BACKGROUND Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. METHODS We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemia attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first HF hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. CONCLUSIONS In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.

中文翻译：

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认知功能障碍对心力衰竭和射血分数保留患者的临床相关性和预后影响：来自 PARAGON-HF 的见解。


背景 认知障碍在射血分数保留的心力衰竭患者中很常见，但对其临床相关性和预后关联知之甚少。方法 我们使用简易精神状态检查 （MMSE） 分析了射血分数保留患者的认知功能，这些患者参加了 PARAGON-HF 试验的预先指定子研究 （血管紧张素受体脑啡肽酶抑制剂与血管紧张素受体阻滞剂在射血分数保留的心力衰竭中的总体结局）。进行 Logistic 回归分析以确定与基线时 MMSE 评分较低和 48 周时 MMSE 评分基线后下降相关的变量。Cox 比例风险回归和半参数比例率模型用于检查与基线 MMSE 评分相关的临床结局风险，以及随访期间 MMSE 评分的下降，根据包括 NT-proBNP （N 末端 pro B 型利钠肽） 在内的预后变量进行调整。结果 基线时，2895 例患者中有 1809 例 （MMSE 评分 28-30） 认知功能正常 （MMSE 评分 62.5%），794 例 （27.4%） 认知功能正常 （评分 24-27），292 例 （10.1%） 受损 （评分 <24）。与基线时较低的 MMSE 评分和较基线的评分下降相关的变量包括年龄较大、中风或短暂性脑缺血发作史以及血清白蛋白较低。与基线 MMSE 评分为 28 至 30 分的患者相比，较低 MMSE 评分类别的患者首次 HF 住院时间或心血管死亡的综合风险逐步增加，评分为 24 至 27 和 1.58 的患者调整后风险比为 1.27 （95% CI，1.06-1.53） （95% CI， 1.21-2.06） 分别用于分数为 <24 的玩家。在复合死亡和全因死亡的各个组成部分中也发现了这些关联。同样，认知障碍与总（第一次和重复）心力衰竭住院和心血管死亡的风险增加 50% 相关。检查 MMSE 评分相对于基线的变化，随访期间 MMSE 评分降低与较高的死亡风险相关。结论 在射血分数保留的心力衰竭患者中，即使是适度的认知功能基线损害也与更差的结局相关，包括死亡。随访期间 MMSE 评分的下降是死亡率的强预测指标，独立于其他预后变量。