ADMA

Optimal Result: 0 - 100 ng/mL.

ADMA/SDMA may be measured in individuals with multiple risk factors for the development of CVD.

One of the earliest manifestations of endothelial dysfunction is nitric oxide (NO) deficiency, which promotes atherosclerosis. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), its structural isomer, are metabolites of L-arginine, an amino acid that is catalyzed to L-citrulline and NO by nitric oxide synthase (NOS).

Both ADMA and SDMA have distinct pathophysiologies and manifestations. ADMA is a competitive inhibitor of NOS thereby reducing NO production and promoting endothelial dysfunction. SDMA also interferes with NO production, but does so indirectly by reducing the cellular availability of arginine. ADMA is primarily cleared through enzymatic degradation in the bloodstream and its presence identifies subclinical cardiovascular disease (CVD). Conversely, SDMA is primarily excreted in the urine and identifies reduced renal function.

Interpretation:

ADMA: Low // SDMA: Low

Normal endothelial function Med High Low

ADMA: Med / High // SDMA: Low

Endothelial dysfunction and possible presence of pre-diabetes/diabetes or CVD

ADMA: Low // SDMA: High

Reduced renal function

ADMA: Med / High // SDMA: High

- Endothelial dysfunction and possible presence of pre-diabetes/diabetes or CVD

- Reduced renal function

References:

American Diabetes Association Professional Practice Committee; 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2022Diabetes Care 1 January 2022; 45 (Supplement_1): S125–S143. https://doi.org/10.2337/dc22-S009

What does it mean if your ADMA result is too high?

Elevated levels of ADMA may identify:

- Endothelial dysfunction

- Pre-diabetes/diabetes

- Subclinical cardiovascular disease

Higher levels of ADMA are associated with a 1.40x increased risk of CVD and coronary heart disease, as well as a 1.60x increased risk of stroke, in a general population.

-- Elevated ADMA levels are associated with the presence of hypertension, insulin resistance, and hyperlipidemia.

-- Elevated ADMA levels are associated with subclinical atherosclerosis:

  • Increased ADMA concentrations correlate with internal carotid artery bulb intimal media thickness, a hemodynamically unstable region vulnerable to NO deficiency and plaque formation.
  • Elevated ADMA in young adults is associated with increased coronary artery calcification. 

-- Individuals with established coronary artery disease and elevated ADMA levels have more than twice the risk for adverse events (myocardial infarction, stroke) than those with normal ADMA levels.

Treatment Considerations:

These treatment considerations are for educational purposes only. Specific treatment plans should be provided and reviewed by the treating practitioner.

Assess lifestyle habits.
 - Consider diet, exercise, and weight reduction efforts, if appropriate.

Assess LDL-C levels.
- If not at an optimal level, consider lipid-lowering therapies described in the National Cholesterol Education Program/Adult Treatment Panel III (NCEP ATP III) Guidelines. [L]

Assess insulin sensitivity.

- If not at an optimal level, consider insulin-sensitizing therapies described in the American Diabetes Association guidelines for the management of pre-diabetes/ diabetes. [L]

Assess blood pressure.

- If not at an optimal level, consider initiating, or titrating, antihypertensive therapy.

- Consider L-arginine or L-citrulline supplementation to enhance NO production, and to improve vasodilation and vascular tone.

Assess the presence of coronary artery disease (CAD) with imaging techniques, such as carotid intima-media thickness (CIMT) testing or coronary artery calcium (CAC) scoring.

Assess clotting risk.
- Consider antiplatelet therapy if history of CAD (i.e., myocardial infarction or revascularization) and/or cerebrovascular disease (i.e., transient ischemic attack or stroke).

Assess renal function.

- If SDMA levels are not optimal, consider further assessment and treatment considerations for kidney disease, as outlined in the National Kidney Foundation guidelines. [L]

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