Aims

Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also reported in patients with depression. Emerging evidence suggests that selective serotonin receptor inhibitors (SSRIs) may improve endothelial function. However, clinical studies assessing flow-mediated dilation (FMD), the gold-standard method to evaluate conduit artery endothelial function, in response to SSRIs treatment included limited number of patients and did not provide consistent results. In the present study we aim to evaluate the effect of SSRIs treatment on endothelial function assessed by longitudinal changes in FMD.

Methods and results

We performed a systematic review to retrieve and subsequently meta-analyze eligible studies in patients with depression who received SSRIs and had available measurements of FMD change before and after treatment. In 5 studies and 323 individuals in total, SSRIs were associated with increased FMD at the end of follow-up compared to baseline measurement (pooled mean change 1.97 %, 95 % CI 0.17, 3.77, P = 0.032, I² = 87.4 %). These results did not substantially change when analysis was restricted to patients with history of atherosclerotic cardiovascular disease (ASCVD). Similarly, FMD changes were higher in individuals receiving SSRIs compared to not-treated subjects (pooled mean difference 2.5 %. 95 % CI 0.7, 4.2, P < 0.001, I² = 82.7 %).

Limitations

Substantial heterogeneity regarding with respect to follow-up duration, demographics, and SSRIs agents.

Conclusion

SSRIs significantly improve FMD, the gold-standard marker of endothelial function. Further investigation is warranted for the role of FMD as a possible therapeutic biomarker in patients with depression and established or subclinical ASCVD.

Prospero registration

CRD42021252241.

中文翻译：

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选择性5-羟色胺再摄取抑制剂对内皮功能影响的系统评价和荟萃分析

目标

抑郁症和动脉粥样硬化性心血管疾病（ASCVD）通常聚集在受影响的患者中。内皮功能障碍是 ASCVD 的早期标志物，同时在抑郁症患者中也有报道。新出现的证据表明，选择性血清素受体抑制剂 (SSRIs) 可以改善内皮功能。然而，评估血流介导扩张 (FMD) 的临床研究是评估导管动脉内皮功能的金标准方法，以响应 SSRIs 治疗，包括有限数量的患者，并没有提供一致的结果。在本研究中，我们旨在评估 SSRIs 治疗对通过 FMD 纵向变化评估的内皮功能的影响。

方法和结果

我们进行了一项系统回顾，以检索并随后荟萃分析接受 SSRIs 并在治疗前后获得 FMD 变化测量值的抑郁症患者的合格研究。在 5 项研究和总共 323 名个体中，与基线测量相比，SSRI 与随访结束时 FMD 增加相关（合并平均变化 1.97 %，95 % CI 0.17，3.77，P = 0.032，I ²  = 87.4 %） . 当分析仅限于有动脉粥样硬化性心血管疾病 (ASCVD) 病史的患者时，这些结果没有显着变化。同样，与未治疗的受试者相比，接受 SSRI 的个体的 FMD 变化更高（合并平均差 2.5 %。95 % CI 0.7, 4.2, P < 0.001, I ²  = 82.7 %）。

限制

关于随访时间、人口统计和 SSRI 药物的大量异质性。

结论

SSRIs 显着改善 FMD，这是内皮功能的金标准标志物。有必要进一步研究 FMD 作为抑郁症和已确诊或亚临床 ASCVD 患者可能的治疗性生物标志物的作用。

Prospero 注册

CRD42021252241。