Publications by authors named "Ramachandran Vasan"
Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.
Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).
Background: Nutritional factors can abet or protect against systemic chronic inflammation, which plays an important role in the development and progression of dementia. We evaluated whether higher (i.e.
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- Midlife obesity may increase the risk of late-onset dementia, and studying adipokines (substances secreted by fat cells) could help understand this link in aging brains.
- Researchers analyzed serum concentrations of specific adipokines and their relationships to brain MRI markers in 1,882 middle-aged adults from the Framingham Heart Study.
- The study found that higher levels of certain adipokines, particularly RBP4, were associated with brain atrophy, including reduced brain volumes and increased ventricular sizes, suggesting that these factors could play a role in cognitive decline during midlife.
Article Synopsis
- Dilated cardiomyopathy (DCM) is a major cause of heart failure, and this study analyzes genetic factors by examining 14,256 DCM cases and 36,203 participants from the UK Biobank for related traits.
- Researchers discovered 80 genomic risk loci and pinpointed 62 potential effector genes tied to DCM, including some linked to rare variants.
- The study uses advanced transcriptomics to explore how cellular functions contribute to DCM, showing that polygenic scores can help predict the disease in the general population and emphasize the importance of genetic testing and development of precise treatments.
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- Researchers studied plasma proteomic profiles linked to subclinical mutations in blood cells, particularly focusing on clonal hematopoiesis of indeterminate potential (CHIP) and its connection to various health outcomes, including coronary artery disease (CAD).
- The study involved a large, diverse group of participants and identified a significant number of unique proteins associated with key driver genes, showing differences based on genetics, sex, and race.
- Methods like Mendelian randomization and mouse model tests helped clarify the causal effects of these proteins, revealing shared plasma proteins between CHIP and CAD that could inform future clinical insights.
Background: Nearly 3% to 4% of Black individuals in the United States carry the transthyretin V142I variant, which increases their risk of heart failure. However, the role of cardiovascular (CV) risk factors (RFs) in influencing the risk of clinical outcomes among V142I variant carriers is unknown.
Objectives: This study aimed to assess the impact of CV RFs on the risk of heart failure in V142I carriers.
This cross-sectional study included 18,797 participants from 6 longitudinal cohorts (CARDIA, FHS Gen III, HCHS/SOL, MESA, MiHeart, and REGARDS), and 5,806 of them had high-sensitivity C-reactive protein (hs-CRP) measurements. We found that exclusive electronic cigarette (EC) use was associated with significantly lower hs-CRP levels compared to exclusive combustible cigarette use, suggesting a potentially lower inflammatory burden. hs-CRP levels in dual users and former smokers currently using EC were comparable to those observed in exclusive cigarette smokers.
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- Traditional diagnostic tools may not accurately represent cardiovascular issues in patients with chronic kidney disease (CKD), prompting this study to explore if exercise response patterns can detect these abnormalities in mild-to-moderate CKD.
- The study analyzed data from 3,075 participants in the Framingham Heart Study and 451 from the Massachusetts General Hospital Exercise Study, focusing on measurements like peak oxygen uptake (VO2 Peak) and minute ventilation to carbon dioxide production ratio (VE/VCO2) across different eGFR groups.
- Results indicated that both VO2 Peak and VO2 at anaerobic threshold were significantly lower with decreasing kidney function in all analyses, highlighting a concerning connection between cardiovascular fitness and CKD status.
Article Synopsis
- Whole genome sequencing (WGS) helps identify rare genetic variants that may explain the missing heritability of coronary artery disease (CAD) by analyzing 4,949 cases and 17,494 controls from the NHLBI TOPMed program.
- The study estimates that the heritability of CAD is around 34.3%, with ultra-rare variants contributing about 50%, especially those with low linkage disequilibrium.
- Functional annotations show significant enrichment of CAD heritability, highlighting the importance of ultra-rare variants and specific regulatory mechanisms in different cells as major factors influencing genetic risk for the disease.
We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.
View Article and Find Full Text PDFBackground: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex.
Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models.
Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 years) to 93% (ages, 91-94 years).
Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions.
View Article and Find Full Text PDFMechanisms underlying the cardiovascular-kidney-metabolic (CKM) syndrome are unknown, although key small molecule metabolites may be involved. Bulk and spatial metabolomics identified adenine to be upregulated and specifically enriched in coronary blood vessels in hearts from patients with diabetes and left ventricular hypertrophy. Single nucleus gene expression studies revealed that endothelial methylthioadenosine phosphorylase (MTAP) was increased in human hearts with hypertrophic cardiomyopathy.
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- Circulating metabolite levels are indicators of human health and can be influenced by genetic factors; however, most research has focused on European populations.
- The study utilized metabolomics data from 25,058 diverse individuals, identifying 1,778 gene loci linked to 667 metabolites and providing methods for data analysis and handling.
- Notably, the research uncovered new genetic associations, including 108 novel gene-metabolite pairs, and highlighted sex differences in metabolism, enhancing the understanding of genetic influences on human health.
Heart rate, a measure of the frequency of the cardiac cycle, reflects the health of the cardiovascular system, metabolic rate, and activity of the autonomic nervous system. Whether changes in resting heart rate are related to lifespan has not yet been explored to our best knowledge. In this study, we examined the association between resting heart rate and lifespan using linear regression in the Paris Prospective Study I, the Whitehall I Study, and the Framingham Heart Study.
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- This study evaluated if combining a clinical features model with a polygenic score (AORTA Gene) enhances the estimation of ascending aortic diameter and the prediction of related adverse events compared to using clinical features alone.
- The research involved multiple biobanks and found that the AORTA Gene accounted for significantly more variance in aortic diameter across different populations and improved the identification of significant aortic dilation (≥ 4 cm).
- Results showed that incorporating genetic data with clinical factors improved prediction accuracy for adverse thoracic aortic events, demonstrating the value of a comprehensive approach in assessing aortic health.
Introduction: We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.
Methods: We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays.
Background: Step counting is comparable among many research-grade and consumer-grade accelerometers in laboratory settings.
Objective: The purpose of this study was to compare the agreement between Actical and Apple Watch step-counting in a community setting.
Methods: Among Third Generation Framingham Heart Study participants (N=3486), we examined the agreement of step-counting between those who wore a consumer-grade accelerometer (Apple Watch Series 0) and a research-grade accelerometer (Actical) on the same days.
Background & Aims: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.
View Article and Find Full Text PDFAims: New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long-term HF risk in a large community-based cohort.
Methods And Results: We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.
Purpose: Platelets are key mediators in cardiovascular disease (CVD). Low cardiorespiratory fitness (CRF) is a risk factor for CVD. The purpose of our study was to assess if CRF associates with platelet function.
View Article and Find Full Text PDFCardiovascular disease (CVD) morbidity and mortality are high among black adults. We aimed to study the granular subclinical relations of aortic stiffness and left ventricular (LV) function and remodeling in blacks, in whom limited data are available. In the Jackson Heart Study, 1050 U.
View Article and Find Full Text PDFImportance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.
Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.
Design, Setting, And Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971.