Faculty Bibliography

PURPOSE/OBJECTIVE:Many studies estimate that more than 50% of non-hospitalized patients with long-COVID develop moderate to severe autonomic dysfunction. However, the specific impact of autonomic dysfunction as it relates to quality of life in long-COVID is not fully understood. The aim of the current study is to assess autonomic symptoms and quality-of-life in patients with Post-Acute Sequelae of COVID-19 (PASC) recruited from a neurology department outpatient setting. METHODOLOGY/METHODS:In a two-year follow-up study of a baseline cohort of 93 non-hospitalized SARS-CoV-2 laboratory-positive patients evaluated for PASC between November 2020-August 2021, 44 participants completed follow-up telephone questionnaires examining quality-of-life as well as neurologic and autonomic symptoms. RESULTS:Among 93 participants, 44 (47 %) completed the two-year follow-up evaluation and 27 (61 %) were female with a median age of 55 years (IQR = 24-88). Most participants (95 %, 42/44) were vaccinated against COVID-19 and 43 % (19/44) had a pre-existing neurological disorder. Median time from index COVID-19 infection to follow-up was 26 months (IQR = 23-17), with a median of 15 months (IQR = 15-16) between visits. Fatigue, word finding difficulty, and changes in memory were the most commonly reported PASC symptoms. Sixty-six percent (29/44) of individuals met criteria for autonomic dysfunction as defined by the Composite Autonomic Symptom Score-31 (COMPASS-31) scale. Secretomotor and gastrointestinal subdomains demonstrated significant associations with Neuro-QoL metrics for Anxiety, Depression, and Fatigue. For every 1 additional PASC symptom reported at a follow-up study visit, there was an average increase of 1.5 points on the COMPASS-31 composite score. In addition, visual disturbances and sleep impairment were both associated with increased autonomic dysfunction. CONCLUSION/CONCLUSIONS:The strong association between autonomic dysfunction and reduced QoL in PASC and the relation to insomnia, visual dysfunction, and functional impairment are valuable findings, reinforcing the clinical impact of these symptoms longitudinally after index COVID-19 infection.

Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes¹. Although these methods are conceptually similar, by analysing association studies of 209 quantitative traits in the UK Biobank^2-4, we show that they systematically prioritize different genes. This raises the question of how genes should ideally be prioritized. We propose two prioritization criteria: (1) trait importance - how much a gene quantitatively affects a trait; and (2) trait specificity - the importance of a gene for the trait under study relative to its importance across all traits. We find that GWAS prioritize genes near trait-specific variants, whereas burden tests prioritize trait-specific genes. Because non-coding variants can be context specific, GWAS can prioritize highly pleiotropic genes, whereas burden tests generally cannot. Both study designs are also affected by distinct trait-irrelevant factors, complicating their interpretation. Our results illustrate that burden tests and GWAS reveal different aspects of trait biology and suggest ways to improve their interpretation and usage.

BACKGROUND:Uncontrolled hypertension (HTN) is a leading preventable cause of death. Interventions are needed that activate patients and motivate them to work with clinicians to control their blood pressure (BP). OBJECTIVE:To test whether mailing patients a letter including information about their hypertension and a summary of computerized algorithm-generated medication adjustment suggestions improves BP control processes and outcomes. DESIGN/METHODS:Randomized quality improvement trial. PARTICIPANTS/METHODS:We identified patients receiving primary care at a large academic medical center with diagnosed HTN and uncontrolled BP (> 140 mmHg systolic or > 90 mmHg diastolic) at both of their last 2 visits. INTERVENTIONS/METHODS:Participants were randomized into three groups. The BP Activate Letter group received a letter containing algorithm-generated BP medication adjustment suggestions, and a recommendation to discuss these suggestions with their provider; the Control Letter group received a letter that recommended they talk to their provider about their HTN, without specific medication suggestions; and the No Letter group received no mailed outreach. MAIN MEASURES/METHODS:The primary outcome was time to occurrence of either a BP medication intensification or documented achievement of BP control to < 140/< 90 mmHg using EHR data extracted 6 months after letters were mailed. KEY RESULTS/RESULTS:The primary outcome, which was time to medication intensification or achievement of BP control, did not occur more frequently in the BP Activate Letter group (hazard ratio = 0.86; 95% confidence interval [CI]: 0.65 to 1.14), or in the Control Letter group (0.78; 0.59 to 1.03) compared to the No Letter group, and we saw no evidence of significant improvement in any secondary outcome or subgroup. Time to medication intensification appeared to be significantly longer in the Control Letter compared to the No Letter group (0.50; 0.30 to 0.85). CONCLUSIONS:Mailing patients one letter with computerized BP medication adjustment suggestions to consider did not lead to effective patient activation.

BACKGROUND:Prior prediction equations for heart failure (HF) omitted cardiac biomarkers and used select populations. We assessed the added value of NT-proBNP (NT-terminal pro-brain natriuretic peptide) and hsTnT (high-sensitivity troponin T) as predictors of HF, across a broad population, including participants with chronic kidney disease or atherosclerotic cardiovascular disease. METHODS:Among 41 427 individuals free of HF from 9 prospective cohort studies, we performed an individual-participant data meta-analysis, quantifying the associations of NT-proBNP and hsTnT with incident HF when added to a clinical model. Changes in Harrel's C-statistic with and without NT-proBNP or hsTnT were estimated within each cohort and then pooled using random effects meta-analysis. RESULTS:<0.001). CONCLUSIONS:NT-proBNP improved risk discrimination of incident HF when added to traditional HF risk factors, even in individuals with chronic kidney disease and atherosclerotic cardiovascular disease. The contribution of hsTnT was modest. Measurement of NT-proBNP may help identify individuals at risk of HF.

As a contingency standard of care, telemedicine use surged during the COVID-19 pandemic. The Medicare telehealth flexibilities introduced during the COVID-19 pandemic expired in September 2025. Any ongoing sustained pivot to telemedicine warrants purposeful attentiveness to ethical considerations and not just technology use as an end unto itself. Telemedicine has the potential to complement face-to-face care practices and enhance clinical interactions when its use is based on shared values. Values such as access, equity, justice, compassion, autonomy, and dignity warrant thoughtful use of telemedicine. Patients and families need to be able to trust that clinicians and health systems will place patient welfare and shared values above technical convenience. As demonstrated in this case description, upholding values fundamental to the practice of medicine in telemedicine can enhance patient connection and foster trustworthy post-pandemic practices.

BACKGROUND/UNASSIGNED:Urinary albumin-creatinine ratio (UACR) and urinary protein-creatinine ratio (UPCR) are both used in clinical practice to diagnose and monitor chronic kidney disease (CKD). Which measure exhibits stronger associations with clinical outcomes and whether this varies by patient characteristics are unknown. OBJECTIVE/UNASSIGNED:To assess and compare the performance of UACR and UPCR across CKD-related clinical outcomes. DESIGN/UNASSIGNED:Individual patient-level meta-analysis. SETTING/UNASSIGNED:38 research and clinical cohorts. PARTICIPANTS/UNASSIGNED:148 994 participants with same-day measurements of UACR and UPCR. MEASUREMENTS/UNASSIGNED:, and glomerular disease. RESULTS/UNASSIGNED:, diabetes, and glomerular disease. Associations between UACR and UPCR were generally similar for cardiovascular outcomes but favored UACR in subgroups with moderately to severely elevated UACR. LIMITATION/UNASSIGNED:Assessment of UACR and UPCR in spot urine samples. CONCLUSION/UNASSIGNED:Overall, UACR was more strongly associated with kidney failure than UPCR (particularly in subgroups with higher UACR), supporting the use of UACR rather than UPCR to diagnose and risk-stratify patients. PRIMARY FUNDING SOURCE/UNASSIGNED:National Kidney Foundation and National Institute of Diabetes and Digestive and Kidney Diseases.

BACKGROUND:High 1-h-post-load plasma glucose (1 h-PG) is an early diabetes risk marker. We hypothesized that isolated high 1 h-PG represents an intermediate state between normal glucose regulation (NGR) and impaired glucose regulation (IGR) and is amendable to greater lifestyle intervention (LI) benefit. METHODS:In the Tübingen Lifestyle Intervention Program, 317 people with either NGR, IGR or isolated high 1 h-PG without IGR underwent LI for 9 months to achieve ≥5 % weight loss. RESULTS:Before LI initiation, insulin sensitivity and β-cell function declined progressively from NGR (n = 106) to high 1 h-PG (n = 96) and to IGR (n = 115). Visceral adipose tissue (VAT) volume and liver fat content increased from NGT to high 1 h-PG and to IGR. LI improved insulin sensitivity and ß-cell function in the high 1 h-PG group to levels observed in NGR together with a marked reduction in hepatic fat content. Compared to the IGR group, T2D risk was reduced by 80 % (37-96 %, p = 0.005) in the high 1 h-PG group during a 12-year follow-up period. The odds of remission to complete normoglycemia were doubled in the high 1 h-PG group compared to the IGR group (2.18 [1.13-4.28], p = 0.021). CONCLUSION/CONCLUSIONS:High 1 h-PG indicates an intermediate metabolic state with pathophysiological changes more severe than in NGR but milder than in IGR. In people with high 1 h-PG, LI significantly improved insulin sensitivity and β-cell function and reduced ectopic lipid deposition and the risk of developing T2D compared to IGR. These findings highlight the value of 1 h-PG as a clinically useful biomarker, providing a critical window for early intervention to reverse core metabolic defects driving prediabetes and T2D.

BACKGROUND:In Nigeria, cardiovascular diseases, especially hypertension, are on the rise. This increase in hypertension correlates with more strokes, significantly impacting mortality. Since hypertension often persists into adulthood, early interventions are crucial to prevent its complications. Non-invasive methods, such as music and creative activities, can effectively improve blood pressure and reduce stroke risk. This study aims to improve intergenerational awareness of hypertension and promote sustainable preventive practices by involving youth and caregivers within families and communities. METHODS:We employed a participatory, observational design, incorporating a five-month crowdsourcing open call followed by a designathon event. Participatory social and health innovations were combined and implemented as part of a larger study titled "Innovative Tool to Expand Music-Inspired Strategies for Blood Pressure and Stroke Prevention" (I-TEST BP/Stroke). Our study targeted youths aged 14 to 24, a critical period for shaping health behaviors and attitudes toward diseases. The 20 finalist textual entries were categorized into themes using the PEN-3 cultural model. The PLAN framework analyzed the effectiveness of participants' entries in conveying public health messages. RESULTS:The crowdsourced open call for musical ideas received 85 submissions between October 2023 and March 2024. More males (74.3%) than females, mainly aged 22-24, and mostly undergraduates (44.3%), participated in the open call, with 88.65% having heard of hypertension. Qualitative analysis with PEN-3 highlighted themes regarding Perceptions and Enablers, such as monitoring blood pressure, engaging in physical activity, and avoiding alcohol and smoking. The use of Pidgin English and Nigerian languages in songs represents Positive Cultural Empowerment. The Negative Cultural Empowerment domain addresses misconceptions about hypertension, including the belief that hypertension is a curse. Utilizing the PLAN framework, the submissions demonstrated an effective blend of catchy, memorable tunes with health education messages. CONCLUSION/CONCLUSIONS:The designathon produced various music genres, including afrobeats, rap, and R&B, with lyrics deemed feasible and socio-culturally appropriate. This suggests that music interventions tailored to Nigeria could enhance public awareness of hypertension and stroke prevention if scaled up.

BACKGROUND:The association of PREVENT-HF (Predicting Risk of Cardiovascular Events-Heart Failure) risk estimates with preclinical heart failure (HF) and whether preclinical HF measures add to the predictive utility of PREVENT-HF remain undefined. OBJECTIVES/OBJECTIVE:The aims of this study were to evaluate the association between PREVENT-HF risk estimates and preclinical HF, to examine how preclinical HF measures correspond to absolute HF risk within PREVENT-HF categories, and to determine whether they provide predictive value beyond the PREVENT-HF score. METHODS:The authors performed a prospective analysis of 2,714 ARIC (Atherosclerosis Risk In Communities) Visit 5 participants <80 years of age, without baseline cardiovascular disease. Preclinical HF was defined by elevated cardiac biomarkers (N-terminal of pro-b-type natriuretic peptide ≥125 pg/mL or high-sensitivity cardiac troponin T ≥22 ng/L/≥14 ng/L in men/women) and/or abnormal echocardiographic findings. Within PREVENT-HF 10-year risk categories (<7.5%, ≥7.5% to <10%, ≥10% to <15%, ≥15% to <20%, and ≥20%), we assessed preclinical HF prevalence and compared 10-year HF incidence rates for those with and without preclinical HF. We assessed changes in predictive utility by adding preclinical HF measures to PREVENT-HF. RESULTS:The mean age was 74 years, with 63% women, and 22% Black adults. Higher PREVENT-HF risk was associated with higher preclinical HF prevalence, with the highest prevalence of combined elevated biomarkers plus abnormal echocardiograms (37%) in those with PREVENT-HF ≥20%. Over a median follow-up of 9.9 years, 262 HF events occurred. Within PREVENT-HF categories, preclinical HF measures were strongly associated with absolute HF risk: among those with PREVENT-HF ≥20%, HF incidence rates (per 1,000 person-years) were 9.5 with no preclinical HF and 51.5 with elevated biomarkers plus abnormal echocardiography. Adding cardiac biomarkers to PREVENT-HF improved risk discrimination (C statistic change 0.69 to 0.75; P < 0.001) and reclassification (categorical Net Reclassification Index: 0.17; 95% CI: 0.09-0.26), with modest further improvement from adding echocardiographic measures. CONCLUSIONS:Preclinical HF measures indicate higher absolute HF risk within PREVENT-HF categories and enhance HF risk prediction.