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(Circulation. 2006;114:e384.)
© 2006 American Heart Association, Inc.

Correspondence

Response to Letter Regarding Article, "Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function"

Sekar Kathiresan, MD; Philimon Gona, PhD; Martin G. Larson, ScD; Daniel Levy, MD; Christopher Newton-Cheh, MD, MPH; Thomas J. Wang, MD; Emelia J. Benjamin, MD, ScM; Ramachandran S. Vasan, MD

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

Joseph A. Vita, MD

Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University, Boston, Mass

Gary F. Mitchell, MD

Cardiovascular Engineering, Inc, Holliston, Mass

Geoffrey H. Tofler, MD

Royal North Shore Hospital, Sydney, Australia

We thank Drs. Struthers and Lang for their thoughtful comments on the multiple mechanisms that may underlie the association of circulating natriuretic peptides with endothelial function measures. The authors note that natriuretic peptide levels correlate positively with increased vascular stiffness, subclinical myocardial ischemia, and congestive heart failure.^1–3 Because the latter 2 conditions are in turn associated with endothelial dysfunction, higher natriuretic peptide levels may be associated with lower flow-mediated dilation (FMD).

In our community-based sample,⁴ we observed a directionality of association opposite to that postulated by Drs Struthers and Lang, ie, plasma atrial natriuretic peptide was positively related to endothelial function as assessed by FMD. The cross-sectional nature of our study does not permit us to infer whether elevated natriuretic peptide levels promote increased FMD. Nonetheless, our observations are consistent with the in vitro demonstration of a vascular smooth relaxant effect for natriuretic peptides.⁵ Additionally, in studies of healthy volunteers, infusion of natriuretic peptides increases FMD.⁶

We submit that the contrasting directionality of associations observed in our study versus some other reports^1-3 may be due to differences in the study samples. We studied a large community-based sample with a low prevalence of cardiovascular disease and diabetes, whereas the studies cited by the authors evaluated referral samples with a greater prevalence of risk factors and/or cardiovascular disease. Overall, we believe that the directionality of the relation between natriuretic peptide levels and endothelial function merits further study.

	Acknowledgments

 
Disclosures

Dr Mitchell is owner of Cardiovascular Engineering, Inc, a company that designs and manufactures devices that measure vascular stiffness. The company uses these devices in clinical trials that evaluate the effects of diseases and interventions on vascular stiffness. No other author has any ownership rights or other financial relationship with Cardiovascular Engineering. Dr Levy has served as a consultant to and/or lecturer for Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, and Merck; these consultancies were terminated in 2003 or earlier. The other authors report no conflicts.

	References

Top References

 
1. Dawson A, Davies JI, Morris AD, Struthers AD. B-type natriuretic peptide is associated with both augmentation index and left ventricular mass in diabetic patients without heart failure. Am J Hypertens. 2005; 18: 1586–1591.[CrossRef][Medline] [Order article via Infotrieve]

2. Struthers AD, Davies J. B-type natriuretic peptide: a simple new test to identify coronary artery disease? Q J Med. 2005; 98: 765–769.

3. Chong AY, Blann AD, Patel J, Freestone B, Hughes E, Lip GY. Endothelial dysfunction and damage in congestive heart failure: relation of flow-mediated dilation to circulating endothelial cells, plasma indexes of endothelial damage, and brain natriuretic peptide. Circulation. 2004; 110: 1794–1798.[Abstract/Free Full Text]

4. Kathiresan S, Gona P, Larson MG, Vita JA, Mitchell GF, Tofler GH, Levy D, Newton-Cheh C, Wang TJ, Benjamin EJ, Vasan RS. Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function. Circulation. 2006; 113: 938–945.[Abstract/Free Full Text]

5. Forssmann WG, Hock D, Lottspeich F, Henschen A, Kreye V, Christmann M, Reinecke M, Metz J, Carlquist M, Mutt V. The right auricle of the heart is an endocrine organ. Cardiodilatin as a peptide hormone candidate. Anat Embryol (Berl). 1983; 168: 307–313.[CrossRef][Medline] [Order article via Infotrieve]

6. van der Zander K, Houben AJ, Kroon AA, de Leeuw PW Effects of brain natriuretic peptide on forearm vasculature: comparison with atrial natriuretic peptide. Cardiovasc Res. 1999; 44: 595–600.[Abstract/Free Full Text]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kathiresan, S. Articles by Tofler, G. H. Search for Related Content PubMed Articles by Kathiresan, S. Articles by Tofler, G. H. Related Collections Epidemiology