背景:在美国,癌症人群的有效生存期延长已引起人们对该人群心脏代谢疾病发病率和死亡率上升风险的极大关注.这种增加的风险强调了迫切需要研究癌症幸存者的有效药物干预措施。值得注意的是,二甲双胍,一种具有多效性的众所周知的代谢调节剂,已显示出对糖尿病个体心脏代谢紊乱的保护作用。尽管有这些有希望的迹象,支持其改善癌症幸存者心脏代谢结局的证据仍然很少.
方法:使用美国国家健康和营养调查(NHANES)登记的全国代表性癌症幸存者样本,建立了一个前瞻性队列。从2003年到2018年。结果来自患者访谈,体检,以及截至2019年的公共访问相关死亡率档案。氧化平衡评分用于评估参与者的氧化应激水平。评估二甲双胍使用与心脏代谢疾病风险和相关死亡率之间的相关性。通过Cox比例风险模型进行心脏代谢死亡率的生存分析,使用logistic回归模型对心脏代谢疾病结局进行横断面分析.进行相互作用分析以探讨二甲双胍的具体药理机制。
结果:在3995名癌症幸存者中(加权人群,21,671,061,加权平均数[SE]年龄,62.62[0.33]岁;2119[53.04%]女性;2727[68.26%]非西班牙裔白人),448报告了二甲双胍的使用情况。在长达17年的随访期间(中位数,6.42年),有记录的1233人死亡,包括481例心脏代谢疾病死亡.多变量模型表明,使用二甲双胍与全因风险较低相关(风险比[HR],0.62;95%置信区间[CI],0.47-0.81)和心脏代谢(HR,0.65;95%CI,0.44-0.97)死亡率与非二甲双胍使用者相比。二甲双胍的使用也与总心血管疾病的风险较低相关(比值比[OR],0.41;95%CI,0.28-0.59),stroke(OR,0.44;95%CI,0.26-0.74),高血压(OR,0.27;95%CI,0.14-0.52),和冠心病(或,0.41;95%CI,0.21-0.78)。在四个被确定为心脏代谢高风险组的特定癌症人群中,观察到的逆关联在亚组分析中是一致的。相互作用分析表明,与不使用二甲双胍相比,使用二甲双胍可能会抵消氧化应激。
结论:在这项涉及美国癌症幸存者全国代表性人群的队列研究中,二甲双胍的使用与心脏代谢疾病的风险降低显著相关,全因死亡率,和心脏代谢死亡率。
BACKGROUND: In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce.
METHODS: A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants\' levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin.
RESULTS: Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47-0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44-0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28-0.59), stroke (OR, 0.44; 95% CI, 0.26-0.74), hypertension (OR, 0.27; 95% CI, 0.14-0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21-0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress.
CONCLUSIONS: In this cohort
study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.