基于低钠盐干预人群队列对心脑血管疾病发生的预警研究

There is strong evidence that suggest high salt diet is a major risk factor for increased blood pressure. The relationship between sodium, potassium, and blood pressure has been explored in recent years, in an attempt to find alternative ways to inhibit the harmful effects of salt loading. It had been demonstrated that sodium can increase blood pressure, whereas potassium can decrease blood pressure. This study plans to go on following the population and check the copy number variations(CNVs) of salt sensitive gene which maybe correlate with the salt sensitive gene in the population who participated in the intervention trial about the effect of the low-sodium salt on blood pressure and finished the 3 years follow up. By the comprehensive analysis of the effect of the environment and heredity factors, we want to determine the influence of the CNVS and the environment factors on the blood pressure in the hypertensive and the normotensive population eating low-sodium salt, respectively. Further, we want to constructive the warning model for cardiovascular and cerebrovascular diseases in this population. At present, there is either not any result of the influence of the CNVs on the effect of the low-sodium salt on the blood pressure. This study maybe provides the basis of targeting for dietary.

高盐摄入被认为是原发性高血压发病的重要因素之一，本研究拟对已完成三年低钠盐干预的高血压高发区人群进行队列随访，以评估低钠盐对人群血压及心脑血管事件的长期干预效果；并在该人群中检测盐敏感相关基因组拷贝数变异，综合分析遗传因素和环境因素对低钠盐干预人群血压及心脑血管事件远期效果的影响，构建该人群的心脑血管疾病的预警模型。本研究将为有针对性进行高血压的膳食干预治疗及预防心脑血管事件提供依据。

高盐饮食对高血压和心脑血管疾病（CVD）的危害已得到广泛共识，减盐已成为世界各国预防高血压和CVD最具成本效益的公共卫生措施。但尚缺乏低钠盐能否降低远期CVD事件发生的相关报道。同时本研究团队在前期的随机对照实验中也发现，同为低钠盐干预不同个体的血压水平改变不同，提示低钠盐的干预效果可能受遗传因素的影响。. 本研究在前期随机对照试验的基础上，对已实施低钠盐及普通盐干预结束后的高血压高发区人群进行再次的观察性随访，在获取前期低钠盐干预对远期CVD影响的基础上，通过对干预人群的血压相关基因组拷贝数变异（CNVs）及上皮钠离子通道（ENaC）基因与血压及血压盐敏感性相关的SNPs进行检测分析，在对传统危险因素和遗传因素探讨的同时，构建影响远期CVD事件的整合传统危险因素与遗传因素的风险预测模型，以期为低钠盐适宜人群的选取提供理论依据。. 主要结果：1.全人群及高血压人群中，前期低钠盐干预与远期CVD死亡风险存在着显著的关联性；2.可能与人类原发性高血压或CVD风险相关的CNVs位点为CNVs esv27061和CNVs nsv483076;通过遗传风险评分（GRS）评估，发现ENaC基因与CVD初发和CVD复合事件存在显著关联性，ENaC基因预测CVD复合事件的最优GRS为PG-GRS；3.综合传统环境因素和CNVs遗传因素构建了低钠盐干预人群13年CVD事件发生风险预测模型：P= 1 - 0.9975592^exp(0.050744983*年龄 + 0.366860730*吸烟 + 0.315987955*低密度脂蛋白 + 0.008091269*收缩压 + 0.703396717*心脑血管疾病史 + 0.485283134*CNVs nsv483076)，整合传统因素和经最优GRS评估后确认的ENaC基因遗传因素预测CVD复合事件的最优预测模型为：h0(t) exp (0.067×年龄+0.948×PG-GRS)。