Shah, Amit

Background: The gap between artificial intelligence-derived age (ECG-Age) and chronological age has been validated as a strong predictor of increased cardiovascular morbidity and mortality, independent of age, and is a potential biomarker of biological aging. Acute stress may cause real-time, transient changes in autonomic function via electrophysiological signals that, when repeated over time, may contribute to biological aging and represent mechanisms linking stress and Major Adverse Cardiovascular Events (MACE). We hypothesized that acute mental stress induced in a laboratory is associated with increased ECG and that this increase is associated with a higher risk of MACE among individuals with stable coronary heart disease (CHD). Methods: We pooled two prospective cohorts of participants with stable CHD from a university-based hospital network in Atlanta. Stress was induced using a standardized mental stress test (public speaking task) and measured 12-lead ECGs during rest, mental stress, and recovery periods. To measure ECG-age, we utilized a published algorithm using a neural network on >500,000 independent patients. The study endpoint was MACE including nonfatal myocardial infarction, hospitalization for heart failure, or cardiovascular death. The difference in ECG-Age between resting and acute mental stress was used to define the stress Age-Gap. Cox proportional hazard regression modeled the association of stress Age-Gap operationalized as tertiles adjusting for chronological age, sex, race, cardiovascular risk factors, and baseline Cohen perceived stress scale. Results: 442 participants in the total sample pool (38% women). Over a 5-year median follow-up, 95 participants (21%) experienced MACE. At rest, the mean chronologic age was 55.7±9.9 years, and ECG-Age was 57.1 ±10.7 years, with rest Age-Gap of 0. 9±9.6 (p=0.16). During stress, the stress Age-Gap of 1.95±9.8 (p<0.0001), while recovery Age-Gap was 1.1±10.3 (p=0.13). Those that demonstrated the largest ECG-Age positive change between rest and stress by ECG (top tertile) had a higher risk for MACE when compared to those with the lowest or negative ECG age change (bottom tertile), see Figure. Conclusion: Among patients with stable CHD, acute mental stress caused changes in biological age as measured by AI-ECG consistent with accelerated biological aging. Such changes were associated with MACE. These results uncover accelerated biological aging as a mechanism linking acute stress to CVD outcomes.

Background Atrial fibrillation ( AF ) has been associated with faster cognitive decline and increased dementia risk. Factors associated with dementia in patients with AF have been seldom studied. Methods and Results We studied 6432 individuals from the ARIC ‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study). In 2011 to 2013, participants underwent a physical exam, echocardiography, detailed cognitive assessments, and a subset, brain magnetic resonance imaging. Dementia and mild cognitive impairment ( MCI ), as well as etiology of MCI /dementia, Alzheimer's disease–related or vascular, were adjudicated by an expert panel. AF was defined by study ECGs and past hospitalizations. We used logistic regression to estimate odds ratios and 95% CI of MCI /dementia by AF status and to assess cross‐sectional correlates of MCI /dementia in patients with AF . Among 6432 participants, 611 (9.5%) had prevalent AF . AF was associated with increased odds of dementia and MCI (odds ratio, 95% CI , 2.25, 1.64–3.10, and 1.28, 1.04–1.56, respectively). Prevalence of Alzheimer's disease–related MCI /dementia and vascular MCI /dementia were higher in participants with AF than without AF (odds ratio, 95% CI , 1.29, 1.04–1.61, and 1.50, 0.99–2.25, respectively). In multivariable analyses, older age, lower body mass index, diabetes mellitus, stroke, and APOE genotype were associated with dementia prevalence in participants with AF . In models evaluating MCI /dementia subtypes, diabetes mellitus was associated with Alzheimer's disease–related MCI /dementia, whereas male sex and stroke were risk factors for vascular MCI /dementia. Conclusions In a large, community‐based study, AF was associated with higher prevalence of MCI and dementia. Controlling cardiometabolic risk factors is a potential target for prevention of adverse cognitive outcomes in AF patients.