Publications by authors named "Michael Tsai"
Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).
View Article and Find Full Text PDFAims: To assess the association of traditional risk factor burden and Life's Simple 7 (LS7) score with incident atherosclerotic cardiovascular disease (ASCVD) across Lp(a) levels.
Methods: There were 6,676 participants without clinical ASCVD from the Multi-Ethnic Study of Atherosclerosis who underwent Lp(a) testing and were followed for incident ASCVD events (coronary heart disease and stroke). Low, intermediate, and elevated Lp(a) were defined as <30, 30-49, and >50 mg/dL, respectively.
Background: Oxidized phospholipids (OxPLs) are carried by apolipoprotein B-100-containing lipoproteins (OxPL-apoB) including lipoprotein(a) (Lp[a]). Both OxPL-apoB and Lp(a) have been associated with calcific aortic valve disease (CAVD).
Objectives: This study aimed to evaluate the associations between OxPL-apoB, Lp(a) and the prevalence, incidence, and progression of CAVD.
Article Synopsis
- Lipid-lowering therapy (LLT) is crucial for managing atherosclerotic cardiovascular disease (ASCVD) risk, but it is underused by over 40% of eligible individuals in the U.S.
- A study analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA) to understand the demographics and health conditions influencing LLT usage between 2010-2012 and 2016-2018.
- Findings revealed that Black participants were less likely to be on LLT, while higher body mass index (BMI) and the presence of coronary artery calcium (CAC) were strongly associated with LLT use, indicating healthcare disparities and the importance of CAC measurement.
Article Synopsis
- * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
- * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
Background: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS.
Methods: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002).
Background: We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.
View Article and Find Full Text PDFArticle Synopsis
- - The study investigates the impact of lipoprotein(a) (Lp[a]) on the risk of atherosclerotic cardiovascular disease (ASCVD) using data from 27,756 participants across five major U.S. studies, with a follow-up period averaging 21.1 years.
- - Results indicate that higher Lp(a) levels correlate with increased risk of ASCVD events, especially among individuals with diabetes, with adjusted hazard ratios showing significant risk elevation at higher Lp(a) percentiles.
- - The findings highlight that elevated Lp(a) independently predicts various cardiovascular events, including heart attacks and strokes, reinforcing its role as a genetic risk factor for ASCVD in diverse populations.
Article Synopsis
- A study explored how polyunsaturated fatty acids (PUFAs) in early pregnancy affect thyroid function, which is important for both maternal health and fetal brain development.
- Researchers analyzed plasma samples from 214 pregnant women (107 with gestational diabetes and 107 without) to measure levels of various PUFAs and thyroid biomarkers at different stages of pregnancy.
- The findings indicated that specific PUFAs, like EPA and DHA, are linked to improved thyroid hormone levels and lower risks of gestational hypothyroidism, suggesting that a PUFA-enriched diet may benefit maternal thyroid health during pregnancy.
Aims: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC.
Methods And Results: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.
Article Synopsis
- Large-scale studies on gene-environment interactions often simplify outcomes and covariates to improve data consistency, which can hinder the understanding of complex relationships, such as those between physical activity and HDL cholesterol.* -
- The study refined a previously identified interaction between the rs295849 genotype and physical activity on HDL cholesterol levels, using datasets from the Women's Genome Health Study, UK Biobank, and Multi-Ethnic Study of Atherosclerosis.* -
- Findings showed that the interaction effect was stronger when looking at medium-sized HDL particles compared to total HDL cholesterol, highlighting variations based on gender and the specific lipid metrics used.*
Background: Effective therapies for reducing cardiovascular disease (CVD) risk in people with elevated lipoprotein(a) are lacking, especially for primary prevention. Because of the potential association of lipoprotein(a) with thrombosis, we evaluated the relationship between aspirin use and CVD events in people with elevated lipoprotein(a).
Methods And Results: We used data from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of baseline cardiovascular disease.
Background And Aims: Although several biomarkers have been studied in thromboembolic stroke, measuring the balance between thrombus formation and thrombolysis and data on its role in predicting stroke and atrial fibrillation (AF)-related stroke is limited. We sought to assess atherothrombotic biomarkers grouped into composite factors that reflect thrombotic and thrombolytic potential, and the balance between these factors as it relates to incident stroke or transient ischemic attack (TIA) and stroke/TIA in AF.
Methods: A Thrombotic Factor, derived from fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a); and a Thrombolytic Factor, derived from plasminogen and oxidized phospholipids on plasminogen, were evaluated at baseline in 5,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants.
Article Synopsis
- The study examined the relationship between omega-3 PUFAs and stroke risk across 29 global cohorts, focusing on total, ischemic, and hemorrhagic strokes.
- Results showed that higher levels of eicosapentaenoic acid reduced the incidence of total and ischemic strokes by 17% and 18%, respectively, while docosahexaenoic acid also lowered these risks by 12% and 14%.
- The findings indicate that although higher omega-3 PUFA levels are linked to reduced total and ischemic stroke risks, there is no effect on hemorrhagic strokes.
Introduction: Physical activity (PA), regardless of domain, is recommended for pregnant individuals in clinical guidelines, but limited evidence is available for work-related PA. This study aimed to examine the associations of occupational (OPA) and leisure-time PA (LTPA) with plasma high-sensitivity C-reactive protein (hs-CRP), a risk marker for adverse pregnancy outcomes, among pregnant individuals.
Methods: This longitudinal study included 257 workers in the fetal growth cohort.
Article Synopsis
- The study examines the link between lipoprotein(a) (Lp[a]) levels and myocardial fibrosis (IMF) as well as cardiac remodeling using advanced imaging techniques in a diverse group of participants from the MESA cohort.
- Results showed that higher Lp(a) levels were significantly associated with increased measures of myocardial fibrosis and a greater risk of clinically significant IMF, as measured by the extracellular volume fraction and native T1 times.
- The findings suggest that elevated Lp(a) levels not only indicate higher prevalence of myocardial scarring but also correlate with left atrial enlargement and dysfunction, highlighting Lp(a) as a potential marker for adverse cardiovascular outcomes.
Background: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.
Methods: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed.
Article Synopsis
- Educational attainment is linked to cardiovascular health, and a large genomic study examined how it interacts with cholesterol and triglyceride levels in nearly 226,315 individuals across five population groups.
- The study identified 18 new genetic variations related to lipid levels—nine for low-density lipoprotein (LDL), seven for high-density lipoprotein (HDL), and two for triglycerides (TG)—some of which interact with educational attainment.
- Researchers also found five gene targets that potentially interact with FDA-approved drugs, suggesting a connection between genetics and drug responses related to lipid metabolism and overall health.
Background: Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort.
Methods: We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively.
Background: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce.
Objectives: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts.
Background: Glycated albumin (GA) has recently been proposed as a screening marker for diabetes among non-pregnant individuals. However, data on GA during pregnancy are sparse and lacking among women of diverse race/ethnicity. We investigated longitudinal concentrations of GA among multiracial pregnant women in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons.
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- Long non-coding RNAs (lncRNAs) play crucial roles in regulating lipid metabolism and have been studied in relation to genetic variants and complex traits.
- This research utilized high-coverage whole-genome sequencing of over 66,000 diverse participants to assess how rare variants in lncRNA genes affect blood lipid levels, using a statistical framework to analyze the associations.
- The study found 83 lncRNA variants significantly linked to lipid levels, with many being independent of common genetic variations, and replicated a majority of these findings with data from another large cohort.
Background: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited.
Objectives: We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF.
Introduction: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.
Methods: Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations.