Section of Inflammation and Cardiometabolic Disease, National Heart, Lung, and Blood Institute; National Institutes of Health, Bethesda, MD, USA.
DermAssociates, Silver Spring, MD, USA.
Cardiovasc Res. 2019 Mar 15;115(4):721-728. doi: 10.1093/cvr/cvz009.
The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy.
In a prospective, observational study, 290 participants were recruited from 1 January 2013 through 31 October 2018 with 215 completing one-year follow-up. Of the 238, 121 consecutive participants who were biologic treatment naïve at baseline were included. A blinded reader (blinded to patient demographics, visit and treatment) quantified total coronary plaque burden and plaque subcomponents (calcified and non-calcified) in the three main coronary vessels >2 mm using dedicated software (QAngio, Medis, Netherlands). Psoriasis patients were middle-aged [mean (standard deviation) age, 50.5 (12.1) years], mostly male (n = 70, 58%) with low cardiovascular risk by Framingham score [median (interquartile range, IQR), 3 (1-6)] and had moderate to severe skin disease at baseline [median (IQR) Psoriasis Area Severity Index, PASI, 8.6 (5.3-14.0)]. Biologic therapy was associated with a 6% reduction in non-calcified plaque burden (P = 0.005) reduction in necrotic core (P = 0.03), with no effect on fibrous burden (P = 0.71). Decrease in non-calcified plaque burden in the biologic treated group was significant compared with slow plaque progression in non-biologic treated (Δ, -0.07 mm2 vs. 0.06 mm2; P = 0.02) and associated with biologic treatment beyond adjustment for traditional cardiovascular risk factors (β = 0.20, P = 0.02).
In this observational study, we demonstrate that biologic therapy in severe psoriasis was associated with favourable modulation of coronary plaque indices by CCTA. These findings highlight the importance of systemic inflammation in coronary artery disease and support the conduct of larger, randomized trials.
在过去的十年中，生物疗法的使用已经大大超出了原发性自身免疫性疾病的范围。事实上，最近一项使用抗 IL-1β 抗体的试验表明，该药物可降低曾患心肌梗死（MI）患者的第二次 MI。银屑病是一种慢性炎症性疾病，在严重时通常使用生物制剂治疗，与 MI 风险增加有关，部分原因是冠状动脉 CT 血管造影（CCTA）显示高危冠状动脉斑块表型。我们假设，与非生物治疗相比，在经过一年的生物治疗后，那些接受生物治疗的患者的冠状动脉斑块的炎症驱动表型，包括非钙化性冠状动脉斑块负担和富含脂质的坏死核心，会减少。
在一项前瞻性观察性研究中，我们于 2013 年 1 月 1 日至 2018 年 10 月 31 日期间招募了 290 名参与者，其中 215 名完成了为期一年的随访。在 238 名参与者中，我们纳入了 238 名基线时未接受生物治疗的连续参与者（121 名）。一名盲法读者（对患者的人口统计学信息、就诊和治疗情况均不知情）使用专用软件（QAngio，Medis，荷兰）对三个主要冠状动脉（＞2mm）的总冠状动脉斑块负担和斑块亚成分（钙化和非钙化）进行了定量评估。银屑病患者为中年人[平均（标准差）年龄，50.5（12.1）岁]，大多数为男性（n=70，58%），根据 Framingham 评分，心血管风险较低[中位数（四分位距，IQR），3（1-6）]，基线时有中度至重度皮肤疾病[中位数（IQR）银屑病面积严重程度指数，PASI，8.6（5.3-14.0）]。生物治疗与非钙化斑块负担降低 6%相关（P=0.005），与坏死核心减少相关（P=0.03），与纤维负担无关（P=0.71）。与非生物治疗相比，生物治疗组的非钙化斑块负担减少具有统计学意义（Δ，-0.07mm2 vs. 0.06mm2；P=0.02），并且与生物治疗的相关性超过了对传统心血管危险因素的调整（β=0.20，P=0.02）。
在这项观察性研究中，我们证明了严重银屑病患者的生物治疗与 CCTA 检测的冠状动脉斑块指数的有利调节有关。这些发现强调了系统性炎症在冠状动脉疾病中的重要性，并支持开展更大规模的随机试验。
