CLINICAL STUDY: ENDOTHELIAL FUNCTION
The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine
Jan L. Houghton, MD, FACC*,*,
Edward F. Philbin, MD, FACC*,
David S. Strogatz, PhD ,
Mikhail T. Torosoff, MD*,
Steven A. Fein, MD, FACC*,
Patricia A. Kuhner, RN*,
Vivienne E. Smith, MD, FACC* and
Albert A. Carr, MD
* Division of Cardiology, Department of Medicine, Albany Medical College, Albany, New York, USA
School of Public Health, State University of New York at Albany, Albany, New York, USA
Augusta Preventive Cardiology, Inc., Augusta, Georgia, USA
Manuscript received November 10, 2000;
revised manuscript received January 7, 2002,
accepted January 18, 2002.
* Reprint requests and correspondence: Dr. Jan L. Houghton, Division of Cardiology, A-44, Albany Medical College, Albany, New York 12208, USA
Houghtj{at}mail.amc.edu
OBJECTIVES: The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine.
BACKGROUND: Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied.
METHODS: Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) ± L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol.
RESULTS: In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 ± 10% vs. 4 ± 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans.
CONCLUSIONS: We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.
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Abbreviations and Acronyms
| | ACh | | acetylcholine | | ADMA | | asymmetric dimethylarginine | | ANOVA | | analysis of variance | | BMI | | body mass index | | CAD | | coronary atherosclerotic disease | | CBF | | coronary blood flow | | HDLC | | high-density lipoprotein cholesterol | | LDLC | | low-density lipoprotein cholesterol | | LV | | left ventricle/ventricular | | LVMI | | left ventricular mass indexed by body surface area | | NO | | nitric oxide |
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