流感疫苗与心血管风险下降相关

《JAMA》10月23日在线发表的一份研究报告称，基于全球医学文献的meta分析显示，使用流感疫苗与不良心血管事件风险下降一致相关。在心血管风险最高的人群中，风险下降最为明显。



许多观察性研究表明急性呼吸道感染与心脏和脑血管事件风险增加相关，有的研究还指出这种感染可能诱发动脉粥样硬化斑块破裂，液体超负荷心衰、心肌炎或者心律失常。但是至于注射流感疫苗是否确实能够预防这类事件，还一直存在争议。

加拿大多伦多大学附属妇女医院的Jacob A. Udell博士及其同事为此开展了一项系统评价，对从数据库建立(1946年)至今的所有医学文献进行了检索，找到了71项可能相关的研究供进一步评价。然后，他们对12项比较接种流感疫苗与安慰剂或者标准护理的临床随机试验进行了meta分析，这些试验均报告了接种后1年内的心血管结局。

在这12项临床随机试验中，5项被视为高质量试验，其余则为低质量或者质量不确定。Meta分析总共涉及6,469例受试者(平均年龄67岁)，他们存在不同程度的心血管风险。

研究者称：“尽管这些研究在试验设计、偏倚风险、样本量大小、受试者的心血管风险、流行流感活性、接种方案、随访持续时间以及所观察事件的数量上存在差异，但我们的meta分析显示接种流感疫苗与心血管事件风险下降一致相关。”

主要终点，即所有重大心血管不良事件(心血管死亡或住院治疗、心肌梗死、卒中、心衰、紧急冠脉血运重建和不稳定性心绞痛)的复合终点，在接种了流感疫苗的人群中其总发生率约为2.9% (95/ 3,238)。这显著低于对照受试者4.7%(151/3,231)的总发生率。

Udell博士及其同事报告称，预防1例重大心血管不良事件所需治疗的人数为58人(JAMA 2013 Oct. 23 [doi:10.1001/jama.2013.279206])。

在由已知患有冠状动脉疾病的患者组成的亚组中，接种流感疫苗的保护作用更加明显。例如，在近期有急性冠脉综合征病史的患者中，接种者的重大心血管不良事件发生率为10.25%，而对照受试者的发生率达到了23.1%。在这个患者亚组中，预防1例心血管事件所需治疗的人数仅为8人。

研究者称，目前北美总人口中只有不到1/3的人每年接种流感疫苗，存在心血管高风险的人群中只有不到一半的人会每年接种流感疫苗。因此，流感疫苗“可能解决很大一部分现有治疗没有解决的残余心血管风险，一次简单的接种就可以提供一整年的保护。”

研究者指出：“上述研究结果在一定程度上支持了现行指南推荐意见，即建议急性冠脉综合征患者接种流感疫苗。”他们补充道，特别是每年一次的简单注射就能降低所有心血管事件的发生风险，这一结果“对于临床实践和卫生政策都有十分重要的意义，因为目前公众对于疫苗接种明显使用不足，而这一预防策略能对高危患者产生如此大的潜在影响。”

“仍需开展进一步的研究，通过检验效能足够大的多中心试验来确认这种低成本、每年一次、安全、操作简便且耐受良好的预防手段在现有治疗的基础上进一步降低心血管风险的功效。”

这项研究由加拿大卫生研究院以及加拿大妇女健康基金会共同资助。Udell博士声明无相关经济利益冲突；其他作者声明与业界存在多种利益关系。

爱思唯尔版权所有  未经授权请勿转载

By: MARY ANN MOON, Cardiology News Digital Network

Use of the flu vaccine was consistently associated with a lower risk of adverse cardiovascular events in a meta-analysis of the worldwide medical literature, according to a report published online Oct. 23 in JAMA.

The risk reduction was greatest among people at highest cardiovascular risk, said Dr. Jacob A. Udell of Women’s College Hospital, University of Toronto, and his associates.

"Our findings provide some support for current guideline recommendations for influenza vaccination of patients with acute coronary syndromes," they noted.
 
In particular, the finding that a simple, once-yearly injection may prevent scores of cardiovascular deaths, hospitalizations, MIs, strokes, and cases of heart failure, urgent coronary revascularization, and unstable angina also is of "considerable clinical and health policy importance, given the profound underuse of vaccination among the general public and the potential impact this preventive strategy may have on high-risk patients," the investigators added.

Several observational studies have suggested an association between acute respiratory infection and increased risk of cardiac and cerebrovascular events, and some have suggested that such infection may trigger rupturing of atherosclerotic plaque, fluid-overload heart failure, myocarditis, or arrhythmia. But whether or not influenza immunization could actually prevent such events remains controversial.

Dr. Udell and his colleagues performed a systematic review of the literature from the inception of database entry (1946) to the present, identifying 71 potentially relevant studies to review. They then performed a meta-analysis of the 12 randomized clinical trials in which influenza vaccination was compared against either placebo or standard care, and in which cardiovascular outcomes during the year following vaccination were reported.

Five of the 12 randomized clinical trials were considered to be of high quality and the remainder were of low or uncertain quality. The meta-analysis included 6,469 participants (mean age, 67 years) who had varying degrees of cardiovascular risk.

"Despite differences in trial designs, risk of bias, sample size, cardiovascular risk of participants, circulating influenza activity, vaccination strategy, duration of follow-up, and number of observed events, our meta-analysis demonstrated a consistent association between influenza vaccination and a lower risk of CV events," the investigators said.

The overall rate of the primary end point, a composite of all major adverse cardiovascular events, was 2.9% among recipients of the influenza vaccine (95 of 3,238 patients). This was significantly lower than the 4.7% rate (151 of 3,231 patients) among control subjects.

The number needed to treat to prevent a single major adverse CV event was 58, Dr. Udell and his associates said (JAMA 2013 Oct. 23 [doi:10.1001/jama.2013.279206]).

In a subgroup analysis involving patients known to have coronary artery disease, influenza vaccination was even more protective. For example, the rate of major adverse CV events was 10.25% among vaccinated patients with a history of recent acute coronary syndrome, compared with a rate of 23.1% among control subjects. The number needed to treat to prevent a single CV event in this subset of patients was only 8.

Less than one-third of the general population in North America and less than half of those at high cardiovascular risk currently receive the annual flu vaccine. Therefore, the flu vaccine "could address a sizable component of residual CV risk not addressed by current therapy, and provide yearlong coverage through a simple inoculation," the researchers said.

"Future research with an adequately powered multicenter trial to confirm the efficacy of this low-cost, annual, safe, easily administered, and well-tolerated therapy to reduce CV risk beyond current therapies is warranted."

The Canadian Institutes for Health Research and the Canadian Foundation for Women’s Health supported the study. Dr. Udell reported no financial conflicts of interest; his associates reported numerous ties to industry sources.