Exaggerated serotonin-mediated platelet reactivity as a possible link in depression and acute coronary syndromes

Serotonin modulates vascular, immune, and neurophysiology and is dysregulated in preeclampsia. Despite biological plausibility that selective serotonin reuptake inhibitors (SSRIs) prevent preeclampsia pathophysiology, observational studies have indicated increased risk and providers may be hesitant. The objective of this meta-analysis and quality assessment was to evaluate the evidence linking SSRI use in pregnancy to preeclampsia/gestational hypertension.

PubMed was searched through June 5, 2020 manually and using combinations of terms: “preeclampsia”, “serotonin”, and “SSRI”. This review followed MOOSE guidelines. Inclusion criteria were: 1) Observational cohort or population study, 2) exposure defined as SSRI use during pregnancy, 3) cases defined as preeclampsia or gestational hypertension, and 4) human participants. Studies were selected that addressed the hypothesis that gestational SSRI use modulates preeclampsia and/or gestational hypertension risk. Review Manager Web was used to synthesize study findings. Articles were read and scored (Newcastle-Ottawa Quality Assessment Scale) for quality by two independent reviewers. Publication bias was assessed using a funnel plot and the Egger test.

Of 179 screened studies, nine were included. The pooled risk ratio (random effects model) was 1.43 (95 % CI: 1.15–1.78, P < 0.001; range 0.96–4.86). Two studies were rated as moderate quality (both with total score of 6); others were high quality. Heterogeneity was high (I2 = 88 %) and funnel asymmetry was significant (p < 0.00001).

Despite evidence for increased preeclampsia risk with SSRIs, shared risk factors and other variables are poorly controlled. Depression treatment should not be withheld due to perceived gestational hypertension risk. Mechanistic evidence for serotonin modulation in preeclampsia demonstrates a need for future research.

Diabetes and depression are risk factors for cardiovascular disease, but the evidence about their interaction effect on long-term health outcomes among Latinos is lacking. We aimed to investigate the joint association of diabetes and subsequent depressive symptoms with mortality among older Latinos, an understudied racial/ethnic group with high prevalence of diabetes.

This study included 1,495 adults from the Sacramento Area Latino Study on Aging. We employed Cox proportional-hazards models to estimate the adjusted hazard ratios [aHRs] for cardiovascular and all-cause mortality according to diabetes status at enrollment and depressive symptoms a year after the enrollment. We used marginal structural models to adjust for time-varying confounders.

The mean age (standard deviation) of participants was 70 (6.6) years. Over follow-up (median 7.7 years), diabetes and depressive symptoms were individually associated with increased risk of cardiovascular mortality (diabetes, aHR[95% CI]=2.13[1.60–2.84]; depressive symptoms, aHR[95% CI]=1.62[1.09–2.39]) and all-cause mortality (diabetes, aHR[95% CI]=1.92[1.53–2.41]; depressive symptoms, aHR[95% CI]=1.41[1.02–1.94]). After adjusting for time-varying confounders, we found a multiplicative interaction between diabetes and subsequent depressive symptoms for cardiovascular mortality (aHR[95% CI]=2.94[1.07–8.39]), but not all-cause mortality (aHR[95% CI]=1.80[0.81–4.35]).

Using a longitudinal cohort of community-dwelling older Latinos, we found that diabetes and subsequent depressive symptoms were jointly associated with increased risk of cardiovascular mortality.

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4–24.0] vs. 4.0 [2.5–8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = −0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC₅₀) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

To provide updated systematic and quantitative summary of the association between depression and the risk of CVD events among individuals with type 2 diabetes. We also aimed to examine the sensitivity of the association to uncontrolled confounding.

Data sources included Medline, Embase, and PsycInfo through September 2019. Two independent reviewers selected cohort studies that evaluated the association between depression and fatal or non-fatal CVD events among individuals with type 2 diabetes. Bias analysis was performed using the bias formula approach.

Of 2527 citations screened, 17 eligible studies with a total of 1,033,131 participants were identified. Based on random-effects meta-analysis, depression was associated with higher risks of non-fatal CVD events (relative risk 1.35, 95% confidence interval [CI] 1.20 to 1.53) and fatal CVD event (relative risk 1.47, 95% CI 1.21 to 1.77). Bias analysis indicated that unmeasured confounders alone may not explain the observed association between depression and CVD events among individuals with type 2 diabetes.

Depression was associated with a higher risk of non-fatal and fatal CVD events among individuals with type 2 diabetes. Our findings provide updated and robust evidence about the association between depression and CVD events among individuals with type 2 diabetes.