Hayes, Sharonne N.

Abstract Background Despite advances in cardiovascular (CV) care, African American adults experience worse CV disease (CVD) outcomes than White adults, warranting the investigation of CVD prediction biomarkers. Plasma ceramides are bioactive lipids that are biomarkers of adverse cardiovascular risk for both primary and secondary prevention. However, racial/ethnic differences in ceramide levels and their link to CV health (CVH) in African American adults remain underexplored. Purpose This study aimed to: 1) assess the association between ceramide scores and CVH and atherosclerotic CVD (ASCVD) risk among African American adults and 2) compare ceramide scores between African American and White adults. Methods Health surveys and ceramides measurements were conducted for African American and White adults, both recruited from population-based observational study cohorts. Ten-year pooled cohort risk ASCVD scores were calculated based on American College of Cardiology guidelines. CVH was assessed using Life’s Essential 8 (LE8) scores, as per American Heart Association rubrics. CV risk factors in the two cohorts were compared using Chi-squared tests. Linear regression and Pearson correlation assessed the association between ceramide, LE8, and ASCVD risk scores. Linear regression, adjusted for age and sex, compared ASCVD risk and ceramide scores between the two cohorts. Results In total, 58 African American (mean age [SD] 54.5 [11.9] years, 67.9% women) and 1103 White (mean age [SD] 64.5 [11.9] years, 52.1% women) adults were included (Table 1). Compared to White adults, African American adults had a higher prevalence of overweight/obesity (92.9% vs 33.6%; p<0.001), hypertension (69.6% vs 42.5%; p<0.001), diabetes (30.4% vs 12.2%; p<0.001), and hyperlipidaemia (42.9% vs 30.0%; p=0.03). No difference in mean ASCVD risk was observed between the African American (12.8% [SD 10.4]) and White (12.6% [SD 11.1]) cohorts (p= 0.91). African American adults had lower 18:0 (0.08 [0.03] vs 0.10 [0.04] μmol/L) and 24:1 (0.91 [0.31] vs 1.17 [0.33] μmol/L) ceramides compared to White adults (p<0.001). Ceramide scores among African American adults were not associated with LE8 scores (p=0.077) or ASCVD risk scores (r=-0.12, p=0.428). Adjusting for age and sex, African American adults had lower ceramide scores compared to White adults (mean [SD] 1.90 [1.97] vs 3.48 [2.88], p=0.006). Conclusions In our study comparing African American and White adults in the community, the association observed between ceramide scores and CVH or ASCVD risk scores in the African American cohort did not reach statistical significance. Interestingly, despite a more suboptimal cardiometabolic profile, African American adults had lower ceramide scores compared to White adults. Our findings suggest that ceramide profiles may not accurately reflect cardiovascular risk in African American adults, warranting further exploration of alternative sphingolipid biomarkers of risk for this population.

Background: Spontaneous coronary artery dissection (SCAD) causes acute coronary syndrome or sudden cardiac death due to a separation of arterial wall layers. The majority of patients with SCAD are females (>80%) with few to no traditional cardiovascular risk factors. Though the physiological mechanisms that predispose to SCAD are unknown, common triggers for SCAD events include sympathoexcitatory stimuli, such as mental and emotional stress. Additionally, studies report high prevalence of depression and anxiety among patients with SCAD. Our study aimed to investigate cardiovascular responses to mental stress in patients with SCAD. We hypothesized that patients with SCAD would have exaggerated cardiovascular responses to mental stress compared to healthy controls. Methods: Four female patients with SCAD were age-, and BMI-matched with 4 healthy females. Participants underwent 2 minutes of baseline quiet rest, a 5-minute Stroop Color Word Test to induce mental stress, followed by 2 minutes of recovery. Continuous beat-to-beat blood pressure (BP, finger photoplethysmography) and heart rate (HR, 3-lead ECG) were recorded. Venous occlusion plethysmography was used to measure forearm blood flow (FBF). Forearm vascular conductance (FVC) was calculated as FBF/mean BP×100. Data are presented as change from baseline (Δmean±SD). Group data were compared using independent samples t-tests. Results: Resting hemodynamic parameters (Systolic [SBP], Diastolic [DBP], and Mean BP [MBP], Pulse pressure [PP], and HR) and FVC were similar between groups. Patients with SCAD had greater increases in DBP (Δ12±5 vs. Δ1±5 mmHg, p=0.02) and PP (Δ5±3 vs. Δ-7±8 mmHg, p=0.04) during the last minute of mental stress test compared to controls. Although, there were no differences in the changes of SBP (Δ17±7 vs. Δ-1±13 mmHg, p=0.05), MBP (Δ13±6 vs. Δ3±8 mmHg, p=0.08), HR (Δ8±0 vs. Δ10±2 bpm, p=0.12), or FVC (Δ1.5±1.2 vs. Δ1.8±1.3 ml/min/100 mmHg, p=0.80) between groups. During the last minute of recovery, there were no differences in hemodynamic parameters (SBP: Δ6±9 vs. Δ-4±10 mmHg, p=0.23; DBP: Δ2±7 vs. Δ-3±2 mmHg, p=0.22; MBP: Δ3±7 vs. Δ-3±5 mmHg, p=0.22; PP: Δ4±5 vs. Δ-1±8 mmHg, p= 0.35; HR: Δ-1±3 vs. Δ0±3 bpm, p=0.64), or FVC (Δ1.3±1.7 vs. Δ0.5±0.3 ml/min/100 mmHg, p= 0.35) between groups. Conclusion: These preliminary data suggest that patients with SCAD have greater increases in DBP and PP in response to mental stress compared to healthy controls. These exaggerated pressor responses might have implications for the pathophysiology of SCAD. NIH K23 HL155506, T32 DK07352, K01 HL148144, UL1 TR0022377, and AHA 898649. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: Physical inactivity and poor adherence to healthy eating guidelines impact cardiovascular health (CVH) outcomes in African American (AAs). Our randomized controlled trial (RCT) testing the FAITH! App, an mHealth lifestyle intervention, showed efficacy in promoting ideal CVH, particularly diet and physical activity (PA) among AAs, warranting exploration of underlying factors. Psychosocial factors (e.g., self-regulation, self-efficacy, social support) are key to healthy behavior adoption. Hypothesis: The intervention group would have greater improvements in diet and PA-related psychosocial factors than the control group after using the FAITH! App. Methods: A 2-arm cluster RCT was conducted among AAs from 16 churches in Minnesota comparing the FAITH! App intervention to a delayed intervention control group. The FAITH! App included culturally relevant, CVH-focused education modules, diet/PA self-monitoring and a sharing board. The outcomes were change in diet and PA self-regulation and self-efficacy (primary) and social support and barriers (secondary) at 6 months post-intervention. The intervention effect was assessed using linear regression. Results: Sixty-eight participants were included (71% female; mean age [SD]: 54.7 [12.6] years) ( Table 1 ). The intervention group showed a significantly greater increase in diet self-regulation [planning/tracking nutrition] (+0.66, p<.03) and PA self-regulation [step count strategies] (+0.47, p=.003) than the control group. Within groups, the intervention group demonstrated significant improvements across diet and PA self-regulation measures, while the control group showed an improvement only in fruit/vegetable and grain intake. No effect was observed in self-efficacy, social support, or barriers. Conclusions: Our culturally tailored mHealth lifestyle intervention was associated with notable increases in diet and PA self-regulation, suggesting a potential mechanism by which the FAITH! App improves healthy eating and PA among AAs.

Introduction: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of acute coronary syndrome. While most patients are managed conservatively, some patients may require percutaneous or surgical revascularization. Limited data exist on SCAD patients referred for coronary artery bypass graft (CABG) surgery. Hypothesis: Examine the clinical characteristics, management, and outcomes of SCAD patients referred for CABG. Methods: Retrospective study of patients enrolled in the Mayo Clinic SCAD Registry between 2010-2020 who underwent CABG during the initial management of acute SCAD episode. Results: Among the 81 patients with SCAD referred for CABG, 3 (4%) were men, mean age was 40.6 +/- 8.4 years; the majority were white (91%), and 24 (30%) had pregnancy-associated SCAD (P-SCAD). The most common presenting symptom was chest pain 80 (99%); 57 (70%) presented with ST elevation myocardial infarction (STEMI), and 21 (26%) presented with non-ST elevation MI. Multivessel dissection occurred in 40 (49%), left anterior descending artery (LAD) involvement occurred in 66 (81%) and left main (LM) in 32 (40%). Left ventricular ejection fraction was <50% in 40 patients (49%) at time of initial SCAD. The most common reasons for CABG were the presence of high-risk anatomy (56%), hemodynamic instability/active ischemia (7%), failed PCI (9%), and other/unknown (12%). Most patients received venous plus arterial bypass grafts 42 (52%), saphenous vein grafts in 20 (25%), and left internal mammary artery in 17 (21%). Screening for underlying arteriopathy was performed in 50 (62%) of whom 29 (36%) had fibromuscular dysplasia. Recurrent SCAD occurred in 10 (12%) after an average of 6.2 +/- 5 years after initial SCAD. Of those with recurrent SCAD, none required repeat surgical revascularization and 6 required percutaneous intervention (PCI). There were no deaths. Conclusions: Patients undergoing CABG for SCAD commonly present with STEMI, LM, or multivessel dissection, and failed percutaneous intervention attempts. In addition, CABG for P-SCAD was more frequent than expected and may relate to the increased prevalence of multivessel dissection. CABG was associated with low mortality, but recurrent SCAD may still occur.

Objective: To evaluate outcomes of acute spontaneous coronary artery dissection (SCAD) managed with percutaneous coronary intervention (PCI) or conservative therapy. Background: SCAD is a non-atherosclerotic acute coronary syndrome that typically affects young otherwise healthy females. Whether SCAD with normal vessel flow at presentation should be managed with PCI or conservative therapy remains unknown. Methods: We performed a retrospective study of patients after a first SCAD episode (n=142). We excluded those treated with fibrinolysis (n=12) or coronary artery bypass grafting (CABG, n=8). We evaluated in-hospital and late outcomes in three SCAD groups: Vessel occlusion at presentation treated with PCI (Occ-PCI, n=30); normal vessel flow treated with PCI (NF-PCI, n=34) and those managed conservatively (CON, n=58). Results: Overall mean age was 42+9 years, 91% were female and 41% presented with STEMI. Outcomes are shown in the table below. In Occ-PCI, technical failure occurred in 8/30 (27%), of whom 5 required emergency CABG with one in-hospital death. Comparing NF-PCI with CON, there were no differences in clinical characteristics. Technical failure occurred in 16/34 (47%) of NF-PCI due to failure to cross with wire/device (8/34) or final loss of flow (8/34). Emergency CABG was required in 5 (15%). In CON, 54/58 had an uneventful in-hospital course. Four (7%) exhibited early dissection progression of whom two received PCI and one CABG. Long-term rates of target vessel revascularization, but not recurrent SCAD, were higher in NF-PCI vs CON (26% vs 9%, p=0.02; 24% vs 14%, p=0.23). Conclusions: PCI for acute SCAD is associated with high rates of technical failure and adverse clinical outcomes. In SCAD with normal vessel flow, conservative management may be preferable, with close early observation due to a hazard of progression of dissection. These findings underscore the importance of tailoring therapy to etiology of coronary obstruction.

Introduction: Current dietary guidelines no longer recommend against egg consumption despite the high cholesterol content. However, considerable controversy remains on the relationship between high egg consumption and cardiovascular disease (CVD) risk. The objective of this systematic review and meta-analysis was to explore the association between egg consumption and CVD events. Methods: We systematically searched PubMed, Scopus, and the Cochrane Database of Systematic Reviews from database inception through April 2015 for observational studies with hazard ratio (HRs) or relative risks (RRs) and 95% confidence intervals (95% CI) that reported the association between egg consumption and CVD events which included coronary heart disease (CHD) and stroke. Data were extracted by one reviewer followed by independent screening and extraction of study characteristics and outcome data by two other reviewers. Conflicts were resolved through consensus. Random-effects meta-analyses were used to pool the hazard ratios or relative risks from the included studies. Subgroup analyses were performed to explore the potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. Results: We identified 5 cross-sectional and 6 prospective studies with median follow-up of 13.1 years. A total of 301,339 individuals and 10,262 total CVD events were included with 7,225 CHD and 3,037 stroke cases. Compared to consumption of less than 1 egg/day, higher egg consumption was associated with an increased risk of CVD events (pooled HR, 1.43; 95% CI, 1.01-2.03; p=0.012; I 2 = 65.7% and pooled RR, 1.09; 95% CI, 0.89-1.34; p=0.145; I 2 = 41.4%). Conclusions: Our analysis suggests that higher consumption of eggs (more than 1 egg/day) may be associated with increased risk of cardiovascular disease. Large and diverse prospective community-based cohorts will be necessary to establish optimal dietary recommendations for public health.

Background Cardio-ankle vascular index (CAVI) is a measure of arterial stiffness associated with cardiovascular (CV) events and mortality. African American (AA) adults have a higher prevalence of CV risk factors (RFs) and adverse social determinants of health (SDOH) leading to a higher CV mortality risk than White adults. These disparities may be associated with arterial stiffness, however limited research exists on the association of CV RFs, SDOH, and CAVI among AAs. Hypotheses We hypothesized that CV RFs (eg, diabetes) and SDOH (eg, income) would be associated with CAVI among AA adults. Our secondary hypothesis was that AA adults would have a higher prevalence of abnormal CAVI scores (≥8.0) than White adults. Methods In the FAITH! HH+ study, CAVI measurements, CV RFs, and SDOH surveys were obtained. We collected CAVI readings and CV RFs from a secondary cohort of White adults (n=600), referred for echocardiography and without structural cardiac disease. The association of CV RFs, SDOH and CAVI scores among AAs was assessed via ANOVA and univariable linear regression. We compared CV RFs among both cohorts using Chi-squared tests and ANOVA, followed by comparing CAVI scores between cohorts using a multivariable linear regression model. Results In total, 48 AAs were included from the FAITH! HH+ cohort (mean age [SD]: 54.2 [11.5] years, 67.4% women). There was no significant association between CV RFs or SDOH with CAVI scores. In the 600 White adults assessed, mean age was 59.5 [14.7] years and 45.7% were women. Compared to White adults, AA participants had a lower burden of hyperlipidemia (43.5% vs 61.4%; p=0.017), but a higher burden of hypertension (73.9% vs 57.7%; p=0.031), diabetes (28.3% vs 9.3%; p<0.001), and obesity (71.7% obese vs 36.0%; p<0.001). There was no significant difference in CAVI scores between groups when adjusted for age, sex, and CV RFs (AA cohort: mean: 8.0 [1.4] vs White cohort: 8.4 [1.5]; p=0.790). Conclusions In this pilot study, SDOH and CV RFs were not associated with CAVI scores among AAs. There was no significant difference in CAVI scores between AA and White adults, despite a significantly higher burden of CV RFs in the AA cohort. Further studies are warranted to identify factors linked with onset and progression of arterial stiffness among AAs.

Rare familial spontaneous coronary artery dissection (SCAD) kindreds implicate genetic disease predisposition and provide a unique opportunity for candidate gene discovery. Whole-genome sequencing was performed in fifteen probands with non-syndromic SCAD who had a relative with SCAD, eight of whom had a second relative with extra-coronary arteriopathy. Co-segregating variants and associated genes were prioritized by quantitative variant, gene, and disease-level metrics. Curated public databases were queried for functional relationships among encoded proteins. Fifty-four heterozygous coding variants in thirteen families co-segregated with disease and fulfilled primary filters of rarity, gene variation constraint, and predicted-deleterious protein effect. Secondary filters yielded 11 prioritized candidate genes in 12 families, with high arterial tissue expression (n = 7), high-confidence protein-level interactions with genes associated with SCAD previously (n = 10), and/or previous associations with connective tissue disorders and aortopathies (n = 3) or other vascular phenotypes in mice or humans (n = 11). High-confidence associations were identified among 10 familial SCAD candidate-gene-encoded proteins. A collagen-encoding gene was identified in five families, two with distinct variants in COL4A2. Familial SCAD is genetically heterogeneous, yet perturbations of extracellular matrix, cytoskeletal, and cell–cell adhesion proteins implicate common disease-susceptibility pathways. Incomplete penetrance and variable expression suggest genetic or environmental modifiers.

Introduction: Spontaneous coronary artery dissection (SCAD) is an understudied cause of acute myocardial infarction due to hematoma formation in coronary arteries primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Methods and Results: Through a meta-analysis of 8 GWAS (1917 cases, 9292 controls of European ancestry), we identified 17 risk loci, including 12 new. Functional annotations pointed at enrichment in enhancer marks of arteries, specifically smooth muscle cells, and strong candidate genes, such as tissue factor gene ( F3 ) on Chr1 near rs1146473 (OR=1.32, P=5.8 х10 -9 ). F3 is novel for SCAD or any cardiovascular disease. The risk allele correlated with F3 lower expression in arteries, supporting a mechanism consistent with hematoma formation. Bayesian gene regulatory networks constructed from expression and genetics data indicated the extracellular matrix organization in arteries as the biological function where most prioritized genes clustered (e.g. COL4A1/A2, HTRA1, and TIMP3 ). Overall, we report substantial polygenicity for SCAD (LDSC: h 2 SNP = 0.71 ± 0.11) and shared genetics with several neurovascular diseases (e.g intracranial aneurysm). Intriguingly, for 6 loci, colocalization analyses showed that SCAD and CAD are likely to share the same causal variants but involve opposite risk alleles (e.g COL4A1/A2 ). In addition, a negative genetic correlation was found between SCAD and CAD (rg=-0.12; P=3.7х10 -3 ), including after conditioning on BP (mt-COJO: rg CAD/SBP =-0.19, P=4.6х10 -6 ). Mendelian randomization analyses indicated higher BP to associate with increased risk for SCAD (beta IVW-SBP =0.05, P=7.6х10 -6 , beta IVW-DBP =0.10, P=1.9х10 -6 ) and CAD (beta IVW-SBP =0.04, P=8.6х10 -49 ; DBP: beta IVW-DBP =0.06, P=1.6х10 -44 ) but not BMI, lipids, or type 2 diabetes, which we confirmed as genetic risk factors for CAD Conclusions: Our results set the stage for future investigation of novel biological pathways relevant to both SCAD and CAD and potential therapeutic and preventive strategies specifically targeting this ischemic disease predominantly affecting women.

Background: African-American (AA) adults have a higher prevalence of cardiovascular (CV) risk factors, leading to higher CV disease mortality than White adults. Prior findings of our mobile health (mHealth) lifestyle intervention (FAITH! App) demonstrated efficacy in promoting ideal cardiovascular health (CVH) in AAs. Hypothesis: We hypothesized that the intervention group with preexisting CV risk factors would have a greater increase in LS7 scores than the control group with the same risk factors following use of the FAITH! App. Methods: A cluster randomized controlled trial was conducted among AAs from 16 churches in Minnesota. The intervention included culturally relevant, LS7-focused education modules, diet/physical activity self-monitoring and a group sharing board. A subgroup of participants with ≥1 diagnosis of overweight/obesity, hyperlipidemia, hypertension (HTN) or diabetes was examined. The primary outcome was change in LS7 score—a measure of CVH ranging from poor to ideal (range 0-14 points)—at 6 months post-intervention. Results: Forty-nine participants (75.5% female) were included in the intervention (n=20; mean age [SD]: 58.8 [9.5]) or control (n=29, mean age [SD]: 52.5 [10.7]) groups (Table 1). There was no significant difference in the CV risk factor prevalence between the two groups. There was a greater increase in LS7 score in the intervention vs. control group across all CV risk factors, with significant differences among those with overweight/obesity (1.77, p<.0001) and with 2+ or 3+ CV risk factors (1.00, p=.03; 1.09, p=.04). Compared to the control group, the increase in the percentage of participants with ideal LS7 scores in the intervention group was higher among those with overweight/obesity, HTN, diabetes and 3+ CV risk factors. Conclusions: Our culturally tailored mHealth lifestyle intervention was associated with notable increases in LS7 scores among AAs with preexisting CV risk factors, suggesting its efficacy in improving CVH among this population.