Abstract
Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study – United Kingdom Biobank – PTSD symptoms were negatively associated with SBP levels (β = −1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.
Highlights
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide (Virani et al, 2020), and longitudinal research has found that posttraumatic stress disorder (PTSD) – the quintessential trauma-related mental disorder – precedes and predicts the onset of incident CVD (Kubzansky et al, 2007, 2009; Vaccarino et al, 2013; Sumner et al, 2015)
Average PTSD symptoms on the transformed 0–1 scale varied across studies, with the lowest mean symptom levels detected for GMRF-QUT and United Kingdom Biobank (UKBB) and the highest mean symptom levels detected for TRACTS and the three treatment studies: CHOICE, D-cycloserine study (DCS), and Optimizing Treatment for PTSD (OPT)
Higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) polygenic scores (PGS) were each associated with higher SBP and DBP levels, respectively. In their genome-wide association study (GWAS) results, Giri et al (2019) found that significant sentinel single nucleotide polymorphisms (SNPs) at independent loci accounted for more variance in SBP (3.56%) than for DBP (1.06%), and we found that effect sizes of PGS on blood pressure levels – small – were larger for SBP than for DBP in trans-ethnic meta-analyses
Summary
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide (Virani et al, 2020), and longitudinal research has found that posttraumatic stress disorder (PTSD) – the quintessential trauma-related mental disorder – precedes and predicts the onset of incident CVD (Kubzansky et al, 2007, 2009; Vaccarino et al, 2013; Sumner et al, 2015). PTSD has been associated with elevated blood pressure and hypertension in a variety of trauma-exposed populations, including military veteran and community-based samples (Schnurr et al, 2000; Kibler et al, 2009; Sumner et al, 2016; Burg et al, 2017; Edmondson et al, 2018; Howard et al, 2018). In a predominantly male sample of younger veterans, Wolf et al (2017) found that obesity polygenic risk, reflecting additive risk for obesity based on thousands of genotypes across the genome, moderated the relation between PTSD and metabolic syndrome (an indicator of cardiometabolic risk). Examining whether genetic liability moderates associations of PTSD with physical health indicators, such as blood pressure (i.e., Gene × Environment interactions) may further our understanding of chronic disease risk and inform more targeted allocation of screening and intervention efforts
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