Abstract：
OBJECTIVE: High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables.
RESULTS: In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population-based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase-2 (MMP-2), insulin-like growth factor binding protein-2 (IGFBP-2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (false discovery rates [FDR] <0.05). These associations were externally replicated in STANISLAS (all FDR <0.05). Among these biomarkers, spironolactone decreased concentrations of MMP-2 and NT-proBNP, regardless of baseline LAVi (pinteraction > 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e\', blood pressure and serum procollagen type I C-terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction > 0.10).
CONCLUSIONS: In individuals without heart failure, LAVi was associated with MMP-2, IGFBP-2 and NT-proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.
RESULTS: In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population-based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase-2 (MMP-2), insulin-like growth factor binding protein-2 (IGFBP-2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (false discovery rates [FDR] <0.05). These associations were externally replicated in STANISLAS (all FDR <0.05). Among these biomarkers, spironolactone decreased concentrations of MMP-2 and NT-proBNP, regardless of baseline LAVi (pinteraction > 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e\', blood pressure and serum procollagen type I C-terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction > 0.10).
CONCLUSIONS: In individuals without heart failure, LAVi was associated with MMP-2, IGFBP-2 and NT-proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.
摘要：
目的：高左心室充盈压增加左心房容积，引起心肌纤维化，螺内酯可能会减少。我们研究了与通过体表面积（LAVi）索引的左心房容积相关的临床和蛋白质组学特征，以及LAVi是否影响对螺内酯的反应对生物标志物表达和临床变量的影响。
结果：在HOMAGE试验中，有心力衰竭风险的人被随机分为螺内酯或对照组，我们分析了421名参与者的LAVi和276名蛋白质组测量值（Olink），1个月和9个月（平均年龄73±6岁；女性26％；LAVi32±9ml/m2）。还在基于人群的队列(STANISLAS;n=1640;平均年龄49±14岁;女性51%;LAVi23±7ml/m2)的无症状个体中评估了与LAVi相关的循环蛋白。在两项研究中，较大的LAVi与较大的左心室质量和容积显著相关.在HOMAGE,在多次测试的调整和校正后，较大的LAVi与较高浓度的基质金属肽酶-2（MMP-2）相关，胰岛素样生长因子结合蛋白-2（IGFBP-2）和N末端B型利钠肽原（NT-proBNP）（假发现率[FDR]<0.05）。这些关联在STANISLAS中外部复制(所有FDR<0.05)。在这些生物标志物中,螺内酯降低MMP-2和NT-proBNP的浓度，不考虑基线LAVi(p相互作用>0.10)。螺内酯也显著降低LAVi，改善左心室射血分数，降低了E/E\'，血压和血清I型前胶原C端前肽（PICP）浓度，胶原蛋白合成标记，不考虑基线LAVi(p相互作用>0.10)。
结论：在没有心力衰竭的个体中，LAVi与MMP-2、IGFBP-2和NT-proBNP相关。螺内酯降低了这些生物标志物的浓度以及LAVi和PICP，与左心房大小无关。
结果：在HOMAGE试验中，有心力衰竭风险的人被随机分为螺内酯或对照组，我们分析了421名参与者的LAVi和276名蛋白质组测量值（Olink），1个月和9个月（平均年龄73±6岁；女性26％；LAVi32±9ml/m2）。还在基于人群的队列(STANISLAS;n=1640;平均年龄49±14岁;女性51%;LAVi23±7ml/m2)的无症状个体中评估了与LAVi相关的循环蛋白。在两项研究中，较大的LAVi与较大的左心室质量和容积显著相关.在HOMAGE,在多次测试的调整和校正后，较大的LAVi与较高浓度的基质金属肽酶-2（MMP-2）相关，胰岛素样生长因子结合蛋白-2（IGFBP-2）和N末端B型利钠肽原（NT-proBNP）（假发现率[FDR]<0.05）。这些关联在STANISLAS中外部复制(所有FDR<0.05)。在这些生物标志物中,螺内酯降低MMP-2和NT-proBNP的浓度，不考虑基线LAVi(p相互作用>0.10)。螺内酯也显著降低LAVi，改善左心室射血分数，降低了E/E\'，血压和血清I型前胶原C端前肽（PICP）浓度，胶原蛋白合成标记，不考虑基线LAVi(p相互作用>0.10)。
结论：在没有心力衰竭的个体中，LAVi与MMP-2、IGFBP-2和NT-proBNP相关。螺内酯降低了这些生物标志物的浓度以及LAVi和PICP，与左心房大小无关。
