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Circulation. 2006;113:e406-e407
doi: 10.1161/CIRCULATIONAHA.105.105.583252
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(Circulation. 2006;113:e406-e407.)
© 2006 American Heart Association, Inc.


Correspondence

Letter Regarding Article by Arnlov et al, "Low-Grade Albuminuria and Incidence of Cardiovascular Disease Events in Nonhypertensive and Nondiabetic Individuals"

Folkert W. Asselbergs, MD, PhD; P. van der Harst, MD; Wiek H. van Gilst, PhD

Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands, fwasselbergs{at}hotmail.com

To the Editor:

Recently, researchers from the Framingham Heart Study reported in Circulation that in middle-aged, nonhypertensive, nondiabetic subjects, low-grade albuminuria predicted the development of cardiovascular disease.1 Subjects with previous coronary heart disease, diabetes mellitus, proteinuria, and hypertension (≥140/90 mm Hg) were excluded from these analyses. In addition to the strong prognostic value of urine albumin excretion in the lower range, another intriguing finding was reported: Baseline characteristics did not differ between subjects with urinary albumin excretion above or below the median. More specifically, body mass index, systolic and diastolic blood pressures, and smoking status did not differ between these groups. All of these factors have previously been reported to influence microalbuminuria.2 In particular, blood pressure is strongly related to the presence and level of albuminuria. We believe that there is no apparent reason to assume that the cutoff value for blood pressure, below which blood pressure would not affect the level of microalbuminuria, be set at 140/90 mm Hg. Therefore, we question how the authors can explain the absence of any association between low-grade albuminuria and traditional cardiovascular risk factors in The Framingham Heart Study.


*    Acknowledgments
 
Disclosures

None.


*    References
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*References
down arrowAcknowledgments 
down arrowReferences 
 

  1. Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, Benjamin EJ, D’Agostino RB, Vasan RS. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation. 2005; 112: 969–975.[Abstract/Free Full Text]
  2. Barzilay JI, Peterson D, Cushman M, Heckbert SR, Cao JJ, Blaum C, Tracy RP, Klein R, Herrington DM. The relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: the Cardiovascular Health Study. Am J Kidney Dis. 2004; 44: 25–34.[CrossRef][Medline] [Order article via Infotrieve]

 

Johan Ärnlöv, MD, PhD; Jane C. Evans, DSc; Thomas J. Wang, MD; Caroline S. Fox, MD, MPH; Emelia J. Benjamin, MD, ScM; Daniel Levy, MD; Ralph B. D’Agostino, PhD; Ramachandran S. Vasan, MD

From the National Heart, Lung, and Blood Institute, Framingham Heart Study, Framingham, Mass, vasan{at}bu.edu

James B. Meigs, MD, MPH

General Medicine Division, Massachusetts General Hospital, Boston, Mass

Response

We thank Dr Asselbergs and colleagues for their careful inspection of the Table in our report1 and for their expert comments. Dr Asselbergs and colleagues concluded, based on the similarity of mean values of several cardiovascular disease risk factors in subjects with urine albumin–to–creatinine ratio (UACR) values above versus below the sex-specific median, that low-grade albuminuria was not associated with cardiovascular risk factors in our study sample of individuals free of diabetes and hypertension. That conclusion, however, is not supported by our data.

It is important to clarify that the Table in our report was intended to be descriptive rather than analytic. The relations of UACR to cardiovascular risk factor levels in our sample are better assessed by multivariable linear-regression analysis. The Table presented herein shows the results of linear-regression models that identify the cross-sectional correlates of UACR (logarithmically transformed to normalize the skewed distribution). In our sample of nonhypertensive nondiabetic individuals, age, female sex, and systolic blood pressure were related directly to UACR, whereas body mass index was related inversely.


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Cross-Sectional Relations of Cardiovascular Risk Factors to (Natural Log) UACR

Also shown in the Table are results of multivariable linear-regression analysis in our complete study sample, ie, including subjects with diabetes and/or hypertension. The relations of hypertension and diabetes to UACR were modeled in 2 ways: adjusting for continuous systolic and diastolic blood pressure, hypertension treatment (yes/no), and continuous fasting blood glucose (model 1) and adjusting for hypertension (blood pressure ≥140/90 mm Hg or using antihypertensive medications) and diabetes (fasting blood glucose ≥126 mg/dL) as dichotomous variables (model 2). The larger sample size and a wider distribution of continuous risk factor values increased our statistical power to detect modest associations of cardiovascular risk factors and UACR. In model 1, UACR was related positively to age, female sex, systolic blood pressure, fasting blood sugar, and smoking but was inversely related to body mass index. Similar relations were observed for model 2. The ratio of total to HDL cholesterol was not related to UACR in any of the models that we examined.

In summary, we observed that UACR was related to select cardiovascular risk factors in both our healthier subsample and in our larger, more general study sample (consistent with other reports2–6). Our observations concur with those of other investigators who have reported weaker relations of cardiovascular risk factors to UACR in low-risk samples compared with samples including higher-risk individuals.5


*    Acknowledgments 
up arrowTop
up arrowReferences
*Acknowledgments 
down arrowReferences 
 
Disclosures

None.


*    References 
up arrowTop
up arrowReferences
up arrowAcknowledgments 
*References 
 

  1. Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, Benjamin EJ, D’Agostino RB, Vasan RS. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation. 2005; 112: 969–975.[Abstract/Free Full Text]
  2. Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R, Panarelli W, De Santo NG. Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: the Gubbio Population Study. Arch Intern Med. 1998; 158: 1933–1939.[Abstract/Free Full Text]
  3. Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, Kusek JW, Byrd-Holt D, Narayan KM, Herman WH, Jones CP, Salive M, Agodoa LY. Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2002; 39: 445–459.[Medline] [Order article via Infotrieve]
  4. Murtaugh MA, Jacobs DR Jr, Yu X, Gross MD, Steffes M. Correlates of urinary albumin excretion in young adult blacks and whites: the Coronary Artery Risk Development in Young Adults Study. Am J Epidemiol. 2003; 158: 676–686.[Abstract/Free Full Text]
  5. Romundstad S, Holmen J, Hallan H, Kvenild K, Kruger O, Midthjell K. Microalbuminuria, cardiovascular disease and risk factors in a nondiabetic/nonhypertensive population: the Nord-Trondelag Health Study (HUNT, 1995–1997), Norway. J Intern Med. 2002; 252: 164–172.[CrossRef][Medline] [Order article via Infotrieve]
  6. Yuyun MF, Khaw KT, Luben R, Welch A, Bingham S, Day NE, Wareham NJ. Microalbuminuria, cardiovascular risk factors and cardiovascular morbidity in a British population: the EPIC-Norfolk population-based study. Eur J Cardiovasc Prev Rehabil. 2004; 11: 207–213.[CrossRef][Medline] [Order article via Infotrieve]

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