Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: Markers for diabetes and cardiovascular risk?

Anderson, Jeffrey L.; Carlquist, John F.; Roberts, William L.; Horne, Benjamin D.; May, Heidi T.; Schwarz, Elisabeth L.; Pasquali, Marzia; Nielson, Rebecca; Kushnir, Mark M.; Rockwood, Alan L.; Bair, Tami L.; Muhlestein, Joseph B.; for the Intermountain Heart Collaborative (IHC) Study Group,

doi:10.1016/j.ahj.2006.10.014

« Previous Next »American Heart Journal
Volume 153, Issue 1 , Pages 67-73, January 2007

Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: Markers for diabetes and cardiovascular risk?

Jeffrey L. Anderson, MD
- Cardiovascular Department, LDS Hospital
- University of Utah, Salt Lake City, UT
- Reprint requests: Jeffrey L. Anderson, MD, LDS Hospital, Cardiovascular Department, 8th Avenue and C Street, Salt Lake City, UT 84143.
John F. Carlquist, PhD
- Cardiovascular Department, LDS Hospital
- University of Utah, Salt Lake City, UT
William L. Roberts, MD PhD
- University of Utah, Salt Lake City, UT
- ARUP Laboratories, Salt Lake City, UT
Benjamin D. Horne, PhD, MPH
- Cardiovascular Department, LDS Hospital
Heidi T. May, MSPH
- Cardiovascular Department, LDS Hospital
Elisabeth L. Schwarz
- ARUP Laboratories, Salt Lake City, UT
Marzia Pasquali, PhD
- University of Utah, Salt Lake City, UT
- ARUP Laboratories, Salt Lake City, UT
Rebecca Nielson
- ARUP Laboratories, Salt Lake City, UT
Mark M. Kushnir, MS
- ARUP Laboratories, Salt Lake City, UT
Alan L. Rockwood, PhD
- ARUP Laboratories, Salt Lake City, UT
Tami L. Bair, BS
- Cardiovascular Department, LDS Hospital
Joseph B. Muhlestein, MD
- Cardiovascular Department, LDS Hospital
- University of Utah, Salt Lake City, UT
for the Intermountain Heart Collaborative (IHC) Study Group

Received 20 July 2006; accepted 9 October 2006.

Background

Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (<110 mg/dL), impaired fasting glucose (110-125), or diabetic (≥126) status.

Methods

High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 ± 1.4 years. High-pressure liquid chromatography with pre–column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoassay for C-peptide.

Results

Asymmetric dimethylarginine levels were positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA also conferred increased risk of death/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not predict outcomes.

Conclusions

Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.