Publications by authors named "Susan Heckbert"
People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.
View Article and Find Full Text PDFTo broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.
View Article and Find Full Text PDFStatin use after cancer diagnosis and survival among patients with cancer.
Cancer Causes Control
December 2024
Purpose: The association between statin use and cancer survival has been investigated in previous studies with conflicting findings. This study aimed to assess the association between statin use following cancer diagnosis and survival in six common cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
Methods: Individuals aged ≥ 66 years diagnosed with prostate cancer, colorectal cancer, lung cancer, bladder cancer, pancreatic cancer, or non-Hodgkin lymphoma (NHL) from 2008 through 2017 were identified.
Article Synopsis
- Findings indicate that higher cumulative HIV viral load (VL) and lower CD4 cell counts are significantly linked to an increased risk of developing venous thromboembolism (VTE) in people living with HIV (PWH).
- A study involving over 21,000 PWH over nearly five years revealed that those with higher cumulative VL had a 45% increased risk of VTE compared to those with lower VL. Additionally, a CD4 count below 100 cells/mm³ was associated with a fourfold increase in risk.
- The research suggests that managing HIV viral load and maintaining CD4 levels could be crucial strategies to lower the risk of VTE in PWH.
Background: Available evidence supports the importance of inflammation in atrial fibrillation (AF) pathogenesis, yet general anti-inflammatory therapies have failed to show benefit for prevention of the arrhythmia. Better understanding of the specific inflammatory pathways involved is necessary to advance therapeutics.
Methods And Results: We evaluated 9 circulating markers of inflammation measured by immunoassays and incidence of AF in a population-based older cohort.
Importance: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.
Objective: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).
Design, Setting, And Participants: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018.
Article Synopsis
- Coagulation factor XI (FXI) inhibitors show potential as new anticoagulants but may worsen heart failure and diastolic dysfunction according to an animal study.
- In the ARIC study, involving 4,471 older participants, researchers found that lower plasma FXI levels were linked to a higher incidence of heart failure over a median follow-up of 9 years, especially in those aged 75 and older.
- The study also noted that while lower FXI levels were associated with increased prevalence of diastolic dysfunction, they correlated with a higher likelihood of atrial fibrillation at the baseline, but not with new cases of atrial fibrillation during the follow-up.
Importance: Resting heart rate (RHR) is a widely available measure of cardiovascular fitness that has been associated with several cardiovascular outcomes. RHR has previously been associated with the risk of atrial fibrillation (AF) among individuals of European ancestry, but little is known about this association in Black adults.
Objective: To evaluate the association between RHR and incident AF in a large community-based sample of Black adults, independently of established risk factors.
Most prior studies of cardiovascular (CVD) events have focused on incident events. We analyzed differences by race/ethnicity in incident and recurrent CVD events in the Multi-Ethnic Study of Atherosclerosis from baseline in 2000-2002 through 2019 using joint and multivariable adjusted Cox proportional hazards modeling. Among 6,814 men and women aged 45-85 years without known CVD at enrollment, during median follow up of 17.
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- The study investigates how obstructive sleep apnea (OSA) affects cognitive function, focusing on the role of hypoxemia (hypoxic burden) as a potential cause of white matter injuries in the brain.
- Researchers analyzed data from 587 older adults, measuring the association between hypoxic burden and white matter hyperintensity volume (WMH), while considering other factors like ventilatory burden and arousal burden.
- Findings revealed that an increase in hypoxic burden correlated with higher WMH volume, highlighting the importance of oxygen desaturation in understanding brain health in individuals with OSA.
Article Synopsis
- Alzheimer's disease (AD) exhibits varied brain atrophy patterns, identified through a semi-supervised learning technique (Surreal-GAN) that distinguishes between "diffuse-AD" (widespread atrophy) and "MTL-AD" (focal atrophy in the medial temporal lobe) dimensions in patients with mild cognitive impairment (MCI) and AD.
- Only the "MTL-AD" dimension was linked to known AD genetic risk factors like APOE ε4, and both dimensions were later detected in asymptomatic individuals, revealing their association with different genetic and pathological mechanisms.
- Aside from brain-related genes, up to 77 additional genes were identified in various organs, pointing to broader
Smoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g.
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- The study investigates the relationship between serum calcium levels and ventricular repolarization time, specifically the QT and JT intervals, which are important for heart health.
- Researchers conducted large-scale genome-wide analyses to explore potential interactions between calcium levels and genetic variants associated with QT and JT intervals, using over 122,000 participants.
- The results showed limited evidence for the hypothesized calcium interaction effects, suggesting that other factors, such as rare genetic variations or environmental influences, likely play a larger role in the unexplained heritability of QT and JT intervals.
Article Synopsis
- - The aging process of the brain is affected by lifestyle, environmental, genetic factors, and age-related diseases, with advanced imaging and AI techniques helping to reveal the complexities of neuroanatomical changes.
- - A study involving nearly 50,000 participants identified five major patterns of brain atrophy, which are quantified using R-indices to analyze their connections to various biomedical, lifestyle, and genetic factors.
- - These R-indices not only predict disease progression and mortality but also offer a new, nuanced framework for understanding brain aging, which may enhance personalized diagnostics and improve clinical trial strategies.
Stroke is a leading cause of death in the United States across all race/ethnicity and sex groups, though disparities exist. We investigated the potential for primary prevention of total first stroke for Americans aged 20 years or older, stratified by sex and race/ethnicity. Specifically, we calculated population attributable fractions (PAFs) of first stroke for 7 potentially modifiable risk factors: smoking, physical inactivity, poor diet, obesity, hypertension, diabetes, and atrial fibrillation.
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- A study investigated how changes in left atrial (LA) function may indicate the risk of developing heart failure (HF) in a diverse group of nearly 2,500 participants over an average of 9 years.
- The researchers found that a decrease in peak LA strain is closely linked to heart failure with preserved ejection fraction (HFpEF), while a decrease in indexed LA volume is linked to heart failure with reduced ejection fraction (HFrEF).
- Both LA function metrics significantly improved the prediction models for these conditions, highlighting their potential as early indicators of heart failure in subjects with early signs of cardiovascular disease.
Background: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA.
Methods: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes.
Clonal hematopoiesis of indeterminate potential (CHIP), whereby somatic mutations in hematopoietic stem cells confer a selective advantage and drive clonal expansion, not only correlates with age but also confers increased risk of morbidity and mortality. Here, we leverage genetically predicted traits to identify factors that determine CHIP clonal expansion rate. We used the passenger-approximated clonal expansion rate method to quantify the clonal expansion rate for 4,370 individuals in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) cohort and calculated polygenic risk scores for DNA methylation aging, inflammation-related measures and circulating protein levels.
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- Genome-wide association studies (GWAS) have successfully identified genes linked to telomere length, but previous research hadn't validated these findings until now.
- In a large analysis involving over 211,000 people, the study discovered five new signals linked to telomere length and highlighted the importance of blood/immune cells in this area.
- The researchers confirmed that the genes KBTBD6 and POP5 truly affect telomere length by demonstrating that manipulating these genes can lengthen telomeres and that their regulation is crucial for understanding telomere biology.
Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes.
View Article and Find Full Text PDFBackground: Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients.
Methods: In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database.
Importance: Stroke risk varies by systolic blood pressure (SBP), race, and ethnicity. The association between cumulative mean SBP and incident stroke type is unclear, and whether this association differs by race and ethnicity remains unknown.
Objective: To examine the association between cumulative mean SBP and first incident stroke among 3 major stroke types-ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)-and explore how these associations vary by race and ethnicity.
Background: Coronary artery calcium (CAC) scans contain actionable information beyond CAC scores that is not currently reported.
Methods: We have applied artificial intelligence-enabled automated cardiac chambers volumetry to CAC scans (AI-CAC) to 5535 asymptomatic individuals (52.2% women, ages 45-84) that were previously obtained for CAC scoring in the baseline examination (2000-2002) of the Multi-Ethnic Study of Atherosclerosis (MESA).
Article Synopsis
- The study aimed to find genetic risk factors for cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) through a genome-wide association approach.
- Out of 49,230 T2D participants, 8,956 experienced incident CVD events, revealing three new genetic loci associated with increased CVD risk and confirming five known coronary artery disease variants.
- The findings suggest both novel and established genetic factors contribute to CVD risk in T2D patients, highlighting the importance of genetic screening in this population.
Article Synopsis
- The study investigates the links between vascular health and the development of dementia in a diverse group of participants with cardiovascular issues.
- Using a large database of 6806 individuals, researchers analyzed various health metrics and found 326 cases of dementia over 14 years.
- Key factors influencing dementia risk included coronary artery health, inflammation, and lifestyle choices, highlighting that age is not the only significant determinant of cognitive decline.