 and 2003. Random coefficients regression models were fitted to estimate the mean and variance of the annualized change in maximum renal artery peak systolic velocity. Significant change in RVD for the CHS cohort was defined as a change in peak systolic velocity of greater that two times the estimated standard deviation of the mean change over time or progression to renal artery occlusion. Kidney-based estimates of RVD progression and univariate examination of associations between risk factors and RVD progression were performed using generalized estimating equation (GEE) models that controlled for within-person correlation. Changes in renal length were examined using repeated measures linear regression models that controlled for within-person correlation. Changes in blood pressure and serum creatinine were examined using linear regression models.
Results: Of the 834 technically-satisfactory examination performed from 1995 through 1996, 119 (14.3%) participants from the original cohort returned for repeat RDS. The repeat study cohort had a mean age of 82.8 + 3.4 years and included 65% women and 35% men. Seventy seven percent of participants were Caucasians and 23% were African-American. Among 235 kidneys with technically satisfactory repeat RDS, RVD was present at the first RDS in 14 kidneys (6.0%; 95% CI: 3.2%-11.2%). On repeat study there were no cases of progression of initial renal artery stenosis to occlusion. Incident disease was identified in 9 kidneys (8 new stenoses; 1 new occlusion), yielding an overall estimated progression of 4.0% (95% CI: 1.9%-8.2%). A significant decrease in peak systolic velocity was observed in 7 kidneys identified as having RVD at initial RDS, including 5 which no longer met criteria for stenosis. Additionally, a significant increase in peak systolic velocity was observed in 25 kidneys; including the 8 incident cases of RVD. In participants with repeat RDS, mean blood pressure was 136+21/80+9 mmHg at initial RDS and 146+23/72+12 at follow-up exam. Mean serum creatinine was 1.0+0.3 mg/dL at initial exam versus 1.3+0.3 mg/dL at follow-up (mean increase 0.29 mg/dL; SEM 0.04; 95% CI: 0.21-0.37 mg/dL). For 228 kidneys with serial length measurements, average maximum pole-to-pole renal length decreased by 0.37+1.17 cm (SEM 0.9 cm; 95% CI: 0.20-0.55). By univariate analysis, longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression of RVD but not prevalent RVD.
Discussion: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. Anatomic progression of RVD was observed in only 4% of participants on mean follow-up of 8 years - an annualized disease progression rate of 0.5% per year. Moreover, no cohort participant with prevalent RVD at initial examination progressed to occlusion on follow-up.
These study results contrast sharply with retrospective angiographic clinical studies, prospective angiographic studies, and prospective duplex studies which describe progression of RVD. Considered collectively, the retrospective angiographic case series studies of Wollenweber, Meaney, Schreiber, Tollefson, Crowley, and Chabova suggest that atherosclerotic lesions of the renal arteries demonstrate anatomic progression over relatively short periods of follow-up. On mean follow-up of 50 months, roughly one-third of renal artery lesions demonstrated radiographic progression, while 10% progressed to occlusion. These rates of progression are supported by prospective angiographic studies by Dean, Plouin, Webster, van Jaarsveld, and Pillay. Collectively, these latter studies suggested a 20% rate of progression, with a 5% rate of progression to occlusion over a mean follow-up of 24 months.
Perhaps the most informative prospective study of RVD was provided by Capps, et al. These authors provided five-year follow-up for 170 patients with 295 kidneys. Disease progression was defined by 100 cm/s increase renal artery PSV from the baseline examination. The authors described progression in 31% of renal arteries in this study, while 3% of arteries progressed to occlusion. The authors created a model to predict the two-year cumulative incidence of disease progression. For renal arteries without ipsilateral or contralateral stenosis in a non-diabetic patient with systolic blood pressure <160 mmHg, the calculated risk of annual progression was 7%.
The reports reviewed above are frequently cited as rationale for intervention for RVD discovered incidentally. However, if one considers the potential benefit of prophylactic renal artery intervention in a normotensive individual without renal insufficiency, the unique benefit from prophylactic RA intervention is not justified by the risk. When considered in terms of the data provided by the current study, there appears to be no justification for prophylactic renal artery intervention, either as an open operative procedure performed in combination with aortic repair or as an independent catheter-based intervention.
Although this prospective study provides unique data, it suffers from a number of limitations. The index participants for CHS were selected through a two-step random process that included eligible members from the sampled individual's household. Although this strategy was adopted to enhance recruitment and retention, the final CHS cohort consisted of 70% of individuals initially sampled and 30% who shared the same household. Significant differences existed between randomly selected participants and those who chose not to participate in the CHS. Refusal rate was higher among women as compared with men. The enrolled participants were younger, more highly education, more likely to be married, and less likely to be smokers. This "healthy cohort effect " may have contributed to a decreased rate of progression of RVD. In addition, the long period of follow-up may demonstrate a survivorship effect. Prevalent RVD demonstrated significant and independent associations with both prevalent cardiovascular disease and subsequent adverse cardiovascular events. In addition, this study was constructed with assumptions not met by prospective observation. Originally, the study was constructed to include 300 participants, anticipating a 20% rate of progression during follow-up. When considered collectively, these limitations may have led to underestimation of RVD progression.
Despite these potential limitations, the study of the Forsyth CHS cohort allows for longitudinal follow-up of a large, diffuse group of community-dwelling black and white men and women. As our population ages and as advanced imaging techniques define incidental vascular disease, asymptomatic RA lesions may be best described by disease progression observed in the CHS cohort.
In summary, this prospective, population-based evaluation of prevalent RVD among free-living, elderly Americans suggests that the rate of progression is quite low. This low rate of progression does not justify prophylactic intervention for asymptomatic renovascular disease in the elderly.