Abstract 11661: A Family History of Premature Coronary Artery Disease is Associated With Location and Severity of Angiographically Defined Coronary Artery Stenosis

Introduction: A family history (FH) of premature coronary artery disease (CAD) is an important prognostic risk factor. Emerging evidence suggests that CAD location as well as severity may be heritable. We sought to investigate the association between a FH of premature CAD with the location and severity of angiographically phenotyped CAD. Methods: 2854 patients undergoing coronary angiography were enrolled from the Emory Cardiovascular Biobank. A FH of CAD was defined as having any male or female relative with history of CAD at age ≤55 or ≤65 year old respectively. Coronary angiograms were phenotyped using a 17 segment AHA model. Proximal disease was defined as having ≥70% lesion in the left main or proximal portion of any of the three major epicardial arteries, while CAD severity was assessed by counting the number of vessels with ≥70% stenosis. Results: Among this population (mean age 63±12, male 67%, diabetes 33%), 21% reported a positive FH of premature CAD. After adjustment for age, gender, and tradit..

Abstract 17927: A Cumulative Family History Score is Associated with Greater Severity and Progression of Angiographic Coronary Artery Disease

Introduction: A family history (FH) of coronary heart disease (CHD) is a significant risk factor for development of atherosclerosis. We sought to determine whether a greater number of affected firs..

Early Life Trauma Is Associated With Increased Microvolt T‐Wave Alternans During Mental Stress Challenge: A Substudy of Mental Stress Ischemia: Prognosis and Genetic Influences

Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T‐wave alternans (TWA), a measure of repolarization heterogeneity and sudden cardiac death risk. Methods and Results In a cohort with stable coronary artery disease (NCT04123197), we examined early life trauma with the Early Trauma Inventory Self Report‐Short Form. Participants underwent a laboratory‐based mental stress speech task with Holter monitoring, as well as a structured psychiatric interview. We measured TWA during rest, mental stress, and recovery with ambulatory electrocardiographic monitoring. We adjusted for sociodemographic factors, cardiac history, psychiatric comorbidity, and hemodynamic stress reactivity with multivariable linear regression models. We examined 320 participants with noise‐ and arrhythmia‐free ECGs. The mean (SD) age was 63.8 (8.7) years, 27% were women, and 27% reported significant childhood trauma (Early Trauma Inventory Self Report‐Short Form ≥10). High childhood trauma was associated with a multivariable‐adjusted 17% increase in TWA (P=0.04) during stress, and each unit increase in the Early Trauma Inventory Self Report‐Short Form total score was associated with a 1.7% higher stress TWA (P=0.02). The largest effect sizes were found with the emotional trauma subtype. Conclusions In a cohort with stable coronary artery disease, early life trauma, and in particular emotional trauma, is associated with increased TWA, a marker of increased arrhythmic risk, during mental stress. This association suggests that early trauma exposures may affect long‐term sudden cardiac death risk during emotional triggers, although more studies are warranted

Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction: Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study.

BackgroundWomen with chest pain, ischemia, and no obstructive coronary artery disease often have coronary vascular dysfunction (CVaD). Peripheral vascular reactivity to mental stress may contribute mechanistic understanding of stress-induced ischemia in women with CVaD.Methods62 women (41 CVaD and 21 controls) underwent mental stress testing (MST) with anger recall, mental arithmetic, and forehead cold pressor (COP) challenge. Emotional arousal was measured (Likert scale). Reactive hyperemia index (RHI) was calculated before and after MST by peripheral arterial tonometry (PAT). Stress PAT ratio (SPR) of pulse amplitude during stress to rest was obtained to measure vasoconstriction. Wilcoxson rank sum test was used for analysis.ResultsMean age of CVaD and control groups was 58±9 and 55±10years (p=0.73). Baseline RHI correlated with coronary endothelial function (r=0.36, p=0.03) and inversely with RHI change post-MST (r=-0.51, p<0.001). During MST, 10% of controls reported chest pain vs. 41% of CVaD subjects (p=0.01). RHI did not change significantly after MST in either group. CVaD subjects had lower SPR vs. controls during mental arithmetic (0.54 [0.15, 1.46] vs. 0.67 [0.36, 1.8], p=0.039), not evident in the other tasks. Vasoconstriction inversely correlated with anxiety (r=-3.4, p=0.03), frustration (r=-0.37, p=0.02), and feeling challenged (r=-0.37, p=0.02) in CVaD but not controls.ConclusionsMental stress peripheral vascular reactivity is elevated in women with CVaD compared to controls. Elevated vascular reactivity may be one contributor to stress-induced chest pain in CVaD. Interventions that modulate vasoconstrictive responses may be of benefit and should be tested in clinical trials in women with CVaD

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

RATIONALE: Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. OBJECTIVE: To examine the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes. METHODS AND RESULTS: We measured LTL by quantitative PCR in 566 outpatients (age 63±9 years, 76% male) with coronary artery disease (CAD). Circulating PCs were enumerated by flow cytometry. After adjustment for age, gender, race, BMI, smoking and previous myocardial infarction, a shorter LTL was associated with a lower CD34(+) cell count: for each 10% shorter LTL, CD34(+) levels were 5.2% lower (p<0.001). After adjustment for the aforementioned factors, both short LTL (<Q1) and low CD34+ levels (<Q1) predicted adverse cardiovascular outcomes (death, myocardial infarction, coronary revascularization or cerebrovascular events) independently of each other, with a hazards ratio (HR) of 1.8, 95% confidence interval (CI), 1.1–2.0, and a HR of 2.1, 95% CI, 1.3–3.0, respectively, comparing Q1 to Q2–4. Patients who had both short LTL (<Q1) and low CD34+ cell count (<Q1), had the greatest risk of adverse outcomes (HR=3.5, 95% CI, 1.7–7.1). CONCLUSION: Although shorter LTL is associated with decreased regenerative capacity, both LTL and circulating PC levels are independent and additive predictors of adverse cardiovascular outcomes in CAD patients. Our results suggest that both biological aging and reduced regenerative capacity contribute to cardiovascular events, independent of conventional risk factors