Post-traumatic stress disorder (PTSD) appears to share a genetic risk with cardiovascular disease (CVD), indicating that PTSD is a contributing factor to the development of coronary heart disease (CAD) and hypertension, study finds .
“People with PTSD are much more likely to be diagnosed with CVD (eg, myocardial infarction, stroke),” the researchers said. “The evidence for this link is so compelling that the National Institutes of Health convened a task force to determine gaps in the literature, including the need for large-scale genomic studies to identify shared genetic risk.”
The research team used a large healthcare biobank dataset (n=36,412), combined with genome-wide association study (GWAS) summary statistics from studies on publicly available PTSD and cardiovascular disease. They collected disease phenotypes from electronic records and genotyped anonymized genetic data from the biobank using the Illumina SNP matrix.
Summary statistical datasets were processed using the following criteria: heritability of SNPs h2 > 0.05, calculate z-statistics (z=beta/SE or z=log(OR)/SE), filter non-variable SNPs (0
PTSD has shown significant genetic associations with CVD (rg=0.24, SE=0.06). Mendelian randomization analyzes revealed a possible causal link between PTSD and hypertension (β=0.20, SE=0.04), but not vice versa. [Am J Psychiatry 2022;179:814-823]
PTSD summary statistics were a robust predictor of PTSD diagnostic status (R2= 0.27), which was significantly improved by including summary statistics for cardiovascular disease and major depressive disorder (MDD; R2=1.30). Pathway enrichment analyzes also revealed the contribution of genetic variants to the shared risk of PTSD-CVD, such as those involved in postsynaptic structure, synapse organization, and interleukin-mediated signaling pathways. 7.
“Our results indicate that there is substantial genetic overlap between PTSD and CVD, PTSD and MDD may be risk factors leading to the development of hypertension and coronary artery disease, and the genetic prediction of PTSD risk is enhanced by accounting for polygenic risk of CVD and MDD,” the researchers said.
Mechanisms
One of the potential drivers of the association between PTSD/MDD and CVD is elevated sympathetic arousal that leads to hypertension, both directly (i.e. chronically elevated blood pressure due to stress) and via the renin-angiotensin system (i.e. elevated blood pressure upon release of renin and angiotensin-II which causes vasoconstriction).
“Our results support this mechanism, but we cannot exclude the possibility that confounding factors or mediating effects (eg, diet, smoking) are responsible for these associations, which should be examined in future research” , the researchers said.
“Future studies of genetic risk and diagnostic prediction would benefit from incorporating this polygenic risk approach,” they added.
Clinical implication
These findings may provide benefits in risk identification, which can be used to improve PTSD treatment and reduce CVD risk. Identifying people at shared risk for PTSD and CVD, for example, will help clinicians choose interventions that may improve certain characteristics of cardiovascular function, the researchers say.
Previous studies have documented the effects of certain psychiatric and cardiovascular medications on cardiovascular function, but only a few have tested the effects of these treatments on subsequent cardiovascular risk in people with PTSD. [Neuropharmacology 2012;62:617-627;
N Engl J Med 2018;378:507-517]
“Drugs targeting the renin-angiotensin system (eg, ACE inhibitors, beta-blockers) have demonstrated efficacy in rodent models, but research in humans with PTSD has been mixed,” noted the researchers. [Biol Psychiatry 2014;75:864-872;
Biol Psychiatry 2021;90:473-481]
“A next step in this line of work is to determine whether existing cognitive-behavioral and pharmacological treatments actually reduce the risk of CVD in PTSD, and to determine whether they are more effective for people at high genetic risk for PTSD. and MCV,” they added. .
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