Response to Letter Regarding Article, “Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function”
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 reports1-3 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.
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.
Struthers AD, Davies J. B-type natriuretic peptide: a simple new test to identify coronary artery disease? Q J Med. 2005; 98: 765–769.
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.
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.
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.