Published online before print November 17, 2003, doi: 10.1161/01.CIR.0000103667.27493.32
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;108:2783.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Microalbuminuria and All-Cause Mortality in Treated Hypertensive Individuals
Does Sex Matter?: The Nord-Trøndelag Health Study (HUNT), Norway
From the HUNT Research Center, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Verdal (S.R., J.H., K.K.); the Department of Internal Medicine, Levanger Hospital, Levanger (S.R., H.H., H.E.); and the Nærøy Health Center, Nærøy (K.K.), Norway.
Correspondence to Solfrid Romundstad, HUNT Research Center, Faculty of Medicine, NTNU, Neptunvegen 1, N-7650 Verdal, Norway. E-mail solfrid.romundstad{at}medisin.ntnu.no
Received March 19, 2003; de novo received June 17, 2003; revision received September 11, 2003; accepted September 12, 2003.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— In hypertensive individuals, few prospective studies are available in which the association between microalbuminuria (MA) and all-cause mortality in the 2 sexes have been studied within the same population.
Methods and Results— We conducted a 4.3-year follow-up of 2307 men and 3062 women (
20 years old) with self-reported treated hypertension, all identified in the Nord-Trøndelag Health Study (HUNT), Norway, 1995 to 1997 (n=65 258). The main outcome measures were relative risk (RR) of all-cause mortality according to increasing albuminuria, defined at different levels of albumin-to-creatinine ratio (ACR). There was a consistent positive association between increasing ACR and all-cause mortality in men. The adjusted RR for ACR in the fourth quartile (1.70 mg/mmol) was 1.6 (95% CI, 1.0 to 2.6), compared with ACR in the first quartile (<0.55 mg/mmol). The corresponding RR in women was 1.5 (95% CI, 0.8 to 3.1). We found a positive association between mortality and increasing number of urine samples with ACR above different cutoff levels, especially in men. In 3 urine samples, the lowest ACR level associated with mortality in men was 0.86 mg/mmol, RR 1.6 (95% CI, 1.1 to 2.4). The sex differences persisted after exclusion of those who died during the first year of follow-up, those with hypertension not treated optimally, and those with known cardiovascular disease.
Conclusions— The association between ACR and all-cause mortality was stronger in treated hypertensive men than in women. The persistent sex differences indicate that hypertensive women tolerate MA better than men and that MA in women should be interpreted differently than in men.
Key Words: albuminuria • hypertension • mortality • follow-up studies • sex
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The excretion of small amounts of albumin in the urine, ie, microalbuminuria (MA), has been well documented to predict renal failure and cardiovascular (CV) morbidity and mortality in diabetic persons.1–5 In hypertensive persons, the prognostic significance of MA remains controversial, because few prospective studies are available in hypertensive individuals without diabetes mellitus.6 Several cross-sectional studies have been performed in hypertensive individuals, and the association between MA and CV risk factors has been found in some studies but not in others.7–9 In addition, the relationship between MA and indicators of hypertensive target organ damage, such as left heart ventricular hypertrophy,10 increased carotid intima-media thickness,11,12 and funduscopic changes,9 has been found in cross-sectional studies. In follow-up studies in nondiabetic hypertensive individuals published to date, MA seems to predict an increased risk of CV morbidity and mortality,13–17 but the study populations are small, with few cases, and some of the studies have included diabetic subjects. Furthermore, in some studies, only men are included.13,14 The aim of this study was to examine the association between MA and 4.3-year all-cause mortality in both men and women in a wide age range, without known diabetes mellitus but with treated hypertension, all selected from the large population-based Nord-Trøndelag Health Study (HUNT). We also wanted to examine the lowest ACR level and the number of positive urine samples needed to demonstrate all-cause mortality.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Subjects
During 1995 to 1997, a general health survey was conducted in Nord-Trøndelag County, Norway. All residents
20 years old (n=92 703) were invited, and 70.4% participated. The survey comprised a questionnaire, which included questions on CV disease (CVD; angina pectoris, myocardial infarction, and stroke), smoking habits, etc, and a clinical examination. Details of the HUNT study design and MA screening have been published.18 Briefly, those who self-reported diabetes mellitus and/or treated hypertension and a 5% randomly selected sample of the total population were included in MA screening. A total of 9598 participants delivered 3 morning urine samples for MA analysis (overall response rate, 82.3%). The present analysis is limited to the nondiabetic individuals who reported use of "antihypertensive medication now," in which 5755 subjects (89.4%) attended. Those who answered "yes" to one of the questions about urinary tract infection (UTI) in the previous week, persistent hematuria in the previous year, and menstruation at time of collection were excluded from the analysis (73 men, 139 women), as were 37 individuals with glucose 11.1 mmol/L and 134 individuals with macroalbuminuria (ACR 30 mg/mmol), leaving 2307 men and 3062 women to be included in the analyses.
Clinical Examination
The clinical examination included measurement of height, weight, blood pressure, and resting pulse rate. Height was measured without shoes to the nearest centimeter, and weight was measured to the nearest half-kilogram with the subject wearing light clothing without shoes. Three consecutive standardized blood pressure measurements were recorded at 1-minute interval. The measurements were performed in the sitting position, after a minimum of 2 minutes of rest, by an automatic oscillometric method (Dinamap 845XT; Criticon).
Urine Sampling
The participants included in MA screening received a unit with 3 plastic receptacles for 3 first morning urine samples and 3 transport tubes and 1 envelope for return by mail back to the laboratory. Written instructions were included, describing how to collect urine, information about the MA screening, and a questionnaire about UTI in the previous week, persistent hematuria in the last year, and menstruation at time of collection.
Blood Sampling: Laboratory Procedures
Blood sampling was performed whenever subjects attended (ie, in the nonfasting state). Fresh serum and urine samples were analyzed at the Central Laboratory at Levanger Hospital on a Hitachi 91 Autoanalyzer. Details of the laboratory methods have been published elsewhere.19 Urine albumin and creatinine were measured by an immunoturbidimetric method (anti-human serum albumin, Dako Norway) and the Jaffé method, respectively.9,20 The albumin-to-creatinine ratio (ACR) was used as an expression for urine albumin excretion.9
Follow-Up and End Points
The unique 11-digit identification number of every Norwegian citizen enabled individual linkage between the collected information and the Death Registry at Statistics Norway to determine vital status (alive, emigrated, dead). Each participant contributed person-years from the date of study entry (date of clinical examination) until the date of death or the end of follow-up of December 31, 2000. Median and mean follow-up times were 4.3 years.
Statistical Analysis
Body mass index was calculated in kilograms per meter squared. Systolic (SBP) and diastolic (DBP) blood pressures were calculated as the mean of the second and third of 3 measurements. Pack-years was defined as the product of number of cigarettes smoked daily and the number of years with daily smoking divided by 20. ACR was calculated as mean of 3 ACRs. Unpaired t tests or 
2 statistics were used to examine for baseline differences between 2 means or proportions.
The Cox proportional hazards model21 was used to calculate age- and multivariate-adjusted risk ratios (RRs) with 95% confidence interval (CI) for all-cause mortality according to increasing albuminuria, defined at different ACR levels expressed in quartiles and in 1, 2, or 3 urine samples above the different levels. A 2-sided test for trend across ACR categories was calculated by treating the categories as ordinal variables in the proportional hazards model. The individual number of person-years was included as the dependent variable. We evaluated potentially confounding factors in a multivariate analysis, including history of CVD, cancer, and long-term illness (yes/no); years of education (primary and lower secondary school [<10 years], upper secondary school [10 to 12 years], and college or university [>12 years]); pack-years (0, 1 to 10, >10); and continuous variables as duration of hypertensive treatment, body mass index, creatinine, triglycerides, cholesterol/HDL ratio, glucose, SBP, and DBP. Adjustment for age was obtained by using 5-year categories (55 years). The age groups <55 years were analyzed combined. Variables that significantly predicted the point estimate in bivariate analyses were included and adjusted for in forward and backward multiple analyses. Variables that did not change the point estimates (>20%) in the multivariate model were excluded from the fully adjusted model.
We ran the main analyses with the sexes combined. Men and women differ with regard to atherosclerotic risk factors and CVD, also associated with MA.22 We provided the interaction analyses sexxACR and sexxage, in which the interaction sexxACR was statistically significant in several of the analyses. Analyzing men and women combined revealed the interaction sexxACR to be highly significant (P=0.003) (see Table 2). We therefore chose to stratify by sex in the main analyses. To reduce further confounding with underlying disease, we also performed analyses by excluding individuals with known CVD, those who died during the first year of follow-up, and those with SBP 160 mm Hg and/or DBP 90 mm Hg. All statistical analyses were performed using the software SPSS, version 11.0.
|
Consent
Attendance was voluntary, and each participant signed a written consent. All surveys were approved by the Norwegian Data Inspectorate and by the Regional Committee for Ethics in Medical Research. The Ministry of Health accepted linkage to mortality statistics.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
During 23 153 person-years of follow-up, 256 men and 237 women died. Table 1 shows the baseline characteristics of men and women with ACR in the fourth quartile (men
1.70, women 1.48 mg/mmol) compared with those with ACR level in the 3 lower quartiles. Those with ACR level in the fourth quartile were older and had higher mean SBP, DBP, and creatinine values than those with lower ACR. They also had a higher mean duration of treated hypertension. Women had a more favorable lipid risk profile, with higher mean HDL cholesterol, than men. The prevalence of CVD and cancer and the proportion of daily smokers were higher in both sexes with ACR in the fourth quartile compared with those below (Table 1). Although this was a treated hypertensive sample, 
50% had elevated BP (SBP 160 mm Hg/DBP 90 mm Hg). Table 2 shows the results of age- and multivariate-adjusted analyses at different ACR levels expressed in quartiles for men and women separately. We found a positive association between increasing ACR and all-cause mortality in men, in which the test for trend across levels of ACR was statistically significant. In men, ACR in the fourth quartile (1.70 mg/mmol) was associated with increased RR of all-cause mortality, 1.6 (95% CI, 1.0 to 2.6), compared with ACR in the first quartile (<0.55 mg/mmol). In women, the corresponding result was RR 1.5 (95% CI, 0.8 to 3.1). Table 3 shows the results of age- and multivariate-adjusted analyses with 1, 2, or 3 of 3 ACRs above different levels. There was a positive association between all-cause mortality and increasing number of urine samples with ACR above the different cutoff levels in men. In 3 urine samples, the lowest ACR level associated with mortality in men was 0.86 mg/mmol (the cutoff level between the first and second quartiles), RR 1.6 (95% CI, 1.1 to 2.4). The corresponding result in women was RR 1.3 (95% CI, 0.8 to 2.3). The associations between all-cause mortality and 1 or 2 ACRs above the different levels were not statistically significant.
|
|
In separate analyses, we excluded those with hypertension not treated optimally (SBP 160 mm Hg and/or DBP 90 mm Hg), those with known CVD, and those who died during the first year of follow-up, thereby reducing the effects of preterminal or serious disease at baseline. In men, there was still a positive association between mortality and 3 ACRs above the different cutoff levels. P for trend across number of urine samples was statistically significant in men but not in women (Table 4). Blood sampling was performed in the nonfasting state, and some undetected diabetic subjects might have been included. We repeated the analyses without individuals who had glucose values >7.0 and <11.0 mmol/L after 5 hours or more (n=24) since eating/drinking. The main results did not change.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This study demonstrated a positive association between all-cause mortality and MA, expressed as ACR, in hypertensive men. Although this was a treated hypertensive sample,
50% had SBP 160 mm Hg and/or DBP 90 mm Hg, indicating that it was not an optimally treated population. When we compared ACR in the fourth quartile with the first quartile, men had a 60% higher risk of death. The association in women was weaker, and in contrast to men, there was no positive association with increasing number of urine samples with ACR above the different cutoff levels. The sex differences persisted after adjustment for several confounders and exclusion of individuals with SBP 160 mm Hg, DBP 90 mm Hg, known CVD, and those who died during the first year of follow-up.
This is one of the largest follow-up studies of the association between MA and mortality in hypertensive men and women 20 years old. The population-based approach and the high attendance rate make selection bias unlikely. The response rate was especially high in the hypertensive persons who were screened for MA. Approximately 90% handed in all 3 urine samples.18 Another strength of this study was that MA analyses were performed in fresh urine samples without long-term storage, in contrast to other studies.17 Several studies conclude that measuring ACR is a specific and sensitive alternative to 24-hour urine collection in population-based MA screenings.20,23,24 We chose to analyze on all-cause mortality, because data on vital status were complete and data on CV mortality were not yet obtainable. In addition, in Norway, the main cause of death is CV events.25
One of the limitations of the study is the selection of treated hypertensive subjects. This might reduce the generalizability. However, several of the participants in this sample were not treated optimally, and they would probably be more similar to untreated than treated hypertensive individuals.
Comparison of follow-up studies of hypertensive individuals with MA are difficult because of the different selection criteria and end points, different methods of urine collection, and number of urine samples used to define MA. In untreated hypertensive persons, women are included in 3 follow-up studies.15–17 In 2 of these, MA, defined as 30 to 300 mg over a 24-hour period and ACR 90th percentile (1.07 mg/mmol) in 1 morning spot urine predicted the development of ischemic heart disease after 715 and 10 years,17 respectively. In the third study, the RR of all-cause mortality in the nondiabetic hypertensive subgroup was not significantly associated with MA, defined as ACR >2.0 mg/mmol in 1 morning spot urine.16 In prospective studies in treated hypertensive persons, only men are included, and Agewall et al14 found that only macroalbuminuria predicted total and CV death, not MA, defined as 21 to 200 µg/min in 1 overnight urine sample. Also, in our study, 1 urine sample with ACR above a chosen cutoff level did not predict increased mortality.
Sex Differences
To the best of our knowledge, this is the first study demonstrating a stronger association between MA and total mortality in hypertensive men than in women, and we have reviewed several potential explanations behind this finding. The RR values of 1.6 (1.0 to 2.6) in men and 1.5 (0.8 to 3.1) in women (Table 2) are rather similar and might be caused by chance. However, the interaction sexxACR was statistically significant (P=0.003) and supports a sex difference. Lack of statistical power seems unlikely to explain the sex differences, because more women than men and almost equal numbers of cases were included in the analysis (Tables 3 and 4
). Better-treated BP levels could not explain the differences either, because mean SBP and proportion with SBP 160 mm Hg were higher in women than in men. However, women generally have white-coat hypertension more often than men,26,27 and this could weaken the MA-mortality association. Compared with men, the lipid profile in women was more favorable with higher mean HDL level and a lower proportion had known CVD, indicating that women had a generally lower CV risk at baseline than men. Women might have had more asymptomatic UTI than men,28 leading to a misclassification in which MA does not reflect increased CV risk/disease. Those who reported UTI were excluded from the analyses, but we were not able to adjust for asymptomatic UTI. Theoretically, women could have died of causes other than CVD, and the follow-up time could have been too short to detect CV death in women. However, in this elderly hypertensive population, the risk of CV death is higher than in the general population in both men and women. Men and women might need different ACR cutoff levels for risk prediction, because men have greater muscle mass and thus higher creatinine excretion than women, although the albumin excretion levels are equal. Applying higher cutoff levels in women, we found a positive association between mortality and 3 ACRs, but not until ACR 95th percentile (4.70 mg/mmol), RR 2.8 (95% CI, 1.2 to 6.5), also with a significant trend across number of urine samples (data not shown).
Whatever the explanation, the persistent sex differences in this study indicate that hypertensive women tolerate MA identified in a screening better than men and that MA in women should be interpreted differently than in men. Generally, women tolerate CV risk factors better than men do, and our data indicate that this includes MA.
Levels of Association
In hypertensive individuals, there are no established clinical cutoff levels of urine albumin excretion. In the study from Denmark,17 ACR level above the 90th percentile (1.07 mg/mmol) significantly predicted ischemic heart disease after 10 years of follow-up. In our study, men showed a statistically significant increase in RR at ACR levels as low as 0.86 mg/mmol, with use of 3 urine samples. This level of association, however, should not be misinterpreted as a clinical cutoff level at which therapeutic interventions should be initiated. Thus far, we have no clinical trials demonstrating treatment effect on morbidity and mortality at such low ACR levels.
Number of Urine Samples
Until now, no other study has compared 1, 2, or 3 urine samples with elevated ACR and the prediction of all-cause mortality. One or 2 urine samples with elevated ACR might simply reflect the biological variation with intermittent albuminuria, whereas elevated ACR in 3 urine samples reflects persistent albuminuria and more likely explains a constant CV risk/disease. Three urine samples were superior in predicting all-cause mortality in the present study.
Conclusions
This large prospective study on the relationship between MA and mortality in hypertensive individuals indicates sex differences in the association between all-cause mortality and MA, a stronger association in men than in women. Women seemed to tolerate MA better than men. Thus far, we do not know whether MA in treated hypertensive individuals indicates that a more aggressive treatment of risk factors should be initiated. Before clinical cutoff levels are established, intervention trials are necessary.
|
Acknowledgments |
|---|
The Nord-Trøndelag Health Study (HUNT Study) is a collaboration between the HUNT Research Center, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Verdal; the Norwegian Institute of Public Health, Oslo; Nord-Trøndelag County Council; and Levanger Hospital, Levanger, Norway. The microalbuminuria study was also supported financially by the Norwegian Health Association, Norway, and Merck Sharp & Dohme. We especially thank the health service and people of Nord-Trøndelag for their endurance and participation.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984; 310: 356–360.[Abstract]
2. Messent JWC, Elliott TG, Hill RD, et al. Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. Kidney Int. 1992; 41: 836–839.[Medline] [Order article via Infotrieve]
3. Neil A, Hawkins M, Potok M, et al. A prospective population-based study of microalbuminuria as a predictor of mortality in NIDDM. Diabetes Care. 1993; 16: 996–1000.[Abstract]
4. Dineen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview. Arch Intern Med. 1997; 157: 1413–1418.
5. Spoelstra-de Man AME, Brouwer CB, Stehouwer CDA, et al. Rapid progression of albumin excretion is an independent predictor of cardiovascular mortality in patients with type 2 diabetes and microalbuminuria. Diabetes Care. 2001; 24: 2097–2101.
6. Rosa TT, Palatini P. Clinical value of microalbuminuria in hypertension. J Hypertens. 2000; 18: 645–654.[CrossRef][Medline] [Order article via Infotrieve]
7. Summerson JH, Bell RA, Konen JC. Racial differences in the prevalence of microalbuminuria in hypertension. Am J Kidney Dis. 1995; 26: 577–579.[Medline] [Order article via Infotrieve]
8. Jensen JS, Feldt-Rasmussen B, Borch-Johansen K, et al. Microalbuminuria and its relation to cardiovascular disease and risk factors: a population-based study of 1245 hypertensive individuals. J Hum Hypertens. 1997; 11: 727–732.[CrossRef][Medline] [Order article via Infotrieve]
9. Pontremoli R, Sofia A, Ravera M, et al. Prevalence and clinical correlates of microalbuminuria in essential hypertension (the MAGIC study). Hypertension. 1997; 30: 1135–1143.
10. Pontremoli R, Nicolella C, Viazzi F, et al. Microalbuminuria is an early marker of target organ damage in essential hypertension. Am J Hypertens. 1998; 11: 430–438.[CrossRef][Medline] [Order article via Infotrieve]
11. Bigazzi R, Bianchi S, Nenci R, et al. Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria. J Hum Hypertens. 1995; 9: 827–833.[Medline] [Order article via Infotrieve]
12. Mykkanen L, Zaccaro DJ, O’Leary DH, et al. Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke. 1997; 28: 1710–1716.
13. Ljungman S, Wikstrand J, Hartford M, et al. Urinary albumin excretion: a predictor of risk of cardiovascular disease: a prospective 10-year follow-up of middle-aged nondiabetic normal and hypertensive men. Am J Hypertens. 1996; 9: 770–778.[CrossRef][Medline] [Order article via Infotrieve]
14. Agewall S, Wikstrand J, Ljungman S, et al. Usefulness of microalbuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Am J Cardiol. 1997; 80: 164–169.[CrossRef][Medline] [Order article via Infotrieve]
15. Bigazzi R, Bianchi S, Baldari D, et al. Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. J Hypertens. 1998; 16: 1325–1333.[CrossRef][Medline] [Order article via Infotrieve]
16. Jager A, Kostense PJ, Ruhé HG, et al. 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. 1999; 19: 617–624.
17. Jensen JS, Feldt-Rasmussen B, Strandgaard S, et al. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension. 2000; 35: 898–903.
18. Hallan H, Romundstad S, Kvenild KT, et al. Microalbuminuria in diabetic and hypertensive patients and the general population: consequences of various diagnostic criteria. The Nord-Trøndelag Health Study (HUNT). Scand J Urol Nephrol. 2003; 37: 151–158.[CrossRef][Medline] [Order article via Infotrieve]
19. Midthjell K, Krüger Ø, Holmen J, et al. Rapid changes in the prevalence of obesity and known diabetes in an adult Norwegian population. Diabetes Care. 1999; 22: 1813–1820.
20. Gatling W, Knight C, Mullee MA, et al. Microalbuminuria in diabetes: a population study of prevalence and an assessment of three screening tests. Diabetic Med. 1988; 5: 343–347.[Medline] [Order article via Infotrieve]
21. Kleinbaum DG. Survival Analysis: A Self Learning Approach. New York: Springer-Verlag; 1996.
22. Verhave JC, Hillege HL, Burgerhof JGM, et al. Cardiovascular risk factors are differently associated with urinary albumin excretion in men and women. J Am Soc Nephrol. 2003; 14: 1330–1335.
23. Bakker AJ. Detection of microalbuminuria: receiver operating characteristic curve analysis favors albumin-to-creatinine ratio over albumin concentration. Diabetes Care. 1999; 22: 307–313.
24. Jensen JS, Clausen P, Borch-Johnsen K, et al. Detecting microalbuminuria by urinary albumin/creatinine concentration ratio. Nephrol Dial Transplant. 1997; 12 (suppl 2): 6–9.
25. Statistical Yearbook of Norway. Central Bureau of Statistics: Kongsvinger, Oslo; 2000.
26. MacDonald MB, Laing GP, Wilson MP, et al. Prevalence and predictors of white-coat response in patients with treated hypertension. CMAJ. 1999; 161: 265–269.
27. Martínez MA, García-Puig J, Martín JC, et al. Frequency and determinants of white coat hypertension in mild to moderate hypertension: a primary care-based study. Am J Hypertens. 1999; 12: 251–259.[CrossRef][Medline] [Order article via Infotrieve]
28. Stein G, Fünfstück R. Asymptomatic bacteriuria: what to do? Nephrol Dial Transplant. 1999; 14: 1618–1621.
This article has been cited by other articles:
 |
|
 |
|
  M. Baekken, I. Os, L. Sandvik, and O. Oektedalen Microalbuminuria associated with indicators of inflammatory activity in an HIV-positive population Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3130 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Danziger Importance of Low-Grade Albuminuria Mayo Clin. Proc., July 1, 2008; 83(7): 806 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Basi, P. Fesler, A. Mimran, and J. B. Lewis Microalbuminuria in Type 2 Diabetes and Hypertension: A marker, treatment target, or innocent bystander? Diabetes Care, February 1, 2008; 31(Supplement_2): S194 - S201. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Redon, F. Morales-Olivas, A. Galgo, M. A. Brito, J. Mediavilla, R. Marin, P. Rodriguez, S. Tranche, J. V. Lozano, C. Filozof, et al. Urinary Albumin Excretion and Glomerular Filtration Rate across the Spectrum of Glucose Abnormalities in Essential Hypertension J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S236 - S245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, E. T Lee, L. G Best, M. Begum, W. C Knowler, R. R Fabsitz, and B. V Howard Association of albuminuria with all-cause and cardiovascular disease mortality in diabetes: the Strong Heart Study The British Journal of Diabetes & Vascular Disease, November 1, 2005; 5(6): 334 - 340. [Abstract] [PDF]
|
|
|
|
 |
|
 K. P. Klausen, H. Scharling, G. Jensen, and J. S. Jensen New Definition of Microalbuminuria in Hypertensive Subjects: Association With Incident Coronary Heart Disease and Death Hypertension, July 1, 2005; 46(1): 33 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Klausen, K. Borch-Johnsen, B. Feldt-Rasmussen, G. Jensen, P. Clausen, H. Scharling, M. Appleyard, and J. S. Jensen Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes Circulation, July 6, 2004; 110(1): 32 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. SoRelle Cardiovascular News Circulation, December 2, 2003; 108 (22): e9072 - e9076. [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||