Letter by Struthers et al Regarding Article, “Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function”
To the Editors:
We read with interest the article by Kathiresan et al,1 who showed that natriuretic peptides were the only biomarker independently related to endothelial function. The authors appear to imply, especially in their Clinical Perspective on page 945, that their results may be the result of natriuretic peptides influencing endothelial function. We feel that 2 other possible explanations for their finding are more likely. We previously showed in patients with diabetes that B-type natriuretic peptide (BNP) increases as the augmentation index increases.2 This suggests that stiff arteries/arterioles could increase afterload and subtly increase intracardiac pressure and thus natriuretic peptides. Endothelial dysfunction tracks with stiff arteries/arterioles.
A second possible explanation is that endothelial dysfunction may be a sign of early atherosclerosis in a wide variety of blood vessels, including the coronary vessels. In turn, coronary atherosclerosis could produce myocardial ischemia. In fact, myocardial tissue that is injured in any way such as by ischemia appears to express and release more BNP than noninjured or nonischemic myocardial tissue, irrespective of hemodynamic considerations.3,4 Thus, endothelial dysfunction could imply subtle but asymptomatic myocardial ischemia that is identifiable by a subtly elevated natriuretic peptide level. In fact, we recently showed that subtle elevations in BNP are indicative of silent myocardial ischemia in type 2 diabetics.5 We feel some combination of the above mechanisms is the likely explanation for the interesting observation from Kathiresan et al.1
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.
Goetze JP, Christoffersen C, Perko M, Arendup H, Rehfeld JF, Kastrup J, Nielsen LB. Increased cardiac expression associated with myocardial ischaemia. FASEB J. 2003; 17: 1105–1107.
Struthers AD, Davies JI. β-type natriuretic peptide: a simple new test to identify coronary artery disease? Q J Med. 2005; 98: 765–769.
Rana BS, Davies JI, Band MM, Pringle SD, Morris AD, Struthers AD β-type natriuretic peptide can detect silent myocardial ischaemia in asymptomatic type II diabetic patients. Heart. 2006; 92: 916–920.