Heart, Vascular & Thoracic Institute, Cleveland Clinic, Cleveland, Ohio.
University of Texas School of Public Health, Houston, Texas.
Am J Cardiol. 2024 Nov 15;231:1-10. doi: 10.1016/j.amjcard.2024.08.033. Epub 2024 Sep 5.
In modern clinical practice, less than half of patients with new-onset heart failure (HF) undergo ischemic evaluation and only a minority undergo revascularization. We aimed to assess the proportion of the effect of hypertension (antihypertensive treatment) on incident HF to be eliminated by prevention of coronary heart disease (CHD) event treated with or without revascularization, considering possible treatment-mediator interaction. The causal mediation analysis of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) included 42,418 participants (age 66.9 ± 7.7, 35.6% black, 53.2% men). A new CHD event (myocardial infarction or angina) that occurred after randomization but before the incident HF outcome was the mediator. Incident symptomatic congestive HF (CHF) and hospitalized/fatal HF (HHF) were the primary and secondary outcomes, respectively. Logistic regression (for mediator) and Cox proportional hazards regression (for outcome) were adjusted for demographics, cardiovascular disease history, and risk factors. During a median 4.5-year follow-up, 2,785 patients developed CHF, including 2,216 HHF events. Participants who developed CHD events had twice the higher incidence rate of CHF than CHD-free (28.5 vs 13.9 events/1,000 person-years). The proportion of reference interaction indicating direct harm because of a CHD event for lisinopril (234% for CHF, 355% for HHF) and amlodipine (244% for CHF, 468% for HHF) was greater than for chlortalidone (143% for CHF, 269% for HHF). In patients with revascularized CHD events, chlortalidone and amlodipine eliminated 21% to 24% and lisinopril eliminated -45% of HHF. Antihypertensive treatment could not eliminate harm from CHD events treated without revascularization. In conclusion, the antihypertensive drugs (chlortalidone, lisinopril, and amlodipine) prevent HF not principally by preventing CHD events but by way of other pathways. HF is moderated but not mediated by CHD events. Revascularization of CHD events is paramount for HF prevention.
在现代临床实践中，不到一半的新发心力衰竭 (HF) 患者接受缺血评估，只有少数患者接受血运重建。我们旨在评估高血压（降压治疗）对 HF 事件的影响比例，以消除经或不经血运重建治疗的冠心病 (CHD) 事件，同时考虑可能的治疗中介相互作用。抗高血压和降脂治疗预防心脏病发作试验 (ALLHAT) 的因果中介分析包括 42418 名参与者（年龄 66.9±7.7 岁，35.6%为黑人，53.2%为男性）。随机分组后但在发生 HF 事件之前发生的新 CHD 事件（心肌梗死或心绞痛）是中介。新发有症状充血性 HF（CHF）和住院/致死性 HF（HHF）分别为主要和次要结局。逻辑回归（中介）和 Cox 比例风险回归（结局）均调整了人口统计学、心血管疾病史和危险因素。在中位 4.5 年的随访期间，2785 名患者发生 HF，其中 2216 名患者发生 HHF 事件。发生 CHD 事件的患者 HF 发生率是无 CHD 事件患者的两倍（28.5 比 13.9 事件/1000 人年）。由于 CHD 事件导致的参考交互作用比例指示直接危害的程度，对于赖诺普利（HF 为 234%，HHF 为 355%）和氨氯地平（HF 为 244%，HHF 为 468%）大于氯噻酮（HF 为 143%，HHF 为 269%）。对于有血运重建的 CHD 事件患者，氯噻酮和氨氯地平消除了 21%至 24%的 HHF，赖诺普利消除了-45%的 HHF。没有进行血运重建的 CHD 事件治疗不能消除降压治疗带来的危害。总之，降压药物（氯噻酮、赖诺普利和氨氯地平）预防 HF 主要不是通过预防 CHD 事件，而是通过其他途径。HF 受 CHD 事件的调节，但不受其介导。CHD 事件的血运重建对于 HF 预防至关重要。
