Hall, Michael E.

Background: Chronic kidney disease (CKD) has been linked to elevated inflammatory biomarkers, yet few studies have evaluated these associations using iothalamate-based measures of kidney function, highlighting the need for further research. Research question: Is CKD associated with elevated inflammatory markers when defined by measured glomerular filtration rate (mGFR) and urinary albumin-to-creatinine ratio (UACR)? Methods: Participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort were included if they had data available for at least one inflammatory marker at visit 2. 17 inflammatory markers were assessed, including C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), serum amyloid A, intercellular and vascular adhesion molecules (ICAM, VCAM), E-selectin, P-selectin, monocyte chemoattractant protein (MCP), myeloperoxidase (MPO), receptor for advanced glycation end products (RAGE), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2). Kindey function was assessed using the urinary clearance of iothalamate. CKD was defined as mGFR < 60 mL/min/1.73 m 2 or UACR ≥ 30 mg/g. To further assess whether associations persisted without albuminuria, we also defined CKD solely by mGFR < 60 mL/min/1.73 m 2 . Generalized estimating equations (GEE) were used to assess associations between CKD status and inflammatory markers, accounting for familial clustering. Exponentiated beta coefficients from GEE models were used to present geometric mean (GM) ratios of each biomarker by CKD status, adjusted for demographics, lifestyle factors, cardiovascular risk factors, and medication use. Results: Among 1,010 participants (mean age 61 ± 10 years; 67% women; 48% Black adults), 207 were classified as having CKD. After adjusting for potential confounders, individuals with CKD had significantly higher levels of hsCRP, VCAM, TNFR1, and TNFR2 compared to those without CKD (GM ratios > 1; p < 0.05), while the remaining inflammatory markers showed no significant differences ( Figure 1 ). Importantly, these elevations remained significant when CKD was defined by mGFR alone ( Figure 2 ). Conclusion: Our findings suggest that CKD, defined by mGFR, is associated with specific inflammatory biomarkers, underscoring the need for mechanistic studies to investigate these associations.

Background: Hypertension and systemic inflammation are independently associated with adverse cardiovascular outcomes. While hypertension is a known risk factor for left ventricular (LV) hypertrophy, the role of inflammation in LV structural changes remains unclear. It is also uncertain whether concomitant inflammation and hypertension ("inflammatory hypertension") exacerbate LV hypertrophy. Research Question: Is inflammatory hypertension associated with increased LV mass index (LVMI) compared to hypertension without inflammation? Methods: We analyzed baseline data from Black adults enrolled in the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort in Jackson, Mississippi. Inflammation was defined by high sensitivity C-reactive protein (hsCRP) >3 mg/L, and hypertension as systolic blood pressure (SBP) >130 mmHg. Participants were classified into four groups: noninflammatory-normotensive (reference group), noninflammatory-hypertensive, inflammatory-normotensive, and inflammatory-hypertensive. The primary outcome was LVMI, assessed by echocardiography. Associations between groups and LVMI were evaluated using generalized estimating equations to account for familial clustering and adjusted for covariates including age, sex, education, smoking status, body mass index, number of antihypertensive medications, statin use, cholesterol, and diabetes. Results: Among 1,027 participants (mean age 64 ± 8.5 years; 71% women), baseline LVMI differed by inflammation-hypertension status. Compared with the LVMI in noninflammatory-normotensive cohort (n=108; 74.5 g/m 2 [70.4–78.6]), significantly higher LVMI was observed in noninflammatory-hypertensive (n=343; 83.6 g/m 2 [81.3–85.9], p<0.001) and inflammatory-hypertensive groups (n=497; 84.7 g/m 2 [82.8–86.7], p<0.001). There was no statistically significant difference between inflammatory-hypertensive and noninflammatory-hypertensive groups (84.7 vs 83.6 g/m 2 )(p=0.460). The inflammatory-normotensive cohort also did not differ from the reference group (74.9 g/m 2 [70.2–79.5], p=0.901). Secondary analyses using elevated IL-6 to define inflammation yielded similar findings ( Figure 1 ). Conclusion: In individuals with inflammatory hypertension, hypertension appears to be the primary driver of LV hypertrophy. Further studies in larger, diverse populations are needed to definitively evaluate the potential additive effect of inflammatory hypertension on LV remodeling.

Background: Cardiac rehabilitation (CR) is essential to secondary cardiovascular disease prevention and management of cardiac patients. Despite its proven benefits, CR remains underutilized with enrollment and completion rates ranging from 10-30% in the US. Yet, there is a scarcity of nationally representative data among diverse populations on socioeconomic differences in barriers and beliefs of CR participation and delivery mode preferences. Hypothesis: The perceptions (barriers, beliefs), CR delivery mode preferences, and CR utilization (prior enrollment) varies by socioeconomic status (SES) among CR-eligible individuals. Methods: We conducted an anonymous national electronic survey from March 2023 to January 2024 of individuals self-reporting a prior CR-eligible diagnosis. The 22-item CR Barriers Scale assessed perceived barriers to CR enrollment and participation using a 5-point Likert scale (strongly disagree to strongly agree). A 13-item, validated questionnaire assessed 4 subscales pertaining to patients’ beliefs about CR, each rated on a 5-point Likert scale (strongly disagree to strongly agree): perceived necessity, concerns about exercise, practical barriers and perceived suitability. CR delivery mode preferences were ascertained (eg, virtual, at-home, etc.). Mean barriers and belief scores as well as delivery mode preferences were stratified by SES. Low SES was defined as ≤ high school education, Medicaid insurance, or uninsured. High SES was defined as > high school education and non-Medicaid health insurance. Responses were analyzed using descriptive statistics with R software. Results: A total of 466 participants completed the survey (38.1% women, 30.6% minoritized racial/ethnic group, 29.6% low SES, 95% response rate) ( Table 1 ). The majority indicated prior enrollment in CR (81.5%) with no difference by SES. CR barrier scores did not differ significantly by SES (p=0.331) ( Table 2 ). Beliefs about CR perceived necessity and perceived suitability differed by SES (p<0.001 and p=0.025), but beliefs regarding concerns about exercise and practical barriers did not. The low SES group reported a higher preference for completely at-home CR compared to the high SES group (33.6% vs 7.4%, p<0.001). Conclusion: Our findings suggest that CR beliefs varied by SES while utilization did not. For CR-eligible patients experiencing socioeconomic disadvantage, at-home CR may be a preferred alternative to center-based CR to increase CR participation and adherence.

Summary We describe a case of culture-negative infective endocarditis due to Neisseria gonorrhoeae, where the application of metagenomics shotgun sequencing in blood played a pivotal role in elucidating the underlying aetiology, guiding targeted therapy and ultimately resulting in the patient’s complete recovery. Beyond its immediate clinical impact, prompt treatment bears significant implications for public health. The utilisation of molecular testing emerges as a valuable strategy to enhance diagnostic accuracy, particularly in cases involving fastidious organisms that are infrequently associated with infective endocarditis.

Background Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. Destination Cardiac Rehab is a novel virtual world technology‐based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center‐based CR. This study aims to evaluate efficacy and adherence of the virtual world–based CR program compared with center‐based CR within a community‐informed, implementation science framework. Methods Using a noninferiority, hybrid type 1 effectiveness‐implementation, randomized controlled trial, 150 patients with an eligible cardiovascular event will be recruited from 6 geographically diverse CR centers across the United States. Participants will be randomized 1:1 to either the 12‐week Destination Cardiac Rehab or the center‐based CR control groups. The primary efficacy outcome is a composite cardiovascular health score based on the American Heart Association Life's Essential 8 at 3 and 6 months. Adherence outcomes include CR session attendance and participation in exercise sessions. A diverse patient/caregiver/stakeholder advisory board was assembled to guide recruitment, implementation, and dissemination plans and to contextualize study findings. The institutional review board–approved randomized controlled trial will enroll and randomize patients to the intervention (or control group) in 3 consecutive waves/year over 3 years. The results will be published at data collection and analyses completion. Conclusions The Destination Cardiac Rehab randomized controlled trial tests an innovative and potentially scalable model to enhance CR participation and advance health equity. Our findings will inform the use of effective virtual CR programs to expand equitable access to diverse patient populations. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05897710.

Key Points Using multiple markers may improve GFR estimation especially in settings where creatinine and cystatin C are known to be limited. Panel eGFR is a novel multimarker eGFR equation consisting of age, sex, cystatin C, and nuclear magnetic resonance–measured creatinine, valine, and myo-inositol. eGFR-Cr and eGFR-Cr-CysC may underestimate measured GFR, while panel eGFR was unbiased among younger Black male individuals. Background Using multiple markers may improve accuracy in GFR estimation. We sought to externally validate and compare the performance of a novel multimarker eGFR (panel eGFR) equation among Black and White persons using the Genetic Epidemiology Network of Arteriopathy cohort. Methods We included 224 sex, race/ethnicity, and measured GFR (mGFR) category–matched persons, with GFR measured using urinary clearance of iothalamate. We calculated panel eGFR using serum creatinine, valine, myo-inositol, cystatin C, age, and sex. We compared its reliability with current eGFR equations (2021 CKD Epidemiology Collaboration creatinine [eGFR-Cr] and creatinine with cystatin C [eGFR-Cr-CysC]) using median bias, precision, and accuracy metrics. We evaluated each equation's performance in age, sex, and race subgroups. Results In the overall cohort, 49% were Black individuals, and mean mGFR was 79 ml/min per 1.73 m 2 . Panel eGFR overestimated mGFR (bias: −2.4 ml/min per 1.73 m 2 ; 95% confidence interval [CI], −4.4 to −0.7), eGFR-Cr-CysC underestimated mGFR (bias: 4.8 ml/min per 1.73 m 2 ; 95% CI, 2.1 to 6.7), while eGFR-Cr was unbiased (bias: 2.0 ml/min per 1.73 m 2 ; 95% CI, −1.1 to 4.6). All equations had comparable accuracy. Among Black male individuals younger than 65 years, both eGFR-Cr (bias: 17.0 ml/min per 1.73 m 2 ; 95% CI, 8.6 to 23.5) and eGFR-Cr-CysC (bias: 14.5 ml/min per 1.73 m 2 ; 95% CI, 6.0 to 19.7) underestimated mGFR, whereas panel eGFR was unbiased (bias: 1.7 ml/min per 1.73 m 2 ; 95% CI, −3.4 to 10.0). Metrics of accuracy for all eGFRs were acceptable in all subgroups except for panel eGFR in Black female individuals younger than 65 years (P30: 73.3%). Conclusions Panel eGFR can be used to estimate mGFR and may have utility among Black male individuals younger than 65 years where current CKD Epidemiology Collaboration equations are biased.

Background: RCTs studying the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on cardiovascular (CV) risk factors and outcomes have been underpowered to assess patients with overweight or obesity, thus presenting the need for a meta-analysis. Methods: Electronic databases were queried up till February 2022 for RCTs comparing SGLT2i with placebo in patients with overweight (BMI ≥25 kg/m2) or obesity (BMI ≥30 kg/m2) - irrespective of diabetes status - with a follow-up of ≥24 weeks. Meta-analyses were performed using the generic inverse variance technique and a random-effects model. Results are presented as weighted mean differences (WMD) for continuous outcomes, and hazard ratios (HR) for dichotomous outcomes. Outcomes studied were: (i) weight; (ii) systolic BP; (iii) diastolic BP; (iv) heart rate; (v) HDL-C; (vi) LDL-C; (vii) major adverse cardiac events (MACE), i.e., composite of CV death, non-fatal myocardial infarction (MI) and non-fatal stroke; (viii) composite of heart failure hospitalization and CV death (HFH/CV death); (ix) mortality; (x) MI; and (xi) stroke. Results: Seventeen RCTs (47,649 patients) were included. Compared with placebo, SGLT2i significantly reduced weight (WMD: -2.32 kg [-2.77, -1.88]), HbA1c (WMD: -0.79 % [-0.98, - 0.61]) and systolic BP (WMD: -2.15 mm Hg [-3.08, - 1.22]). SGLT2i did not have a significant effect on diastolic BP (WMD: -0.55 mmHg [-1.51, 0.41]), heart rate (WMD: 0.08 bpm. [-0.21, 0.37]), HDL-C (WMD: 1.62 mmol l -1 [-0.21, 3.45]) or LDL-C (WMD: 0.53 mmol l -1 [-0.88, 1.94]). Amongst CV outcomes, SGLT2i reduced the risk of MACE (HR: 0.90 [0.81, 0.99]), HFH/CV death (HR: 0.82 [0.75, 0.90]), and mortality (HR: 0.85 [0.77, 0.94]). No effect was noted on stroke (HR: 0.99 [0.85, 1.26]) or MI (HR: 0.89 [0.77, 1.02]). Conclusions: In patients with overweight or obesity, SGLT2i produce a modest but significant reduction in weight, systolic BP and HbA1c. SGLT2i may also reduce the risk of MACE, HFH/CV death, and mortality.

Abstract Background and Aims The use of multiple markers may improve the accuracy in glomerular filtration rate (GFR) estimation especially when the interpretation of creatinine and cystatin C is limited. We sought to externally validate a recently developed multi-marker nuclear magnetic resonance (NMR)-based estimated GFR equation (eGFR-NMR) using the biracial Genetic Epidemiology Network of Arteriopathy cohort. Method We included 224 sex, race/ethnicity, and mGFR-category-matched participants. GFR was measured using urinary clearance of iothalamate (mGFR). We calculated eGFR-NMR using serum creatinine, valine, myo-inositol, and cystatin C, age, and sex. We compared the reliability of eGFR-NMR with current eGFR equations (2021 Chronic Kidney Disease Epidemiology Collaboration equations for creatinine [eGFR-Cr] and creatinine with cystatin C [eGFR-Cr-CysC]) using median bias, precision, and accuracy metrics. In particular, we evaluated its performance in age, sex, and race subgroups. Results In the overall cohort, mean age was 63 (±8) years, 54% were females, 49% were Black individuals, and mean mGFR was 78.7 (±24.3) ml/min/1.73 m2. eGFR-NMR overestimated mGFR by 2 mL/min/1.73 m2 (95% CI, 4 to 0.7) while eGFR-Cr-CysC underestimated mGFR by −5 mL/min/1.73 m2 (95% CI, −2 to −7). All equations had acceptable accuracy metrics. When stratified by age, sex, and race, eGFR-NMR performed the best among Black males age &lt;65 years compared to current equations (Figure 1). In this subgroup, eGFR-NMR was unbiased (bias, 2mL/min/1.73 m2 [95% CI, -3 to 10]) compared to substantial biases of eGFR-Cr (bias, 17 mL/min/1.73 m2 [95% CI, 9 to 24]) and eGFR-Cr-CysC (bias, 15 mL/min/1.73 m2 [95% CI, 6 to 20]). In other subgroups, measures of accuracy for eGFR-NMR, eGFR-Cr, eGFR-Cr-CysC were generally similar. Conclusion eGFR-NMR can be used to estimate mGFR and was more accurate than CKD-EPI equations among Black males age &lt;65 years.