van Ommen Anne Margje Lisa Naomi, Dal Canto Elisa, Diez Benavente Ernest, Cramer Maarten Jan, Teske Arco J, Menken Roxana, Taha Karim, Handoko M Louis, Duncker Dirk J, Verhaar Marianne C, Rutten Frans H, Onland-Moret N Charlotte, den Ruijter Hester M
Laboratory of Experimental Cardiology, University Medical Center, Utrecht University, Utrecht, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
Open Heart. 2025 May 4;12(1):e003105. doi: 10.1136/openhrt-2024-003105.
The progression of left ventricular diastolic dysfunction (LVDD) over time may lead to the development of heart failure with preserved ejection fraction (HFpEF). HFpEF is twice as common in women compared with men; however, the sex-specific progression from LVDD towards HFpEF is poorly described. Therefore, we aim to evaluate changes over time in markers of LVDD severity and HFpEF in women and men with preclinical LVDD.
We reassessed 146 participants from the HELPFul study (58% women and 42% men) with preclinical LVDD after a median follow-up of 4.3 (IQR: 3.9-4.7) years. The follow-up measurements mirrored baseline measurements, encompassing clinical examination, blood draw for biomarkers and echocardiography. We determined HFpEF incidence and report changes over time in echocardiography. Additionally, we studied how blood pressure and kidney function affected LVDD progression, including plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, using generalised mixed models. All analyses were performed for women and men combined, and sex stratified. Out of 146 participants, 15 (10%) developed HF of whom 13 had HFpEF (9 women and 4 men). Over time, mean kidney function (estimated glomerular filtration rate, eGFR) declined from 89±14.4 to 81±16.9 mL/min/1.73 m and median NT-proBNP plasma levels increased from 71 (IQR: 44-120) to 100 (IQR: 51-157) pg/mL. In women, a higher systolic and in men a higher diastolic blood pressure were associated with an increase in NT-proBNP plasma levels over time. Lower eGFR levels were related to increased NT-proBNP plasma levels over time in both men and women.
Our study demonstrates that only a small proportion of women and men with preclinical LVDD develop incident HF over a roughly 5-year follow-up period. High blood pressure and decreased kidney function were associated with higher levels of NT-proBNP. This highlights the need to further explore cardiorenal protection as a method to prevent HFpEF.
左心室舒张功能障碍（LVDD）随时间进展可能导致射血分数保留的心力衰竭（HFpEF）的发生。HFpEF在女性中的发病率是男性的两倍；然而，LVDD向HFpEF的性别特异性进展情况描述较少。因此，我们旨在评估临床前LVDD的女性和男性中LVDD严重程度和HFpEF标志物随时间的变化。
我们对来自HELPful研究的146名参与者（58%为女性，42%为男性）进行了重新评估，这些参与者患有临床前LVDD，中位随访时间为4.3年（四分位间距：3.9 - 4.7年）。随访测量反映了基线测量情况，包括临床检查、采集血样检测生物标志物以及超声心动图检查。我们确定了HFpEF的发病率，并报告了超声心动图随时间的变化。此外，我们使用广义混合模型研究了血压和肾功能如何影响LVDD的进展，包括血浆N末端B型利钠肽原（NT - proBNP）水平。所有分析均对合并的女性和男性以及按性别分层进行。在146名参与者中，15人（10%）发生了心力衰竭，其中13人患有HFpEF（9名女性和4名男性）。随着时间的推移，平均肾功能（估计肾小球滤过率，eGFR）从89±14.4降至81±16.9 mL/min/1.73 m²，NT - proBNP血浆中位水平从71（四分位间距：44 - 120）升至100（四分位间距：51 - 157）pg/mL。在女性中，较高的收缩压以及在男性中较高的舒张压与NT - proBNP血浆水平随时间增加相关。较低的eGFR水平与男性和女性NT - proBNP血浆水平随时间增加相关。
我们的研究表明，在大约5年的随访期内，只有一小部分患有临床前LVDD的女性和男性发生了新发心力衰竭。高血压和肾功能下降与较高水平的NT - proBNP相关。这突出了进一步探索心肾保护作为预防HFpEF方法的必要性。
