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 receivingatorvastatin 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 adhesionmolecule-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.
RCT Entities:
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: A T Hirsch; M H Criqui; D Treat-Jacobson; J G Regensteiner; M A Creager; J W Olin; S H Krook; D B Hunninghake; A J Comerota; M E Walsh; M M McDermott; W R Hiatt Journal: JAMA Date: 2001-09-19 Impact factor: 56.272
Authors: Alexander Thompson; Pei Gao; Lia Orfei; Sarah Watson; Emanuele Di Angelantonio; Stephen Kaptoge; Christie Ballantyne; Christopher P Cannon; Michael Criqui; Mary Cushman; Albert Hofman; Chris Packard; Simon G Thompson; Rory Collins; John Danesh Journal: Lancet Date: 2010-05-01 Impact factor: 79.321
Authors: Christopher P Cannon; Eugene Braunwald; Carolyn H McCabe; Daniel J Rader; Jean L Rouleau; Rene Belder; Steven V Joyal; Karen A Hill; Marc A Pfeffer; Allan M Skene Journal: N Engl J Med Date: 2004-03-08 Impact factor: 91.245
Authors: Mark J Alberts; Deepak L Bhatt; Jean-Louis Mas; E Magnus Ohman; Alan T Hirsch; Joachim Röther; Geneviève Salette; Shinya Goto; Sidney C Smith; Chiau-Suong Liau; Peter W F Wilson; Ph Gabriel Steg Journal: Eur Heart J Date: 2009-08-31 Impact factor: 29.983
Authors: Cameron W Donaldson; David J Schneider; Daniel J Bertges; Julie E Adams; Nader Z Elgharib; Enkhtuyaa L Mueller; William Prabhu; Taka Ashikaga; Harold L Dauerman Journal: J Thromb Thrombolysis Date: 2013-10 Impact factor: 2.300
Authors: Ewelina Bąk; Czesław Marcisz; Monika Kadłubowska; Anna Michalik; Bożena Krawczyk; Dorota Dobrzyń-Matusiak; Sylwia Krzemińska; Tomasz Fiałkowski; Elżbieta Glądys; Agnieszka Drosdzol-Cop Journal: Int J Environ Res Public Health Date: 2016-11-08 Impact factor: 3.390