Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, United Kingdom; University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, United Kingdom.
Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Clin Gastroenterol Hepatol. 2024 Aug;22(8):1657-1667. doi: 10.1016/j.cgh.2024.03.045. Epub 2024 May 8.
BACKGROUND & AIMS: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association.
Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test.
A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3, a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure.
In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.
本研究旨在确定一般人群中肝纤维化是否与心力衰竭相关，以及与肝纤维化风险增加和冠心病风险降低相关的遗传多态性（PNPLA3 rs738409；TM6SF2 rs58542926）是否会改变这种相关性。
我们使用英国生物库（UK Biobank）数据前瞻性地研究了非侵入性纤维化标志物（非酒精性脂肪性肝病纤维化评分[NFS]、纤维化 4 指数[FIB-4]和天门冬氨酸氨基转移酶与血小板比值指数[APRI]）与心力衰竭（n=413860）住院/死亡事件之间的关系。Cox 回归估计了心力衰竭的发生率。通过基因型分层并使用似然比检验检验基因型与肝纤维化之间的交互作用，估计 PNPLA3 和 TM6SF2 对肝纤维化与心力衰竭之间相关性的影响。
中位随访 10.7 年后共发生 12527 例心力衰竭事件。肝纤维化与心力衰竭住院/死亡风险增加相关（多变量校正后高危 NFS 评分 HR，1.59；95%置信区间[CI]，1.47-1.76；P<0.0001；FIB-4 HR，1.69；95%CI，1.55-1.84；P<0.0001；APRI HR，1.85；95%CI，1.56-2.19；P<0.0001；联合纤维化评分 HR，1.90；95%CI，1.44-2.49；P<0.0001）。这些相关性在代谢功能障碍相关脂肪性肝病（MASLD）、伴有酒精摄入的 MASLD（Met-ALD）和有害酒精摄入人群中持续存在。PNPLA3 rs738409 GG 和 TM6SF2 rs58542926 TT 并未减弱纤维化标志物与心力衰竭之间的正相关关系。对于 PNPLA3，在 PNPLA3 rs738409、FIB-4、APRI 评分和心力衰竭之间发现了统计学上显著的交互作用。
在一般人群中，血清肝纤维化标志物与心力衰竭住院/死亡风险增加相关。与肝纤维化相关的遗传多态性与升高的心力衰竭风险无正相关关系。
