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Albuminuria and Risk of Cardiovascular Events, Death, and Heart Failure in Diabetic and Nondiabetic Individuals
Hertzel C. Gerstein, MD,MSc;
Johannes F. E. Mann, MD;
Qilong Yi, PhD;
Bernard Zinman, MD,CM;
Sean F. Dinneen, MD,MSc;
Byron Hoogwerf, MD;
Jean Pierre Hallé, MD;
James Young, MD;
Andrew Rashkow, MD;
Carol Joyce, MD;
Shah Nawaz, MD;
Salim Yusuf, MBBS,DPhil;
for the HOPE Study Investigators
JAMA. 2001;286:421-426.
ABSTRACT
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Context Microalbuminuria is a risk factor for cardiovascular (CV) events. The relationship between the degree of albuminuria and CV risk is unclear.
Objectives To estimate the risk of CV events in high-risk individuals with diabetes mellitus (DM) and without DM who have microalbuminuria and to determine whether levels of albuminuria below the microalbuminuria threshold increase CV risk.
Design The Heart Outcomes Prevention Evaluation study, a cohort study conducted between 1994 and 1999 with a median 4.5 years of follow-up.
Setting Community and academic practices in North and South America and Europe.
Participants Individuals aged 55 years or more with a history of CV disease (n = 5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine albumin/creatinine ratio (ACR) measurement.
Main Outcome Measures Cardiovascular events (myocardial infarction, stroke, or CV death); all-cause death; and hospitalization for congestive heart failure.
Results Microalbuminuria was detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those without DM).Compared with the lowest quartile of ACR (<0.22 mg/mmol), the RRs of the primary aggregate end point in the second quartile (ie, ACR range, 0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95% CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95% CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend <.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol increase in ACR level, the adjusted hazard of major CV events increased by 5.9% (95% CI, 4.9%-7.0%).
Conclusions Our results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria identifies people at high risk for CV events.
INTRODUCTION
Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV) disease.1 Compared with those who do not have DM, people with DM have a 2- to 4-fold increased risk of subsequent CV disease.2-4 Risk factors that independently increase CV risk in people with DM include smoking, hypertension, dyslipidemia,3 renal dysfunction,5 and hyperglycemia.6-10 Recently, data from several studies have established microalbuminuria (MA), or dipstick-negative albuminuria, as another CV risk factor. Microalbuminuria is reported in approximately 30% of middle-aged patients with either type 1 or type 2 DM and in approximately 10% to 15% of middle-aged individuals who do not have DM.11-13 Although MA is associated with other risk factors in those with or without DM,11, 13-14 it is also an independent predictor of future strokes, death, and myocardial infarction (MI).15-19 Moreover, MA may also predict future congestive heart failure (CHF). However, at present, there are few prospective data regarding this association.20-23
Despite being increasingly recognized as a CV risk factor, the definition of MA was based on its ability to predict diabetic nephropathy (ie, macroalbuminuria or clinical proteinuria). Whether individuals with albumin excretion rates below the MA threshold are also at risk for CV disease or whether there is a progressive graded relationship between different degrees of albuminuria and CV events is unclear.
Our study examines the relationship between baseline albuminuria levels and future CV events using data collected from individuals with or without DM enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Participants were followed-up for a median of 4.5 years
METHODS
Participants and Overview of Study Design
Detailed descriptions of the HOPE study and MICRO (Microalbuminuria, Cardiovascular and Renal Outcomes) HOPE substudy have been published previously.24-27 In brief, individuals with or without DM aged 55 years or older with a history of previous CV disease (either coronary artery disease, stroke, or peripheral vascular disease) or with a history of DM plus at least 1 other CV risk factor (total cholesterol >200 mg/dL [>5.2 mmol/L], high-density lipoprotein cholesterol  35 mg/dL [0.9 mmol/L], hypertension, known MA, or current smoker) were studied between 1994 and 1999 in North and South America and Europe. Key exclusion criteria included dipstick-positive proteinuria or established diabetic nephropathy, other significant renal disease, hyperkalemia, CHF, low-ejection fraction, or hypersensitivity to vitamin E or angiotensin-converting enzyme inhibitors.24 The aggregate primary end point of the study was the development of either MI, stroke, or CV death. This analysis is restricted to the 97% of all HOPE participants (3498 with DM and 5545 without DM) randomized to receive either 10 mg of ramipril or placebo and in whom baseline urine albumin measurements were available.
Clinical Data Collection
Diabetes status and other demographic and clinical variables were determined by history and physical examination. Glycated hemoglobin was assayed for participants with a history of DM in each study center's local laboratory. Results were expressed as the percentage above the upper limit of normal for the assay used. Serum creatinine was measured at each study site in all participants at baseline and was only measured in the participants with DM at follow-up visits. The results were expressed in International System of Units.
Urine Collection and Analysis
Urinary albumin was measured in 9043 (97%) of HOPE study participants at baseline; the assays used have been described previously.24-25 A first morning urine was collected at baseline, 1 year, and study end. Urinary albumin levels were measured by either radioassay (Europe and North America) or immunoturbidimetry (South America), and urinary creatinine levels were measured by the Jaffe method.25 The degree of albuminuria, expressed as the albumin/creatinine ratio (ACR), was entered into the database so that the relationship between baseline ACR and future outcomes could be analyzed. Microalbuminuria was defined as an ACR of 2 mg/mmol or more for both men and women; dipstick-positive (ie,  1 +) proteinuria (ie, a level with >70% sensitivity and 90% specificity for detecting MA) was an exclusion criteria.28
Outcome Assessment
Participants were assessed every 6 months. Myocardial infarction, stroke, CV death (the primary aggregate end point), and hospitalization for CHF (a secondary end point), were documented and adjudicated centrally as described previously. As reported, the study was approved by local ethics boards, and all participants signed written informed consent.27
Statistical Analysis
The univariate and multivariate relative risks (RRs) of the primary study end point MI, stroke, or CV death; all-cause mortality; and hospitalization for CHF in participants with and without MA were calculated using Cox regression models. The proportionality assumption of the Cox model was assessed by inspection of the Kaplan Meier curves for those with and without MA; these showed no evidence of a time-dependent hazard. Variables entered into the multivariate model for all participants included age, sex, smoking status, hypertension, history of dyslipidemia (ie, a total cholesterol >200 mg/dL [>5.2 mmol/L] or high-density lipoprotein cholesterol 35 mg/dL [0.9 mmol/L]), DM status, abdominal obesity, and baseline serum creatinine level; for participants with DM, duration of DM, use of oral glucose-lowering agents or insulin, and glycated hemoglobin level were also included. Population attributable risk for MA in all participants (ie, the proportion of events attributable to MA) was estimated as the proportion of all people with MA x (the difference in event rates between those with and without MA)/the overall event rate.
All participants were categorized by quartiles of albuminuria levels. Tests for linear trend across quartiles were performed using Cox regression after adjusting for (1) age and sex; (2) age, sex, systolic blood pressure, diastolic blood pressure, waist-hip ratio, DM status (in all participants), and glycated hemoglobin (in diabetic participants) in all the participants and in those with no MA (ie, with an ACR <2 mg/mmol); and (3) randomization to receive ramipril in the previous model. The unadjusted RR and 95% confidence intervals (CIs) of outcomes in each quartile with reference to the first quartile were also calculated. Model fit was assessed using the likelihood ratio test. All statistical analyses were performed using SAS version 6.11.
RESULTS
Baseline Associations
Microalbuminuria was detected in 1140 (32.6%) of participants with DM and 823 (14.8%) of participants without DM at baseline. A detailed description of the baseline characteristics of the HOPE participants according to the presence or absence of MA has been published previously.11 Both diabetic and nondiabetic individuals with MA were older, had higher systolic and diastolic blood pressure, had a lower ankle-arm blood systolic pressure ratio, and had a higher serum creatinine concentration than individuals without MA; patients with DM and with MA also had a longer duration of DM and had higher glycated hemoglobin level and waist-hip ratio than those without MA.
Impact of MA
Table 1 and Table 2 list the incidence and risk of the primary aggregate end point of the HOPE study MI, stroke, or CV death; all-cause mortality; and hospitalization for CHF according to the presence of MA. After controlling for randomization to receive ramipril, baseline MA increased the adjusted RR for major CV events by 1.83-fold (95% CI, 1.64-2.05; P<.001); (2) all-cause mortality by 2.09-fold (95% CI, 1.84-2.38); and (3) hospitalization for heart failure by 3.23-fold (95% CI, 2.54-4.10). Similar estimates were noted in individuals with and without a history of DM at the time of randomization (Table 1 and Table 2). The close association between MA and these outcomes persisted even after controlling for other CV risk factors in the placebo and ramipril groups (Table 2). The population attributable RRs were 12.7% (95% CI, 9.9%-15.5%) for major CV events; 16.9% (95% CI, 13.4%-20.4%) for all-cause mortality; and 31.1% (95% CI, 24.0%-38.3%) for hospitalization for heart failure.
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Table 1. Incidence and Risk of Cardiovascular Events in HOPE Study Participants With and Without Baseline Microalbuminuria*
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Table 2. Incidence and Risk of Cardiovascular Events in HOPE Study Participants With and Without Baseline Microalbuminuria by Randomized Group*
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Impact of ACRs Below the MA Threshold
These CV outcomes were also analyzed according to the level of albuminuria (expressed in quartiles) to determine the CV importance of ACRs below the MA threshold. The ACR cutpoints for each quartile of all HOPE participants who had a baseline determination for albuminuria are shown in Table 3. There was a graded relationship between the baseline ACR and the risk of both CV outcomes and mortality; this relationship extended into the "submicroalbuminuric" range. For example, the RR of all-cause death for each quartile compared with the first quartile (ACR <0.22 mg/mmol), was 1.08 (95% CI, 0.89-1.42) for an ACR of 0.22 to 0.57 mg/mmol, 1.46 (95% CI, 1.21-1.75) for an ACR of 0.58 to 1.62 mg/mmol, and 2.34 (95% CI, 1.99-2.77) for an ACR >1.62 mg/mmol. For major CV events, all-cause mortality and hospitalization for CHF in all participants, this linear trend was significant after (1) controlling for age and sex (P<.001); (2) controlling for age, sex, systolic blood pressure, diastolic blood pressure, waist-hip ratio, and DM status (in all participants) or glycated hemoglobin in diabetic participants (P<.001); and (3) after removing individuals with MA and then controlling for age, sex, systolic blood pressure, diastolic blood pressure, waist-hip ratio, and DM status in all participants or glycated hemoglobin in participants with DM (P<.001 for major CV events and all-cause mortality, and P = .05 for CHF hospitalization). Similar findings were noted in the subgroups of participants with or without DM (Table 3). Finally, the linear trends remained significant when the 3 models were repeated for all participants and for the subgroups of participants with or without DM after randomization to receive ramipril was also included in the model (P for trend <.001 except where indicated in Table 3).
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Table 3. Relative Risk of Outcomes According to Quartile of Albuminuria in HOPE Participants
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The ACR as a Continuous Risk Factor
To further assess the ACR as a continuous CV risk factor, the incidence of the primary outcome, all-cause death, and hospitalization for CHF was plotted against the ACR (partitioned according to deciles in all participants with a baseline measurement). Figure 1 illustrates the progressive nature of this relationship. In addition, the hazard for these events for every increment in the ACR (by Cox regression) was calculated after adjustment for age, sex, and randomization to receive ramipril: for every 0.4-mg/mmol increase in ACR, the hazard of the primary outcome increased by 5.9% (95% CI, 4.9-7.0); all-cause death increased by 6.8% (95% CI, 5.6-8.0%); and hospitalization for CHF increased by 10.6% (95% CI, 8.4-13.0).
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Figure. Incidence of Cardiovascular Outcomes According to Degree of Albuminuria
Panels A, B, and C show the rate of major cardiovascular events (myocardial infarction, stroke, or cardiovascular death), all-cause mortality, and hospitalization for congestive heart failure in each decile of albumin/creatinine ratio (ACR) for all participants, participants with diabetes mellitus, and participants without diabetes mellitus. Decile 1 and 2 are combined because of very low incidence rates in these 2 deciles. The 8th decile includes ACR of 2 mg/mmol, which is the microalbuminuria threshold.
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COMMENT
A growing number of prospective epidemiologic studies have reported that MA is a strong independent risk factor for CV events.15-19 The data presented herein support this conclusion and also show that MA is a strong independent risk factor for hospitalization for CHF and for all-cause mortality in people with no prior history of CHF and show that the relationship between albuminuria and experiencing a CV event is not restricted to the MA range. Indeed, they indicate that the relationship between the ACR and CV disease extends at least as low as 0.5 mg/mmol (Table 3), well below currently accepted screening thresholds for a diagnosis of MA.29 This is consistent with a recent prospective study in which individuals with an ACR of >0.65 mg/mmol had an RR for ischemic heart disease of 2.3 (P = .002) compared with people with a lower degree of albuminuria.30 Thus, an ACR of 2.0 mg/mmol—a threshold used to screen for MA and risk for diabetic nephropathy—may not be relevant when considering the risk for CV outcomes; lower degrees of albuminuria are also predictive.
Taken together these observations support the suggestion that albuminuria reflects underlying vascular disease. These data also suggest that measurement of urinary albumin may help estimate the absolute risk of experiencing a CV event for individuals with or without DM. Patients with a high absolute risk will experience a higher absolute risk reduction when given preventive interventions than patients with a lower absolute risk. Therefore, a test that identifies high-risk patients provides useful information that will help clinicians estimate the benefits that may be expected from adding a proven preventive therapy.
Why is albuminuria a risk factor for CV disease? Clearly, a very small concentration of urinary albumin is unlikely to be a direct cause. Albuminuria is, however, associated with several other risk factors that may themselves be causal or linked with causal processes. These include both diabetic and nondiabetic degrees of hyperglycemia,31-33 hypertension,34-35 renal dysfunction,36 dyslipidemia,31 hyperhomocysteinemia,37 dietary protein,37 smoking,38 and markers of an acute phase response.39 Albuminuria also reveals increased renal endothelial permeability and may be an easily measured marker of diffuse endothelial dysfunction.40 Thus albuminuria is an easily measured marker of other CV factors, as well as existing endothelial dysfunction, that likely reflects underlying macrovascular and microvascular disease.
The measurement of only 1 ACR at baseline and previous observations that the degree of albuminuria varies from day-to-day are 2 limitations of the data.41 Nevertheless, the large sample size, central assay of the ACR, and the high diagnostic accuracy of a single urine collection42-45 minimize the uncertainty associated with a single measurement. Moreover, the regression dilution bias introduced by a single measurement of a risk factor tends to underestimate the strength of the risk factor. This suggests that the true association between ACR and CV events is likely to be even stronger than observed in our study.46-47
Albuminuria is therefore a robust independent continuous risk factor for future CV events, CHF, and all-cause mortality in middle-age dipstick-negative individuals with or without DM at high risk for CV disease. It is also relatively inexpensive and can be assayed for less than $10 in most laboratories. It can therefore be used as a simple test to identify individuals at high risk for future events who could be targeted for preventive strategies.
AUTHOR INFORMATION
A complete listing of Hope investigators appeared in 2 previously published articles (Lancet. 2000;255:253-259 and N Engl J Med. 2000;342:145-153).
Author Contributions: Study concept and design: Gerstein, Mann, Zinman, Dinneen, Hoogwerf, Hallé, Young, Rashkow, Joyce, Yusuf.
Acquisition of data: Gerstein, Mann Zinman, Dinneen, Hoogwerf, Hallé, Young, Rashkow, Joyce, Nawaz, Yusuf.
Analysis and interpretation of data: Gerstein, Mann, Yi, Zinman, Dinneen, Hoogwerf, Hallé, Young, Rashkow, Yusuf.
Drafting of the manuscript: Gerstein, Mann, Hallé, Nawaz, Yusuf.
Critical revision of the manuscript for important intellectual content: Gerstein, Mann, Yi, Zinman, Dinneen, Hoogwerf, Hallé, Young, Rashkow, Joyce, Nawaz, Yusuf.
Statistical expertise: Yi.
Obtained funding: Gerstein, Zinman, Yusuf.
Study supervision: Gerstein, Mann, Zinman, Dinneen, Hoogwerf, Hallé, Young, Rashkow, Joyce, Nawaz, Yusuf.
Funding/Support: Medical Research Council of Canada grants MT12790 and UI12362. Hoechst Marion Roussell, Astra, Natural Source Vitamin E Association, NEGMA, and King Pharmaceuticals also provided grant support.
Corresponding Author and Reprints: Hertzel C. Gerstein, MD, MSc, Department of Medicine, Room 3V38, 1200 Main St W, Hamilton, Ontario, L8N 3Z5 (e-mail: gerstein{at}mcmaster.ca).
Reprints: Canadian Cardiovascular Collaboration Project Office, HGH-McMaster Clinic, 237 Barton St E, Hamilton, Ontario, L8L 2X2.
Author Affiliations: McMaster University, Hamilton, Ontario (Drs Gerstein, Yi, and Yusuf); Klinikum Schwabing, LMU, Munich, Germany (Dr Mann); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Dr Zinman); Addenbrookes Hospital, Cambridge, England (Dr Dinneen); Cleveland Clinic Foundation, Cleveland, Ohio (Drs Hoogwerf and Young); Université de Montréal, Montréal, Québec (Dr Hallé); Griffin Hospital, Derby, Conn (Dr Rashkow); Memorial University, St John's, Newfoundland (Dr Joyce); and Sudbury Regional Hospital, Sudbury, Ontario (Dr Nawaz).
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Dual Blockade of the Renin-Angiotensin System in Diabetic Nephropathy
Ravid
Diabetes Care 2009;32:S410-S413.
FULL TEXT
Proteinuria, Chronic Kidney Disease, and the Effect of an Angiotensin Receptor Blocker in Addition to an Angiotensin-Converting Enzyme Inhibitor in Patients With Moderate to Severe Heart Failure
Anand et al.
Circulation 2009;120:1577-1584.
ABSTRACT
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Cost-Effectiveness of Aliskiren in Type 2 Diabetes, Hypertension, and Albuminuria
Delea et al.
J. Am. Soc. Nephrol. 2009;20:2205-2213.
ABSTRACT
| FULL TEXT
Microalbuminuria and Cardiovascular Autonomic Dysfunction Are Independently Associated With Cardiovascular Mortality: Evidence for Distinct Pathways: The Hoorn Study
Beijers et al.
Diabetes Care 2009;32:1698-1703.
ABSTRACT
| FULL TEXT
Urinary Adiponectin Excretion: A Novel Marker for Vascular Damage in Type 2 Diabetes
von Eynatten et al.
Diabetes 2009;58:2093-2099.
ABSTRACT
| FULL TEXT
Effect of Modest Salt Reduction on Blood Pressure, Urinary Albumin, and Pulse Wave Velocity in White, Black, and Asian Mild Hypertensives
He et al.
Hypertension 2009;54:482-488.
ABSTRACT
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Alcohol consumption and 5-year onset of chronic kidney disease: the AusDiab study
White et al.
Nephrol Dial Transplant 2009;24:2464-2472.
ABSTRACT
| FULL TEXT
Counterpoint: Clinical Islet Transplantation: Not Ready for Prime Time
Khan and Harlan
Diabetes Care 2009;32:1570-1574.
FULL TEXT
Higher Levels of Urinary Albumin Excretion Within the Normal Range Predict Faster Decline in Glomerular Filtration Rate in Diabetic Patients
Babazono et al.
Diabetes Care 2009;32:1518-1520.
ABSTRACT
| FULL TEXT
Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in Diabetes
Ninomiya et al.
J. Am. Soc. Nephrol. 2009;20:1813-1821.
ABSTRACT
| FULL TEXT
Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress
Fujii et al.
Nephrol Dial Transplant 2009;24:2089-2095.
ABSTRACT
| FULL TEXT
Linkage Analysis of Albuminuria
Mottl et al.
J. Am. Soc. Nephrol. 2009;20:1597-1606.
ABSTRACT
| FULL TEXT
Association of CKD and Cancer Risk in Older People
Wong et al.
J. Am. Soc. Nephrol. 2009;20:1341-1350.
ABSTRACT
| FULL TEXT
Microalbuminuria and Risk of Venous Thromboembolism
Mahmoodi et al.
JAMA 2009;301:1790-1797.
ABSTRACT
| FULL TEXT
Does bacteriuria interfere with albuminuria measurements of patients with diabetes?
Kramer et al.
Nephrol Dial Transplant 2009;24:1193-1196.
ABSTRACT
| FULL TEXT
Screening for Albuminuria Identifies Individuals at Increased Renal Risk
van der Velde et al.
J. Am. Soc. Nephrol. 2009;20:852-862.
ABSTRACT
| FULL TEXT
Chronic Kidney Disease and Clinical Outcome in Patients With Acute Stroke
Yahalom et al.
Stroke 2009;40:1296-1303.
ABSTRACT
| FULL TEXT
The Case for Using Albuminuria in Staging Chronic Kidney Disease
Gansevoort and de Jong
J. Am. Soc. Nephrol. 2009;20:465-468.
FULL TEXT
Myogenic tone and small artery remodelling: insight into diabetic nephropathy
Khavandi et al.
Nephrol Dial Transplant 2009;24:361-369.
FULL TEXT
YKL-40, a Marker of Inflammation and Endothelial Dysfunction, Is Elevated in Patients With Type 1 Diabetes and Increases With Levels of Albuminuria
Rathcke et al.
Diabetes Care 2009;32:323-328.
ABSTRACT
| FULL TEXT
The Costs and Benefits of Automatic Estimated Glomerular Filtration Rate Reporting
den Hartog et al.
CJASN 2009;4:419-427.
ABSTRACT
| FULL TEXT
Ambulatory Blood Pressure Monitoring and All-Cause Mortality in Elderly People With Diabetes Mellitus
Palmas et al.
Hypertension 2009;53:120-127.
ABSTRACT
| FULL TEXT
Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
WRITING GROUP MEMBERS et al.
Circulation 2009;119:e21-e181.
FULL TEXT
Body Mass Index and Vigorous Physical Activity and the Risk of Heart Failure Among Men
Kenchaiah et al.
Circulation 2009;119:44-52.
ABSTRACT
| FULL TEXT
Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion
Brantsma et al.
Nephrol Dial Transplant 2008;23:3851-3858.
ABSTRACT
| FULL TEXT
Value of Urinary Albumin-to-Creatinine Ratio as a Predictor of Type 2 Diabetes in Pre-Diabetic Individuals
Friedman et al.
Diabetes Care 2008;31:2344-2348.
ABSTRACT
| FULL TEXT
Rationale and Strategies for Early Detection and Management of Diabetic Kidney Disease
Radbill et al.
Mayo Clin Proc. 2008;83:1373-1381.
ABSTRACT
| FULL TEXT
Guidelines for the management of chronic kidney disease
Levin et al.
CMAJ 2008;179:1154-1162.
FULL TEXT
Primary Care Approach to Proteinuria
Naderi and Reilly
J Am Board Fam Med 2008;21:569-574.
ABSTRACT
| FULL TEXT
Albuminuria Assessed From First-Morning-Void Urine Samples Versus 24-Hour Urine Collections as a Predictor of Cardiovascular Morbidity and Mortality
Lambers Heerspink et al.
Am J Epidemiol 2008;168:897-905.
ABSTRACT
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Higher Levels of Albuminuria within the Normal Range Predict Incident Hypertension
Forman et al.
J. Am. Soc. Nephrol. 2008;19:1983-1988.
ABSTRACT
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Extended Prognostic Value of Urinary Albumin Excretion for Cardiovascular Events
Brantsma et al.
J. Am. Soc. Nephrol. 2008;19:1785-1791.
ABSTRACT
| FULL TEXT
Airborne particulate matter exposure and urinary albumin excretion: the Multi-Ethnic Study of Atherosclerosis
O'Neill et al.
Occup. Environ. Med. 2008;65:534-540.
ABSTRACT
| FULL TEXT
Association of a CYP4A11 Variant and Blood Pressure in Black Men
Gainer et al.
J. Am. Soc. Nephrol. 2008;19:1606-1612.
ABSTRACT
| FULL TEXT
Novel Links between the Long Pentraxin 3, Endothelial Dysfunction, and Albuminuria in Early and Advanced Chronic Kidney Disease
Suliman et al.
CJASN 2008;3:976-985.
ABSTRACT
| FULL TEXT
Importance of Low-Grade Albuminuria
Danziger
Mayo Clin Proc. 2008;83:806-812.
ABSTRACT
| FULL TEXT
Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes
The ADVANCE Collaborative Group
NEJM 2008;358:2560-2572.
ABSTRACT
| FULL TEXT
Glomerular filtration rate <45 ml/min/1.73 m2 with microalbuminuria was associated with increased CV death
Rifkin and Sarnak
Evid. Based Med. 2008;13:89-89.
FULL TEXT
Glomerular Filtration Rate, Albuminuria, and Risk of Cardiovascular and All-Cause Mortality in the US Population
Astor et al.
Am J Epidemiol 2008;167:1226-1234.
ABSTRACT
| FULL TEXT
Prevention of Heart Failure: A Scientific Statement From the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group
Schocken et al.
Circulation 2008;117:2544-2565.
ABSTRACT
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Novel Metabolic Risk Factors for Incident Heart Failure and Their Relationship With Obesity: The MESA (Multi-Ethnic Study of Atherosclerosis) Study
Bahrami et al.
J Am Coll Cardiol 2008;51:1775-1783.
ABSTRACT
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The long pentraxin PTX-3 in prevalent hemodialysis patients: associations with comorbidities and mortality
Suliman et al.
QJM 2008;101:397-405.
ABSTRACT
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Relation of Low Glomerular Filtration Rate to Metabolic Disorders in Individuals without Diabetes and with Normoalbuminuria
Lorenzo et al.
CJASN 2008;3:783-789.
ABSTRACT
| FULL TEXT
Association of Albuminuria and Cancer Incidence
Jorgensen et al.
J. Am. Soc. Nephrol. 2008;19:992-998.
ABSTRACT
| FULL TEXT
Telemedicine Home Blood Pressure Measurements and Progression of Albuminuria in Elderly People With Diabetes
Palmas et al.
Hypertension 2008;51:1282-1288.
ABSTRACT
| FULL TEXT
Predictors of new-onset decline in kidney function in a general middle-european population
Obermayr et al.
Nephrol Dial Transplant 2008;23:1265-1273.
ABSTRACT
| FULL TEXT
A health economic analysis of screening and optimal treatment of nephropathy in patients with type 2 diabetes and hypertension in the USA
Palmer et al.
Nephrol Dial Transplant 2008;23:1216-1223.
ABSTRACT
| FULL TEXT
Development and Validation of an All-Cause Mortality Risk Score in Type 2 Diabetes: The Hong Kong Diabetes Registry
Yang et al.
Arch Intern Med 2008;168:451-457.
ABSTRACT
| FULL TEXT
Cardiovascular Literature--Beyond Nephrology
Ritz
CJASN 2008;3:317-323.
FULL TEXT
Medical Treatment of Advanced Testicular Cancer
Feldman et al.
JAMA 2008;299:672-684.
ABSTRACT
| FULL TEXT
Microalbuminuria in Type 2 Diabetes and Hypertension: A marker, treatment target, or innocent bystander?
Basi et al.
Diabetes Care 2008;31:S194-S201.
FULL TEXT
Heart Disease and Stroke Statistics--2008 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Writing Group Members et al.
Circulation 2008;117:e25-e146.
FULL TEXT
Mild renal dysfunction associated with incident coronary artery disease in young males
Pereg et al.
Eur Heart J 2008;29:198-203.
ABSTRACT
| FULL TEXT
Evaluation of renal function in leprosy: a study of 59 consecutive patients
Oliveira et al.
Nephrol Dial Transplant 2008;23:256-262.
ABSTRACT
| FULL TEXT
Renal Insufficiency and Mortality in Patients with Known or Suspected Coronary Artery Disease
van Domburg et al.
J. Am. Soc. Nephrol. 2008;19:158-163.
ABSTRACT
| FULL TEXT
Being Overweight Modifies the Association Between Cardiovascular Risk Factors and Microalbuminuria in Adolescents
Nguyen et al.
Pediatrics 2008;121:37-45.
ABSTRACT
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Influence of Albuminuria on Cardiovascular Risk in Patients With Stable Coronary Artery Disease
Solomon et al.
Circulation 2007;116:2687-2693.
ABSTRACT
| FULL TEXT
Plasma matrix metalloproteinase-9 and ACE-inhibitor-induced improvement of urinary albumin excretion in non-diabetic, microalbuminuric subjects
van de Wal et al.
Journal of Renin-Angiotensin-Aldosterone System 2007;8:177-180.
ABSTRACT
Change in Albuminuria Is Predictive of Cardiovascular Outcome in Normotensive Patients With Type 2 Diabetes and Microalbuminuria
Zandbergen et al.
Diabetes Care 2007;30:3119-3121.
FULL TEXT
Diabetes, the Metabolic Syndrome, and Ischemic Stroke: Epidemiology and possible mechanisms
Air and Kissela
Diabetes Care 2007;30:3131-3140.
FULL TEXT
Review: Renin-angiotensin-aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection
Whaley-Connell et al.
Ther Adv Cardiovasc Dis 2007;1:27-35.
ABSTRACT
Screening for Coronary Artery Disease in Patients With Diabetes
Bax et al.
Diabetes Care 2007;30:2729-2736.
ABSTRACT
| FULL TEXT
Relation of Left Ventricular Hypertrophy With Systemic Inflammation and Endothelial Damage in Resistant Hypertension
Salles et al.
Hypertension 2007;50:723-728.
ABSTRACT
| FULL TEXT
How common is early chronic kidney disease?: A Background Paper prepared for the UK Consensus Conference on Early Chronic Kidney Disease
MacGregor
Nephrol Dial Transplant 2007;22:ix8-ix18.
FULL TEXT
Are Patients Who Have Metabolic Syndrome without Diabetes at Risk for Developing Chronic Kidney Disease? Evidence Based on Data from a Large Cohort Screening Population
Rashidi et al.
CJASN 2007;2:976-983.
ABSTRACT
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Exacerbation of Albuminuria and Renal Fibrosis in Subtotal Renal Ablation Model of Adiponectin-Knockout Mice
Ohashi et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:1910-1917.
ABSTRACT
| FULL TEXT
Albuminuria and Risk of Nonvertebral Fractures
Jorgensen et al.
Arch Intern Med 2007;167:1379-1385.
ABSTRACT
| FULL TEXT
Cross-Classification of Microalbuminuria and Reduced Glomerular Filtration Rate: Associations Between Cardiovascular Disease Risk Factors and Clinical Outcomes
Foster et al.
Arch Intern Med 2007;167:1386-1392.
ABSTRACT
| FULL TEXT
Chronic Kidney Disease: Effects on the Cardiovascular System
Schiffrin et al.
Circulation 2007;116:85-97.
ABSTRACT
| FULL TEXT
Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men
Ingelsson et al.
Eur Heart J 2007;28:1739-1745.
ABSTRACT
| FULL TEXT
The Unique Character of Cardiovascular Disease in Chronic Kidney Disease and Its Implications for Treatment with Lipid-Lowering Drugs
Nogueira and Weir
CJASN 2007;2:766-785.
ABSTRACT
| FULL TEXT
Central Obesity Is an Independent Risk Factor for Albuminuria in Nondiabetic South Asian Subjects
Chandie Shaw et al.
Diabetes Care 2007;30:1840-1844.
ABSTRACT
| FULL TEXT
Pharmacoeconomic Analysis of Angiotensin-Converting Enzyme Inhibitors in Type 2 Diabetes: A Markov Model
Campbell et al.
The Annals of Pharmacotherapy 2007;41:1101-1110.
ABSTRACT
| FULL TEXT
2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)
Authors/Task Force Members: et al.
Eur Heart J 2007;0:ehm236v1-75.
FULL TEXT
Dyslipidaemia as predictor of progressive renal failure and the impact of treatment with atorvastatin
Ozsoy et al.
Nephrol Dial Transplant 2007;22:1578-1586.
ABSTRACT
| FULL TEXT
Reduction in Microalbuminuria as an Integrated Indicator for Renal and Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
Araki et al.
Diabetes 2007;56:1727-1730.
ABSTRACT
| FULL TEXT
Estimated Glomerular Filtration Rate and Urinary Albumin Excretion Are Independently Associated with Greater Arterial Stiffness: The Hoorn Study
Hermans et al.
J. Am. Soc. Nephrol. 2007;18:1942-1952.
ABSTRACT
| FULL TEXT
Microalbuminuria and Cardiovascular Disease
Weir
CJASN 2007;2:581-590.
ABSTRACT
| FULL TEXT
Albuminuria as risk factor for initiation and progression of carotid atherosclerosis in non-diabetic persons: the Tromso Study
Jorgensen et al.
Eur Heart J 2007;28:363-369.
ABSTRACT
| FULL TEXT
What Predicts Progression and Regression of Urinary Albumin Excretion in the Nondiabetic Population?
Brantsma et al.
J. Am. Soc. Nephrol. 2007;18:637-645.
ABSTRACT
| FULL TEXT
What's new in hypertension?
Mann
Nephrol Dial Transplant 2007;22:47-52.
FULL TEXT
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