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Peripheral artery disease, biomarkers, and darapladib.
Am Heart J. 2011 May; 161(5):972-8.AH

Abstract

OBJECTIVE

Subjects with peripheral artery disease (PAD) are at increased risk of cardiovascular morbidity and mortality, perhaps in part, related to increased levels of inflammation, platelet activity, and lipids. We therefore sought to investigate the relationship between PAD and levels of inflammatory, platelet, and lipid biomarkers and the treatment effect of darapladib, a novel lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) inhibitor.

METHODS

This is a post hoc analysis of the 959 patients with coronary disease or their risk equivalent receiving atorvastatin who were randomized to receive darapladib or placebo to examine the effects of an Lp-PLA(2) inhibitor on the biomarkers of cardiovascular risk. We conducted an exploratory analysis evaluating the levels of biomarkers in subjects with PAD (n = 172) compared with those without PAD (n = 787).

RESULTS

After adjustment for age, sex, smoking, body mass index, and diabetes, subjects with PAD had greater levels of matrix metalloproteinase-9 (between group comparisons 22%, 95% confidence interval [10-31], P < .01), myeloperoxidase (12% [2-20], P = .01), interleukin-6 (13% [4-21], P = .01), adiponectin (17% [7-26], P < .01), intercellular adhesion molecule-1 (7% [2-11], P < .01), osteoprotegrin (6% [1-10], P = .02), CD40 ligand (15% [1-28], P = .04), high-sensitivity C-reactive protein (17% [1-31], P = .04), and triglycerides (11% [0.2-21], P = .05). No significant difference was detected for Lp-PLA(2) activity, P-selectin, urinary 11-dehydrothroboxane B2, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between subjects with and without PAD. Darapladib produced highly significant inhibition of Lp-PLA(2) activity when compared with placebo at weeks 4 and 12 (P < .01) in patients with and without PAD.

CONCLUSIONS

Subjects with PAD had elevated levels of matrix metalloproteinase-9, myeloperoxidase, interleukin-6, adiponectin, intercellular adhesion molecule-1, osteoprotegrin, CD40 ligand, high-sensitivity C-reactive protein, and triglycerides compared with those without PAD. Darapladib, a novel Lp-PLA(2) inhibitor, was equally effective in reducing Lp-PLA(2) activity levels in subjects with and without PAD.

Authors+Show Affiliations

New York University School of Medicine, NY, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

21570531

Citation

Berger, Jeffrey S., et al. "Peripheral Artery Disease, Biomarkers, and Darapladib." American Heart Journal, vol. 161, no. 5, 2011, pp. 972-8.
Berger JS, Ballantyne CM, Davidson MH, et al. Peripheral artery disease, biomarkers, and darapladib. Am Heart J. 2011;161(5):972-8.
Berger, J. S., Ballantyne, C. M., Davidson, M. H., Johnson, J. L., Tarka, E. A., Lawrence, D., Trivedi, T., Zalewski, A., & Mohler, E. R. (2011). Peripheral artery disease, biomarkers, and darapladib. American Heart Journal, 161(5), 972-8. https://doi.org/10.1016/j.ahj.2011.01.017
Berger JS, et al. Peripheral Artery Disease, Biomarkers, and Darapladib. Am Heart J. 2011;161(5):972-8. PubMed PMID: 21570531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peripheral artery disease, biomarkers, and darapladib. AU - Berger,Jeffrey S, AU - Ballantyne,Christie M, AU - Davidson,Michael H, AU - Johnson,Joel L, AU - Tarka,Elizabeth A, AU - Lawrence,Denise, AU - Trivedi,Trupti, AU - Zalewski,Andrew, AU - Mohler,Emile R,3rd PY - 2010/10/19/received PY - 2011/01/25/accepted PY - 2011/5/17/entrez PY - 2011/5/17/pubmed PY - 2011/7/22/medline SP - 972 EP - 8 JF - American heart journal JO - Am. Heart J. VL - 161 IS - 5 N2 - OBJECTIVE: Subjects with peripheral artery disease (PAD) are at increased risk of cardiovascular morbidity and mortality, perhaps in part, related to increased levels of inflammation, platelet activity, and lipids. We therefore sought to investigate the relationship between PAD and levels of inflammatory, platelet, and lipid biomarkers and the treatment effect of darapladib, a novel lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) inhibitor. METHODS: This is a post hoc analysis of the 959 patients with coronary disease or their risk equivalent receiving atorvastatin who were randomized to receive darapladib or placebo to examine the effects of an Lp-PLA(2) inhibitor on the biomarkers of cardiovascular risk. We conducted an exploratory analysis evaluating the levels of biomarkers in subjects with PAD (n = 172) compared with those without PAD (n = 787). RESULTS: After adjustment for age, sex, smoking, body mass index, and diabetes, subjects with PAD had greater levels of matrix metalloproteinase-9 (between group comparisons 22%, 95% confidence interval [10-31], P < .01), myeloperoxidase (12% [2-20], P = .01), interleukin-6 (13% [4-21], P = .01), adiponectin (17% [7-26], P < .01), intercellular adhesion molecule-1 (7% [2-11], P < .01), osteoprotegrin (6% [1-10], P = .02), CD40 ligand (15% [1-28], P = .04), high-sensitivity C-reactive protein (17% [1-31], P = .04), and triglycerides (11% [0.2-21], P = .05). No significant difference was detected for Lp-PLA(2) activity, P-selectin, urinary 11-dehydrothroboxane B2, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between subjects with and without PAD. Darapladib produced highly significant inhibition of Lp-PLA(2) activity when compared with placebo at weeks 4 and 12 (P < .01) in patients with and without PAD. CONCLUSIONS: Subjects with PAD had elevated levels of matrix metalloproteinase-9, myeloperoxidase, interleukin-6, adiponectin, intercellular adhesion molecule-1, osteoprotegrin, CD40 ligand, high-sensitivity C-reactive protein, and triglycerides compared with those without PAD. Darapladib, a novel Lp-PLA(2) inhibitor, was equally effective in reducing Lp-PLA(2) activity levels in subjects with and without PAD. SN - 1097-6744 UR - https://www.unboundmedicine.com/medline/citation/21570531/Peripheral_artery_disease_biomarkers_and_darapladib_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-8703(11)00087-1 DB - PRIME DP - Unbound Medicine ER -