National Medical Research Center for Preventive Medicine of the Ministry of Healthcare of Russian Federation, Moscow, Russia.
Department of Anatomy and Regenerative Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia.
Eur J Clin Invest. 2019 Mar;49(3):e13061. doi: 10.1111/eci.13061. Epub 2019 Jan 11.
Nitric oxide (NO) is one of the key regulators of vascular function. Abnormal NO signalling is linked to various cardiovascular diseases. We studied associations between circulating levels of NO metabolites, nitrite and nitrate (NOx) and total and cardiovascular mortality in a prospective 8-year follow-up cohort study in 1869 patients aged over 55 years.
The Cox proportional hazard ratio (HR) regression models were adjusted for multiple risk-related variables. Post hoc Kaplan-Meier survival curves were compared by the Log-rank test.
Proportional Cox regression analysis demonstrated that high serum levels of NOx over 70 µmol/L were associated with elevated total mortality (HR 1.4; 95% CI: 1.06-1.80; P = 0.02) and cardiovascular mortality (HR 1.4; 95% CI: 0.98-1.98; P = 0.03) when HR was adjusted for age, sex, smoking and urinary creatinine. Additional adjustments for various mortality-associated baseline comorbidities did not influence associations of elevated NOx with total and cardiovascular mortality. Association of elevated NOx with total mortality persisted in the multivariate regression model combining a number of other characteristics while association of NOx with cardiovascular mortality became non-significant in the multivariate model. Specific subset of patients contributing to these associations was determined by Kaplan-Meier survival analysis indicating that cardiovascular and total mortality were increased in men with high serum levels of NOx over 70 µmol/L (Log-rank test P = 0.01). These associations were not observed in women.
Elevated concentrations of serum NOx over 70 µmol/L can be used to predict mortality in men over 55 years of age.
一氧化氮（NO）是血管功能的关键调节因子之一。NO 信号异常与各种心血管疾病有关。我们研究了在一项针对 1869 名 55 岁以上患者的前瞻性 8 年随访队列研究中，循环 NO 代谢物亚硝酸盐和硝酸盐（NOx）的水平与总死亡率和心血管死亡率之间的关系。
Cox 比例风险比（HR）回归模型调整了多个与风险相关的变量。通过对数秩检验比较事后 Kaplan-Meier 生存曲线。
比例 Cox 回归分析表明，血清 NOx 水平高于 70μmol/L 与总死亡率（HR 1.4；95%CI：1.06-1.80；P=0.02）和心血管死亡率（HR 1.4；95%CI：0.98-1.98；P=0.03）升高相关，当 HR 调整为年龄、性别、吸烟和尿肌酐时。对各种与死亡率相关的基线合并症进行额外调整并未影响升高的 NOx 与总死亡率和心血管死亡率之间的关联。在包含多项其他特征的多变量回归模型中，升高的 NOx 与总死亡率之间的关联仍然存在，而 NOx 与心血管死亡率之间的关联在多变量模型中变得不显著。Kaplan-Meier 生存分析确定了导致这些关联的特定亚组患者，表明血清 NOx 水平高于 70μmol/L 的男性心血管和总死亡率增加（对数秩检验 P=0.01）。这些关联在女性中未观察到。
血清 NOx 浓度升高超过 70μmol/L 可用于预测 55 岁以上男性的死亡率。
