PTSD may increase risk of cardiovascular diseases

Post-traumatic stress disorder (PTSD) appears to share a genetic risk with cardiovascular disease (CVD), indicating that PTSD is a factor that contributes to the development of coronary artery disease (CAD) and hypertension, reveals a study.

“Individuals with PTSD are significantly 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 working group to determine gaps in the literature, including the need for large-scale genomic studies to identify shared genetic risk.”

The research team utilized a large healthcare biobank dataset (n=36,412), combined with genome-wide association study (GWAS) summary statistics from publicly available PTSD and CVD studies. They collected disease phenotypes from electronic records and genotyped de-identified genetic data from the biobank using Illumina SNP array.

Summary statistics data sets were processed using the following criteria: SNP heritability h² >0.05, compute z-statistics (z=beta/SE or z=log(OR)/SE), filter nonvariable SNPs (0<freq<1), and filter SNPs with low number of samples. Finally, the researchers used the multitrait analysis of GWAS approach to combine GWAS summary statistics.

PTSD showed significant genetic associations with CVD (r_G=0.24, SE=0.06). Mendelian randomization analyses revealed a possible causal link from PTSD to hypertension (β=0.20, SE=0.04), but not the opposite. [Am J Psychiatry 2022;179:814-823]

PTSD summary statistics was a robust predictor of PTSD diagnostic status (R²=0.27), which was markedly improved by including summary statistics from CVD and major depressive disorder (MDD; R²=1.30). Pathway enrichment analyses also revealed the contribution of genetic variants in shared PTSD-CVD risk, such as those involved in postsynaptic structure, synapse organization, and interleukin-7-mediated signaling pathways.

“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 CAD, and the genetic prediction of PTSD risk is improved by the consideration of polygenic risk for 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 (ie, chronically elevated blood pressure due to stress) and via the renin-angiotensin system (ie, elevated blood pressure due to renin and angiotensin-II release that causes vasoconstriction).

“Our findings provide support for 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 the risk of CVD. Identifying individuals with shared PTSD and CVD risk, for instance, will help clinicians choose interventions that can improve certain features of cardiovascular function, according to the researchers.

Previous studies have documented the effects of some psychiatric and CVD medications on cardiovascular function, but only a few have tested the effects of these treatments on subsequent CVD risk in individuals with PTSD. [Neuropharmacology 2012;62:617-627; N Engl J Med 2018;378:507-517]

“Medications 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,” the researchers noted. [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 CVD risk in PTSD, and to determine whether they are more efficacious for individuals with high genetic risk for both PTSD and CVD,” they added.