Background: Treatment of post-traumatic stress disorder (PTSD) may help prevent cardiovascular diseases (CVD,) which is a leading cause of death. Randomized controlled trials comparing the effect of PTSD treatment vs. placebo on CVD risk would be unable to assess the relation of duration of PTSD symptoms (“dose”) to CVD risk (e.g., CHD morbidity and mortality) rather than pathophysiological markers, given the duration of study and sample size needed. Here, we propose to collect data to complement the results of the ideal trial – that is, to use observational data appropriately and efficiently – by making use of our longitudinal study tracking the time-varying symptoms of PTSD, time-varying conventional CVD risk factors and, as outcome, incidence and mortality from CVD. The multi- ethnic WTC-Heart cohort study will be accompanied by a sub-study assessing whether, as assumed, individuals with lower PTSD dose have lower exposure to markers of stress, trauma, and CVD risk factors. Preliminary work: 1. A cohort study of initially 6481 first responders with a long term follow up and high retention rate: In 2012-2013 WTC-Heart enrolled 6481 first-responders in the WTC Health Program (WTCHP) to assess the determinants of incident cases of CVD reported by cohort members and validated in medical charts, and incident hospitalizations from the NY State hospitalization registry (SPARCS). Retention was 91% as of 2016. 2. Longitudinal assessment of PSTD symptoms and conventional CVD risk factors: The cohort members have had up to 15 visits at the WTCHP in which mental health and CVD factors were assessed. 3. A diverse gender and race/ethnic composition: the cohort comprises 17% of women and 54% Non-Hispanic Whites. Specific Aims: Aim 1. To perform a second in-person, standardized assessment in 2022-23 of the WTC-Heart cohort with follow-up until 2026, taking advantage of the statistical power resulting from 13-14 years of follow-up, high prevalence of PTSD, linkage with National Death Index. Aim 2. To estimate the causal effect of PTSD dose and its potential changes on total (fatal and non-fatal) and non-fatal CVD, coronary artery disease, and cerebrovascular diseases, overall and among ethnic (non-Hispanic white, non-Hispanic Black, and Hispanic) groups. Analyses will use repeated assessments of PTSD and CVD between 2012 and 2026, and appropriate adjustment for time-updating CVD risk factors, and for COVID-19 exposure, using G- methods. Aim 3. To assess the biological, behavioral and trauma history plausibility of the epidemiological associations between PTSD dose and CVD risk by measuring biological indicators of chronic stress, history of trauma, and CVD risk factor among a subsample of 240 participants randomly recruited within tertiles of PTSD dose. Innovation and Significance: The proposed study has a potentially major clinical and public health significance if it helps to determine whether: 1) risk of CVD morbidity and mortality is inversely related to P...