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Figure.
Distribution of ankle-brachial index (ABI) by approximate quartile of estimated creatinine clearance in milliliters per minute: first quartile, ≤64; second quartile, 65 to 75; third quartile, 76 to 89; fourth quartile, ≥90.

Distribution of ankle-brachial index (ABI) by approximate quartile of estimated creatinine clearance in milliliters per minute: first quartile, ≤64; second quartile, 65 to 75; third quartile, 76 to 89; fourth quartile, ≥90.

Table 1. 
Baseline Characteristics by Ankle-Brachial Index (ABI)*
Baseline Characteristics by Ankle-Brachial Index (ABI)*
Table 2. 
Association of Baseline Ankle-Brachial Index (ABI) With Worsening Renal Function During Follow-up
Association of Baseline Ankle-Brachial Index (ABI) With Worsening Renal Function During Follow-up
1.
Fried  LFShlipak  MGCrump  C  et al.  Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003;411364- 1372
PubMedArticle
2.
Garg  AXClark  WFHaynes  RBHouse  AA Moderate renal insufficiency and the risk of cardiovascular mortality: results from the NHANES I. Kidney Int 2002;611486- 1494
PubMedArticle
3.
Manjunath  GTighiouart  HCoresh  J  et al.  Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003;631121- 1129
PubMedArticle
4.
Muntner  PHe  JHamm  LLoria  CWhelton  PK Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002;13745- 753
PubMed
5.
Shlipak  MGSimon  JAGrady  DLin  FWenger  NKFurberg  CD Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease. J Am Coll Cardiol 2001;38705- 711
PubMedArticle
6.
O'Hare  AMVittinghoff  EHsia  JShlipak  MG Renal insufficiency and the risk of lower extremity peripheral arterial disease: results from the Heart and Estrogen/Progestin Replacement Study (HERS). J Am Soc Nephrol 2004;151046- 1051
PubMedArticle
7.
Weiner  DETighiouart  HAmin  MG  et al.  Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;151307- 1315
PubMedArticle
8.
O'Hare  AMGlidden  DVFox  CSHsu  CY High prevalence of peripheral arterial disease in persons with renal insufficiency: results from the National Health and Nutrition Examination Survey 1999-2000. Circulation 2004;109320- 323
PubMedArticle
9.
Mann  JFGerstein  HCPogue  JBosch  JYusuf  S Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001;134629- 636
PubMedArticle
10.
Go  ASChertow  GMFan  DMcCulloch  CEHsu  CY Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;3511296- 1305
PubMedArticle
11.
Brancati  FLWhelton  PKRandall  BLNeaton  JDStamler  JKlag  MJ Risk of end-stage renal disease in diabetes mellitus: a prospective cohort study of men screened for MRFIT (Multiple Risk Factor Intervention Trial). JAMA 1997;2782069- 2074
PubMedArticle
12.
Klag  MJWhelton  PKRandall  BL  et al.  Blood pressure and end-stage renal disease in men. N Engl J Med 1996;33413- 18
PubMedArticle
13.
Klag  MJWhelton  PKRandall  BLNeaton  JDBrancati  FLStamler  J End-stage renal disease in African-American and white men: 16-year MRFIT findings. JAMA 1997;2771293- 1298
PubMedArticle
14.
Muntner  PCoresh  JSmith  JCEckfeldt  JKlag  MJ Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 2000;58293- 301
PubMedArticle
15.
Young  JHKlag  MJMuntner  PWhyte  JLPahor  MCoresh  J Blood pressure and decline in kidney function: findings from the Systolic Hypertension in the Elderly Program (SHEP). J Am Soc Nephrol 2002;132776- 2782
PubMedArticle
16.
Haroun  MKJaar  BGHoffman  SCComstock  GWKlag  MJCoresh  J Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol 2003;142934- 2941
PubMedArticle
17.
Perneger  TVBrancati  FLWhelton  PKKlag  MJ End-stage renal disease attributable to diabetes mellitus. Ann Intern Med 1994;121912- 918
PubMedArticle
18.
Perneger  TVWhelton  PKKlag  MJ Race and end-stage renal disease: socioeconomic status and access to health care as mediating factors. Arch Intern Med 1995;1551201- 1208
PubMedArticle
19.
Perneger  TVWhelton  PKPuddey  IBKlag  MJ Risk of end-stage renal disease associated with alcohol consumption. Am J Epidemiol 1999;1501275- 1281
PubMedArticle
20.
Goetz  FCJacobs  DR  JrChavers  BRoel  JYelle  MSprafka  JM Risk factors for kidney damage in the adult population of Wadena, Minnesota: a prospective study. Am J Epidemiol 1997;14591- 102
PubMedArticle
21.
Fox  CSLarson  MGLeip  EPCulleton  BWilson  PWLevy  D Predictors of new-onset kidney disease in a community-based population. JAMA 2004;291844- 850
PubMedArticle
22.
Bleyer  AJShemanski  LRBurke  GLHansen  KJAppel  RG Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population. Kidney Int 2000;572072- 2079
PubMedArticle
23.
Zheng  ZJSharrett  ARChambless  LE  et al.  Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 1997;131115- 125
PubMedArticle
24.
Leng  GCFowkes  FGLee  AJDunbar  JHousley  ERuckley  CV Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. BMJ 1996;3131440- 1444
PubMedArticle
25.
Newman  ABShemanski  LManolio  TA  et al.  Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999;19538- 545
PubMedArticle
26.
Abbott  RDRodriguez  BLPetrovitch  H  et al.  Ankle-brachial blood pressure in elderly men and the risk of stroke: the Honolulu Heart Program. J Clin Epidemiol 2001;54973- 978
PubMedArticle
27.
Murabito  JMEvans  JCLarson  MGNieto  KLevy  DWilson  PW The ankle-brachial index in the elderly and risk of stroke, coronary disease, and death: the Framingham Study. Arch Intern Med 2003;1631939- 1942
PubMedArticle
28.
Tsai  AWFolsom  ARRosamond  WDJones  DW Ankle-brachial index and 7-year ischemic stroke incidence: the ARIC study. Stroke 2001;321721- 1724
PubMedArticle
29.
The ARIC Investigators, The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol 1989;129687- 702
PubMed
30.
Sacks  DBakal  CWBeatty  PT  et al.  Position statement on the use of the ankle-brachial index in the evaluation of patients with peripheral vascular disease: a consensus statement developed by the standards division of the society of cardiovascular & interventional radiology. J Vasc Interv Radiol 2002;13353
PubMedArticle
31.
Cockcroft  DWGault  MH Prediction of creatinine clearance from serum creatinine. Nephron 1976;1631- 41
PubMedArticle
32.
Newman  ABSiscovick  DSManolio  TA  et al.  Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation 1993;88837- 845
PubMedArticle
33.
Otah  KEMadan  AOtah  EBadero  OClark  LTSalifu  MO Usefulness of an abnormal ankle-brachial index to predict presence of coronary artery disease in African-Americans. Am J Cardiol 2004;93481- 483
PubMedArticle
34.
Aronow  WSAhn  C Prevalence of coexistence of coronary artery disease, peripheral arterial disease, and atherothrombotic brain infarction in men and women ≥62 years of age. Am J Cardiol 1994;7464- 65
PubMedArticle
35.
Shlipak  MGFried  LFCrump  C  et al.  Cardiovascular disease risk status in elderly persons with renal insufficiency. Kidney Int 2002;62997- 1004
PubMedArticle
36.
Zoccali  CMallamaci  FTripepi  G Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int Suppl 2003;JunS105- S110
PubMedArticle
37.
Levin  ADjurdjev  OBarrett  B  et al.  Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter. Am J Kidney Dis 2001;381398- 1407
PubMedArticle
38.
McClellan  WMLangston  RDPresley  R Medicare patients with cardiovascular disease have a high prevalence of chronic kidney disease and a high rate of progression to end-stage renal disease. J Am Soc Nephrol 2004;151912- 1919
PubMedArticle
39.
Kasiske  BL Relationship between vascular disease and age-associated changes in the human kidney. Kidney Int 1987;311153- 1159
PubMedArticle
40.
Tracy  REStrong  JPNewman  WP  IIIMalcom  GTOalmann  MCGuzman  MA Renovasculopathies of nephrosclerosis in relation to atherosclerosis at ages 25 to 54 years. Kidney Int 1996;49564- 570
PubMedArticle
41.
Sarnak  MJLevey  ASSchoolwerth  AC  et al.  Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;1082154- 2169
PubMedArticle
Original Investigation
July 11, 2005

Low Ankle-Brachial Index Associated With Rise in Creatinine Level Over TimeResults From the Atherosclerosis Risk in Communities Study

Author Affiliations

Author Affiliations: Departments of Medicine (Drs O’Hare and Rodriguez) and Epidemiology and Biostatistics (Dr Bacchetti), University of California, and Departments of Medicine, Veterans Affairs Medical Center (Dr O’Hare) and San Francisco General Hospital (Dr Rodriguez), San Francisco, Calif.

Arch Intern Med. 2005;165(13):1481-1485. doi:10.1001/archinte.165.13.1481
Abstract

Background  A low ankle-brachial index (ABI) predicts risk of cardiovascular death, myocardial infarction, peripheral arterial disease events, and stroke. However, it is unknown whether a low ABI also predicts a decline in renal function.

Methods  We examined the association between ABI and change in serum creatinine level over time among 13 655 participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent serum creatinine and ABI measurement at baseline and also underwent serum creatinine measurement 3 years later at the second study visit. The study outcome was a 50% rise in serum creatinine level from baseline to the second study visit.

Results  Overall, 0.48% of participants with an ABI of 1 or higher, 0.9% of participants with an ABI between 0.9 and 0.99, and 2.16% of participants with an ABI lower than 0.9 experienced a 50% or greater increase in serum creatinine level. In multivariate analysis, participants with an ABI lower than 0.9 were still more than twice as likely as those in the referent category (ABI ≥1) to experience an increase in serum creatinine level (odds ratio 2.5; 95% confidence interval, 1.1-5.7) (P = .04), and a linear trend in the incidence of worsening renal function was noted across ABI categories (P = .02). Analyses excluding participants with renal insufficiency, diabetes, and hypertension at baseline all produced similar results.

Conclusion  In addition to known associations of the ABI with stroke, myocardial infarction, peripheral arterial disease events, and cardiovascular death, a low ABI also predicts an increase in serum creatinine level over time.

The prevalence and incidence of cardiovascular disease are both high among those with renal insufficiency,110 and chronic kidney disease and cardiovascular disease share many of the same risk factors.1122 However, the contribution of preexisting cardiovascular disease to progression of renal disease has not been examined in detail.

We hypothesized that a low ankle-brachial index (ABI)—a marker for both lower extremity and more generalized atherosclerotic disease23 and a known predictor of cardiovascular death, myocardial infarction, peripheral arterial disease events, and stroke2428—would also be associated with a decline in renal function over time. We tested this hypothesis using publicly available data from the first and second study visits of the Atherosclerosis Risk in Communities (ARIC) study.29

METHODS

The ARIC study29 was a prospective cohort study of cardiovascular disease among a community sample of middle-aged residents of Jackson, Miss; Forsyth County, North Carolina; Washington County, Maryland; and several suburbs of Minneapolis, Minn. The study consisted of 15 792 men and women aged 45 to 64 years at baseline. Participant recruitment and baseline data collection were completed between 1987 and 1989, and participants subsequently returned for 3 visits, each spaced 3 years apart. The present analysis uses publicly available data from the first and second study visits and was approved by the institutional review board at the University of California, San Francisco.

OUTCOME MEASURE AND PREDICTOR VARIABLES

The primary predictor variable for the present analysis was ABI at the first study visit. The ABI is the ratio of systolic blood pressure at the ankle to systolic blood pressure at the brachial artery. Ankle and brachial systolic blood pressure measurements were ascertained using the Dinamap 1846 SX (Critixon, Tampa, Fla). Ankle blood pressure was measured at the posterior tibial artery in one leg. Two measurements were taken 5 to 8 minutes apart while the participant was in the prone position. Brachial artery systolic blood pressure measurements were taken 5 minutes apart with the participant in the supine position. The ABI was computed by dividing the average of the 2 ankle systolic blood pressure measurements by the average of the first 2 brachial readings. For the purposes of this analysis, we divided ABI measurements into 3 categories at the clinically established cutoffs of 0.9 and 1.0.30

The outcome measure for the present analysis was the occurrence of at least a 50% rise in serum creatinine level between baseline and the first follow-up visit approximately 3 years later. Too few participants experienced a doubling of serum creatinine level (a more conventional measure of renal functional decline) during follow-up for this to be used as an outcome. Regardless of initial creatinine level, a 50% increase in serum creatinine level translates into an approximately 25% decrease in creatinine clearance. This outcome is more easily interpreted than either a fixed increase in serum creatinine level or a fixed decrease in estimated creatinine clearance or glomerular filtration rate. The correlation between fixed increases in serum creatinine level and creatinine clearance is highly variable, depending on the initial creatinine level, and since values can be very inflated in patients with normal renal function, fixed decrements over time in calculated creatinine clearance or glomerular filtration rate may be misleading.

Our analysis was adjusted for the following covariates ascertained at visit 1: demographic characteristics (age, race [black vs nonblack], and sex), baseline Cockcroft-Gault–estimated creatinine clearance,31 comorbid conditions including diabetes (previously diagnosed or fasting glucose level ≥126 mg/dL [≥6.99 mmol/L]), smoking behavior (participants were classified as current smokers, former smokers, or nonsmokers), body mass index, fasting lipid levels (low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglyceride levels), alcohol use, hematocrit values, mean systolic and diastolic blood pressures, and educational level (college vs no college). To account for the slight differences in follow-up time from visit 1 to visit 2 between study participants, exact follow-up time was also included in the multivariable analysis.

STATISTICAL ANALYSIS

All statistical analyses were performed using STATA statistical software (College Station, Tex). We compared baseline characteristics (ascertained at visit 1) across ABI categories. Normally distributed continuous variables were compared using the t test; nonnormally distributed variables (eg, triglyceride levels) were compared using the Mann-Whitney U test; and categorical variables were compared using the χ2 test. For all analyses, participants with an ABI of 1 or higher served as the referent category with which the other groups were compared. The association of ABI with worsening renal function was measured using bivariate and multivariate logistic regression analysis. We checked the linearity assumption for numeric predictors by including log-transformed and quadratic terms and breaking the predictor into quartiles. To satisfy the linearity assumption, triglyceride levels, systolic blood pressure, and hematocrit values were log transformed, and estimated creatinine clearance was modeled by quartile. We tested for the presence of a linear trend in the odds of a 50% increase in creatinine level across ABI categories by incorporating the categorical ABI variable into the logistic regression analysis as a numeric variable (scored 0-1-2).

SENSITIVITY ANALYSES

We confirmed the presence of an association between low ABI and the study outcome after excluding, one group at a time, participants with an estimated creatinine clearance lower than 60 mL/min, diabetes, and hypertension (defined as either a mean systolic blood pressure of ≥140 mm Hg, a mean diastolic blood pressure of ≥90 mm Hg, or use of antihypertensive medication). To evaluate the impact of possible measurement error for serum creatinine on our results, we performed a companion analysis in which we defined the outcome as a 50% rise in serum creatinine level with an absolute rise in creatinine level of at least 0.4 mg/dL (35.4 μmol/L).14 This analysis was designed to ignore small increases in serum creatinine level occurring among cohort patients with low baseline serum creatinine levels that might be due solely to measurement error.

RESULTS

A total of 13 655 ARIC participants29 underwent creatinine and ABI measurement at visit 1 and creatinine measurement again at visit 2. Among these, 12 179 participants (89%) had an ABI of 1 or higher; 1105 (8%) had an ABI between 0.9 and 0.99; and 371 (3%) had an ABI lower than 0.9. Compared with the referent category of participants with an ABI of 1 or higher, the mean serum creatinine level was similar, but mean creatinine clearance was slightly lower among those with an ABI lower than 0.9 (Table 1). The relationship between baseline creatinine clearance and ABI was nonlinear: a disproportionate number of participants in the lowest and highest quartiles of creatinine clearance had low ABIs (Figure).

Compared with participants with an ABI of 1 or higher, those with an ABI lower than 0.9 were older; included a higher percentage of women, blacks, and persons with diabetes; had lower HDL and higher LDL and triglyceride levels; had a slightly lower mean BMI; included a smaller percentage of alcohol users and college graduates and a higher percentage of current smokers; had a higher mean systolic blood pressure and lower mean diastolic blood pressure; and included a higher percentage of participants using antihypertensive medications (Table 1). Overall, serum creatinine level increased in 0.56% of participants (n = 76): 0.48% of those with an ABI of 1 or higher (n = 58), 0.9% of those with an ABI between 0.9 and 0.99 (n = 10), and 2.16% of those with an ABI lower than 0.9 (n = 8). Baseline serum creatinine levels were not significantly different among patients who did and did not experience a 50% rise in serum creatinine level (median creatinine level, 1 mg/dL [88.4 μmol/L] with 25th-75th percentile range, 0.8-1.4 mg/dL [123.8 μmol/L] vs 1.1 mg/dL [97.2 μmol/L] with 25th-75th percentile range, 1.1-1.2 mg/dL [97.2-106.1 μmol/L]) (P = .36). In both bivariate and multivariate analyses, an ABI lower than 0.9 was associated with an increase in serum creatinine level during follow-up, and there was a linear trend across ABI categories (Table 2).

Results were similar after exclusion, one group at a time, of those with an estimated clearance lower than 60 mL/min (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.04-6.61) (P = .04), diabetes (OR, 3.5; 95% CI, 1.2-10.5) (P = .03), and hypertension or use of antihypertensive medications (OR, 5.5; 95% CI, 1.4-21.4) (P = .02) at baseline. When we defined the outcome as a 50% rise in serum creatinine level with at least a 0.4 mg/dL (35.4 μmol/L) absolute increase in serum creatinine level (n = 66), the results did not differ substantially from the primary analysis: patients with an ABI lower than 0.9 still had a more than 2-fold adjusted risk of this outcome compared with the referent category (OR, 2.3; 95% CI, 0.92-5.8) (P = .07), and there was a trend across ABI categories (P = .03).

COMMENT

The present study demonstrates that, in addition to its previously demonstrated associations with stroke, myocardial infarction, peripheral arterial disease events, and cardiovascular death,2428 a low ABI is also associated with an increase in serum creatinine level over time. Participants with an ABI lower than 0.9 had more than 4-fold odds of experiencing a 50% rise in creatinine level compared with those with an ABI of 1 or higher, and the association persisted after adjustment for known predictors of renal functional decline. Because a low ABI is a specific measure of overall atherosclerotic burden,23,3234 the existence of an association between baseline ABI and subsequent increase in serum creatinine supports the notion that preexisting atherosclerosis may be a risk factor for deterioration of renal function over time. Furthermore, the strong association of ABI with a rise in serum creatinine level in both unadjusted and adjusted analysis highlights the possible importance of ABI measurement as a means to identify patients at greatest risk for deterioration of renal function over time.

Many studies have reported both cross-sectional and longitudinal associations between baseline renal insufficiency and coronary, cerebral, and peripheral arterial disease.19,35 There is also extensive research exploring possible causal mechanisms for an association between renal insufficiency and cardiovascular disease. For example, hyperhomocysteinemia, oxidant stress, elevated levels of lipoprotein(a) and inflammatory markers, and disordered calcium phosphorous metabolism all represent potential pathways for accelerated atherosclerosis in patients with renal insufficiency.36

There has been much less interest in the reverse association: the contribution of atherosclerosis to progression of renal disease. Using baseline data on screenees for the Multiple Risk Factor Intervention Trial (MRFIT), Klag et al12 reported that a history of myocardial infarction was independently associated with an increased risk of end-stage renal disease, though this was not the primary focus of the analysis. Levin et al37 found that among patients with existing chronic kidney disease, the presence of cardiovascular disease predicted time to onset of end-stage renal disease. Bleyer et al22 described a positive independent association between maximum carotid intimal thickness and subsequent rise in serum creatinine level of at least 0.3 mg/dL (26.5 μmol/L) over a 3- to 4-year period among subjects without diabetes enrolled in the Cardiovascular Health Study. Finally, a recent study by McClellan et al38 demonstrated a high rate of progression to end-stage renal disease among Medicare beneficiaries hospitalized for congestive heart failure and for acute myocardial infarction.

Data from several autopsy series also lend some support to the notion that systemic atherosclerosis may predispose to renal insufficiency. Among persons free of clinical renal disease and renal artery stenosis, the prevalence of glomerulosclerosis was noted to be higher among those with moderate to severe intrarenal atherosclerosis than among those with mild atherosclerosis.39 In a second autopsy series of persons aged 25 to 54 years, renal arteriolar hyalinization was correlated with raised lesions in the coronary arteries and aorta.40

While the association reported herein between low ABI and rising creatinine level may reflect a shared risk factor profile between renal disease and atherosclerosis,41 we were not able to explain away this association by controlling for many of the known risk factors for renal disease. Because the kidney is a highly vascular organ whose function is dependent on an intact circulatory system, it makes intuitive sense that systemic atherosclerotic disease could be causally associated with declining renal function. Based on our findings and the aforementioned studies, we would argue that systemic atherosclerosis may be a risk factor for renal insufficiency as it is for myocardial infarction, stroke, and peripheral arterial disease events.

A limitation of the present study is that our definition of worsening renal function may be inaccurate owing to changes in patient age and muscle mass over time. While measured changes in creatinine clearance would probably be the best way to identify those with declining renal function, these data were not collected in ARIC.29 Alternate measures of declining renal function such as fixed changes in serum creatinine level, calculated clearance, or glomerular filtration rate are less clearly interpretable than a percentage change in serum creatinine level. Finally, we were unable to use incidence of new onset of renal insufficiency (defined as incidence of a calculated creatinine clearance of <60 mL/min) among patients experiencing a 50% increase in serum creatinine level because of the rarity of this outcome (n = 41) over the short follow-up period. Thus, in the absence of measured creatinine clearance, we believe that our definition of worsening renal function as a percentage rise in serum creatinine level represents the most appropriate choice.

A second limitation is that our analysis did not include detailed information on the severity of important confounding comorbid conditions such as diabetes and hypertension. However, it is somewhat reassuring that even after excluding participants with diabetes or hypertension at baseline, a low ABI was still strongly associated with the study outcome.

Finally, declining renal function was a relatively uncommon outcome in this sample of middle-aged community-dwelling adults. Therefore, the clinical importance of ABI measurement as a predictor of declining renal function would be best assessed in populations where worsening renal function is a more common outcome.

In conclusion, a low ABI is predictive not just of recognized atherosclerotic events such as stroke, myocardial infarction, peripheral arterial disease events, and cardiovascular death, but also of rising creatinine level over time. These findings support the notion of systemic atherosclerosis as a risk factor for decline in renal function and also highlight the possible importance of ABI measurement as a means to identify patients at greatest risk for deterioration of renal function over time.

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Article Information

Correspondence: Ann M. O'Hare, MA, MD, Veterans Affairs Medical Center, Box 111J (Nephrology), 4150 Clement St, San Francisco, CA 94121 (Ann.O'Hare@med.va.gov).

Accepted for Publication: November 3, 2004.

Financial Disclosure: None.

Funding/Support: Dr O'Hare is supported by a Career Development Award from the Department of Veterans Affairs Health Services Research and Development Service, Washington, DC.

References
1.
Fried  LFShlipak  MGCrump  C  et al.  Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003;411364- 1372
PubMedArticle
2.
Garg  AXClark  WFHaynes  RBHouse  AA Moderate renal insufficiency and the risk of cardiovascular mortality: results from the NHANES I. Kidney Int 2002;611486- 1494
PubMedArticle
3.
Manjunath  GTighiouart  HCoresh  J  et al.  Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003;631121- 1129
PubMedArticle
4.
Muntner  PHe  JHamm  LLoria  CWhelton  PK Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002;13745- 753
PubMed
5.
Shlipak  MGSimon  JAGrady  DLin  FWenger  NKFurberg  CD Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease. J Am Coll Cardiol 2001;38705- 711
PubMedArticle
6.
O'Hare  AMVittinghoff  EHsia  JShlipak  MG Renal insufficiency and the risk of lower extremity peripheral arterial disease: results from the Heart and Estrogen/Progestin Replacement Study (HERS). J Am Soc Nephrol 2004;151046- 1051
PubMedArticle
7.
Weiner  DETighiouart  HAmin  MG  et al.  Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;151307- 1315
PubMedArticle
8.
O'Hare  AMGlidden  DVFox  CSHsu  CY High prevalence of peripheral arterial disease in persons with renal insufficiency: results from the National Health and Nutrition Examination Survey 1999-2000. Circulation 2004;109320- 323
PubMedArticle
9.
Mann  JFGerstein  HCPogue  JBosch  JYusuf  S Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001;134629- 636
PubMedArticle
10.
Go  ASChertow  GMFan  DMcCulloch  CEHsu  CY Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;3511296- 1305
PubMedArticle
11.
Brancati  FLWhelton  PKRandall  BLNeaton  JDStamler  JKlag  MJ Risk of end-stage renal disease in diabetes mellitus: a prospective cohort study of men screened for MRFIT (Multiple Risk Factor Intervention Trial). JAMA 1997;2782069- 2074
PubMedArticle
12.
Klag  MJWhelton  PKRandall  BL  et al.  Blood pressure and end-stage renal disease in men. N Engl J Med 1996;33413- 18
PubMedArticle
13.
Klag  MJWhelton  PKRandall  BLNeaton  JDBrancati  FLStamler  J End-stage renal disease in African-American and white men: 16-year MRFIT findings. JAMA 1997;2771293- 1298
PubMedArticle
14.
Muntner  PCoresh  JSmith  JCEckfeldt  JKlag  MJ Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 2000;58293- 301
PubMedArticle
15.
Young  JHKlag  MJMuntner  PWhyte  JLPahor  MCoresh  J Blood pressure and decline in kidney function: findings from the Systolic Hypertension in the Elderly Program (SHEP). J Am Soc Nephrol 2002;132776- 2782
PubMedArticle
16.
Haroun  MKJaar  BGHoffman  SCComstock  GWKlag  MJCoresh  J Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol 2003;142934- 2941
PubMedArticle
17.
Perneger  TVBrancati  FLWhelton  PKKlag  MJ End-stage renal disease attributable to diabetes mellitus. Ann Intern Med 1994;121912- 918
PubMedArticle
18.
Perneger  TVWhelton  PKKlag  MJ Race and end-stage renal disease: socioeconomic status and access to health care as mediating factors. Arch Intern Med 1995;1551201- 1208
PubMedArticle
19.
Perneger  TVWhelton  PKPuddey  IBKlag  MJ Risk of end-stage renal disease associated with alcohol consumption. Am J Epidemiol 1999;1501275- 1281
PubMedArticle
20.
Goetz  FCJacobs  DR  JrChavers  BRoel  JYelle  MSprafka  JM Risk factors for kidney damage in the adult population of Wadena, Minnesota: a prospective study. Am J Epidemiol 1997;14591- 102
PubMedArticle
21.
Fox  CSLarson  MGLeip  EPCulleton  BWilson  PWLevy  D Predictors of new-onset kidney disease in a community-based population. JAMA 2004;291844- 850
PubMedArticle
22.
Bleyer  AJShemanski  LRBurke  GLHansen  KJAppel  RG Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population. Kidney Int 2000;572072- 2079
PubMedArticle
23.
Zheng  ZJSharrett  ARChambless  LE  et al.  Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 1997;131115- 125
PubMedArticle
24.
Leng  GCFowkes  FGLee  AJDunbar  JHousley  ERuckley  CV Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. BMJ 1996;3131440- 1444
PubMedArticle
25.
Newman  ABShemanski  LManolio  TA  et al.  Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999;19538- 545
PubMedArticle
26.
Abbott  RDRodriguez  BLPetrovitch  H  et al.  Ankle-brachial blood pressure in elderly men and the risk of stroke: the Honolulu Heart Program. J Clin Epidemiol 2001;54973- 978
PubMedArticle
27.
Murabito  JMEvans  JCLarson  MGNieto  KLevy  DWilson  PW The ankle-brachial index in the elderly and risk of stroke, coronary disease, and death: the Framingham Study. Arch Intern Med 2003;1631939- 1942
PubMedArticle
28.
Tsai  AWFolsom  ARRosamond  WDJones  DW Ankle-brachial index and 7-year ischemic stroke incidence: the ARIC study. Stroke 2001;321721- 1724
PubMedArticle
29.
The ARIC Investigators, The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol 1989;129687- 702
PubMed
30.
Sacks  DBakal  CWBeatty  PT  et al.  Position statement on the use of the ankle-brachial index in the evaluation of patients with peripheral vascular disease: a consensus statement developed by the standards division of the society of cardiovascular & interventional radiology. J Vasc Interv Radiol 2002;13353
PubMedArticle
31.
Cockcroft  DWGault  MH Prediction of creatinine clearance from serum creatinine. Nephron 1976;1631- 41
PubMedArticle
32.
Newman  ABSiscovick  DSManolio  TA  et al.  Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation 1993;88837- 845
PubMedArticle
33.
Otah  KEMadan  AOtah  EBadero  OClark  LTSalifu  MO Usefulness of an abnormal ankle-brachial index to predict presence of coronary artery disease in African-Americans. Am J Cardiol 2004;93481- 483
PubMedArticle
34.
Aronow  WSAhn  C Prevalence of coexistence of coronary artery disease, peripheral arterial disease, and atherothrombotic brain infarction in men and women ≥62 years of age. Am J Cardiol 1994;7464- 65
PubMedArticle
35.
Shlipak  MGFried  LFCrump  C  et al.  Cardiovascular disease risk status in elderly persons with renal insufficiency. Kidney Int 2002;62997- 1004
PubMedArticle
36.
Zoccali  CMallamaci  FTripepi  G Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int Suppl 2003;JunS105- S110
PubMedArticle
37.
Levin  ADjurdjev  OBarrett  B  et al.  Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter. Am J Kidney Dis 2001;381398- 1407
PubMedArticle
38.
McClellan  WMLangston  RDPresley  R Medicare patients with cardiovascular disease have a high prevalence of chronic kidney disease and a high rate of progression to end-stage renal disease. J Am Soc Nephrol 2004;151912- 1919
PubMedArticle
39.
Kasiske  BL Relationship between vascular disease and age-associated changes in the human kidney. Kidney Int 1987;311153- 1159
PubMedArticle
40.
Tracy  REStrong  JPNewman  WP  IIIMalcom  GTOalmann  MCGuzman  MA Renovasculopathies of nephrosclerosis in relation to atherosclerosis at ages 25 to 54 years. Kidney Int 1996;49564- 570
PubMedArticle
41.
Sarnak  MJLevey  ASSchoolwerth  AC  et al.  Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;1082154- 2169
PubMedArticle
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