Relationship between Ankle-Brachial Index and Chronic Kidney Disease in Hypertensive Patients with No Known Cardiovascular Disease
Jose M. Mostaza*,
Carmen Suarez,
Luis Manzano,
Marc Cairols,
Francisca García-Iglesias*,
Julio Sanchez-Alvarez||,
Javier Ampuero¶,
Diego Godoy**,
Andrés Rodriguez-Samaniego,
Miguel A. Sanchez-Zamorano on behalf of the MERITO Study Group
* Atherosclerosis Unit, Hospital Carlos III, Internal Medicine Department, Hospital de la Princesa, Internal Medicine Department, Hospital Ramón y Cajal, Madrid, Vascular Surgery Department, Hospital Bellvitge, Barcelona, || Internal Medicine Department, Hospital Virgen del Camino, Pamplona, ¶ Internal Medicine Department Hospital Provincial, Cordoba, ** Internal Medicine Department, Hospital General Valencia, Valencia, Internal Medicine Department, Hospital Rio Carrión, Palencia, and Medical Department, Bristol Myers-Squibb, Madrid, Spain
Address correspondence to: Dr. Jose M. Mostaza, Unidad de Arteriosclerosis, Hospital Carlos III, Sinesio Delgado, 10, 28029 Madrid, Spain. Phone: +34-91-453-2670; Fax: +34-91-733-6614; E-mail: jmostaza.hciii{at}salud.madrid.org
Both decreased GFR and albuminuria are associated with an elevatedprevalence of peripheral artery disease. However, the combinedeffects of these alterations previously were not evaluated.Patients with hypertension and with no known vascular disease(n = 955; mean age 66 yr; 56% male) were selected from internalmedicine outpatient clinics throughout Spain. Cardiovascularrisk factors, urinary albumin excretion, and the ankle-brachialindex (ABI) were assessed in all participants. GFR was estimatedaccording to the Cockroft-Gault equation. Of the study population,62% had diabetes, 23.8% had a GFR <60 ml/min per 1.73 m2,and 43.8% had albuminuria. The prevalence of ABI <0.9 wasgreater in patients with a GFR <60 ml/min per 1.73 m2 (37.4versus 24.3%; P < 0.0001) and in those who had albuminuria(32.2 versus 23.3%; P = 0.001). In patients with both alterations,the prevalence of ABI <0.9 was 45.7%. Multivariate analysisindicated that the factors that were associated independentlywith low ABI were age (odds ratio [OR] 1.06; 95% confidenceinterval [CI] 1.03 to 1.08; P < 0.0001), triglyceride concentration(OR 1.003; 95% CI 1.001 to 1.005; P = 0.001), presence of albuminuria(OR 1.61; 95% CI 1.18 to 2.20; P = 0.003), smoking habit (OR1.72; 95% CI 1.13 to 2.63; P = 0.012), and a GFR <60 ml/minper 1.73 m2 (OR 1.47; 95% CI 1.01 to 2.17; P = 0.049). In patientswith hypertension and without known vascular disease, reducedGFR and albuminuria are associated independently with an ABI<0.9. Their combined presence characterizes a subgroup ofthe population who have an elevated prevalence of peripheralartery disease and could benefit from early diagnosis and treatment.
Patients with peripheral artery disease (PAD) of the lower limbs,whether symptomatic or not, have an elevated risk for cardiovasculardisease and premature death (1,2). Early detection of PAD identifiesa group of patients who would benefit from aggressive cardiovascularrisk factor modification and from antiplatelet therapy. Severalfactors have been associated with the development of PAD, amongwhich are age, gender, diabetes, smoking habit, dyslipidemia,and hypertension. High BP is an important risk factor in theprogressive deterioration of renal function and in the developmentof albuminuria, particularly in patients of advanced age. Althoughboth a decreased GFR (3–7) and the presence of albuminuria(8,9) have been associated independently with an elevated prevalenceof PAD, their combined effects were not evaluated previously.This is of considerable importance given that not only PAD butalso chronic renal disease is additive, and both are independentrisk factors for the development of cardiovascular disease (10,11).Their simultaneous presence characterizes a subgroup of patientswho have very high risk for cardiovascular disease and couldbenefit from early diagnosis and treatment (12). The objectiveof the present study was to determine the association betweenthe GFR and albuminuria with the presence of subclinical PADof the lower limbs in a large population of hypertensive patientswith no known cardiovascular disease.
Patients
Participants in the Modificacion de le Estratificacióndel Riesgo con el Indice Tobillo-brazo (MERITO) study were ofboth genders, were between the ages of 50 and 85 yr, and attendedinternal medicine outpatient clinics in hospitals throughoutSpain. Each investigator was required to measure the ankle-brachialindex (ABI) in 20 consecutive patients who attended the clinic;10 had type 2 diabetes, and 10 did not have diabetes but hada risk for death from cardiovascular disease 3% over the next10 yr, calculated according to the equation of the SystematicCoronary Risk Evaluation (SCORE) Project for low-risk countries(13). The diagnosis of hypertension required that the patienthad had such a diagnosis made previously by the treating physician,a BP 140/90 mmHg in patients without diabetes or 130/80 mmHgin patients with diabetes recorded on two separate occasions,or treatment with antihypertensive drugs. Of the participantsin the MERITO study, 85% were hypertensive and were selectedfor the current study. The diagnosis of diabetes was establishedin accordance with the criteria of the American Diabetes Association(14). All individuals with a definitive or suspected diagnosisof vascular disease, including coronary, cerebral, or PAD, wereexcluded from the study.
On entry into the study, a clinical history was taken and athorough physical examination was made. Fasting venous bloodwas taken for biochemical analyses. Plasma concentrations ofglucose, glycated hemoglobin, creatinine, lipids, and lipoproteinswere measured using standardized biochemical methods. Estimatedcreatinine clearance was calculated by the Cockroft-Gault equationstandardized to body surface area (15). Urinary albumin excretionwas estimated using one or more of the following methods: Quantificationof 24-h albumin excretion (54.8% of study patients), albumin-to-creatinineratio on a spot urine specimen (36.5% of study patients), orquantification of albumin in an overnight sample (8.6% of studypatients). Albuminuria was present when the albumin-to-creatinineratio was >30 mg/g, the 24-h albumin excretion was >30mg/24 h, or the concentration of albumin in the overnight samplewas >20 µg/min.
The ABI was determined with a bidirectional portable echo-Dopplerof 8 MHz (Mini Doppler HADECO ES-100, Kawasaki, Japan) and acalibrated mercury sphygmomanometer. The systolic BP (SBP) wasmeasured in the posterior tibial and pedal arteries of bothlower limbs and the brachial artery of both upper limbs. Thevalue of the ABI was calculated using the greater SBP obtainedin the lower limbs divided by the SBP of whichever was the higherin the upper limbs. The lowest ABI so obtained for each patientwas used in the subsequent statistical analyses. A value ofABI <0.9 was considered pathologically low. All patientsgave written informed consent, and the study was approved bythe Committee on Ethics and Research of the Hospital Ramóny Cajal in Madrid.
Statistical Analyses
The quantitative variables are presented as the mean (SD), andthe qualitative variables are presented as percentages. Thecomparisons between the quantitative variables were with thet test, and the comparisons between the qualitative variableswere with the 2 test. To evaluate the independent associationbetween ABI (dependent variable) and renal disease, we performedlogistic regression analyses in which the independent variablessuch as age, gender, and classical risk factors all were enteredinto the model. Statistic software program used for all analyseswas the SAS package (version 8.2; SAS Institute, Cary, NC).
There were 955 white patients included in the study, 56% weremale, and the overall mean age was 66 yr (8.1). Of these, 62%had diabetes, 21% were current smokers, 85% were receiving antihypertensivetreatment, and 65% were receiving hypolipemic agents. Of theparticipants, 34.3% had a creatinine clearance >90 ml/minper 1.73 m2, 41.9% had a mildly decreased GFR (between 60 and89 ml/min per 1.73 m2), 21.8% had a moderately decreased GFR(between 30 and 59 ml/min per 1.73 m2), and 2% had a severelydecreased GFR (<30 ml/min per 1.73 m2). Albuminuria was notedin 43.8% of patients. Patients without diabetes had a poorerrisk profile. They were older and had a greater proportion ofcardiovascular disease risk factors. However, the percentageof those with albuminuria and/or a decreased GFR did not differbetween patients with and without diabetes (data not shown).The mean ABI of the overall population was 0.97 (0.16); 27.4%of the participants had an ABI <0.9, 22.6% between 0.7 and0.9, and 4.7% between 0.4 and 0.7, and only one participanthad an ABI <0.4.
The patients with a GFR <60 ml/min per 1.73 m2 (Table 1)were predominantly female, older, and on antihypertensive treatment.Conversely, body mass index, diastolic BP and LDL cholesterolwere lower, and there was a lower prevalence of smoking habit.Also, the presence of albuminuria was greater in these patientswith a decreased GFR (51.1 versus 41.5%; P = 0.007).
Table 1. Characteristics of the study population as a function of creatinine clearancea
The percentage of patients with low ABI was greater among participantswith a GFR <60 ml/min per 1.73 m2 (37.4 versus 24.3%; P <0.0001), with a significant positive correlation between theGFR and the ABI (r = 0.097, P = 0.003). The prevalence of ABI<0.9 as a function of the grade of deterioration of the GFRcan be seen in Table 2: The lower the GFR, the higher the prevalenceof PAD. The patients with albuminuria had, as well, a greaterprevalence of low ABI (32.2 versus 23.3%; P = 0.001).
Table 2. OR (95% CI) for an ABI <0.9 segregated with respect to GFRa
We performed multivariate analysis to assess the factors thatwere related to a low ABI. The continuous variables that wereincluded in the model were age in years; body mass index inkg/m2; and LDL cholesterol, HDL cholesterol, and triglyceridesin mg/dl. The categorical variables were gender, current smoking,presence or absence of diabetes, presence or absence of proteinuria,and a GFR < or >60 ml/min per 1.73 m2. The factors thatwere associated independently with a low ABI were age (oddsratio [OR] 1.06; 95% confidence interval [CI] 1.03 to 1.08;P < 0.0001), triglyceride concentration (OR 1.003; 95% CI1.001 to 1.005; P = 0.001), the presence of albuminuria (OR1.61; 95% CI 1.18 to 2.20; P = 0.003), being a current smoker(OR 1.72; 95% CI 1.13 to 2.63; P = 0.012), and the presenceof GFR <60 ml/min per 1.73 m2 (OR 1.47; 95% CI 1.01 to 2.17;P = 0.049). The inclusion of the use of inhibitors of the renin-angiotensinsystem into the model did not alter the findings.
The prevalence of a low ABI in patients who had a GFR 60 ml/minper 1.73 m2 and did not have albuminuria was 21.8%; in patientswho had only a GFR <60 ml/min per 1.73 m2, the prevalencewas 27.2%; in patients with only albuminuria, the prevalencewas 28.8%; and in patients with both a GFR <60 ml/min per1.73 m2 and albuminuria, the prevalence was 45.7% (P < 0.001;Figure 1).
Although the presence of chronic kidney disease, either as reductionin the GFR or as albuminuria, was shown previously to be associatedindependently with the risk for PAD (3–6), cardiovasculardisease, and premature death (3,16–19), the combined effectsof small decreases in GFR and albuminuria were not evaluatedpreviously in relation to arteriosclerosis of the lower limbs.Our present data, obtained in a population of patients withhypertension and with no known cardiovascular disease, demonstratedthat a GFR <60 ml/min per 1.73 m2 and the presence of albuminuriaboth were associated with a reduced ABI and that these relationshipswere independent of other classical risk factors of cardiovasculardisease. More than one quarter of the participants with a reducedGFR or with albuminuria had a low ABI, and this prevalence increasedup to 50% in the group of patients with both disorders. Thepercentage of patients with a low ABI increased with decreasingGFR, and this was apparent even in patients with a modest reductionin renal function.
Our results are useful because they enable the identificationof a section of the population with a high prevalence of PADand, as such, with an elevated risk for developing coronaryartery disease, cerebrovascular disease, or premature death.This elevated prevalence would justify the recommendation toperform an ABI measurement in patients with a reduced GFR and/oralbuminuria so that if a low ABI is recorded, then aggressivemeasures of secondary prevention of cardiovascular disease canbe implemented. Given the additive and independent cardiovasculardisease risk that is conferred by both PAD and chronic renaldisease, particularly in patients with hypertension (11), furtherstudies would be warranted to determine the efficacy of recommendinga routine evaluation of the presence of atherosclerosis in othervascular beds in these patients.
Several mechanisms can be hypothesized to explain the associationbetween a reduction in GFR and vascular disease. Despite thatthe two entities have risk factors in common, our results indicatethat the relationship is independent of the presence of otherclassical risk factors. In patients with diabetes and a reducedGFR and without albuminuria, the underlying cause of the renalinsufficiency could be the presence of arteriosclerosis in therenal artery or in arteries of narrow diameter (20). Other factorsthat are present in patients with chronic kidney disease, suchas hyperhomocystinemia, increase in inflammation activity, oxidativestress, and endothelial dysfunction, also could underlie thehigher prevalence of PAD in patients with impaired renal function.Factors that link albuminuria to vascular disease have not beenascertained unambiguously. Albuminuria seems to identify individualswith generalized endothelial dysfunction and also may be a markerof a prothrombotic state (21,22). What is clear, however, isthat it acts as a risk factor that is independent of renal function.Our present results demonstrate that low GFR and albuminuriaare alterations that are associated independently with a lowABI, suggesting that the underlying routes of their associationwith vascular disease may be different.
In our study, reduced GFR was highly prevalent as a result ofthe advanced age of the patients, of all participants’having hypertension, and of there being an elevated prevalenceof diabetes. These observations coincide with other data thathave been published on similar populations (23).
Our study has several limitations. The number of participantsis relatively small in epidemiologic terms, which suggests thatthere may not have been sufficient numbers of patients representingthe whole range of renal function deterioration. Other shortcomingsof the study are that the albuminuria was measured using onlyone sample of urine, that a urinary sedimentation analysis wasnot performed simultaneously, and that the analyses were notconducted centrally. Nevertheless, all of these limitationswould have served to reduce the possibilities of finding significantassociations.
Our data indicate that both a reduction in the GFR and albuminuriaare independent as well as additive factors for the presenceof subclinical PAD in hypertensive patients with no known cardiovasculardisease. Given our findings of an elevated prevalence of PADin asymptomatic patients with an estimated creatinine clearance<60 ml/min per 1.73 m2 and with albuminuria, we suggest thatroutine measurement of ABI be performed in these patients toidentify individuals who are at very high risk and would benefitfrom the early implementation of appropriate therapeutic strategies.
Acknowledgments
This study was funded, in part, by a grant from Bristol MyersSquibb. The funding source had no involvement in the collectionof the data or in their analyses and interpretation.
Members of the MERITO study group: P. Abizanda Soler (Albacete),A. Acosta Socorro (Las Palmas de Gran Canaria), O. ArámburuBodas (Sevilla), C. Argüello Martín (Arriendas),A. Baamonde Carrasco (El Bierzo), J.M. Baucells Azcona (Barcelona),M. Beltrán Salvador (Castellón de la Plana), J.L.Bianchi Llaves (Algeciras), J.C. Blázquez Encinar (Alicante),P. Burillo Fuertes (Alcañiz), M. Cabre Roure (Mataró),J.M. Calbo Mayo (Albacete), E. Calderón Sandubete (Sevilla),L. Caminal Montero (Asturias), R. Cañizares Navarro (Alicante),F. Carrasco Miras (Huercal-Overa), J. Cebollada del Hoyo (Huesca),J.M. Cepeda Rodrigo (Orihuela), F. Civeira Murillo (Zaragoza),L. Comas Montgall (Vic), P. Conthe Gutiérrez (Madrid),A. Costo Campoamor (Cáceres), J.I. Cuende Melero (Palencia),A. de la Peña Fernández (Palma de Mallorca), J.del Valle Gutiérrez (Madrid), F. Diosdado Fernández(Jerez de la Frontera), F. Diz Lois Martínez (A Coruña),C. Dueñas Gutiérrez (Burgos), O. FernándezÁlvarez (Ourense), I. Fernández Galante (Valladolid),F. Fernández Monras (Barcelona), J. FernándezPardo (Murcia), J.L. Fernández Reyes (Jaén). J.Ferrando Vela (Zaragoza), E.M. Ferreira Pasos (Segovia), P.Férriz Moreno (Elda), M.J. Forner Giner (Valencia), F.Fuentes Lopez (Córdoba), J.D. García Díaz(Alcalá de Henares), I. García Polo (Madrid),V. Giner Galván (Valencia), P. González Blanco(Don Benito), J.J. González Igual (Barbastro), E. GonzálezSarmiento (Valladolid), J.L. Griera Borras (Sevilla), A. GriloReina (Sevilla), J.L. Hernández Hernández (Santander),P. Horcajo Aranda (Guadalajara), E. Iranzo Gómez (Valencia),M. Jiménez Pascual (Murcia), J. Lapaza Andueza (San Sebastián),J.J. Linares Linares (Granada), E. Llarges Rocabruna (Granollers),F. López Fernández (Jarrio), E. Luna Heredia (Móstoles),G. Luna Rodrigo (Salamanca), F. Luque Ruiz (Jaén), A.Mangas Rojas (Cádiz), J. Maraver Delgado (Jerez de laFrontera), J.M. Marco Lattur (Castellón), L. Mateos Polo(Salamanca), M. Mauri Pont (Terrassa), J.D. Mediavilla García(Granada), M. Monreal Bosch (Barcelona), F. Montaner Batlle(Martorell), R. Monte Secade (Lugo), M. Montero Perez-Barquero(Córdoba), J. Montes Santiago (Lugo), J. Moreno Palomares(Segovia), J.L. Mulero Conde (Murcia), M. Muñoz Rodríguez(León), A.I. Muñoz Ruiz (Talavera), I. OterminMaya (Elcano), G. Penades Cervera (Alicante), L. PérezAlonso (Madrid), A.I. Pérez Caballero (Pozoblanco), A.Pérez del Molino Castellanos (Torrelavega), N. PlanaGil (Reus), A. Pose Reino (Santiago de Compostela), G. RamírezOlivencia (Madrid), R. Redondo Fernández (Madrid), A.Ribera Gallego (Vigo), M.A. Rico Corral (Sevilla), E. RodillaSalas (Sagunto), M. Rodríguez Gaspar (Las Palmas de GranCanarias), P. Román Sánchez (Requena), E. RoviraDaudí (Valencia), M. Ruiz Climente (Cuenca), D. SánchezFuentes (Ávila), H. Sánchez Huelva (Sevilla),A. Sánchez Purificación (Fuenlabrada), M.V. SánchezSimonet (Málaga), J.L. Sanpedro Villasanz (Jaén),F. Sena Ferrer (Tortosa), M. Tasías Pitarch (Valencia),S. Tenes Rodrigo (Castellón de la Plana), I. Tinoco Bernal(Cádiz), R. Tirado Miranda (Cabra), I. Trouillhet Manso(Sanlúcar de Barrameda), M. Ulla Anes (Lanzarote), P.Valdivieso Felices (Málaga), J.M. Varela Aguilar (Sevilla),J.A. Vargas Núñez (Madrid), F. Vega Rollán(El Bierzo), J.M. Vega Vázquez (Sevilla), D. VinuesaGarcía (Granada), and M.A. Zarraga Fernández (Avilés).
Resnick HE, Lindsay RS, McDermott MM, Devereux RB, Jones KL, Fabsitz RR, Howard BV: Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: The Strong Heart Study.
Circulation 109
: 733
–739, 2004
Lee AJ, Price JF, Russell MJ, Smith FB, van Wijk MC, Fowkes FG: Improved prediction of fatal myocardial infarction using the ankle brachial index in addition to conventional risk factors: The Edinburgh Artery Study.
Circulation 110
: 3075
–3080, 2004
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.
N Engl J Med 351
: 1296
–1305, 2004[Abstract/Free Full Text]
O’Hare AM, Glidden DV, Fox CS, Hsu CY: High prevalence of peripheral arterial disease in persons with renal insufficiency: Results from the National Health and Nutrition Examination Survey 1999–2000.
Circulation 109
: 320
–323, 2004
O’Hare AM, Vittinghoff E, Hsia J, Shlipak 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 15
: 1046
–1051, 2004[Abstract/Free Full Text]
Selvin E, Erlinger TP: Prevalence of and risk factors for peripheral arterial disease in the United States: Results from the National Health and Nutrition Examination Survey, 1999–2000.
Circulation 110
: 738
–743, 2004
de Vinuesa SG, Ortega M, Martinez P, Goicoechea M, Campdera FG, Luno J: Subclinical peripheral arterial disease in patients with chronic kidney disease: Prevalence and related risk factors.
Kidney Int Suppl 93
: S44
–S47, 2005
Fabsitz RR, Sidawy AN, Go O, Lee ET, Welty TK, Devereux RB, Howard BV: Prevalence of peripheral arterial disease and associated risk factors in American Indians: The Strong Heart Study.
Am J Epidemiol 149
: 330
–338, 1999[Abstract/Free Full Text]
Tseng CH, Tseng CP, Tai TY, Chong CK: Effect of angiotensin blockade on the association between albuminuria and peripheral arterial disease in elderly Taiwanese patients with type 2 diabetes mellitus.
Circ J 69
: 965
–970, 2005[CrossRef][Medline]
Rutter MK, Wahid ST, McComb JM, Marshall SM: Significance of silent ischemia and microalbuminuria in predicting coronary events in asymptomatic patients with type 2 diabetes.
J Am Coll Cardiol 40
: 56
–61, 2002[Abstract/Free Full Text]
Jager A, Kostense PJ, Ruhe HG, Heine RJ, Nijpels G, Dekker JM, Bouter LM, Stehouwer CD: Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: Five-year follow-up of the Hoorn Study.
Arterioscler Thromb Vasc Biol 19
: 617
–624, 1999[Abstract/Free Full Text]
Knobler H, Zornitzki T, Vered S, Oettinger M, Levy R, Caspi A, Faraggi D, Livschitz S: Reduced glomerular filtration rate in asymptomatic diabetic patients: Predictor of increased risk for cardiac events independent of albuminuria.
J Am Coll Cardiol 44
: 2142
–2148, 2004[Abstract/Free Full Text]
Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, De Bacquer D, Ducimetiere P, Jousilahti P, Keil U, Njolstad I, Oganov RG, Thomsen T, Tunstall-Pedoe H, Tverdal A, Wedel H, Whincup P, Wilhelmsen L, Graham IM: Estimation of ten-year risk of fatal cardiovascular disease in Europe: The SCORE project.
Eur Heart J 24
: 987
–1003, 2004
American Diabetes Association: Clinical practice recommendations 2002.
Diabetes Care 25[Suppl 1]
: S1
–S147, 2002
Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine.
Nephron 16
: 31
–41, 1976[Medline]
Anavekar NS, Gans DJ, Berl T, Rohde RD, Cooper W, Bhaumik A, Hunsicker LG, Rouleau JL, Lewis JB, Rosendorff C, Porush JG, Drury PL, Esmatjes E, Raz I, Vanhille P, Locatelli F, Goldhaber S, Lewis EJ, Pfeffer MA: Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: A case for albuminuria.
Kidney Int Suppl 92
: S50
–S55, 2004
Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA: Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.
N Engl J Med 351
: 1285
–1295, 2004[Abstract/Free Full Text]
Ibsen H, Wachtell K, Olsen MH, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlof B: Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: The LIFE Study.
Kidney Int Suppl 92
: S56
–S58, 2004
Brugts JJ, Knetsch AM, Mattace-Raso FU, Hofman A, Witteman JC: Renal function and risk of myocardial infarction in an elderly population: The Rotterdam Study.
Arch Intern Med 165
: 2659
–2665, 2005[Abstract/Free Full Text]
Kramer HJ, Nguyen QD, Curhan G, Hsu CY: Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus.
JAMA 289
: 3273
–3277, 2003[Abstract/Free Full Text]
Kario K, Matsuo T, Kobayashi H, Matsuo M, Sakata T, Miyata T: Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria.
Arterioscler Thromb Vasc Biol 15
: 1114
–1120, 1995[Abstract/Free Full Text]
Rahman M, Brown CD, Coresh J, Davis BR, Eckfeldt JH, Kopyt N, Levey AS, Nwachuku C, Pressel S, Reisin E, Walworth C: The prevalence of reduced glomerular filtration rate in older hypertensive patients and its association with cardiovascular disease: A report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
Arch Intern Med 164
: 969
–976, 2004[Abstract/Free Full Text]
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Abstract
Introduction
3% over the next 10 yr, calculated according to the equation of the Systematic Coronary Risk Evaluation (SCORE) Project for low-risk countries (13). The diagnosis of hypertension required that the patient had had such a diagnosis made previously by the treating physician, a BP 
2 test. To evaluate the independent association between ABI (dependent variable) and renal disease, we performed logistic regression analyses in which the independent variables such as age, gender, and classical risk factors all were entered into the model. Statistic software program used for all analyses was the SAS package (version 8.2; SAS Institute, Cary, NC). 
