Cited by 355Nitric Oxide and Endothelin EffectsCancer-related gene regulationCardiovascular Health and Disease Prevention

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Plasma Asymmetric Dimethylarginine and Incidence of Cardiovascular Disease and Death in the Community

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Böger, Rainer H., Sullivan, Lisa M., Schwedhelm, Edzard, Wang, Thomas J., Maas, Renke, Benjamin, Emelia J., Schulze, Friedrich, Xanthakis, Vanessa, Benndorf, Ralf A., Vasan, Ramachandran S.·2009·Circulation

DOI 10.1161/circulationaha.108.838268PMC PMC2742491

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Abstract

Background— Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, induces endothelial dysfunction. Although elevated ADMA has been associated with an increased risk of cardiovascular disease events and death in referral samples, the prognostic significance of ADMA in the community has not been adequately evaluated. Methods and Results— We related plasma ADMA, l -arginine (Arg), and the ratio of Arg to ADMA to the incidence of cardiovascular disease (fatal or nonfatal myocardial infarction, coronary insufficiency, angina pectoris, stroke or transient ischemic attack, intermittent claudication, or heart failure) and death in 3320 Framingham Offspring Study participants (1769 women; mean age, 59 years). Over a follow-up period of 10.9 years, 281 individuals of 2956 free of cardiovascular disease at baseline developed incident cardiovascular disease, and 285 participants died. In multivariable models adjusting for established risk factors and other biomarkers (B-type natriuretic peptide, renin, homocysteine, urine albumin excretion, and C-reactive protein), ADMA and the ratio of Arg to ADMA were significantly associated with all-cause mortality (adjusted-hazard ratio [HR] per 1-SD increment, 1.21; 95% CI, 1.07 to 1.37; and HR per 1-SD increment, 0.80; 95% CI, 0.69 to 0.93, respectively), whereas Arg was not (HR per 1-SD increment, 0.89; 95% CI, 0.77 to 1.02). We noted effect modification by diabetes status; ADMA was associated with death in individuals without diabetes (adjusted HR per 1-SD increment, 1.30; 95% CI, 1.13 to 1.50) but not in individuals with diabetes (adjusted HR per 1-SD increment, 0.85; 95% CI, 0.62 to 1.16). ADMA, Arg, and the ratio of Arg to ADMA were not associated with cardiovascular disease incidence ( P >0.10). Conclusions— In our large community-based sample, ADMA was significantly associated with all-cause mortality, particularly in nondiabetic individuals.

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Authors: Böger, R. H., Sullivan, L. M., Schwedhelm, E., Wang, T. J., Maas, R., Benjamin, E. J., Schulze, F., Xanthakis, V., Benndorf, R. A., & Vasan, R. S.
Affiliations: From the Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.H.B., E.S., R.M., F.S., R.A.B.); Framingham Heart Study, Framingham, Mass (L.M.S., T.J.W., E.J.B., V.X., R.S.V.); Department of Biostatistics (L.M.S., V.X.) and Cardiology Division and Preventive Medicine (E.J.B., R.S.V.), Boston University School of Public Health, Boston, Mass; and Cardiology Division, Massachusetts General Hospital, Boston (T.J...
Boston University (US)
ORCID: Sullivan, Lisa M.
Schwedhelm, Edzard
Wang, Thomas J.
Maas, Renke
Benjamin, Emelia J.
Schulze, Friedrich
Xanthakis, Vanessa
Benndorf, Ralf A.
Vasan, Ramachandran S.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-03-31
Volume: 119
Issue: 12
Pages: 1592-1600
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.108.838268
PMC: PMC2742491
OpenAlex: W2136960413
Cited by: 351
References: 41
Citations by year: 2026: 2 · 2025: 8 · 2024: 11 · 2023: 13 · 2022: 17 · 2021: 10 · 2020: 20 · 2019: 15 · 2018: 21 · 2017: 21 · 2016: 24 · 2015: 33 · 2014: 29 · 2013: 21 · 2012: 29
FWCI: 23.49
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Deutsche Forschungsgemeinschaft
National Institutes of Health (5k23hl074077-03, n01hc25195-41-0-1, n01hv28178-12-0-0)
National Heart, Lung, and Blood Institute (K23 HL074077-01, 2K24 HL 04334, N01‐HC25195, K23-HL-074077, K24HL004334, N01-HC-025195, N01-HV-028178)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords: asymmetric dimethylarginine, L-arginine, endothelial dysfunction, nitric oxide synthase inhibition, cardiovascular disease incidence, all-cause mortality, cardiovascular mortality, diabetes mellitus, Framingham Offspring Study, community-based cohort, prognostic factors
MeSH terms: Aged, Arginine, Cardiovascular Diseases, Cause of Death, Diabetes Mellitus, Follow-Up Studies, Humans, Middle Aged, Mortality, Predictive Value of Tests, Prognosis, Incidence, Proportional Hazards Models

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Plasma Asymmetric Dimethylarginine and Incidence of Cardiovascular Disease and Death in the Community

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