Division of Rheumatology, Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0656.
Division of Environmental Science and Health, Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA; The California Preterm Birth Initiative, University of California San Francisco, San Francisco, CA.
Am J Obstet Gynecol MFM. 2024 Apr;6(4):101319. doi: 10.1016/j.ajogmf.2024.101319. Epub 2024 Feb 29.
: Antiphospholipid syndrome (APS) and autoimmune rheumatic diseases (ARDs) are known to increase the risk for cardiovascular events (CVEs) in the general population. However, research in pregnancy is limited. We compared the occurrence of acute CVEs in pregnant women with and without ARDs or primary APS using a Californian population-based cohort.
: This was a retrospective cohort study of pregnant individuals who delivered singleton infants in California between 2005 and 2020. Birth certificates were linked by the Study of Outcomes of Mothers and Infants to maternal records. The study was approved by institutional review boards of the State of California and the University of California San Diego. Pregnancies with ARDs were identified by ≥1 International Classification of Diseases (ICD) code for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthritis, Sjogren’s syndrome, and other ARDs (systemic sclerosis, inflammatory myositis, and vasculitides) in maternal hospital discharge, emergency, or ambulatory surgery records. Lupus nephritis (LN) was defined as SLE plus glomerulonephritis, renal failure, nephritic or nephrotic syndrome, or proteinuria. Primary APS included women with APS without concurrent ARDs. Women without ARDs or APS comprised the reference group. Acute CVEs during pregnancy and up to 6 weeks postpartum were identified by ICD codes and compared between groups. CVEs were classified as myocardial infarction, cardiovascular accident, heart failure and peripartum cardiomyopathy, inflammatory heart diseases, cardiac dysrhythmias, and venous thromboembolism (VTE). Covariates identified and adjusted for include age, race and ethnicity, insurance, education, prepregnancy body mass index, preexisting hypertension, diabetes, hyperlipidemia, depression, and substance use disorders. A log linear regression with a Poisson distribution was used to estimate the adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the associations of ARDs and APS with CVEs. Analyses were performed using Statistical Analysis Software (SAS), version 9.4 (SAS Institute, Cary, NC). Causal mediation analyses were performed for potential mediators, such as gestational diabetes, gestational hypertension, and preeclampsia.
: Overall, 19,340 women had ARDs, 7758 had primary APS, and 7,004,334 had neither condition. The ARD and APS groups had more traditional cardiovascular risk factors. Acute CVEs were observed in 2.0% of ARD cases (388/19,340), 7.0% of primary APS cases (540/7,758), and 0.4% of reference group cases (24,402/7,004,334). The aRR for CVEs in the ARD and APS groups in comparison with the reference group was 4.1-fold (95% CI, 3.7–4.5) and 14.7-fold (95% CI, 13.5–16.0), respectively (Table). Of the 388 CVEs that occurred in women with ARDs, 164 (42%) were VTEs, 96 (25%) were heart failure or peripartum cardiomyopathy, and 92 (24%) were cardiac dysrhythmias. In primary APS cases, 453 of 540 (83%) CVEs were VTE. Acute CVEs occurred in 3.1% (159/8,422) of patients with overall SLE, in 10.7% (55/513) of patients with SLE with APS, and in 8.5% (77/903) of patients with SLE with LN (Table). The aRR for CVEs was 6-fold higher among those with SLE (95% CI, 5.3–6.8) and was notably increased with concurrent APS or LN, with aRRs of 18.1 (95% CI, 13.9–23.6) and 12.7 (95% CI, 10.1–15.9), respectively (Figure). The risks for both VTE and non-VTE CVEs was increased among pregnancies affected by ARD and APS (Figure). Five of 6 in-hospital deaths in ARD pregnancies (5/388 or 1.3%) occurred among women with acute CVEs (Table). The risks for CVEs were higher during all perinatal periods. In mediation analyses, 11.2% of the excess risk for CVE in ARD pregnancies was mediated by preeclampsia, whereas <0.5% was mediated by gestational diabetes or hypertension.
: Pregnancies affected by ARDs and APS had both more traditional cardiovascular risk factors and about a 4-fold and 15-fold higher CVE risk, respectively, than the reference group. Pregnancies affected by SLE with APS (18.1-fold) and LN (12.7-fold) had substantial increased risks for CVEs. VTEs were the most frequently observed CVEs. The in-hospital mortality rate for any acute CVE in ARD pregnancies was 1.3% (Table).
已知抗磷脂综合征（APS）和自身免疫性风湿病（ARD）会增加普通人群心血管事件（CVE）的风险。然而，关于妊娠的研究有限。我们比较了加利福尼亚州基于人群的队列中患有 ARD 或原发性 APS 的孕妇与无 ARD 或原发性 APS 的孕妇发生急性 CVE 的情况。
这是一项回顾性队列研究，研究对象为 2005 年至 2020 年期间在加利福尼亚分娩单胎婴儿的孕妇。通过母亲和婴儿研究将出生证明与母亲记录相关联。该研究得到了加利福尼亚州和加利福尼亚大学圣地亚哥分校机构审查委员会的批准。通过≥1 项国际疾病分类（ICD）编码识别出患有 ARD 的妊娠，包括类风湿关节炎（RA）、系统性红斑狼疮（SLE）、脊柱关节炎、干燥综合征和其他 ARD（系统性硬化症、炎性肌病和血管炎）在母亲的住院、急诊或门诊手术记录中。狼疮性肾炎（LN）定义为 SLE 伴肾小球肾炎、肾衰竭、肾炎或肾病综合征或蛋白尿。原发性 APS 包括无并发 ARD 的 APS 妇女。无 ARD 或 APS 的妇女为参考组。通过 ICD 编码识别并比较妊娠期间和产后 6 周内的急性 CVE。CVE 分为心肌梗死、心血管意外、心力衰竭和围产期心肌病、炎症性心脏病、心律失常和静脉血栓栓塞（VTE）。确定并调整了年龄、种族和民族、保险、教育、孕前体重指数、孕前高血压、糖尿病、高脂血症、抑郁和物质使用障碍等混杂因素。使用具有泊松分布的对数线性回归估计 ARD 和 APS 与 CVE 相关的调整后相对风险（aRR）和 95%置信区间（CI）。使用统计分析软件（SAS）版本 9.4（SAS Institute，Cary，NC）进行分析。对可能的中介因素（如妊娠期糖尿病、妊娠期高血压和子痫前期）进行因果中介分析。
共有 19340 名妇女患有 ARD，7758 名患有原发性 APS，7004334 名妇女既没有 ARD 也没有原发性 APS。ARD 和 APS 组有更多的传统心血管危险因素。在 ARD 病例（388/19340）、原发性 APS 病例（540/7758）和参考组病例（24/7004334）中分别观察到 2.0%、7.0%和 0.4%的急性 CVE。ARD 和 APS 组与参考组相比，CVE 的 aRR 分别为 4.1 倍（95%CI，3.7-4.5）和 14.7 倍（95%CI，13.5-16.0）（表）。在患有 ARD 的 388 例 CVE 中，164 例（42%）为 VTE，96 例（25%）为心力衰竭或围产期心肌病，92 例（24%）为心律失常。在原发性 APS 病例中，540 例 CVE 中有 453 例（83%）为 VTE。8422 例整体 SLE 患者中有 3.1%（159/8422）发生急性 CVE，513 例 SLE 合并 APS 患者中有 10.7%（55/513），903 例 SLE 合并 LN 患者中有 8.5%（77/903）（表）。SLE 患者的 CVE 风险增加 6 倍（95%CI，5.3-6.8），同时并发 APS 或 LN 时风险明显增加，aRR 分别为 18.1（95%CI，13.9-23.6）和 12.7（95%CI，10.1-15.9）（图）。ARD 和 APS 妊娠的 VTE 和非 VTE 急性 CVE 风险均增加（图）。在 ARD 妊娠中，5 例住院死亡（5/388 或 1.3%）中的 5 例发生在急性 CVE 患者中（表）。CVE 的风险在所有围产期均较高。在中介分析中，ARD 妊娠中 CVE 的超额风险有 11.2%是由子痫前期介导的，而由妊娠期糖尿病或高血压介导的风险不到 0.5%。
患有 ARD 和 APS 的妊娠既有更多的传统心血管危险因素，又分别有大约 4 倍和 15 倍的急性 CVE 风险，明显高于参考组。患有 APS（18.1 倍）和 LN（12.7 倍）的 SLE 妊娠发生 CVE 的风险显著增加。VTE 是最常见的 CVE。ARD 妊娠任何急性 CVE 的院内死亡率为 1.3%（表）。
