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The role of asymmetric dimethylarginine alone and in combination with N-terminal pro-B-type natriuretic peptide as a screening biomarker for systemic sclerosis-related pulmonary arterial hypertension: a case control study.
Clin Exp Rheumatol. 2016 Sep-Oct; 34 Suppl 100(5):129-136.CE

Abstract

OBJECTIVES

Asymmetric dimethylarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this proof of concept study, we sought to evaluate the role of ADMA as a screening biomarker for incident systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH).

METHODS

ADMA levels were measured using high performance liquid chromatography in 15 consecutive treatment-naive patients with newly-diagnosed SSc-PAH and compared with 30 SSc-controls without PAH. Logistic regression models were used to evaluate the independent association of ADMA with PAH. The optimal cut-point of ADMA for SSc-PAH screening was determined. NT-proBNP levels were previously measured in the same patients and the optimal cut-point of NT-proBNP of ≥210ng/mL was coupled with the optimal cut-point of ADMA to create a screening model that combined the two biomarkers.

RESULTS

The PAH group had significantly higher mean ADMA levels than the control group (0.76±0.14 μM versus 0.59±0.07 μM; p<0.0001). ADMA levels remained significantly associated with PAH after the adjustment for specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications (all p<0.01). An ADMA level ≥0.7 μM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. A screening model that combined an NT-proBNP ≥210ng/mL and/ or ADMA ≥0.7 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH.

CONCLUSIONS

In this small study, use of ADMA in combination with NT-proBNP produced excellent sensitivity and specificity for the non-invasive identification of SSc-PAH. The role of ADMA as a screening biomarker for SSc-PAH merits further evaluation.

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Authors+Show Affiliations

Thakkar V
Department of Medicine; Department of Rheumatology, St. Vincent's Hospital Melbourne, Fitzroy; Department of Rheumatology, Liverpool Hospital, Liverpool; and School of Medicine, University of Western Sydney, Penrith, Australia.
Stevens W
Department of Medicine, St. Vincent's Hospital Melbourne, Fitzroy, Australia.
Prior D
Department of Cardiology, St Vincent's Hospital Melbourne, Fitzroy, Australia.
Rabusa C
Department of Rheumatology, St. Vincent's Hospital Melbourne, Fitzroy, Australia.
Sahhar J
Department of Rheumatology, Monash Medical Centre, Clayton, Australia.
Walker JG
Department of Rheumatology, Flinders Medical Centre, Bedford Park, Australia.
Roddy J
Department of Rheumatology, Royal Perth Hospital, Perth, Australia.
Lester S
Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, Australia.
Rischmueller M
Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, Australia.
Zochling J
Department of Rheumatology, The Menzies Institute, Hobart, Australia.
Nash P
Rheumatology Research Unit, Department of Medicine, University of Queensland, Maroochydore, Australia.
Gabbay E
The University of Notre Dame, Fremantle, Australia.
Youssef P
Institute of Rheumatology and Orthopaedics, Royal Prince Alfred Hospital, Camperdown, Australia.
Proudman SM
Royal Adelaide Hospital, North Terrace; and Discipline of Medicine, University of Adelaide, Australia.
Nikpour M
Department of Medicine; and Department of Rheumatology, St. Vincent's Hospital Melbourne, Fitzroy, Australia. m.nikpour@unimelb.edu.au.

MeSH

AdultArea Under CurveArginineArterial PressureAustraliaBiomarkersCase-Control StudiesChromatography, High Pressure LiquidFemaleHumansHypertension, PulmonaryLogistic ModelsMaleMiddle AgedNatriuretic Peptide, BrainPeptide FragmentsPredictive Value of TestsPrognosisPulmonary ArteryROC CurveRisk FactorsScleroderma, Systemic

Pub Type(s)

Journal Article
Multicenter Study
Observational Study

Language

eng

PubMed ID

27214686

Citation

Thakkar, Vivek, et al. "The Role of Asymmetric Dimethylarginine Alone and in Combination With N-terminal pro-B-type Natriuretic Peptide as a Screening Biomarker for Systemic Sclerosis-related Pulmonary Arterial Hypertension: a Case Control Study." Clinical and Experimental Rheumatology, vol. 34 Suppl 100, no. 5, 2016, pp. 129-136.
Thakkar V, Stevens W, Prior D, et al. The role of asymmetric dimethylarginine alone and in combination with N-terminal pro-B-type natriuretic peptide as a screening biomarker for systemic sclerosis-related pulmonary arterial hypertension: a case control study. Clin Exp Rheumatol. 2016;34 Suppl 100(5):129-136.
Thakkar, V., Stevens, W., Prior, D., Rabusa, C., Sahhar, J., Walker, J. G., Roddy, J., Lester, S., Rischmueller, M., Zochling, J., Nash, P., Gabbay, E., Youssef, P., Proudman, S. M., & Nikpour, M. (2016). The role of asymmetric dimethylarginine alone and in combination with N-terminal pro-B-type natriuretic peptide as a screening biomarker for systemic sclerosis-related pulmonary arterial hypertension: a case control study. Clinical and Experimental Rheumatology, 34 Suppl 100(5), 129-136.
Thakkar V, et al. The Role of Asymmetric Dimethylarginine Alone and in Combination With N-terminal pro-B-type Natriuretic Peptide as a Screening Biomarker for Systemic Sclerosis-related Pulmonary Arterial Hypertension: a Case Control Study. Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):129-136. PubMed PMID: 27214686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of asymmetric dimethylarginine alone and in combination with N-terminal pro-B-type natriuretic peptide as a screening biomarker for systemic sclerosis-related pulmonary arterial hypertension: a case control study. AU - Thakkar,Vivek, AU - Stevens,Wendy, AU - Prior,David, AU - Rabusa,Candice, AU - Sahhar,Joanne, AU - Walker,Jennifer G, AU - Roddy,Janet, AU - Lester,Susan, AU - Rischmueller,Maureen, AU - Zochling,Jane, AU - Nash,Peter, AU - Gabbay,Eli, AU - Youssef,Peter, AU - Proudman,Susanna M, AU - Nikpour,Mandana, Y1 - 2016/05/23/ PY - 2015/04/14/received PY - 2016/01/08/accepted PY - 2016/10/18/pubmed PY - 2017/1/18/medline PY - 2016/5/24/entrez SP - 129 EP - 136 JF - Clinical and experimental rheumatology JO - Clin. Exp. Rheumatol. VL - 34 Suppl 100 IS - 5 N2 - OBJECTIVES: Asymmetric dimethylarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this proof of concept study, we sought to evaluate the role of ADMA as a screening biomarker for incident systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). METHODS: ADMA levels were measured using high performance liquid chromatography in 15 consecutive treatment-naive patients with newly-diagnosed SSc-PAH and compared with 30 SSc-controls without PAH. Logistic regression models were used to evaluate the independent association of ADMA with PAH. The optimal cut-point of ADMA for SSc-PAH screening was determined. NT-proBNP levels were previously measured in the same patients and the optimal cut-point of NT-proBNP of ≥210ng/mL was coupled with the optimal cut-point of ADMA to create a screening model that combined the two biomarkers. RESULTS: The PAH group had significantly higher mean ADMA levels than the control group (0.76±0.14 μM versus 0.59±0.07 μM; p<0.0001). ADMA levels remained significantly associated with PAH after the adjustment for specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications (all p<0.01). An ADMA level ≥0.7 μM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. A screening model that combined an NT-proBNP ≥210ng/mL and/ or ADMA ≥0.7 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH. CONCLUSIONS: In this small study, use of ADMA in combination with NT-proBNP produced excellent sensitivity and specificity for the non-invasive identification of SSc-PAH. The role of ADMA as a screening biomarker for SSc-PAH merits further evaluation. SN - 0392-856X UR - https://www.unboundmedicine.com/medline/citation/27214686/The_role_of_asymmetric_dimethylarginine_alone_and_in_combination_with_N_terminal_pro_B_type_natriuretic_peptide_as_a_screening_biomarker_for_systemic_sclerosis_related_pulmonary_arterial_hypertension:_a_case_control_study_ L2 - http://www.clinexprheumatol.org/pubmed/find-pii.asp?pii=27214686 DB - PRIME DP - Unbound Medicine ER -
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