Novel insights into the causal effects of triglycerides to high density lipoprotein cholesterol ratio on blood pressure

IF 3.9 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Nutrition Metabolism and Cardiovascular Diseases Pub Date : 2026-04-01 Epub Date: 2025-11-27 DOI:10.1016/j.numecd.2025.104474

Aihong Wan , Yuqin Han , Lingling Wu , Yuanhao Wei , Xiqiao Xiang , Yi Chen , Jinquan Chen , Aihua Song , Kun Zhao

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引用次数: 0

Abstract

Background and aims

Previous studies have suggested links between the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on blood pressure (BP) traits and hypertension (HTN) risk. However, the causal relationships remain unclear.

Methods and results

We conducted genome-wide linkage disequilibrium score regression (LDSC), two-sample Mendelian randomization (MR), colocalization, reverse, and multivariable MR (MVMR) analyses to evaluate the causal relationships between the TG:HDL-C ratio and BP traits. BP traits (systolic BP [SBP], diastolic BP [DBP], and pulse pressure [PP]) were obtained from the International Consortium for Blood Pressure and UK Biobank. HTN data were from GWAS meta-analyses. The primary analysis used the inverse variance method (IVW), with sensitivity analyses for MR. Significant genetic correlations were found between the TG:HDL-C ratio and BP traits (all P values < 0.05). Genetically predicted TG:HDL-C ratio was associated with increased SBP (β = 1.194, 95 % CI: 1.007–1.382), DBP (β = 0.680, 95 % CI: 0.553–0.807), and PP (β = 0.469, 95 % CI: 0.359–0.579). It also increased HTN risk (OR = 1.030, 95 % CI: 1.025–1.036, discovery; OR = 1.169, 95 % CI: 1.138–1.200, replication; OR = 1.089, 95 % CI: 1.049–1.131, meta-analysis). MVMR showed persistent causal relationships with DBP (β = 0.219, 95 % CI: 0.072–0.366) and HTN (OR = 1.010, 95 % CI: 1.005–1.015, discovery; OR = 1.055, 95 % CI: 1.024–1.086, replication). Colocalization analysis supported shared genetic architecture. Sensitivity analyses confirmed robustness.

Conclusions

Our study provides genetic evidence that the TG:HDL-C ratio is causally related to DBP and HTN. These findings were consistent across robust MR methods. However, no independent causal relationship was observed between the TG:HDL-C ratio and SBP or PP after lipid adjustment in MVMR. Further interventional studies are needed.

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甘油三酯与高密度脂蛋白胆固醇比值对血压的因果关系的新见解。

背景和目的：先前的研究表明甘油三酯与高密度脂蛋白胆固醇（TG:HDL-C）比值与血压（BP）特征和高血压（HTN）风险之间存在联系。然而，因果关系尚不清楚。方法和结果：我们通过全基因组连锁不平衡评分回归（LDSC）、双样本孟德尔随机化（MR）、共定位、反向和多变量MR （MVMR）分析来评估TG:HDL-C比率与BP性状之间的因果关系。血压特征（收缩压[SBP]，舒张压[DBP]和脉压[PP]）从国际血压协会和英国生物银行获得。HTN数据来自GWAS荟萃分析。初步分析采用逆方差法（IVW），对mr进行敏感性分析，发现TG:HDL-C比值与BP性状之间存在显著的遗传相关性（P值均为P值）。结论：本研究为TG:HDL-C比值与DBP和HTN之间存在因果关系提供了遗传学证据。这些发现在稳健的MR方法中是一致的。然而，在MVMR中脂质调节后，TG:HDL-C比值与收缩压或PP之间没有独立的因果关系。需要进一步的介入研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nutrition Metabolism and Cardiovascular Diseases 医学-内分泌学与代谢

CiteScore

6.80

自引率

2.60%

发文量

332

审稿时长

57 days

期刊介绍： Nutrition, Metabolism & Cardiovascular Diseases is a forum designed to focus on the powerful interplay between nutritional and metabolic alterations, and cardiovascular disorders. It aims to be a highly qualified tool to help refine strategies against the nutrition-related epidemics of metabolic and cardiovascular diseases. By presenting original clinical and experimental findings, it introduces readers and authors into a rapidly developing area of clinical and preventive medicine, including also vascular biology. Of particular concern are the origins, the mechanisms and the means to prevent and control diabetes, atherosclerosis, hypertension, and other nutrition-related diseases.