Department of Clinical Epidemiology, Leiden University Medical Center, Netherlands.
Department of Radiology, Leiden University Medical Center, Netherlands.
Peptides. 2021 Dec;146:170664. doi: 10.1016/j.peptides.2021.170664. Epub 2021 Sep 28.
High adiponectin concentrations are generally regarded as beneficial with regard to cardiometabolic health, but have been paradoxically associated with increased cardiovascular disease risk, specifically heart failure, in individuals at high cardiovascular risk. We aimed to investigate the association between adiponectin and heart function parameters, and inversely, we estimated the effect of genetically-determined heart function and NT-proBNP as the main marker of heart failure on adiponectin using Mendelian randomisation. Observational analyses between adiponectin and measures of heart function, i.e. E/A ratio, left, and right ventricular ejection fraction, were performed in participants of the Netherlands Epidemiology of Obesity (NEO) study, assessed by MRI of the heart (n = 1,138). Two-sample Mendelian randomisation analyses were conducted to estimate the effect of NT-proBNP and heart function on adiponectin concentrations using publicly-available summary statistics (ADIPOGen; the PLATO trial). The mean (standard deviation) age was 56 (6) years and mean body mass index was 26 (4) kg/m. Per five μg/mL higher adiponectin, the E/A ratio was -0.05 (95 % CI: -0.10, -0.01) lower, left ventricle ejection fraction was -0.5 % (95 % CI: -1.1, 0.1) lower, and right ventricle ejection fraction was 0.5 % (95 % CI: -0.1, 1.2) higher. Genetically-determined NT-proBNP was causally related to adiponectin concentrations in ADIPOGen: per doubling of genetically-determined NT-proBNP, adiponectin concentrations were 11.4 % (95 % CI: 1.7, 21.6) higher. With causal MR methods we showed that NT-proBNP affects adiponectin concentrations, while adiponectin is not associated with heart function parameters. Therefore, reverse causation may explain the adiponectin paradox observed in previous studies.
高浓度的脂联素通常被认为对代谢健康有益，但在心血管风险较高的个体中，它与心血管疾病风险增加（特别是心力衰竭）相关。我们旨在研究脂联素与心脏功能参数之间的关联，反之，我们使用孟德尔随机化估计遗传决定的心脏功能和 NT-proBNP（心力衰竭的主要标志物）对脂联素的影响。在荷兰肥胖症流行病学研究（NEO）中，通过心脏磁共振成像（MRI）评估了参与者的脂联素与心脏功能测量值（E/A 比、左心室和右心室射血分数）之间的观察性分析（n=1138）。使用公开可用的汇总统计数据（ADIPOGen；PLATO 试验）进行了两样本孟德尔随机化分析，以估计 NT-proBNP 和心脏功能对脂联素浓度的影响。参与者的平均（标准差）年龄为 56（6）岁，平均体重指数为 26（4）kg/m。脂联素每增加 5μg/mL，E/A 比降低 0.05（95%置信区间：-0.10，-0.01），左心室射血分数降低 0.5%（95%置信区间：-1.1，0.1），右心室射血分数升高 0.5%（95%置信区间：-0.1，1.2）。遗传决定的 NT-proBNP 在 ADIPOGen 中与脂联素浓度有因果关系：遗传决定的 NT-proBNP 每增加一倍，脂联素浓度就会升高 11.4%（95%置信区间：1.7，21.6）。使用因果 MR 方法，我们表明 NT-proBNP 影响脂联素浓度，而脂联素与心脏功能参数无关。因此，反向因果关系可能解释了先前研究中观察到的脂联素悖论。
