Metabolic Pathways Associated With Obesity and Hypertension in Black Caregivers of Persons Living With Dementia.

BACKGROUND: In the U.S., Black adults have the highest prevalence of obesity and hypertension, increasing their risk of morbidity and mortality. Caregivers of persons with dementia are also at increased risk of morbidity and mortality due to the demands of providing care. Thus, Black caregivers-who are the second largest group of caregivers of persons with dementia in the U.S.-have the highest risks for poor health outcomes among all caregivers. However, the physiologic changes associated with multiple chronic conditions in Black caregivers are poorly understood. OBJECTIVES: In this study, metabolomics were compared to the metabolic profiles of Black caregivers with obesity, with or without hypertension. Our goal was to identify metabolites and metabolic pathways that could be targeted to reduce obesity and hypertension rates in this group. METHODS: High-resolution, untargeted metabolomic assays were performed on plasma samples from 26 self-identified Black caregivers with obesity, 18 of whom had hypertension. Logistic regression and pathway analyses were employed to identify metabolites and metabolic pathways differentiating caregivers with obesity only and caregivers with both obesity and hypertension. RESULTS: Key metabolic pathways discriminating caregivers with obesity only and caregivers with obesity and hypertension were butanoate and glutamate metabolism, fatty acid activation/biosynthesis, and the carnitine shuttle pathway. Metabolites related to glutamate metabolism in the butanoate metabolism pathway were more abundant in caregivers with hypertension, while metabolites identified as butyric acid/butanoate and R-(3)-hydroxybutanoate were less abundant. Caregivers with hypertension also had lower levels of several unsaturated fatty acids. DISCUSSION: In Black caregivers with obesity, multiple metabolic features and pathways differentiated among caregivers with and without hypertension. If confirmed in future studies, these findings would support ongoing clinical monitoring and culturally tailored interventions focused on nutrition (particularly polyunsaturated fats and animal protein), exercise, and stress management to reduce the risk of hypertension in Black caregivers with obesity.

A novel GWAS locus influences microvascular response to mental stress and predicts adverse cardiovascular events.

Excessive peripheral microvascular constriction during acute psychological stress reflects similar changes in coronary blood flow and is a predictor of adverse cardiovascular outcomes. Among individuals with coronary artery disease (CAD), we sought to determine if genetic factors contribute to the degree of microvascular constriction during mental stress. A total of 580 stable CAD individuals from two prospective cohort studies underwent mental stress testing. Digital pulse wave amplitude was continuously measured and the stress/rest (sPAT) ratio of pulse wave amplitude was calculated. Race stratified genome-wide association studies (GWAS) of sPAT-ratio were conducted using linear regression of additive genetic models. A trans-ethnic meta-analysis integrated the four sets of GWAS results. Participants were followed for the outcome of recurrent cardiovascular events (myocardial infarction, heart failure, revascularization, and CV death) for a median of 5 years. We used Wei-Lin-Weissfeld (WLW) model to assess the association between sPAT-ratio with recurrent events. Mean age was 63 ± 9. We identified three SNPs in linkage disequilibrium, closely related to chr7:111,666,943 T > C (rs6466396) that were associated with sPAT-ratio (p = 6.68E-09). Participants homozygous for the T allele had 80% higher risk of incident adverse events (HR 1.8, 95% CI, 1.4-2.2). Also, participants with a lower sPAT-ratio (< median) had a higher adverse event rate, hazard ratio (HR) = 1.3, [95%confidence interval (CI), 1.1-1.6]. However, adjustment for the genotypes did not substantially alter the impact of sPAT ratio on adverse outcome rate. In conclusion, we have identified a genetic basis for stress-induced vasomotion. The 3 linked variants modulate vasoconstriction during mental stress may have a prognostic importance.

A Multivariable Mendelian Randomization Study of Systolic and Diastolic Blood Pressure, Lipid Profile, and Heart Failure Subtypes.

Heart failure (HF) is a significant health burden, with two major clinical subtypes: HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). Blood pressure and lipid profile are established risk factors of HF. We performed univariable and multivariable Mendelian randomization (MR) analyses to assess potential causal effects of blood pressures and lipids on HF subtypes. Genetic instruments for blood pressures and lipids were derived from genome-wide association studies (GWASs) among the European participants of the UK Biobank. GWAS summaries of HFrEF and HFpEF were obtained from the meta-analysis of the European participants from the Million Veteran Program and the Vanderbilt University DNA Databank. Systolic blood pressure exhibited a supportive MR association primarily with HFpEF (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04-1.23), while diastolic blood pressure had an independent MR association with HFrEF (OR, 1.43; 95% CI, 1.13-1.77). MR associations also supported the observation that higher levels of low-density lipoprotein cholesterol increase the risk for both subtypes (HFrEF OR, 1.10 and 95% CI, 1.05-1.17; HFpEF OR, 1.05 and 95% CI, 1.02-1.09). These findings underscore differences in HF subtype-specific risk profiles and mechanisms, which may lead to different interventional strategies for different HF subtypes.

Coronary Artery Calcium for Risk Stratification Among Persons With Very High HDL Cholesterol.

Background: Compared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging. Objectives: Among persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD. Methods: The primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD. Results: The mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84). Conclusions: Measurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.

Patients With Nonobstructive Coronary Artery Disease and Chest Pain: Impact of Obesity and Depressive Symptoms.

BACKGROUND: Chest pain (CP) in patients with nonobstructive coronary artery disease is a therapeutic challenge affecting morbidity and mortality. We aimed to identify clinical factors associated with CP in this population, hypothesizing that obesity and depressive symptoms are associated with CP. METHODS AND RESULTS: In 814 patients with angiographically confirmed nonobstructive coronary artery disease, we measured sociodemographic variables, clinical risk factors, medications, and Patient Health Questionnaire 9 scores for depressive symptoms. We assessed CP frequency and prevalence by using all items from the Seattle Angina Questionnaire angina frequency domain to generate an angina frequency composite score. In the overall sample (58.8±11.7 years old, 52.6% female), 42.8% had obesity, and 71.5% had CP, with an angina frequency composite score (SD) score of 76.4 (22.1). Compared with individuals without obesity, individuals with obesity had a higher prevalence (77.6% versus 67%, P<0.001) and more frequent CP (angina frequency composite score, 74.9 [SD, 22.2] versus 78.3 [SD, 21.9], P=0.02). Obesity was independently associated with CP occurrence (odds ratio [OR], 1.7 [95% CI, 1-2.9], P=0.04). Obesity's connection with CP was only in men: men with obesity had more frequent CP (angina frequency composite score, 75.8 [SD, 20.1] versus 82.1 [SD, 19.9], P=0.002) and more prevalent CP (79.5% versus 58.2%, P<0.001) than their counterparts insofar as men with obesity had similar CP to women. Patient Health Questionnaire 9 score (OR, 1.07 [95% CI, 1.01-1.13], P=0.03) was independently associated with CP and partly mediated the association between obesity and CP. CONCLUSIONS: Obesity and depressive symptoms were independently associated with CP in individuals with nonobstructive coronary artery disease, particularly in men, and depressive symptoms partly mediated this association.

Central Hemodynamics in African American Women: Examining the Role of Superwoman Schema Endorsement.

BACKGROUND: African American women bear a disproportionate burden of cardiovascular diseases, potentially due to altered central hemodynamics. Racism and sexism often lead to African American women taking on numerous caretaking roles and overall increases their use of the Strong Black Woman (ie, Superwoman) mindset, which may have negative health consequences. We hypothesized that endorsing the Superwoman role and its Obligation to Help Others dimension would be associated with a deleterious central hemodynamics profile in African American women. METHODS AND RESULTS: Using cross-sectional data, we examined central systolic blood pressure (mm Hg; n=408), augmentation index (percentage, adjusted for height and heart rate; n=408), and pulse wave velocity (m/s; n=368) in African American women aged 30 to 46 years. The Giscombe Superwoman Schema (SWS) questionnaire assessed endorsement of Overall SWS (range, 0-105) and SWS-Obligation to Help Others (range, 0-3). Multiple linear regression modeled associations between Overall SWS (10-unit increments) and SWS-Obligation to Help Others (1-unit increments) and central hemodynamics while adjusting for pertinent sociodemographic, clinical, and psychosocial factors. In fully adjusted models, central systolic blood pressure was significantly associated with Overall SWS (ß=0.83 [95% CI, 0.19-1.47]) and SWS-Obligation to Help Others (ß=2.03 [95% CI, 0.39-3.67]). Augmentation index was associated with Overall SWS (ß=0.66 [95% CI, 0.02-1.30]) and SWS-Obligation to Help Others (ß=2.21 [95% CI, 0.58-3.84]). Significant associations were not observed between pulse wave velocity and SWS. CONCLUSIONS: Greater endorsement of the Superwoman role and prioritizing caregiving over self-care were associated with higher central systolic blood pressure and augmentation index, which may contribute to adverse cardiovascular health among African American women.

Building Digital Twins for Cardiovascular Health: From Principles to Clinical Impact.

The past several decades have seen rapid advances in diagnosis and treatment of cardiovascular diseases and stroke, enabled by technological breakthroughs in imaging, genomics, and physiological monitoring, coupled with therapeutic interventions. We now face the challenge of how to (1) rapidly process large, complex multimodal and multiscale medical measurements; (2) map all available data streams to the trajectories of disease states over the patient's lifetime; and (3) apply this information for optimal clinical interventions and outcomes. Here we review new advances that may address these challenges using digital twin technology to fulfill the promise of personalized cardiovascular medical practice. Rooted in engineering mechanics and manufacturing, the digital twin is a virtual representation engineered to model and simulate its physical counterpart. Recent breakthroughs in scientific computation, artificial intelligence, and sensor technology have enabled rapid bidirectional interactions between the virtual-physical counterparts with measurements of the physical twin that inform and improve its virtual twin, which in turn provide updated virtual projections of disease trajectories and anticipated clinical outcomes. Verification, validation, and uncertainty quantification builds confidence and trust by clinicians and patients in the digital twin and establishes boundaries for the use of simulations in cardiovascular medicine. Mechanistic physiological models form the fundamental building blocks of the personalized digital twin that continuously forecast optimal management of cardiovascular health using individualized data streams. We present exemplars from the existing body of literature pertaining to mechanistic model development for cardiovascular dynamics and summarize existing technical challenges and opportunities pertaining to the foundation of a digital twin.

The effect of endothelin a receptor inhibition and biological sex on cutaneous microvascular function in non-Hispanic Black and White young adults.

The purpose of this study was to investigate whether endothelin-A receptor (ETAR) inhibition in non-Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self-identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ-123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L-NAME to quantify NO-dependent vasodilation. At control sites, NO-dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO-dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ-123: 85 ± 11 %NO; NHB, BQ-123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ-123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO-dependent vasodilation is influenced by biological sex and racial identity.

Vitamin D Deficiency, Inflammation, and Diminished Endogenous Regenerative Capacity in Coronary Heart Disease.

Background: Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. Objectives: The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. Methods: A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. Results: VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. Conclusions: VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.

Stress-Induced Autonomic Dysfunction is Associated With Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Artery Disease.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse cardiovascular outcomes in individuals with coronary artery disease, but the mechanisms underlying this phenomenon are unknown. We examined the relationship between stress-induced autonomic dysfunction, measured by low heart rate variability (HRV) in response to stress, and MSIMI in patients with stable coronary artery disease. We hypothesized that stress-induced autonomic dysfunction is associated with higher odds of MSIMI. METHODS: In 735 participants with stable coronary artery disease, we measured high- and low-frequency HRV in 5-minute intervals before and during a standardized laboratory-based speech stressor using Holter monitoring. HRV at rest and stress were categorized into low HRV (first quartile) versus high HRV (second to fourth quartiles); the low category was used as an indicator of autonomic dysfunction. Multivariable logistic regression models were used to examine the association of autonomic dysfunction with MSIMI. RESULTS: The mean age was 58 (SD, ±10) years, 35% were women, 44% were Black participants, and 16% developed MSIMI. Compared with high HRV during stress, low HRV during stress (both high and low frequencies) was associated with higher odds of MSIMI after adjusting for demographic and clinical factors (odds ratio for high-frequency HRV, 2.1 [95% CI, 1.3-3.3]; odds ratio for low-frequency HRV, 2.1 [95% CI, 1.3-3.3]). Low-frequency HRV at rest was also associated with MSIMI but with slightly reduced effect estimates. CONCLUSIONS: In individuals with coronary artery disease, mental stress-induced autonomic dysfunction may be a mechanism implicated in the causal pathway of MSIMI.

Association of apolipoprotein B and apolipoprotein A1 levels with social determinants of health and coronary artery disease mortality in the United Kingdom Biobank - is there a need for consideration?

BACKGROUND: A higher prevalence of cardiovascular risk factors has previously been shown to be associated with adverse social determinants of health (SDoH) and to explain some of their impact on cardiovascular risk. Whether there is a relationship between lipid parameters, specifically apolipoprotein B (apoB), apolipoprotein A1 (apoA1), their ratio (apoB/apoA1), and SDoH, and whether coronary artery disease (CAD) mortality risk associated with circulating apoB and apoA1 is modified by SDoH was unclear. METHODS: We investigated associations of apoA1, apoB, and apoB/apoA1 with the level of education and household income and their joint impact on CAD mortality in participants of the UK Biobank (UKB) with and without prevalent CAD at enrollment. Hazard ratios for CAD mortality were estimated after adjusting for SDoH and clinical covariates. RESULTS: In 292 804 participants without established CAD, apoB, and the apoB/apoA1 ratio were inversely associated with level of education and household income, whereas apoA1 was positively associated with household income. Adjustment for education level and household income coupled with the number of people living in the household did not attenuate the association between the apolipoprotein levels and incident CAD mortality rates. In a cohort of 13 826 participants with prevalent CAD, apoA1 levels were inversely associated with level of education. Higher apoB levels were only associated with greater CAD mortality risk after adjustment for risk factors. Risk estimation for CAD death through circulating apoA1 levels requires accounting for significant differences by sex. CONCLUSION: Circulating lipid parameters are associated with SDoH in individuals without CAD. CAD mortality risk estimation through apoA1 and apoB levels does not require accounting for SDoH.

N terminal pro-brain natriuretic peptide level and benefits of chronic total occlusion revascularization.

BACKGROUND: The management of revascularization of chronic total occlusions (CTOs) remains controversial. Whether specific patients gain survival benefit from CTO revascularization remains unknown. OBJECTIVES: We investigated whether (i) patients with CTO have higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO, (ii) in patients with CTO, NT pro-BNP levels predict adverse events, and (iii) those with elevated levels benefit from revascularization. METHODS: In 392 patients with stable, significant coronary artery disease (CAD) and CTO undergoing coronary angiography, rates of all-cause mortality, cardiovascular death, and a composite (cardiovascular death, myocardial infarction and heart failure hospitalizations) were investigated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP levels and incident event rates in patients with CTO. RESULTS: NT pro-BNP levels were higher in patients with, compared to those without CTO (median 230.0 vs. 177.7 pg/mL, p ≤0.001). Every doubling of NT pro-BNP level in patients with CTO was associated with a > 25% higher rate of adverse events. 111 (28.5%) patients underwent CTO revascularization. In patients with elevated NT pro-BNP levels (> 125 pg/mL), those who underwent CTO revascularization had substantially lower adverse event rates compared to patients without CTO revascularization (adjusted cardiovascular death hazard ratio 0.29, 95% confidence interval (0.09-0.88). However, in patients with low NT pro-BNP levels (≤ 125 pg/mL), event rates were similar in those with and without CTO revascularization. CONCLUSION: NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).

Objective: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. Methods: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. Results: Among 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1-2.3 versus 3.9, 95% CI: 2.8-4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28-0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81-1.25; p-interaction=0.001). Conclusion: Regular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention.

Circulating Progenitor Cells and Coronary Collaterals in Chronic Total Occlusion.

BACKGROUND: The role of circulating progenitor cells (CPC) in collateral formation that occurs in the presence of chronic total occlusions (CTO) of a coronary artery is not well established. In stable patients with a CTO, we investigated whether CPC levels are associated with (a) collateral development and (b) ischemic burden, as measured by circulating high sensitivity troponin-I (hsTn-I) levels. METHODS: CPCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34 and both CD34 and CD133 epitopes. The association between CPC counts and both Rentrop collateral grade (0, 1, 2, or 3) and hsTn-I levels were evaluated using multivariate regression analysis, after adjusting for demographic and clinical characteristics. RESULTS: In 89 patients (age 65.5, 72% male, 27% Black), a higher CPC count was positively associated with a higher Rentrop collateral grade; [CD34+ adjusted odds ratio (OR) 1.49 95% confidence interval (CI) (0.95, 2.34) P = 0.082] and [CD34+/CD133+ OR 1.57 95% CI (1.05, 2.36) P = 0.028]. Every doubling of CPC counts was also associated with lower hsTn-I levels [CD34+ ß -0.35 95% CI (-0.49, -0.15) P = 0.002] and [CD34+/CD133+ ß -0.27 95% CI (-0.43, -0.08) P = 0.009] after adjustment. CONCLUSION: Individuals with higher CPC counts have greater collateral development and lower ischemic burden in the presence of a CTO.

Intra- and inter-reader reproducibility in quantitative coronary plaque analysis on coronary computed tomography angiography.

PURPOSE: Coronary artery plaque burden, low attenuation non-calcified plaque (LAP), and pericoronary adipose tissue (PCAT) on coronary CT angiography (CCTA), have been linked to future cardiac events. The purpose of this study was to evaluate intra- and inter reader reproducibility in the quantification of coronary plaque burden and its characteristics using an artificial intelligence-enhanced semi-automated software. MATERIALS AND METHODS: A total of 10 women and 6 men, aged 52 (IQR 49-58) underwent CCTA using a Siemens Somatom Force, Somatom Definition AS and Somatom Definition Flash scanners. Two expert readers utilized dedicated semi-automatic software (vascuCAP, Elucid Bioimaging, Wenham, MA) to assess calcified plaque, low attenuation plaque and PCAT. Readers were blinded to all clinical information and repeated their analysis at 6 weeks in random order to minimize recall bias. Data analysis was performed on the right and left coronary arteries. Intra- and inter-reader reproducibility was compared using Pearson correlation coefficient, while absolute values between analyses and readers were compared with paired non-parametric tests. This is a sub-study of the Specialized Center of Research Excellence (SCORE) clinical trial (5U54AG062334). RESULTS: A total of 64 vessels from 16 patients were analyzed. Intra-reader Pearson correlation coefficients for calcified plaque volume, LAP volume and PCAT volumes were 0.96, 0.99 and 0.92 for reader 1 and 0.94, 0.94 and 0.95 for reader 2, respectively, (all p < 0.0001). Inter-reader Pearson correlation coefficients for calcified plaque volume, LAP and PCAT volumes were 0.92, 0.96 and 0.78, and 0.99, 0.99 and 0.93 on the second analyses, all had a p value <0.0001. There was no significant bias on the corresponding Bland-Altman analyses. CONCLUSION: Volume measurement of coronary plaque burden and PCAT volume can be performed with high intra- and inter-reader agreement.

Inhibition of superoxide and iNOS augment cutaneous nitric oxide-dependent vasodilation in non-Hispanic black young adults.

We assessed the combined effect of superoxide and iNOS inhibition on microvascular function in non-Hispanic Black and non-Hispanic White participants (n = 15 per group). Participants were instrumented with four microdialysis fibers: (1) lactated Ringer's (control), (2) 10 µM tempol (superoxide inhibition), (3) 0.1 mM 1400 W (iNOS inhibition), (4) tempol + 1400 W. Cutaneous vasodilation was induced via local heating and NO-dependent vasodilation was quantified. At control sites, NO-dependent vasodilation was lower in non-Hispanic Black (45 ± 9% NO) relative to non-Hispanic White (79 ± 9% NO; p < 0.01; effect size, d = 3.78) participants. Tempol (62 ± 16% NO), 1400 W (78 ± 12% NO) and tempol +1400 W (80 ± 13% NO) increased NO-dependent vasodilation in non-Hispanic Black participants relative to control sites (all p < 0.01; d = 1.22, 3.05, 3.03, respectively). The effect of 1400 W (p = 0.04, d = 1.11) and tempol +1400 W (p = 0.03, d = 1.22) was greater than tempol in non-Hispanic Black participants. There was no difference between non-Hispanic Black and non-Hispanic White participants at 1400 W or tempol + 1400 W sites. These data suggest iNOS has a greater effect on NO-dependent vasodilation than superoxide in non-Hispanic Black participants.

Heart-brain axis: Pushing the boundaries of cardiovascular molecular imaging.

Despite decades of research, the heart-brain axis continues to challenge investigators seeking to unravel its complex pathobiology. Strong epidemiologic evidence supports a link by which insult or injury to one of the organs increases the risk of pathology in the other. The putative pathways have important differences between sexes and include alterations in autonomic function, metabolism, inflammation, and neurohormonal mechanisms that participate in crosstalk between the heart and brain and contribute to vascular changes, the development of shared risk factors, and oxidative stress. Recently, given its unique ability to characterize biological processes in multiple tissues simultaneously, molecular imaging has yielded important insights into the interplay of these organ systems under conditions of stress and disease. Yet, additional research is needed to probe further into the mechanisms underlying the heart-brain axis and to evaluate the impact of targeted interventions.

Hemodynamic Reactivity to Mental Stress and Cognitive Function in Coronary Artery Disease.

OBJECTIVE: People with coronary artery disease (CAD) are at higher risk of cognitive impairment than those without CAD. Psychological stress is a risk factor for both conditions, and assessing the hemodynamic reactivity to mental stress could explain the link between stress and cognitive function. METHODS: A total of 779 individuals with stable CAD from two prospective cohort studies were included. All individuals underwent acute mental stress testing, as well as conventional stress testing. Cognitive function was assessed both at baseline and at a 2-year follow-up. The rate-pressure product (RPP) was calculated as the mean systolic blood pressure times the mean heart rate at rest. RPP reactivity was defined as the maximum RPP during standardized mental stress test minus the RPP at rest. RESULTS: After multivariable adjustment, every standard deviation decrease in RPP reactivity with mental stress was associated with slower completion of Trail-A and Trail-B in both cohorts (13% and 11% in cohort 1, and 15% and 16% in cohort 2, respectively; p for all <.01). After a 2-year follow-up period, every standard deviation decrease in RPP reactivity with mental stress was associated with a 8% and 9% slower completion of Trail-A and Trail-B, respectively ( p for all <.01). There was no significant association between RPP reactivity with conventional stress testing and any of the cognitive tests. CONCLUSION: In the CAD population, a blunted hemodynamic response to mental stress is associated with slower visuomotor processing and worse executive function at baseline and with greater decline in these abilities over time.

Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies.

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.