Vascular Endothelial Function Is Preserved in Women With a History of Preeclampsia Currently Receiving Antidepressant Pharmacotherapy

Abstract

Women with a history of preeclampsia (hxPE) have elevated risk of cardiovascular disease, likely in part from reduced endothelial function. Preeclampsia is also associated with increased risk of depression. While evidence indicates that antidepressant pharmacotherapy may have vasculoprotective effects, it is unclear whether it preserves endothelial function in women with hxPE. We hypothesized that antidepressant-treated women with hxPE would have preserved endothelial function compared with unmedicated women with hxPE. Ten women with hxPE currently treated with an antidepressant (hxPE+AD), 10 not treated (hxPE−AD), and 10 unmedicated women with a history of uncomplicated pregnancy (HC) participated. Macrovascular endothelial function was measured via brachial artery flow-mediated dilation (FMD). Microvascular endothelial function and the nitric oxide (NO) component were assessed via cutaneous vascular conductance (CVC, %max) responses to graded infusions of acetylcholine (10⁻¹⁰-10⁻¹M) alone or with 15mM N^G-nitro-L-arginine methyl ester [L-NAME; NO-synthase-inhibitor], respectively. Relative and absolute FMD in hxPE−AD were lower compared with HC (5.7±0.3% vs. 7.5±0.3%, P=0.02; 0.18±0.01mm vs. 0.23±0.01mm, P=0.02) and hxPE+AD (vs. 7.2±0.6% and 0.23±0.02mm, both P≤0.047). hxPE−AD had reduced microvascular endothelium-dependent vasodilation responses to acetylcholine compared with HC (10⁻⁵ to 10⁻²M, P=0.017). Peak CVC in hxPE−AD was lower than HC (82.0±2.9%max vs. 96.2±2.0%max, P<0.01) and hxPE+AD (vs. 92.3±3.4%max, P=0.04). L-NAME reduced microvascular dilation in all groups (P<0.001). NO-dependent dilation did not differ among groups (P=0.07). Collectively, macrovascular and microvascular endothelial function in hxPE+AD was greater than hxPE−AD and did not differ from HC, suggesting that antidepressant pharmacotherapy may preserve endothelial function in women with hxPE.

NEW & NOTEWORTHY

To our knowledge, this is the first study to demonstrate that chronic antidepressant use is associated with preserved endothelial function in women with a history of preeclampsia (hxPE). Compared with healthy controls, untreated women with hxPE had reduced macrovascular (brachial artery) and microvascular (cutaneous) endothelial function, whereas those treated with antidepressants exhibited preserved endothelial function. These findings suggest that antidepressants may modulate persistent endothelial dysfunction in these women following preeclampsia.

INTRODUCTION

Preeclampsia is a pregnancy-related hypertensive disorder that affects approximately 5–8% of pregnancies (1). Despite the remission of clinical symptoms after delivery, women who have had preeclampsia remain at elevated risk for cardiovascular disease (CVD) across the lifespan (2). This increased risk is mediated in part by persistent endothelial dysfunction (3), an early marker of CVD that is reversible with pharmacological and/or lifestyle modifications (4, 5), underscoring the need for specific strategies to mitigate this risk by targeting vascular endothelial dysfunction postpartum.

Women with a history of preeclampsia are also more likely to experience postpartum depression compared with women who had an uncomplicated pregnancy, in part due to the added psychological and physical stress associated with a complicated pregnancy (6). Interestingly, beyond being effective in treating mood disorders, accumulating evidence has indicated that antidepressant drugs have off-target effects on vascular function, including improvements in endothelial function (7, 8). In a rat model of renovascular hypertension, venlafaxine improved endothelial function and increased nitric oxide production (9). Clinically, sertraline has been shown to enhance endothelial function, assessed by brachial artery flow-mediated dilation in patients with coronary heart disease and depression (10, 11), and young adults with major depressive disorder treated with an antidepressant have greater microvascular endothelial function than those who are untreated (12). Moreover, in pregnant women with mild depressive symptoms, antidepressant use during pregnancy is associated with reduced risk of preeclampsia (13), suggesting a potential mechanistic link between antidepressant medication and maternal vascular health.

Despite these observations, to our knowledge, no investigation has examined whether chronic antidepressant pharmacotherapy mitigates persistent endothelial dysfunction following a pregnancy complicated by preeclampsia. Therefore, the purpose of this study was to investigate the effects of chronic antidepressant use on both macrovascular (conduit artery) and microvascular endothelial function in women with a history of preeclampsia. We hypothesized that women with a history of preeclampsia who were currently treated with an antidepressant would have greater macro- and microvascular endothelium-dependent dilation, assessed by brachial artery flow-mediated dilation and cutaneous vasodilation response to acetylcholine, respectively, compared with unmedicated women with a history of preeclampsia.

MATERIALS AND METHODS

Thirty healthy, normotensive women within 5 years postpartum participated in this study: 10 women with a history of preeclampsia (hxPE) who were currently medicated with an antidepressant (hxPE+AD), 10 who were not (hxPE−AD), and 10 unmedicated women with a history of healthy pregnancy (HC). All participants provided written and verbal informed consent before completing any study procedures. All experimental protocols were approved by the University of Iowa Institutional Review Board (IRB# 202203433 and #202303799) and by the U.S. Food and Drug Administration (IND# 124294), and complied with the Declaration of Helsinki.

Participants were excluded if they used tobacco or nicotine products, had diagnosed cardiovascular or metabolic diseases, or were taking anti-hypertensive or cholesterol-lowering medications. Race, ethnicity, physical activity, sleep quality, and perceived stress were collected via self-report using the Pregnancy Physical Activity Questionnaire (14-16), the Pittsburgh Sleep Quality Index (15), and the Perceived Stress Scale (16). Pregnancy and psychiatric (depression and/or anxiety) histories were collected through self-report and electronic medical records.

Macrovascular Endothelial Function

Macrovascular endothelial function was assessed using brachial artery flow-mediated dilation (FMD) as previously describedusing high-resolution ultrasound (Logiq E9; GE Healthcare, Milwaukee, WI, USA) with a 9 MHz linear transducer. After ~10 min of supine rest, baseline recordings were obtained, followed by 5 minutes of cuff inflation (250 mmHg). Post-occlusion recordings were assessed for 120 seconds. End-diastolic diameter and mean blood velocity were analyzed using off-line software with automatic wall detection (Vascular Analysis Tool 5.5; Medical Imaging Applications LLC, Coralville, IA, USA). FMD was reported in mm and in percent change (%) from baseline. Shear rate (SR) and SR area under the curve (SR_AUC) were calculated from cuff deflation to peak diameter using trapezoidal rule (17), and SR_AUC for the first 20 cardiac cycles after deflation was identified (SR_peak).

Microvascular Endothelial Function

Cutaneous vascular conductance was measured during graded (10⁻¹⁰-10⁻¹M) infusions of acetylcholine (United States Pharmacopeia, Rockville, MD, USA) alone or mixed with 15mM L-NAME (N^G-nitro-L-arginine methyl ester; Calbiochem, EMD Millipore, Billerica, MA, USA)to assess microvascular endothelium- and NO-dependent dilation as previously described (12). Two intradermal microdialysis fibers (CMA 31 Linear Microdialysis Probe; Harvard Apparatus, Holliston, MA, USA) were placed in the left ventral forearmand . Laser-Doppler flux (LDF) was continually measured by Laser-Doppler flowmetry probes in local-heaters set to 33°C (moorVMS-LDF2 and moorVMS-HEAT; Moor instruments, Wilmington, DE, USA). A Following the dose-response, 28mM sodium nitroprusside (United States Pharmacopeial, Rockville, MD, USA) was perfused through both microdialysis fibers, and the local heater temperature was increased to 43°C to elicit maximal blood flow (~20 minutes). Cutaneous vascular conductance (CVC) was calculated (CVC=LDF/mean arterial pressure) and normalized to maximum (%CVC_max). Microvascular NO-dependent dilation was calculated as the difference in area under the curve between the control and L-NAME sites. Dose-response curves were fitted using 4-parameter nonlinear regression to determine logEC50 and HillSlope (GraphPad Prism 10.2.2, San Diego, CA, USA).

Statistical Analysis

Group differences in participant characteristics and endothelial function measures were analyzed using one-way ANOVA with Tukey’s post hoc corrections. Unpaired Student’s t-test was performed to test the difference in gestational age at preeclampsia diagnosis between the hxPE+AD and hxPE−AD groups. CVC data were analyzed using repeated measures ANOVA (group × site × dose) with Tukey’s post hoc corrections. To further evaluate concentration-specific effects, repeated measures ANOVA (group × dose) was also conducted separately at the control and L-NAME sites. A two-way repeated measures ANOVA was used to evaluate group or site differences in baseline and maximal CVC. Data in tables are presented as mean ± SD, and figures as mean ± SE with individual data points as appropriate. Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and SPSS version 29.0 (IBM, Chicago, IL, USA).

RESULTS

Participant Characteristics

Table 1 presents participant characteristics. Women in the hxPE+AD group had significantly higher weight than the HC and hxPE−AD groups (both P≤0.01). Both hxPE groups also demonstrated elevated systolic blood pressure compared with the HC group (both P≤0.01), while mean arterial pressure was significantly higher only in the hxPE−AD group compared with HC (P=0.03). The hxPE−AD group had a lower gestational age at their most recent delivery compared with the HC group (P=0.03). There were no group differences in age, body mass index, blood chemistry, physical activity, sleep quality, time postpartum, parity, race, or ethnicity between groups (all P≥0.10). Among participants with hxPE, there was no difference in the severity of preeclampsia based on gestational age at diagnosis or presence of severe symptoms (both P≥0.24).

Table 1.

Participant Characteristics

Clinical Characteristics	HC (n=10)	hxPE−AD (n=10)	hxPE+AD (n=10)	P value
Age (years)	35 ± 6	34 ± 4	33 ± 6	0.78
Height (cm)	165.4 ± 8.0	162.6 ± 4.9	168.3 ± 7.5	0.20
Weight (kg)	71.0 ± 9.9	71.2 ± 9.2	87.9 ± 14.8*†	<0.01
BMI (kg/m2)	26.3 ± 5.5	27.0 ± 3.9	31.1 ± 5.9	0.10
SBP (mmHg)	104 ± 6	116 ± 7*	113 ± 7*	<0.01
DBP (mmHg)	65 ± 5	71 ± 7	70 ± 8	0.13
MAP (mmHg)	78 ± 4	86 ± 7*	84 ± 8	0.02
Total cholesterol (mg/dL)	161 ± 27	181 ± 30	181 ± 19	0.16
HDL (mg/dL)	56 ± 15	60 ± 8	59 ± 17	0.80
LDL (mg/dL)	93 ± 23	107 ± 28	101 ± 25	0.46
BUN (mg/dL)	11 ± 3	12 ± 2	14 ± 3	0.10
Creatine (mg/dL)	0.78 ± 0.09	0.80 ± 0.13	0.80 ± 0.07	0.88
BUN/creatine ratio	14.0 ± 3.9	15.3 ± 3.7	17.3 ± 3.6	0.16
Fasting glucose (mg/dL)	82.9 ± 10.3	79.5 ± 6.2	81.5 ± 2.9	0.57
HbA1c (%)	5.2 ± 0.3	5.2 ± 0.3	5.2 ± 0.3	0.87
Lifestyle Characteristics
MVPA (MET-hours/weeks)	102.3 ± 61.4	101.3 ± 34.0	111.5 ± 57.3	0.89
Total PA (MET-hours/weeks)	287.0 ± 82.2	301.8 ± 73.6	274.6 ± 106.8	0.79
PSQI global score	4 ± 2	5 ± 2	6 ± 3	0.17
Perceived stress scale score	12 ± 5	14 ± 8	14 ± 7	0.75
Race [n (%)]
White	8 (80)	6 (60)	10 (100)	0.21
Black or African American	2 (20)	3 (30)	0 (0)
More than one race	0 (0)	1 (10)	0 (0)
Ethnicity [n (%)]
Not Hispanic or Latino	90 (90)	90 (90)	90 (90)	1.00
Hispanic or Latino	1 (10)	1 (10)	1 (10)
Pregnancy History
Time postpartum (month)	34 ± 16	29 ± 16	24 ± 15	0.39
Parity (number)	2 ± 1	2 ± 1	2 ± 1	0.86
GA at delivery (weeks)	39 ± 1	35 ± 4*	36 ± 2	0.03
GA at diagnosis (weeks)		36 ± 4	36 ± 2	0.71
PE with severe symptoms [n (%)]		5 (50)	8 (80)	0.24

Data are means ± SD. HC, healthy pregnancy; hxPE−AD, women with a history of preeclampsia not treated with an antidepressant; hxPE+AD, women with a history of preeclampsia treated with an antidepressant; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BUN, blood urea nitrogen; HbA1c, glycohemoglobin; MVPA, moderate to vigorous physical activity; PA, physical activity; PSQI, Pittsburgh Sleep Quality Index; GA, gestational age; PE, preeclampsia. P values in the table are from one-way ANOVA among groups. *P<0.05 vs. HC; ^†P<0.05 vs. hxPE−AD.

All participants in the hxPE+AD group, one participant in the hxPE−AD group, and none of the participants in the HC group self-reported a prior diagnosis of depression and/or anxiety. All AD-treated participants were treated for ≥4 weeks (range: 1–40 months) before study enrollment and the medications in use included selective serotonin reuptake inhibitors (SSRI; n=6; one was also taking a tricyclic antidepressant), serotonin-norepinephrine reuptake inhibitors (SNRI; n=2), a serotonin antagonist and reuptake inhibitor (SARI; n=1), and a dopamine-norepinephrine reuptake inhibitor (DNRI; n=1; together with a 5-HT₁A partial agonist).

Macrovascular Endothelial Function

Absolute (mm) and relative (%) brachial artery FMD are presented in Figure 1. There were significant group effects in absolute and relative FMD (both P=0.01). The hxPE−AD group had lower absolute and relative FMD compared with the HC and hxPE+AD groups (all P≤0.047), whereas the hxPE+AD group showed no differences from the HC group (both P≥0.90). Shear rate data were collected from 8 participants in the HC, 9 in the hxPE+AD, and 8 in the hxPE−AD. SR_AUC (HC: 52341 ± 6016 s⁻¹; hxPE+AD: 53642 ± 6126 s⁻¹; hxPE−AD: 60132 ± 5147 s⁻¹) and SR_peak (HC: 1710 ± 109 s⁻¹; hxPE+AD: 1658 ± 180 s⁻¹; hxPE−AD: 1646 ± 145 s⁻¹) were not different among groups (both P≥0.61).

Figure 1.

Absolute (A, mm) and Relative (B, %) Flow-Mediated Dilation (FMD). HC, women with a history of healthy pregnancy; hxPE−AD, women with a history of preeclampsia not treated with an antidepressant; hxPE+AD, women with a history of preeclampsia treated with an antidepressant

Microvascular Endothelial Function

Figure 2 presents the cutaneous vasodilation response to acetylcholine in control and L-NAME-treated microdialysis sites. The group × site × dose analysis revealed that the hxPE−AD group exhibited reduced microvascular endothelium-dependent dilation response to acetylcholine in the control site compared with HC (P =0.017). At the control site, a group × dose interaction was observed (P=0.03), with reduced microvascular endothelium-dependent dilation in the hxPE−AD group compared with the HC group across acetylcholine concentrations of 10⁻⁵ to 10⁻²M (P≤0.03) and hxPE+AD group at 10⁻³M (P=0.03). Peak CVC response to acetylcholine in the hxPE−AD group was lower than in the HC and hxPE+AD groups (Figure 2B; both P≤0.04). At the L-NAME site, vasodilatory response was blunted across all groups (P<0.001), with no group difference (Figure 2C; P=0.72). There was no group difference in calculated NO-dependent dilation (Figure 2D; P=0.07). LogEC50 was significantly higher in the hxPE−AD group compared to the HC group at the control site (P=0.02), with no group differences at the L-NAME site (P≥0.90). There were no group differences in HillSlope (P≥0.12). Baseline and maximal CVC did not differ between groups at either the control or L-NAME sites (Table 2; P≥0.36), while the L-NAME sites showed lower baseline CVC compared with the control sites across groups (Table 2; main effect of drug; P≤0.01).

Figure 2.

Vasodilation Responses to Acetylcholine in Control (A, %max) and NO Synthase-Inhibited Sites (C, %max), Peak Cutaneous Vascular Conductance in Control site (B, %max), and NO-Dependent Dilation (D, a.u.). HC, women with a history of healthy pregnancy; hxPE−AD, women with a history of preeclampsia not treated with an antidepressant; hxPE+AD, women with a history of preeclampsia treated with an antidepressant; L-NAME, N^G-nitro-L-arginine methyl ester. *P<0.05 vs. HC, ^†P<0.05 vs. hxPE+AD, ^‡P<0.05 main effect vs. HC, ^#P<0.05 vs. control site within group.

Table 2.

Baseline and Maximal Absolute Cutaneous Vascular Conductance (fux·mmHg⁻¹)

Microdialysis Site	HC (n=10)	hxPE−AD (n=10)	hxPE+AD (n=10)
Acetylcholine + Lactated Ringer’s
Baseline	0.2 ± 0.2	0.2 ± 0.1	0.3 ± 0.2
Maximum	2.0 ± 1.0	1.6 ± 0.5	2.1 ± 1.6
Acetylcholine + L-NAME
Baseline	0.1 ± 0.1	0.1 ± 0.1	0.1 ± 0.1
Maximum	1.7 ± 0.6	1.7 ± 0.5	1.9 ± 1.7

Data are means ± SD. HC, healthy pregnancy; hxPE−AD, women with a history of preeclampsia not treated with an antidepressant; hxPE+AD, women with a history of preeclampsia treated with an antidepressant; L-NAME, N^G-nitro-L-arginine methyl ester.

DISCUSSION

The primary finding of this study is that antidepressant-treated women with hxPE had preserved macrovascular (brachial artery FMD) and microvascular (cutaneous vasodilation to Ach) endothelial function, such that their responses were greater than women with hxPE who were not taking antidepressant medications, and not different from the healthy controls. Furthermore, there was no difference in NO-dependent dilation between antidepressant-treated women with hxPE and the control group. Collectively, these findings suggest that antidepressant pharmacotherapy may preserve vascular endothelial function, which is mediated, in part, by an improvement in NO-dependent mechanisms in women with hxPE.

Preeclampsia and depression have a bidirectional relation during pregnancy, and share common risk factors, including endothelial dysfunction (18). Despite the remission of clinical symptoms after pregnancy, women with hxPE remain at elevated risk of CVD (2), which may be mediated in part by persistent endothelial dysfunction, and are particularly vulnerable to developing depression. Most, but not all, studies show a beneficial effect of antidepressant medications on endothelial function (7, 8), and antidepressant use that reduces depression symptoms during pregnancy decreases preeclampsia risk in pregnant women with mild depressive symptoms (13). However, whether antidepressant pharmacotherapy after preeclampsia improves endothelial function is unknown. The present study found that conduit artery endothelial function assessed with FMD, a predictor for future CVD events (19), was preserved in antidepressant-treated women with hxPE such that there was no difference from women with history of uncomplicated pregnancy. Women with hxPE who were not using an antidepressant had attenuated FMD compared with both hxPE+AD and HC groups. Prior prospective studies have reported improvements in FMD after 5 to 6 months of sertraline or citalopram in patients with coronary heart disease and/or depression (10, 11). Similarly, an observational retrospective study found that the use of an antidepressant was associated with higher FMD in patients with coronary heart disease (20). Collectively, our data extend these prior findings to women with hxPE and suggest that antidepressant use may protect conduit artery endothelial function, a significant predictor of CVD morbidity and mortality, in this cohort of women at high risk for CVD.

We also assessed cutaneous microvascular endothelium- and NO-dependent dilation in this study. Previously, we have shown that women with hxPE have reduced microvascular function compared with controls (3), and that this reduced function is sensitive to interventional approaches (5). In the current study, we found that microvascular endothelium-dependent dilation was preserved in antidepressant-treated women with hxPE compared with healthy controls, while untreated women with hxPE exhibited attenuated dilation compared with healthy controls and women with hxPE treated with antidepressant medication. Greaney et al. reported that NO-mediated microvascular function was blunted in young adults with major depressive disorder (MDD) but preserved in SSRI-treated adults with MDD compared with healthy adults (21). Our data agree with these findings. We found no group differences in the microvascular vasodilatory response to acetylcholine when NO synthase was inhibited, and calculated NO-dependent dilation tended to be lower in untreated women with hxPE but not hxPE treated with antidepressant medication, compared with healthy controls, suggesting that antidepressant pharmacotherapy may be improving endothelial function in women with hxPE through NO-dependent mechanisms. Our data provide initial evidence of the beneficial effects of antidepressant use on endothelial function in women with hxPE. These findings lay the groundwork for several future questions in this area that should be examined with rigorous, prospective, mechanistic studies:

How do drug class, dose, and duration of medication modulate this endothelial effect?

Our cohort of women treated with an antidepressant included women taking any form of antidepressant medication, and we did not control for dosing or duration of medication. The majority of clinical and experimental evidence regarding the effects of antidepressant drugs on vascular function examine selective serotonin reuptake inhibitors (SSRIs), which are considered first-line pharmacotherapy for depression. These studies have suggested that SSRIs show the most consistent vascular benefits, including improved endothelial function and reduced vascular inflammation, whereas the effects of non-SSRI antidepressants remain limited and often contradictory (8). Although some clinical studies have reported that non-SSRIs such as venlafaxine (SNRIs) and bupropion (DNRI) may elevate blood pressure (22, 23), preclinical evidence suggests that venlafaxine can attenuate renovascular-hypertension induced endothelial dysfunction and oxidative stress in animal models (9). We did not observe obvious differences in our vascular measures between participants using an SSRI compared with other antidepressant medications, but our sample size for this comparison was limited and future work should examine the potential mechanistic differences between different therapeutic approaches in this population. Furthermore, we were not able to probe the possible effects of dose or duration of medication, which should also be explored in future work. In contrast to studies demonstrating improved FMD following 5 to 6 months of SSRI treatment in individuals with depression (10, 11), a shorter duration of SSRI (1 month) did not alter FMD in otherwise healthy, young women with depression (24), suggesting that duration may influence the vascular response to antidepressant medication.

What are the vascular mechanisms underlying this response?

The possible mechanisms underlying the beneficial effects of antidepressant use on endothelial function in women with hxPE include enhanced production and bioavailability of NO, reduced oxidative stress, and attenuated inflammation. Both preeclampsia and depression have been associated with impaired NO-mediated vasodilation and increased oxidative stress while antidepressant medications, including fluoxetine (25), sertraline (26) (SSRIs), venlafaxine (9) (SNRI), and amitriptyline (27) (TCA), have been shown to increase NO production and reduce oxidative stress. Our data agree with these findings, suggesting that antidepressant pharmacotherapy improves endothelial function via NO-dependent mechanisms, but the role of oxidative stress in our outcomes remains unknown. Another plausible mechanism underlying our findings is the modulation of inflammatory signaling, which is linked to endothelial function (28) and a therapeutic target in the vascular dysfunction associated with preeclampsia and depression (29, 30). Preclinical and clinical studies have shown that antidepressant pharmacotherapy decreases circulating concentrations of inflammatory cytokines (e.g., IL-1, TNF-α, hs-CRP) (10, 31). Future studies that mechanistically interrogate whether and how antidepressant use improve vascular function after preeclampsia should focus on oxidative stress and inflammation.

How does the efficacy of the medication to reduce depressive symptoms modulate the vascular endothelial response?

Lifestyle characteristics such as physical activity, sleep quality, and perceived stress did not differ among groups, suggesting that these factors were unlikely to influence our findings. However, we did not assess the current severity of depression or depressive episode onset, preventing us from examining the relationship between mood improvement and endothelial function. Several studies have suggested that the beneficial effects of antidepressants on endothelial function may be more evident in individuals who experience a clinical improvement in depression symptoms. Kokras et al. reported that improvements in FMD were observed only in patients who responded to antidepressant medication, whereas those who did not respond to medication showed no significant effects on FMD (11). Similarly, the efficacy of antidepressant pharmacotherapy during pregnancy to reduce preeclampsia risk is dependent on a positive maternal mood response to medication (13). Considering our cross-sectional study design, we are unable to address whether the observed vascular benefits by antidepressant use are due to direct pharmacological effects of antidepressants or secondary to improvements in mood or behaviors which may indirectly benefit endothelial function through a healthier lifestyle, including greater engagement in daily activities, reduced psychological stress, and improved sleep quality (32).Future work should differentiate between responders and non-responders to better understand whether the potential vascular benefits of antidepressant medication among women with hxPE are dependent on depressive symptomology.

Conclusion

In conclusion, our findings suggest that antidepressant use in the postpartum period may preserve both macrovascular and microvascular endothelial function in women with hxPE. Given the persistent endothelial dysfunction and elevated CVD risk after pregnancy complicated by preeclampsia, this preliminary evidence points to a potential vascular benefit of antidepressant use and highlights the need for integrated cardiovascular and mental health management in postpartum women. Future studies should validate and extend these findings to understand the mechanisms by which antidepressant pharmacotherapy may improve endothelial function and determine the long-term clinical implications of antidepressant medication on cardiovascular risk in women with hxPE.

DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.