Yang Mingming, Kondo Toru, Dewan Pooja, Desai Akshay S, Lam Carolyn S P, Lefkowitz Martin P, Packer Milton, Rouleau Jean L, Vaduganathan Muthiah, Zile Michael R, Jhund Pardeep S, Køber Lars, Solomon Scott D, McMurray John J V
School of Cardiovascular and Metabolic Health, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.Y., T.K., P.D., P.S.J., J.J.V.M.).
Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China (M.Y.).
Circ Heart Fail. 2025 Mar;18(3):e011598. doi: 10.1161/CIRCHEARTFAILURE.124.011598. Epub 2025 Mar 3.
How different combinations of comorbidities influence risk at the patient level and population level in patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction is unknown. We aimed to investigate the prevalence of different combinations of cardiovascular and noncardiovascular comorbidities (ie, multimorbidity) and associated risk of death at the patient level and population level.
Using patient-level data from the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) and PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction), we investigated the 5 most common cardiovascular and noncardiovascular comorbidities and the resultant 45 comorbidity pairs. Cox proportional hazard models were used to calculate the population-attributable fractions for all-cause mortality and the relative excess risk due to interaction for each comorbidity pair.
Among 6504 participants, 95.2% had at least 2 of the 10 most prevalent comorbidities. The comorbidity pair with the greatest patient-level risk was stroke and peripheral artery disease (adjusted hazard ratio, 1.88 [95% CI, 1.27-2.79]), followed by peripheral artery disease and chronic obstructive pulmonary disease (1.81 [95% CI, 1.31-2.51]), and coronary artery disease and stroke (1.67 [95% CI, 1.33-2.11]). The pair with the highest population-level risk was hypertension and chronic kidney disease (CKD; adjusted population-attributable fraction, 14.8% [95% CI, 9.2%-19.9%]), followed by diabetes and CKD (13.3% [95% CI, 10.6%-16.0%]), and hypertension and diabetes (11.9% [95% CI, 7.1%-16.5%). A synergistic interaction (more than additive risk) was found for the comorbidity pairs of stroke and coronary artery disease (relative excess risk due to interaction, 0.61 [95% CI, 0.13-1.09]), diabetes and CKD (relative excess risk due to interaction, 0.46 [95% CI, -0.15 to 0.77]), and obesity and CKD (relative excess risk due to interaction, 0.24 [95% CI, 0.01-0.46]).
The risk associated with comorbidity pairs differs at the patient and population levels in heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction. At the population level, hypertension, CKD, and diabetes account for the greatest risk, whereas at the patient level, polyvascular disease and chronic obstructive pulmonary disease are the most important.
射血分数轻度降低的心力衰竭/射血分数保留的心力衰竭患者中，不同合并症组合如何影响患者层面和人群层面的风险尚不清楚。我们旨在调查心血管和非心血管合并症（即多病共存）的不同组合的患病率以及患者层面和人群层面的相关死亡风险。
利用TOPCAT试验（醛固酮拮抗剂治疗射血分数保留的心力衰竭）和PARAGON-HF试验（ARNI与ARB治疗射血分数保留的心力衰竭的全球结局前瞻性比较）的患者层面数据，我们调查了5种最常见的心血管和非心血管合并症以及由此产生的45种合并症组合。采用Cox比例风险模型计算所有原因死亡率的人群归因分数以及每种合并症组合的交互作用导致的相对超额风险。
在6504名参与者中，95.2%的人患有10种最常见合并症中的至少2种。患者层面风险最高的合并症组合是中风和外周动脉疾病（调整后风险比，1.88[95%CI，1.27-2.79]），其次是外周动脉疾病和慢性阻塞性肺疾病（1.81[95%CI，1.31-2.51]），以及冠状动脉疾病和中风（1.67[95%CI，1.33-2.11]）。人群层面风险最高的组合是高血压和慢性肾脏病（CKD；调整后的人群归因分数，14.8%[95%CI，9.2%-19.9%]），其次是糖尿病和CKD（13.3%[95%CI，10.6%-16.0%]），以及高血压和糖尿病（11.9%[95%CI，7.1%-16.5%]）。发现中风和冠状动脉疾病、糖尿病和CKD、肥胖和CKD的合并症组合存在协同交互作用（风险超过相加）（交互作用导致的相对超额风险分别为0.61[95%CI，0.13-1.09]、0.46[95%CI，-0.15至0.77]、0.24[95%CI，0.01-0.46]）。
射血分数轻度降低的心力衰竭/射血分数保留的心力衰竭患者中，合并症组合相关的风险在患者层面和人群层面有所不同。在人群层面，高血压、CKD和糖尿病的风险最大，而在患者层面，多血管疾病和慢性阻塞性肺疾病最为重要。
