Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

New England Journal of Medicine, Год журнала: 2017, Номер 377(12), С. 1119 - 1131

Опубликована: Авг. 27, 2017

Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, inflammatory hypothesis atherothrombosis has remained unproved.We conducted a randomized, double-blind trial canakinumab, therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction high-sensitivity C-reactive protein level 2 mg or more per liter. The compared three doses canakinumab (50 mg, 150 300 administered subcutaneously every 3 months) placebo. primary efficacy end point was nonfatal infarction, stroke, death.At 48 months, median reduction from baseline in 26 percentage points greater group received 50-mg dose 37 150-mg group, 41 300-mg than placebo group. Canakinumab did not baseline. At follow-up 3.7 years, incidence rate for 4.50 events 100 person-years 4.11 3.86 3.90 hazard ratios as were follows: 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); 0.85 CI, 0.74 0.98; P=0.021); 0.86 0.75 0.99; P=0.031). dose, but other doses, met prespecified multiplicity-adjusted threshold statistical significance secondary additionally included hospitalization unstable angina led urgent revascularization (hazard ratio vs. placebo, 0.83; 95% 0.73 0.95; P=0.005). associated higher fatal infection There no significant difference all-cause mortality all 0.94; 0.83 1.06; P=0.31).Antiinflammatory therapy interleukin-1β innate immunity pathway at months significantly lower recurrent independent lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

Язык: Английский

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Atherosclerosis

Nature Reviews Disease Primers, Год журнала: 2019, Номер 5(1)

Опубликована: Авг. 16, 2019

Язык: Английский

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Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease

New England Journal of Medicine, Год журнала: 2017, Номер 377(2), С. 111 - 121

Опубликована: Июнь 21, 2017

Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence an expanded somatic blood-cell clone in persons without other hematologic abnormalities, common among older and associated with increased risk cancer. We previously found preliminary evidence for association between CHIP atherosclerotic cardiovascular disease, but nature this was unclear.

Язык: Английский

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The changing landscape of atherosclerosis

Nature, Год журнала: 2021, Номер 592(7855), С. 524 - 533

Опубликована: Апрель 21, 2021

Язык: Английский

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Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities

Nature reviews. Immunology, Год журнала: 2021, Номер 21(7), С. 426 - 440

Опубликована: Янв. 28, 2021

Язык: Английский

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Clonal hematopoiesis in human aging and disease

Science, Год журнала: 2019, Номер 366(6465)

Опубликована: Окт. 31, 2019

As people age, their tissues accumulate an increasing number of somatic mutations. Although most these mutations are little or no functional consequence, a mutation may arise that confers fitness advantage on cell. When this process happens in the hematopoietic system, substantial proportion circulating blood cells derive from single mutated stem This outgrowth, called "clonal hematopoiesis," is highly prevalent elderly population. Here we discuss recent advances our knowledge clonal hematopoiesis, its relationship to malignancies, link nonmalignant diseases aging, and potential impact immune function. Clonal hematopoiesis provides glimpse into selection likely occurs all tissues.

Язык: Английский

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Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity

Immunity, Год журнала: 2019, Номер 50(4), С. 778 - 795

Опубликована: Апрель 1, 2019

Язык: Английский

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Prediction of acute myeloid leukaemia risk in healthy individuals

Nature, Год журнала: 2018, Номер 559(7714), С. 400 - 404

Опубликована: Июль 1, 2018

Язык: Английский

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Targeting inflammation in atherosclerosis — from experimental insights to the clinic

Nature Reviews Drug Discovery, Год журнала: 2021, Номер 20(8), С. 589 - 610

Опубликована: Май 11, 2021

Язык: Английский

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Western Diet and the Immune System: An Inflammatory Connection

Immunity, Год журнала: 2019, Номер 51(5), С. 794 - 811

Опубликована: Ноя. 1, 2019

Язык: Английский

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