Taneja College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd MDC 30, Tampa, FL, 33612, USA.
Morsani College of Medicine, University of South Florida, 560 Channelside Drive, Tampa, FL, 33602, USA.
BMC Cardiovasc Disord. 2022 May 14;22(1):221. doi: 10.1186/s12872-022-02656-z.
Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous cluster of causes, including non-resolving inflammation, endothelial dysfunction, and multi-organ defects. The present study's objective was to identify novel predictors of HFpEF.
The study analyzed the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of specific markers of inflammation with new onset of HFpEF (interleukin-2 [IL-2], matrix metalloproteinase 3 [MMP3], large low-density lipoprotein cholesterol [LDL-C], and medium high-density lipoprotein cholesterol [HDL-C]). The study included men and women 45 to 84 years of age without cardiovascular disease at baseline. The primary outcome was the multivariate association of the hypothesized markers of inflammation with new-onset of HFpEF versus participants without new-onset heart failure. Participants with missing data were excluded.
The present analysis included 6814 participants, 53% female, with a mean age of 62 years. Among the entire cohort, HFpEF was diagnosed in 151 (2.2%) participants and heart failure with reduced ejection fraction (HFrEF) was diagnosed in 146 (2.1%) participants. Participants were followed for the outcome of heart failure for a median 13.9 years. Baseline IL-2 was available for 2861 participants. The multivariate analysis included 2792 participants. Of these, 2668 did not develop heart failure, 62 developed HFpEF, 47 developed HFrEF, and 15 developed unclassified heart failure. In the multivariate regression model, IL-2 was associated with new-onset HFpEF (OR, 1.00058; 95% confidence interval, 1.00014 to 1.00102, p = 0.009) but not new-onset HFrEF. In multivariate analysis, MMP3, large LDL-C, and medium HDL-C were not associated with HFpEF or HFrEF.
These findings portend IL-2 as an important component of suboptimal inflammation in the pathogenesis of HFpEF.
射血分数保留的心力衰竭（HFpEF）是一种综合征，其病因具有异质性，包括未解决的炎症、内皮功能障碍和多器官缺陷。本研究的目的是确定 HFpEF 的新预测因子。
本研究分析了多民族动脉粥样硬化研究（MESA），以评估特定炎症标志物与新发生的 HFpEF（白细胞介素 2 [IL-2]、基质金属蛋白酶 3 [MMP3]、大低密度脂蛋白胆固醇 [LDL-C] 和中高密度脂蛋白胆固醇 [HDL-C]）之间的关联。该研究纳入了基线时无心血管疾病的 45 至 84 岁的男性和女性。主要结局是假设的炎症标志物与新发生的 HFpEF 与无新发生心力衰竭的参与者之间的多变量关联。排除了数据缺失的参与者。
本分析包括 6814 名参与者，其中 53%为女性，平均年龄为 62 岁。在整个队列中，151 名（2.2%）参与者被诊断为 HFpEF，146 名（2.1%）参与者被诊断为射血分数降低的心力衰竭（HFrEF）。参与者的心力衰竭结局中位随访时间为 13.9 年。有 2861 名参与者的基线 IL-2 可用。多变量分析包括 2792 名参与者。其中，2668 名未发生心力衰竭，62 名发生 HFpEF，47 名发生 HFrEF，15 名发生未分类心力衰竭。在多变量回归模型中，IL-2 与新发生的 HFpEF 相关（OR，1.00058；95%置信区间，1.00014 至 1.00102，p=0.009），但与新发生的 HFrEF 无关。在多变量分析中，MMP3、大 LDL-C 和中 HDL-C 与 HFpEF 或 HFrEF 无关。
这些发现预示着 IL-2 作为 HFpEF 发病机制中未充分炎症的一个重要组成部分。
