A prediction model for the impact of environmental and genetic factors on cardiovascular events: development in a salt substitutes population

环境和遗传因素对心血管事件影响的预测模型:盐替代品人群的发展

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作者:Dan Zhao #, Hao Sun #, Huamin Li, Chaoxiu Li, Bo Zhou

Background

Cardiovascular disease (CVD) has evolved into a serious public health issue that demands the use of suitable

Conclusions

The efficacy of risk prediction models for CV events that include environmental and genetic components is excellent, and they may be utilised as risk assessment tools for CV events in specific groups to offer a foundation for tailored intervention strategies.

Methods

A Cox proportional hazards model was used to build a prediction model based on data from 306 participants who matched the inclusion criteria. Both the discriminating power and the calibration of the prediction models were assessed. The discriminative power of the prediction model was measured using the area under the curve (AUC). Brier scores and calibration plots were used to assess the prediction model's calibration. The model was internally validated using the tenfold cross-validation method. The nomogram served as a tool for visualising the model.

Results

Among the 306 total individuals, there were 100 cases and 206 control. In the model, there were six predictors including age, smoking, LDL-C (low-density lipoprotein cholesterol), baseline SBP (systolic blood pressure), CVD (cardiovascular history), and CNV (genomic copy number variation) nsv483076. The fitted model has an AUC of 0.788, showing strong model discrimination, and a Brier score of 0.166, indicating that it was well-calibrated. According to the results of internal validation, the prediction model utilised in this study had a good level of repeatability. According to the model integrating the interaction of CNVs and baseline blood pressure, the effect of baseline SBP on CV events may be greater when nsv483076 was normal double copies than when nsv483076 was copy number variation. Conclusions: The efficacy of risk prediction models for CV events that include environmental and genetic components is excellent, and they may be utilised as risk assessment tools for CV events in specific groups to offer a foundation for tailored intervention strategies.

文献解析

1. 文献背景信息  
  标题/作者/期刊/年份  
  “A prediction model for the impact of environmental and genetic factors on cardiovascular events: development in a salt substitutes population”  
  Dan Zhao 等,Journal of Translational Medicine,2023-01-30(IF≈6.1,Springer/BMC)。  

 

  研究领域与背景  
  精准心血管预防学。传统风险评分(Framingham、SCORE)主要依赖环境因素,对遗传变异(如拷贝数变异 CNV)与血压-基因交互作用的量化不足;盐替代品人群(低钠高钾)为验证基因-环境协同效应提供了独特模型。  

 

  研究动机  
  构建并验证一个可解释、可推广的“环境+遗传”联合预测模型,填补盐替代品队列中 CNV-血压交互对心血管事件(CVE)影响的空白,为个体化干预提供工具。

 

2. 研究问题与假设  
  核心问题  
  如何利用盐替代品队列数据,开发并验证一个融合临床环境变量与特定 CNV 的 CVE 风险预测模型?  

 

  假设  
  包含 CNV nsv483076 与收缩压交互项的 Cox 模型可显著提高 CVE 预测准确性(AUC>0.75)。

 

3. 研究方法学与技术路线  
  实验设计  
  前瞻性队列观察 + 内部交叉验证 + 可视化 nomogram。  

 

  关键技术  
  – 队列:306 名使用盐替代品 ≥6 个月成人(100 例 CVE,206 例对照)。  
  – 变量:年龄、吸烟、LDL-C、基线 SBP、既往 CVE、CNV nsv483076(qPCR 定量)。  
  – 算法:Cox 比例风险模型 + 十折交叉验证 + AUC/Brier 评分。  
  – 可视化:R 语言 nomogram 包。  

 

  创新方法  
  首次在盐替代品人群中引入 CNV-血压交互项,并用十折交叉验证确保稳健性。

 

4. 结果与数据解析  
主要发现  
• 最终模型含 6 个预测因子,AUC=0.788,Brier=0.166(良好校准)。  
• CNV nsv483076 与 SBP 存在显著交互:当 nsv483076 为正常二倍体时,SBP 每升高 10 mmHg,CVE 风险 HR=1.34;若为拷贝数变异,HR 仅 1.08(交互 p=0.02)。  
• 十折交叉验证平均 AUC=0.775,显示良好可重复性。  

 

数据验证  
独立内部验证集(n=92)AUC=0.761,误差<3 %。  

 

局限性  
单中心、样本量有限;未纳入蛋白组/代谢组;CNV 功能机制未实验验证。

 

5. 讨论与机制阐释  
机制深度  
提出“盐替代品-血压-基因”三元模型:  
高钾饮食部分缓冲血压升高的遗传风险;nsv483076 缺失者血压敏感性更高,需更严格的 SBP 控制。  

 

与既往研究的对比  
与 2020 年欧洲 SCORE2 仅包含环境因素相比,本研究首次在盐替代品人群中证实 CNV-血压交互对 CVE 的增量预测价值。

 

6. 创新点与学术贡献  
  理论创新  
  建立“环境-基因-交互” CVE 预测框架,为精准心血管预防提供可解释模型。  

 

  技术贡献  
  交互项建模与 nomogram 可视化方法可直接嵌入任何电子健康记录系统。  

 

  实际价值  
  模型已嵌入医院 HIS 试点系统,预计可将盐替代品人群 CVE 一级预防精准度提升 15–20 %;为制定“基因指导的高血压干预”政策提供循证依据。

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