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Cited by 464Nitric Oxide and Endothelin EffectsLipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular Diseases

The DOI matches its Crossref record; 41 of the 43 references it cites were found in a registry or an index.

Association of Nitrotyrosine Levels With Cardiovascular Disease and Modulation by Statin Therapy

Shishehbor, Mehdi H., Aviles, Ronnier J., Brennan, Marie-Luise, Fu, Xiaoming, Goormastic, Marlene, Pearce, Gregory L., Gokce, Noyan, Keaney, John F., Penn, Marc S., Sprecher, Dennis L., Vita, Joseph A., Hazen, Stanley L.·2003·JAMA
DOI 10.1001/jama.289.13.1675
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Abstract

Context: Formation of nitric oxide–derived oxidants may serve as a mechanism linking inflammation to development of atherosclerosis. Nitrotyrosine, a specific marker for protein modification by nitric oxide–derived oxidants, is enriched in human atherosclerotic lesions and low-density lipoprotein (LDL) recovered from human atheroma. Objectives: To determine whether systemic levels of nitrotyrosine are associated with the prevalence of coronary artery disease (CAD) and are modulated by hydroxymethylglutaryl coenzyme-A reductase inhibitor (statin) therapy. Design, Setting, and Patients: A case-control and interventional study at 2 urban tertiary-care referral centers; recruitment for each was from June 1, 2001, until January 1, 2002. For the case-control study, 100 case-patients with established CAD and 108 patients with no clinically evident CAD were recruited consecutively. In the interventional study, participants aged 21 years or older with hypercholesterolemia (LDL cholesterol ≥130 mg/dL [≥3.5 mmol/L]) underwent nutrition and exercise counseling. Those whose levels did not decrease with 6 to 8 weeks were enrolled in the study (n = 35). For 12 weeks, they received 10 mg/d of oral atorvastatin therapy. Main Outcome Measures: In the case-control study, the association between systemic levels of protein-bound nitrotyrosine, CAD risk, and presence of CAD. In the interventional study, the change in nitrotyrosine, lipoprotein, and C-reactive protein (CRP) levels. Results: Nitrotyrosine levels were significantly higher among patients with CAD (median 9.1 µmol/mol [interquartile range, 4.8-13.8 µmol/mol] tyrosine vs 5.2 µmol/mol [interquartile range, 2.2-8.4 µmol/mol]; P<.001). Patients in the upper quartile of nitrotyrosine (29%; P<.001) had a higher odds of CAD compared with those in the lowest quartile (unadjusted odds ratio, 6.1; 95% confidence interval, 2.6-14.0; P<.001). In multivariate models adjusting for Framingham Global Risk Score and CRP, upper quartiles of nitrotyrosine remained associated with CAD (odds ratio, 4.4; 95% confidence interval, 1.8-10.6; P<.001). Statin therapy reduced nitrotyrosine levels significantly (25%; P<.02) with a magnitude similar to reductions in total cholesterol levels (25%; P<.001) and LDL particle number (29%; P<.001) yet were independent of alterations in lipoproteins and inflammatory markers like CRP. Conclusions: The findings from this preliminary study indicate that nitrotyrosine levels are associated with the presence of CAD and appear to be modulated by statin therapy. These results suggest a potential role for nitric oxide–derived oxidants as inflammatory mediators in CAD and may have implications for atherosclerosis risk assessment and monitoring of anti-inflammatory actions of statins.

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  1. Abu-Soud, 2000, Nitric oxide is a physiological substrate of plant and mammalian peroxidases., Nitric Oxide, 4, 179

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Metadata

Authors
Shishehbor, M. H., Aviles, R. J., Brennan, M.-L., Fu, X., Goormastic, M., Pearce, G. L., Gokce, N., Keaney, J. F., Penn, M. S., Sprecher, D. L., Vita, J. A., & Hazen, S. L.
Affiliations
  • Cleveland Clinic (US)
  • Boston University (US)
Corresponding author
Hazen, Stanley L.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2003-04-02
Volume
289
Issue
13
Pages
1675
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.289.13.1675
OpenAlex
W2138382873
Cited by
464
References
43
Citations by year
2026: 9 · 2025: 8 · 2024: 11 · 2023: 11 · 2022: 18 · 2021: 12 · 2020: 12 · 2019: 17 · 2018: 9 · 2017: 11 · 2016: 15 · 2015: 14 · 2014: 14 · 2013: 20 · 2012: 18
FWCI
26.83
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL61878, P01HL060886, HL 62526, R01HL061878, HL 70621, R01HL062526, R01HL070621, HL-60886)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
nitrotyrosine, coronary artery disease, statin therapy, atorvastatin, atherosclerosis, inflammation, C-reactive protein, hypercholesterolemia, LDL cholesterol, lipid-lowering therapy, cardiovascular risk markers, protein oxidation, statins, cardiovascular disease prevention
MeSH terms
Atorvastatin, Adult, Aged, Anticholesteremic Agents, C-Reactive Protein, Cardiovascular Diseases, Coronary Artery Disease, Female, Heptanoic Acids, Humans, Hypercholesterolemia, Lipoproteins, Male, Middle Aged, Prospective Studies, Pyrroles, Risk Factors, Tyrosine, Case-Control Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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