Acute Stress and Cardiovascular Health: Is There an ACE Gene Connection?


  • Project funding for the original study was provided by The Josiah Macy Jr. Foundation Grant SF03-09 to E. Alison Holman, and the US National Science Foundation grants BCS-9910223, BCS-0211039, and BCS-0215937 to Roxane Cohen Silver. The supplemental genetic study was supported by The Robert Wood Johnson Foundation Nurse Faculty Scholars grant #68046 and an award from the UC Irvine School of Medicine's Committee on Research and Graduate Academic Programs both given to E. Alison Holman. I thank my colleagues Drs. Roxane Silver, Daniel McIntosh, Virginia Gil-Rivas, Michael Poulin, and Judith Andersen for their integral role in the design and implementation of the original study. I thank Knowledge Networks Government, Academic, and Non-profit Research team of J. Michael Dennis and Rick Li for their assistance with collecting saliva samples; Drs. Richard Wintle and Tara Paton of The Center for Applied Genomics for their expert advice and assistance with genotyping; Dr. Zhaoxia Yu for her expert statistical advice and assistance with Hardy-Weinberg analyses; Dr. Moyra Smith for her genetics advice; Preston Reed for his assistance with data analysis; Dr. Peter Scheid for his assistance with ICD 9 coding; and Dr. Dele Ogunseitan for commenting on earlier versions of this manuscript.

Correspondence concerning this article should be addressed to E. Alison Holman, Program in Nursing Science, 100E Berk Hall, University of California, Irvine, Irvine CA 92697. E-mail:


Cardiovascular disorders (CVD) are associated with acute and posttraumatic stress responses, yet biological processes underlying this association are poorly understood. This study examined whether renin-angiotensin-aldosterone system activity, as indicated by a functional single nucleotide polymorphism (SNP) in the angiotensin converting enzyme (ACE) gene, is associated with both CVD and acute stress related to the September 11, 2001 (9/11) terrorist attacks. European-American respondents (N = 527) from a nationally representative longitudinal study of coping following 9/11 provided saliva for genotyping. Respondents had completed health surveys before 9/11 and annually for 3 years after, and acute stress assessments 9 to 23 days after 9/11. Respondents with rs4291 AA or TT genotypes reported high acute stress twice as often as those with the AT genotype. Individuals with the TT genotype were 43% more likely to report increased physician-diagnosed CVD over 3 years following 9/11, when the following variables were included in the model: (a) pre-9/11 CVD, mental health, and non-CVD ailments; (b) cardiac risk factors; (c) ongoing endocrine disorders; and (d) significant demographics. The ACE rs4291 TT genotype, which has been associated with HPA axis hyperactivity and higher levels of serum angiotensin converting enzyme (ACE), predicted acute stress response and reports of physician-diagnosed CVD in a national sample following collective stress. ACE gene function may be associated with both mental and physical health disorders following collective stress.