69 results on '"Rohatgi, Anand"'
Search Results
2. HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research.
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Rohatgi, Anand, Westerterp, Marit, von Eckardstein, Arnold, Remaley, Alan, and Rye, Kerry-Anne
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DYSLIPIDEMIA , *HDL cholesterol , *HIGH density lipoproteins , *APOLIPOPROTEIN A , *TWENTY-first century , *HEART failure - Abstract
Low high-density lipoprotein cholesterol (HDL-C) characterizes an atherogenic dyslipidemia that reflects adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Low HDL-C is also associated with increased risk of inflammatory disorders, malignancy, diabetes, and other diseases. This epidemiologic evidence has not translated to raising HDL-C as a viable therapeutic target, partly because HDL-C does not reflect high-density lipoprotein (HDL) function. Mendelian randomization analyses that have found no evidence of a causal relationship between HDL-C levels and cardiovascular risk have decreased interest in increasing HDL-C levels as a therapeutic target. HDLs comprise distinct subpopulations of particles of varying size, charge, and composition that have several dynamic and context-dependent functions, especially with respect to acute and chronic inflammatory states. These functions include reverse cholesterol transport, inhibition of inflammation and oxidation, and antidiabetic properties. HDLs can be anti-inflammatory (which may protect against atherosclerosis and diabetes) and proinflammatory (which may help clear pathogens in sepsis). The molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and noncoding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A through I) have revealed nonlinear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus noncoronary events. Novel HDL markers may also have relevance for heart failure, cancer, and diabetes. HDL function markers (namely, cholesterol efflux capacity) are associated with coronary disease, but they remain research tools. Therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None has proven to be successful, but most have targeted HDL-C, not metrics of HDL function. Future therapeutic strategies should focus on optimizing HDL function in the right patients at the optimal time in their disease course. We provide a framework to help the research and clinical communities, as well as funding agencies and stakeholders, obtain insights into current thinking on these topics, and what we predict will be an exciting future for research and development on HDLs. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Stressing the Endothelium to Assess Localized Inflammatory Potential and the Risk for Atherosclerotic Cardiovascular Disease.
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Rohatgi, Anand
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ENDOTHELIUM , *CARDIOVASCULAR diseases , *ATHEROSCLEROSIS , *LIPOPROTEINS , *CARDIOVASCULAR disease diagnosis , *INFLAMMATION , *HIGH density lipoproteins - Abstract
Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]
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- 2021
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4. HDL and Reverse Cholesterol Transport Biomarkers.
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Riggs, Kayla A. and Rohatgi, Anand
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CHOLESTEROL , *HIGH density lipoproteins , *BIOLOGICAL tags , *CARDIOVASCULAR diseases - Abstract
High-density lipoprotein (HDL) is a protein-lipid nanoparticle that has predominately been characterized by its cholesterol concentration (HDL-C). Recent studies have challenged the presumed inverse association between HDL-C and cardiovascular events, suggesting a more U-shaped association. This has opened new opportunities to evaluate more novel measures of HDL metabolism, such as HDL particle number (HDL-P) and one of HDL's key functions, cholesterol efflux. Both HDL-P and cholesterol efflux are inversely associated with incident cardiovascular events and may perhaps be better targets for intervention. This review includes recent research on the emerging U-shaped association between HDL-C and cardiovascular events, recent observational studies related to HDL-P, and the effects of established and novel interventions on cholesterol efflux. [ABSTRACT FROM AUTHOR]
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- 2019
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5. Is RCT (Reverse Cholesterol Transport) Ready for an RCT (Randomized Controlled Trial)?
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Nambi, Vijay, Rohatgi, Anand, and Bhatt, Deepak L
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- 2018
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6. Applying a Big Data Approach to Biomarker Discovery: Running Before We Walk?
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de Lemos, James A., Rohatgi, Anand, and Ayers, Colby R.
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BIG data , *BIOMARKERS , *IMMUNOASSAY , *CARDIOVASCULAR diseases risk factors , *HEALTH outcome assessment - Abstract
The authors reflect on the application of big data to biomarker discovery, focusing on its importance in cardiovascular medicine. They discuss a study by Gerstein and colleagues, which represents the Outcome Reduction With an Initial Glargine Intervention (ORIGIN) Trial using Luminex multiplex immunoassay platform to screen biomarkers for their potential to predict cardiovascular disease (CVD) events. They highlight the need for standard to define optimal strategies for biomarker discovery.
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- 2015
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7. HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events.
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Rohatgi, Anand, Khera, Amit, Berry, Jarett D., Givens, Edward G., Ayers, Colby R., Wedin, Kyle E., Neeland, Ian J., Yuhanna, Ivan S., Rader, Daniel R., de Lemos, James A., and Shaul, Philip W.
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PHYSIOLOGICAL effects of cholesterol , *ATHEROSCLEROSIS , *CARDIOVASCULAR diseases , *HIGH density lipoproteins , *CLINICAL trials - Abstract
The article presents a study on the epidemiology of cholesterol efflux capacity and its connection to incident atherosclerotic cardiovascular disease outcomes. Topics covered include high-density lipoprotein (HDL) cholesterol concentration, the ability to assess the clinical relevance of reverse cholesterol transport in humans, and the use of the National Death Index to determine vital status for trial participants.
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- 2014
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8. Race-specific associations of myeloperoxidase with atherosclerosis in a population-based sample: The Dallas Heart Study
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Chen, Lu Q., Rohatgi, Anand, Ayers, Colby R., Das, Sandeep R., Khera, Amit, Berry, Jarett D., McGuire, Darren K., and de Lemos, James A.
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PEROXIDASE , *LEUCOCYTES , *AFRICAN Americans , *ATHEROSCLEROSIS , *ATHEROSCLEROTIC plaque , *BIOMARKERS , *INFLAMMATION - Abstract
Abstract: Objective: Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. Methods and results: Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p =0.02), and AWT (beta coefficient 0.04, p =0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (p interaction =0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44). Conclusion: Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease. [Copyright &y& Elsevier]
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- 2011
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9. Clinical applications of advanced lipoprotein testing in diabetes mellitus.
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Moin, Danyaal and Rohatgi, Anand
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LIPOPROTEINS , *DIABETES , *DYSLIPIDEMIA , *METABOLIC syndrome , *CARDIOVASCULAR diseases , *LIPIDS - Abstract
Traditional lipid profiles often fail to fully explain the elevated cardiovascular risk of individuals with diabetes mellitus. Advanced lipoprotein testing offers a novel means to evaluate dyslipidemia and reine risk estimation. Numerous observational studies have demonstrated a characteristic pattern of elevated levels of small, dense LDL particles, out of proportion to traditional lipid levels, in patients with both diabetes mellitus and the metabolic syndrome. Commonly used glucose and lipid-lowering agents have varied effects in patients with diabetes on both LDL and HDL subfractions. The exact role of advanced lipoprotein testing in patients with diabetes mellitus and the metabolic syndrome remains unclear but may offer improved assessment of cardiovascular risk compared with traditional lipid measurements. [ABSTRACT FROM AUTHOR]
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- 2011
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10. The association between peptidoglycan recognition protein-1 and coronary and peripheral atherosclerosis: Observations from the Dallas Heart Study
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Rohatgi, Anand, Ayers, Colby R., Khera, Amit, McGuire, Darren K., Das, Sandeep R., Matulevicius, Susan, Timaran, Carlos H., Rosero, Eric B., and de Lemos, James A.
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PEPTIDOGLYCANS , *ATHEROSCLEROSIS , *NATURAL immunity , *BACTERIAL cell walls , *INFLAMMATION , *TOMOGRAPHY , *MAGNETIC resonance imaging , *PERIPHERAL vascular diseases , *DIAGNOSIS - Abstract
Abstract: Background: Peptidoglycan recognition protein-1 (PGLYRP-1) is part of the innate immune system and binds to peptidoglycan, a component of bacterial cell walls that has been found in human atherosclerotic lesions. Chronic exposure to bacterial antigens may cause or exacerbate the inflammatory response to lipid deposition within arterial walls. We hypothesized that PGLYRP-1 is associated with subclinical atherosclerosis as measured by computed tomography and magnetic resonance imaging. Methods and results: PGLYRP-1 was measured in 3222 subjects in the Dallas Heart Study, a probability-based population sample age 30–65 including 50% African-Americans and 56% women. Coronary artery calcium (CAC) was measured by electron beam computed tomography (n =2467), abdominal aortic wall thickness (AWT) by magnetic resonance imaging (MRI) (n =2270), and abdominal aortic plaque burden (APB) by MRI (n =2256). In univariable analyses, increasing levels of PGLYRP-1 were associated with all major cardiovascular risk factors, with inflammatory markers such as C-reactive protein, and with CAC, AWT, and APB (p <0.0001 for each). In multivariable models adjusted for traditional risk factors, logPGLYRP-1 remained significantly associated with CAC (OR 1.1, 95% CI 1.01–1.3 per S.D.; p =0.04) and AWT (p =0.009) but not APB (p =0.09). Further adjustment for novel biomarkers associated with PGLYRP-1 and atherosclerosis attenuated the association with CAC (p =0.18) but not with AWT (p =0.01) or APB (p =0.037). Conclusion: In this first reported clinical study of PGLYRP-1 in humans, PGLYRP-1 levels were independently associated with atherosclerosis phenotypes that represent different vascular beds and stages of atherosclerosis. [Copyright &y& Elsevier]
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- 2009
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11. Cholesterol Efflux Capacity as a Therapeutic Target: Rationale and Clinical Implications.
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Rohatgi, Anand and Grundy, Scott M.
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- 2015
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12. Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice.
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De Oliveira-Gomes, Diana, Joshi, Parag H., Peterson, Eric D., Rohatgi, Anand, Khera, Amit, and Navar, Ann Marie
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APOLIPOPROTEIN B , *LDL cholesterol , *EVIDENCE gaps , *CARDIOVASCULAR diseases , *APOLIPOPROTEIN E4 - Abstract
Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear lowdensity lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Measurement and Application of Incidentally Detected Coronary Calcium: JACC Review Topic of the Week.
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Parsa, Shyon, Saleh, Adam, Raygor, Viraj, Hoeting, Natalie, Rao, Anjali, Navar, Ann Marie, Rohatgi, Anand, Kay, Fernando, Abbara, Suhny, Khera, Amit, and Joshi, Parag H.
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CORONARY artery calcification , *MEDICAL care , *DEEP learning , *CALCIUM , *CARDIOVASCULAR diseases - Abstract
Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems. [Display omitted] • CAC detected incidentally on NCCT scans is strongly correlated with gated CT Agatston scores and cardiovascular disease outcomes. • Challenges include standardizing quantification of CAC detected by NCCT, validating its prospective power, and avoiding unnecessary downstream testing based solely on the findings. • Interdisciplinary collaboration and integration into health care delivery could improve atherosclerotic risk stratification. [ABSTRACT FROM AUTHOR]
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- 2024
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14. HDL-C and apolipoprotein A-I are independently associated with skeletal muscle mitochondrial function in healthy humans.
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Giacona, John M., Petric, Ursa B., Kositanurit, Weerapat, Wang, Jijia, Saldanha, Suzanne, Young, Benjamin E., Khan, Ghazi, Connelly, Margery A., Smith, Scott A., Rohatgi, Anand, and Vongpatanasin, Wanpen
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APOLIPOPROTEIN A , *SKELETAL muscle , *HDL cholesterol , *CYCLIC adenylic acid , *HIGH density lipoproteins - Abstract
Prior animal and cell studies have demonstrated a direct role of high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-I) in enhancing skeletal muscle mitochondrial function and exercise capacity. However, the relevance of these animal and cell investigations in humans remains unknown. Therefore, a cross-sectional study was conducted in 48 adults (67% female, 8% Black participants, age 39 ± 15.4 yr old) to characterize the associations between HDL measures, ApoA-I, and muscle mitochondrial function. Forearm muscle oxygen recovery time (tau) from postexercise recovery kinetics was used to assess skeletal muscle mitochondrial function. Lipoprotein measures were assessed by nuclear magnetic resonance. HDL efflux capacity was assessed using J774 macrophages, radiolabeled cholesterol, and apolipoprotein B-depleted plasma both with and without added cyclic adenosine monophosphate. In univariate analyses, faster skeletal muscle oxygen recovery time (lower tau) was significantly associated with higher levels of HDL cholesterol (HDL-C), ApoA-I, and larger mean HDL size, but not HDL cholesterol efflux capacity. Slower recovery time (higher tau) was positively associated with body mass index (BMI) and fasting plasma glucose (FPG). In multivariable linear regression analyses, higher levels of HDL-C and ApoA-I, as well as larger HDL size, were independently associated with faster skeletal muscle oxygen recovery times that persisted after adjusting for BMI and FPG (all P < 0.05). In conclusion, higher levels of HDL-C, ApoA-I, and larger mean HDL size were independently associated with enhanced skeletal muscle mitochondrial function in healthy humans. NEW & NOTEWORTHY: Our study provides the first direct evidence supporting the beneficial role of HDL-C and ApoA-I on enhanced skeletal muscle mitochondrial function in healthy young to middle-aged humans without cardiometabolic disease. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Dyslipidemia and cardiovascular disease among childhood cancer survivors: a St. Jude Lifetime Cohort report.
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Goldberg, Jason F, Hyun, Geehong, Ness, Kirsten K, Dixon, Stephanie B, Towbin, Jeffrey A, Rhea, Isaac B, Ehrhardt, Matthew J, Srivastava, Deo Kumar, Mulrooney, Daniel A, Hudson, Melissa M, Robison, Leslie L, Jefferies, John L, Rohatgi, Anand, and Armstrong, Gregory T
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DYSLIPIDEMIA , *CHILDHOOD cancer , *CARDIOVASCULAR diseases , *HDL cholesterol , *CANCER survivors , *JUVENILE diseases - Abstract
Background Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors. Methods Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls. Results Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy. Conclusions Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population. [ABSTRACT FROM AUTHOR]
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- 2024
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16. LIPOPROTEIN(A) AND FAMILY HISTORY OF MYOCARDIAL INFARCTION: INSIGHTS FROM THE DALLAS HEART STUDY.
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Mehta, Anurag, Rohatgi, Anand, Ayers, Colby, Berry, Jarett, Joshi, Parag, and Khera, Amit
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- 2018
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17. HDL cholesterol efflux capacity and cardiovascular events.
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Rohatgi, Anand, de Lemos, James A, and Shaul, Philip W
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- 2015
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18. HDL Cholesterol Efflux Capacity and Cardiovascular Events.
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Rohatgi, Anand, de Lemos, James A., and Shaul, Philip W.
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HIGH density lipoproteins , *CHOLESTEROL , *CARDIOVASCULAR diseases - Abstract
A response from the authors of the article "HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events" in the December 18, 2014 issue is presented.
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- 2015
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19. Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study.
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Gangwar, Anamika, Deodhar, Sneha S., Saldanha, Suzanne, Melander, Olle, Abbasi, Fahim, Pearce, Ryan W., Collier, Timothy S., McPhaul, Michael J., Furtado, Jeremy D., Sacks, Frank M., Merrill, Nathaniel J., McDermott, Jason E., Melchior, John T., and Rohatgi, Anand
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PROTEOMICS , *CHOLESTEROL , *FOAM cells , *COMPLEMENT (Immunology) , *HIGH density lipoproteins , *HEART - Abstract
High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Assessing Clinical Utility of Carotid Intima-Media Thickness on the Basis of Reclassification
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Rohatgi, Anand and Berry, Jarett D.
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- 2010
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21. THE RELATIONSHIP BETWEEN DEPRESSED LEFT VENTRICULAR FUNCTION BY CARDIAC MRI AND TRADITIONAL CARDIOVASCULAR RISK FACTORS IN PATIENTS EXPOSED TO ANTHRACYCLINES
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Koshy, Thomas, Rohatgi, Anand, Orlino, Angela, Andrews, Thomas, and Matulevicius, Susan
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- 2013
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22. THE ASSOCIATION BETWEEN 2011 ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR APPROPRIATE USE CRITERIA FOR TRANSTHORACIC ECHOCARDIOGRAPHY AND CLINICAL IMPACT
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Matulevicius, Susan, Rohatgi, Anand, de Luna, Andres, Price, Angela, Das, Sandeep, and Reimold, Sharon
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- 2012
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23. INTERACTIONS BETWEEN SMOKING, CIRCULATING PULMONARY SURFACTANT PROTEIN-B AND AORTIC ATHEROSCLEROSIS IN THE DALLAS HEART STUDY
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Nguyen, Ann B., Rohatgi, Anand, Garcia, Christine K., Ayers, Colby R., Das, Sandeep, Lakoski, Susan, Berry, Jarett, Khera, Amit, McGuire, Darren K., and de Lemos, James
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- 2011
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24. Associations of an HDL apolipoproteomic index with cardiometabolic risk factors before and after exercise training in the HERITAGE Family Study.
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Miranda Maravi, J. Sebastian, Leszczynski, Eric C., Schwartz, Charles S., Dev, Prasun K., Barber, Jacob L., Reasons, Riley J., Pearce, Ryan W., McPhaul, Michael J., Konrad, Robert J., Robbins, Jeremy M., Gerszten, Robert E., Collier, Timothy S., Bouchard, Claude, Rohatgi, Anand, and Sarzynski, Mark A.
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EXERCISE therapy , *APOLIPOPROTEIN E4 , *EXERCISE physiology , *CORONARY artery disease , *BODY composition , *BONFERRONI correction - Abstract
Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease (CAD) risk. However, the associations between pCAD and markers of cardiometabolic health in healthy adults are not known, nor are the effects of regular exercise on pCAD. A total of 641 physically inactive adults free of cardiovascular disease from the HERITAGE Family Study completed 20 weeks of exercise training. The pCAD index (range 0–100) was calculated using measurements of apolipoproteins A-I, C–I, C-II, C-III, and C-IV from ApoA-I-tagged serum (higher index = higher CAD risk). The associations between pCAD index and cardiometabolic traits at baseline and their training responses were assessed with Spearman correlation and general linear models. A Bonferroni correction of p < 8.9 × 10−04 was used to determine statistical significance. The mean ± SD baseline pCAD index was 29 ± 32, with 106 (16.5 %) participants classified as high CAD risk. At baseline, pCAD index was positively associated with blood pressure, systemic inflammation, and body composition. HDL size, VO 2 max, and HDL-C were negatively associated with pCAD index at baseline. Of those classified as high CAD risk at baseline, 52 (49 %) were reclassified as normal risk after training. Following training, pCAD index changes were inversely correlated (p < 1.4 × 10−04) with changes in HDL-C, HDL size, and LDL size. A higher pCAD index was associated with a worse cardiometabolic profile at baseline but improved with regular exercise. The results from this study highlight the potential role of HDL apolipoproteins as therapeutic targets for lifestyle interventions, particularly in high-risk individuals. [Display omitted] • A higher HDL apolipoproteomic index (pCAD) was associated with a worse cardiometabolic profile at baseline. • Individuals with the highest pCAD had the greatest reductions in pCAD following regular exercise. • HDL apolipoproteins are potential therapeutic targets for lifestyle interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is associated with subclinical and clinical atherosclerotic cardiovascular disease: The Dallas Heart Study.
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Mauricio, Rina, Singh, Kavisha, Sanghavi, Monika, Ayers, Colby R., Rohatgi, Anand, Vongpatanasin, Wanpen, de Lemos, James A., and Khera, Amit
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CORONARY artery calcification , *CARDIOVASCULAR diseases , *BIOMARKERS , *LOGISTIC regression analysis , *TYROSINE - Abstract
Soluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown. Participants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors. sFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02–1.73)], greater abdominal aortic wall thickness (p< 0.01) and aortic plaque area (p< 0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p< 0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14–2.18], p< 0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD. In a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease. [Display omitted] • sFlt-1 is associated with markers of inflammation, endothelial function, and myocardial stress or injury. • In a multiethnic, probability-based population, sFlt-1 is associated with subclinical aortic atherosclerosis. • Elevated levels of sFlt-1 are associated with increased incidence of atherosclerotic cardiovascular disease events in a generally healthy population. [ABSTRACT FROM AUTHOR]
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- 2022
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26. HAPTOGLOBIN COPY NUMBER VARIANTS DO NOT DIMINISH THE EFFECT OF CSL112 (APOA-I [HUMAN]) ON HDL FUNCTION.
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Duvalyan, Angela, Gangwar, Anamika, Kramer, Gerald, Velkoska, Elena, Greene, Brandon, Duffy, Danielle, Gibson, C. Michael, Kingwell, Bronwyn, Haley, Robert, and Rohatgi, Anand
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DNA copy number variations , *HUMAN beings - Published
- 2024
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27. Circulating lymphotoxin β receptor and atherosclerosis: Observations from the Dallas Heart Study
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Owens, Andrew W., Matulevicius, Susan, Rohatgi, Anand, Ayers, Colby R., Das, Sandeep R., Khera, Amit, McGuire, Darren K., and de Lemos, James A.
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ATHEROSCLEROSIS , *TUMOR necrosis factors , *BIOMARKERS , *ATHEROSCLEROTIC plaque , *AORTIC diseases , *LIGANDS (Biochemistry) , *LYMPHOCYTES , *ABDOMEN , *MAGNETIC resonance imaging - Abstract
Abstract: Objective: Lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor superfamily, binds ligands expressed by activated lymphocytes. Interruption of LTβR signaling improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTβR and examined its association with atherosclerosis phenotypes in a population-based sample. Methods and results: Plasma LTβR was measured by ELISA in 3215 subjects enrolled in the Dallas Heart Study. Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) and abdominal MRI measurements of aortic plaque (AP) (n =2252) and aortic wall thickness (AWT) (n =2265). We analyzed associations between LTβR and atherosclerosis using multivariable logistic and linear regression methods. Higher levels of LTβR associated with most traditional cardiovascular risk factors, multiple inflammatory markers, and markers of cardiac injury. Univariable analyses demonstrated significant associations of LTβR with CAC, AP, and AWT (p <0.0001 for each). In multivariable models adjusted for traditional risk factors, the 4th vs. the 1st quartile of LTβR remained associated with prevalent CAC, AP, and increased AWT (all p <0.05). Similar associations were observed when LTβR was modeled as a log-transformed continuous variable. Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis. [ABSTRACT FROM AUTHOR]
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- 2010
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28. Cholesterol efflux capacity and its association with prevalent metabolic syndrome in a multi-ethnic population (Dallas Heart Study).
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Akinmolayemi, Oludamilola, Saldanha, Suzanne, Joshi, Parag H., Deodhar, Sneha, Ayers, Colby R., Neeland, Ian J., and Rohatgi, Anand
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HDL cholesterol , *ETHNICITY , *METABOLIC syndrome , *CHOLESTEROL , *TRIGLYCERIDES , *BLOOD cholesterol , *CARDIOVASCULAR diseases , *CARDIOVASCULAR diseases risk factors - Abstract
Metabolic syndrome (MetS) is characterized by adiposity and atherogenic dyslipidemia consisting of elevated triglyceride and decreased high density lipoprotein cholesterol (HDL-C) levels however, cholesterol concentration alone does not reflect HDL functionality. Cholesterol efflux capacity (CEC) captures a key anti-atherosclerotic function of HDL; studies linking CEC to MetS have yielded inconsistent findings and lacked racial/ethnic diversity. The aim of this study was to evaluate the association between CEC and MetS in a large multi-ethnic population utilizing two different CEC assays interrogating overlapping but distinct reverse cholesterol transport pathways. A cross-sectional study was performed using the Dallas Heart Study cohort and cholesterol efflux was measured with radiolabeled and fluorescent cholesterol assays. The relationship between CEC and MetS was assessed using multivariable regression analyses. A total of 2241 participants were included (mean age was 50 years; 38% men and 53% Blacks). CEC was independently and inversely associated with MetS irrespective of efflux assay (CEC-radiolabeled, adjusted OR 0·71 [95% CI 0·65–0·80]. CEC-fluorescent, adjusted OR 0·85 [95% CI 0·77–0·94]). Both CEC measures were inversely associated with waist circumference and directly associated with HDL-C but not with other MetS components. There was an interaction by sex but not by race such that the inverse associations between CEC and MetS were somewhat attenuated in men (OR 0·86, 95%CI 0·74–1·01). In this large multi-ethnic cohort, impaired CEC is linked to MetS irrespective of efflux assay and race/ethnicity but less so among men. Future studies are needed to assess whether CEC mediates the atherosclerotic cardiovascular disease risk of MetS. [ABSTRACT FROM AUTHOR]
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- 2021
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29. Novel plasma biomarkers of coronary artery calcium incidence or progression: Insights from the prospective multi-ethnic Dallas Heart Study cohort.
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Grinberg, Tzlil, Eisen, Alon, Talmor-Barkan, Yeela, Kornowski, Ran, Hamdan, Ashraf, Witberg, Guy, Ayers, Colby, Joshi, Parag, Rohatgi, Anand, Khera, Amit, de Lemos, James A., and Neeland, Ian J.
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CORONARY artery calcification , *BIOMARKERS , *ATHEROSCLEROTIC plaque , *CELL adhesion , *CD54 antigen , *CORONARY artery disease , *CARDIOVASCULAR diseases , *BLOOD plasma - Abstract
Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation. Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis. A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors. Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression. [Display omitted] • CAC is a strong predictor of atherosclerotic cardiovascular disease. • We aimed to identify novel plasma biomarkers associated with CAC incidence or progression. • Among 31 biomarkers only sICAM-1 was independently associated with CAC evolvement. • Alternate measures of coronary atherogenesis may be needed. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity: A Pooled Cohort Analysis.
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Singh, Kavisha, Chandra, Alvin, Sperry, Thomas, Joshi, Parag H., Khera, Amit, Virani, Salim S., Ballantyne, Christie M., Otvos, James D., Dullaart, Robin P.F., Gruppen, Eke G., Connelly, Margery A., Ayers, Colby R., and Rohatgi, Anand
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HIGH density lipoproteins , *PROPORTIONAL hazards models , *COHORT analysis , *ETHNICITY , *MYOCARDIAL infarction - Abstract
Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C.Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke.Results: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52-0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61-0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35-0.69]; for Blacks, 1.22 [95% CI, 0.76-1.98]; Pinteraction=0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36-0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08-2.83]; Pinteraction<0.0001).Conclusions: Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately. [ABSTRACT FROM AUTHOR]- Published
- 2020
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31. Lipoprotein(a) and Family History Predict Cardiovascular Disease Risk.
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Mehta, Anurag, Virani, Salim S, Ayers, Colby R, Sun, Wensheng, Hoogeveen, Ron C, Rohatgi, Anand, Berry, Jarett D, Joshi, Parag H, Ballantyne, Christie M, and Khera, Amit
- Abstract
Background: Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.Objectives: The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.Methods: Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.Results: Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.Conclusions: Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions. [ABSTRACT FROM AUTHOR]- Published
- 2020
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32. Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension.
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Peng, Jun, Vongpatanasin, Wanpen, Sacharidou, Anastasia, Kifer, Domagoj, Yuhanna, Ivan S., Banerjee, Subhashis, Tanigaki, Keiji, Polasek, Ozren, Chu, Haiyan, Sundgren, Nathan C., Rohatgi, Anand, Chambliss, Ken L., Lauc, Gordan, Mineo, Chieko, and Shaul, Philip W.
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SIALIC acids , *VASCULAR endothelial growth factors , *ENDOTHELIAL growth factors , *NITRIC-oxide synthases , *FC receptors , *ENDOTHELIUM diseases , *INTRA-abdominal hypertension - Abstract
Supplemental Digital Content is available in the text. Background: Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory immunoglobulin G (IgG) receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension. Methods: Involvement of IgG was studied using IgG μ heavy chain–null mice deficient in mature B cells and by IgG transfer. Participation of FcγRIIB was interrogated in mice with global or endothelial cell–specific deletion of the receptor. Obesity was induced by high-fat diet (HFD), and blood pressure (BP) was measured by radiotelemetry or tail cuff. The relative sialylation of the Fc glycan on mouse IgG, which influences IgG activation of Fc receptors, was evaluated by Sambucus nigra lectin blotting. Effects of IgG on endothelial NO synthase were assessed in human aortic endothelial cells. IgG Fc glycan sialylation was interrogated in 3442 human participants by mass spectrometry, and the relationship between sialylation and BP was evaluated. Effects of normalizing IgG sialylation were determined in HFD-fed mice administered the sialic acid precursor N-acetyl-D-mannosamine (ManNAc). Results: Mice deficient in B cells were protected from obesity-induced hypertension. Compared with IgG from control chow–fed mice, IgG from HFD-fed mice was hyposialylated, and it raised BP when transferred to recipients lacking IgG; the hypertensive response was absent if recipients were FcγRIIB-deficient. Neuraminidase-treated IgG lacking the Fc glycan terminal sialic acid also raised BP. In cultured endothelial cells, via FcγRIIB, IgG from HFD-fed mice and neuraminidase-treated IgG inhibited vascular endothelial growth factor activation of endothelial NO synthase by altering endothelial NO synthase phosphorylation. In humans, obesity was associated with lower IgG sialylation, and systolic BP was inversely related to IgG sialylation. Mice deficient in FcγRIIB in endothelium were protected from obesity-induced hypertension. Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-induced hypertension. Conclusions: Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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33. Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension.
- Author
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Peng, Jun, Vongpatanasin, Wanpen, Sacharidou, Anastasia, Kifer, Domagoj, Yuhanna, Ivan S., Banerjee, Subhashis, Tanigaki, Keiji, Polasek, Ozren, Chu, Haiyan, Sundgren, Nathan C., Rohatgi, Anand, Chambliss, Ken L., Lauc, Gordan, Mineo, Chieko, and Shaul, Philip W.
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SIALIC acids , *VASCULAR endothelial growth factors , *ENDOTHELIAL growth factors , *NITRIC-oxide synthases , *FC receptors , *HYPERTENSIVE crisis - Abstract
Background: Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory immunoglobulin G (IgG) receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension.Methods: Involvement of IgG was studied using IgG μ heavy chain-null mice deficient in mature B cells and by IgG transfer. Participation of FcγRIIB was interrogated in mice with global or endothelial cell-specific deletion of the receptor. Obesity was induced by high-fat diet (HFD), and blood pressure (BP) was measured by radiotelemetry or tail cuff. The relative sialylation of the Fc glycan on mouse IgG, which influences IgG activation of Fc receptors, was evaluated by Sambucus nigra lectin blotting. Effects of IgG on endothelial NO synthase were assessed in human aortic endothelial cells. IgG Fc glycan sialylation was interrogated in 3442 human participants by mass spectrometry, and the relationship between sialylation and BP was evaluated. Effects of normalizing IgG sialylation were determined in HFD-fed mice administered the sialic acid precursor N-acetyl-D-mannosamine (ManNAc).Results: Mice deficient in B cells were protected from obesity-induced hypertension. Compared with IgG from control chow-fed mice, IgG from HFD-fed mice was hyposialylated, and it raised BP when transferred to recipients lacking IgG; the hypertensive response was absent if recipients were FcγRIIB-deficient. Neuraminidase-treated IgG lacking the Fc glycan terminal sialic acid also raised BP. In cultured endothelial cells, via FcγRIIB, IgG from HFD-fed mice and neuraminidase-treated IgG inhibited vascular endothelial growth factor activation of endothelial NO synthase by altering endothelial NO synthase phosphorylation. In humans, obesity was associated with lower IgG sialylation, and systolic BP was inversely related to IgG sialylation. Mice deficient in FcγRIIB in endothelium were protected from obesity-induced hypertension. Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-induced hypertension.Conclusions: Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension. [ABSTRACT FROM AUTHOR]- Published
- 2019
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34. Abstract 13109: Phenotyping Fat but Fit: Insights From Cardiac Structure and Adiposity Imaging in the Dallas Heart Study.
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Liu, Grace S, Ayers, Colby R, Rohatgi, Anand, and Neeland, Ian J
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CARDIAC imaging , *DUAL-energy X-ray absorptiometry , *FAT , *CHRONIC kidney failure , *HEART beat - Abstract
Obesity and decreased cardiorespiratory fitness (CRF) are independent risk factors for mortality, but higher CRF may minimize the adverse impacts of obesity. Using deep phenotyping, we explored what blood-based and imaging biomarkers were associated with higher CRF among both non-obese and obese individuals in a large multiethnic epidemiological cohort to better understand the biology of the fat but fit phenotype. We performed a cross-sectional analysis of participants enrolled in the Dallas Heart Study between 2007 to 2009 without cardiovascular disease, HIV, cancer, or end-stage renal disease. A total of 2351 individuals were divided into four groups by obesity status (BMI < or ≥30 kg/m2) and CRF (unfit or fit defined as >25th percentile by age and sex, measured using a submaximal treadmill test). Multivariate logistic regression analyses were used to compare circulating biomarkers of cardiometabolic risk, cardiac structure by cardiac magnetic resonance, and adipose depots by dual-energy X-ray absorptiometry between these groups. There were 1052 non-obese and fit, 227 non-obese and unfit, 716 obese and fit, and 356 obese and unfit persons. After adjustment for sex, race, and BMI, factors that were independently associated with fitness in the obese group (versus obese and unfit group) were lower pulse rate (OR, 0.56; 95% CI 0.44-0.71), higher end-diastolic volume indexed to body-surface-area (OR, 1.37; 95% CI 1.06-1.77), and lower subcutaneous fat indexed to body-surface-area (OR, 0.57; 95% CI 0.34-0.96). Lower pulse rate and subcutaneous fat were also associated with being more fit in the non-obese; but contrary to the obese, no cardiac structural measures were statistically significant. These findings suggest that the fat but fit phenotype is characterized by a lower resting pulse, less subcutaneous fat, and a higher left ventricular end-diastolic volume. Being fit is linked to beneficial physiological and cardiovascular changes, irrespective of BMI. [ABSTRACT FROM AUTHOR]
- Published
- 2018
35. Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease.
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Abdullah, Shuaib M., Defina, Laura F., Leonard, David, Barlow, Carolyn E., Radford, Nina B., Willis, Benjamin L., Rohatgi, Anand, McGuire, Darren K., de Lemos, James A., Grundy, Scott M., Berry, Jarett D., and Khera, Amit
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LOW density lipoproteins , *CHOLESTEROL , *ATHEROSCLEROTIC plaque , *CARDIOVASCULAR diseases risk factors , *CARDIOVASCULAR diseases , *COMPARATIVE studies , *HIGH density lipoproteins , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *TRIGLYCERIDES , *EVALUATION research , *PROPORTIONAL hazards models , *KAPLAN-Meier estimator ,CARDIOVASCULAR disease related mortality - Abstract
Background: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non-high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort.Methods: The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.5%) for 10-year atherosclerotic CVD events at baseline based on Pooled Cohort Risk Assessment Equations. The associations of fasting LDL-C and non-HDL-C with CVD mortality were tested with Cox proportional hazards models.Results: In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of CVD death, with hazard ratios of 1.4 (95% CI, 1.1-1.7), 1.3 (95% CI, 1.1-1.6), 1.9 (95% CI, 1.5-2.4), and 1.7 (95% CI, 1.3-2.3), and mean reductions in years free of CVD death of 1.8, 1.1, 4.3, and 3.9, respectively. After adjustment for atherosclerotic CVD risk factors, LDL-C categories 160 to 189 mg/dL and ≥190 mg/dL remained independently associated with CVD mortality, with hazard ratios of 1.7 (95% CI, 1.4-2.2) and 1.5 (95% CI, 1.2-2.1), respectively. In multivariable-adjusted models using non-HDL-C <130 mg/dL as the reference, non-HDL-C 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios of 1.3 (95% CI, 1.1-1.6), 1.8 (95% CI, 1.4-2.2), and 1.5 (95% CI, 1.2-2.0), respectively. Restricting the cohort to those with 10-year risk <5% did not diminish the associations of LDL-C and non-HDL-C with CVD mortality.Conclusions: In a low 10-year risk cohort with long-term follow-up, LDL-C and non-HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms. [ABSTRACT FROM AUTHOR]- Published
- 2018
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36. Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study.
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Khine, Htet W., Teiber, John F., Haley, Robert W., Khera, Amit, Ayers, Colby R., and Rohatgi, Anand
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MYELOPEROXIDASE , *HIGH density lipoproteins , *DISEASE incidence , *CARDIOVASCULAR diseases , *BLOOD serum analysis - Abstract
Background and aims Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. Methods Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). Conclusions Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period. [ABSTRACT FROM AUTHOR]
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- 2017
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37. Sex-Based Differences in Cardiometabolic Biomarkers.
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Lew, Jeanney, Sanghavi, Monika, Ayers, Colby R., McGuire, Darren K., Omland, Torbjørn, Atzler, Dorothee, Gore, Maria O., Neeland, Ian, Berry, Jarett D., Khera, Amit, Rohatgi, Anand, and de Lemos, James A.
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GENDER differences (Psychology) , *CARDIOVASCULAR diseases risk factors , *BIOMARKERS , *CROSS-sectional method , *REGRESSION analysis , *HIGH density lipoproteins , *CARDIOVASCULAR diseases , *RESEARCH funding , *SEX distribution - Abstract
Background: Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology.Methods: A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study. Associations between sex and 30 distinct biomarkers representative of 6 pathophysiological categories were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, kidney function, insulin resistance, MRI and dual-energy x-ray absorptiometry measures of body composition and fat distribution, and left ventricular mass.Results: After excluding participants with CVD, the study population included 3439 individuals, mean age 43 years, 56% women, and 52% black. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney function. In fully adjusted models, women had higher levels of high-density lipoprotein cholesterol and high-density lipoprotein particle concentration, leptin, d-dimer, homoarginine, and N-terminal pro B-type natriuretic peptide, and lower levels of low-density lipoprotein cholesterol, adiponectin, lipoprotein-associated phospholipase A2 mass and activity, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetrical dimethylarginine, asymmetrical dimethylarginine, high-sensitivity troponin T, and cystatin C.Conclusions: Biomarker profiles differ significantly between women and men in the general population. Sex differences were most apparent for biomarkers of adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress and injury. Future studies are needed to characterize whether pathophysiological processes delineated by these biomarkers contribute to sex-based differences in the development and complications of CVD. [ABSTRACT FROM AUTHOR]- Published
- 2017
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38. Beyond Coronary Calcification, Family History, and C-Reactive Protein: Cholesterol Efflux Capacity and Cardiovascular Risk Prediction.
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Mody, Purav, Joshi, Parag H., Khera, Amit, Ayers, Colby R., and Rohatgi, Anand
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CARDIOVASCULAR diseases risk factors , *CALCIFICATION , *FAMILY history (Medicine) , *C-reactive protein , *CHOLESTEROL , *ATHEROSCLEROSIS , *CHOLESTEROL metabolism , *BIOLOGICAL transport , *CORONARY arteries , *CORONARY disease , *DISEASE susceptibility , *LONGITUDINAL method , *MYOCARDIAL infarction , *MYOCARDIAL revascularization , *RESEARCH funding , *RISK assessment , *STROKE , *CORONARY angiography , *CALCINOSIS - Abstract
Background: Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether it predicts ASCVD beyond validated novel risk markers is unknown.Objectives: This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).Methods: CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).Results: The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval [CI]: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).Conclusions: CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker. [ABSTRACT FROM AUTHOR]- Published
- 2016
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39. Impaired Renal Function on Cholesterol Efflux Capacity, HDL Particle Number, and Cardiovascular Events.
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Chindhy, Shahzad, Joshi, Parag, Khera, Amit, Ayers, Colby R., Hedayati, S. Susan, and Rohatgi, Anand
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KIDNEY function tests , *CHOLESTEROL , *CARDIOVASCULAR system , *KIDNEY diseases , *HIGH density lipoproteins , *CARDIOVASCULAR disease diagnosis , *CARDIOVASCULAR diseases , *CHRONIC kidney failure , *LONGITUDINAL method - Published
- 2018
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40. Relation of Black Race Between High Density Lipoprotein Cholesterol Content, High Density Lipoprotein Particles and Coronary Events (from the Dallas Heart Study).
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Chandra, Alvin, Neeland, Ian J., Das, Sandeep R., Khera, Amit, Turer, Asian T., Ayers, Colby R., McGuire, Darren K., and Rohatgi, Anand
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BLACK race , *HIGH density lipoproteins , *CORONARY disease , *BLOOD cholesterol , *ATHEROSCLEROSIS , *MAGNETIC resonance imaging - Abstract
Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probabilitybased, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94,95% CI 0.78 to 1.13, Pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (Pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
41. High‐Density Lipoprotein is Independently Associated with Muscle Mitochondrial Function in Healthy Humans.
- Author
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Giacona, John M., Petric, Ursa B., Saldanha, Suzanne, Smith, Scott A., Rohatgi, Anand, and Vongpatanasin, Wanpen
- Abstract
R2236 --> 889.3 --> High‐density lipoprotein cholesterol (HDL‐C) is well known to play an important anti‐atherogenic role via reverse cholesterol transport. Increasing number of studies in mice have also suggested a protective role of HDL in preserving muscle mitochondrial function via ApoA1‐induced enhancement of cellular respiration of glucose. However, data in humans are lacking. We therefore hypothesize that HDL levels and/or function are correlated with muscle mitochondrial function in humans. Accordingly, we conducted a cross‐sectional study to determine the relationship between levels and function of HDL and skeletal muscle mitochondrial function in 31 healthy adults without diabetes mellitus or cardiovascular disease. To estimate muscle mitochondrial function, we measured the oxygen recovery time constant (Tau) during supra‐systolic cuff‐occlusions following 2 minutes of rhythmic handgrip exercise at 30% maximal voluntary contraction in the forearm muscle, using near infrared spectroscopy (NIRS). To assess cholesterol efflux capacity (CEC), we used J774 macrophages, radiolabeled cholesterol, and ApoB‐depleted plasma to calculate cholesterol efflux normalized to a pooled sample. Of the 31 subjects, 13 (42%) were female, mean age was 40 +/‐ 16, mean BMI was 23.9 +/‐ 3.4 kg/m^2, and the mean total serum cholesterol was 198.4 +/‐ 43.1 mg/dL. We found a significant inverse correlation between HDL‐C levels and Tau, with a correlation coefficient (r) of ‐0.51 (p < 0.01, Figure. 1a). As expected, a positive correlation is observed between BMI and Tau (r= 0.50, p < 0.01, Figure 1c). In contrast, no significant correlation between fasting triglyceride, plasma glucose, insulin levels or HDL efflux function with Tau were found (all p‐values > 0.05). In conclusion, our study identifies a novel association between circulating HDL levels with muscle mitochondrial function. However, the CEC of our sample was not significantly correlated with Tau, therefore future investigations with larger studies or more measures of HDL function and composition may elucidate these findings. The association of HDL‐C and muscle mitochondrial function may explain increased prevalence of physical inactivity among populations with low HDL‐C, such as those with metabolic syndrome. Additionally, future studies are needed to determine if strategies to improve HDL‐C levels will result in improved muscle mitochondrial function and exercise capacity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
42. CORONARY CALCIUM AND FRAMINGHAM RISK SCORE TRAJECTORIES: INSIGHTS FROM THE DALLAS HEART STUDY.
- Author
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Paixao, Andre, Berry, Jarett, Rohatgi, Anand, de Lemos, James, and Khera, Amit
- Published
- 2014
- Full Text
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43. The Relationship of Body Mass and Fat Distribution With Incident Hypertension: Observations From the Dallas Heart Study.
- Author
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Chandra, Alvin, Neeland, Ian J., Berry, Jarett D., Ayers, Colby R., Rohatgi, Anand, Das, Sandeep R., Khera, Amit, McGuire, Darren K., de Lemos, James A., and Turer, Aslan T.
- Subjects
- *
BODY mass index , *SYSTOLIC blood pressure , *OBESITY , *HYPERTENSION , *ADIPOSE tissues , *MAGNETIC resonance imaging , *MULTIVARIABLE testing - Abstract
Background Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear. Objectives This study sought to determine the relationship between adipose tissue distribution and incident hypertension. Methods Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI). Results Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m 2 ), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase). Conclusions Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
44. ASSOCIATIONS OF VISCERAL AND SUBCUTANEOUS ADIPOSE TISSUE MASS WITH MARKERS OF CARDIOMETABOLIC RISK IN OBESE ADULTS: OBSERVATIONS FROM THE DALLAS HEART STUDY
- Author
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Neeland, Ian, Ayers, Colby R., Rohatgi, Anand, Berry, Jarett, Das, Sandeep, Vega, Gloria L., Khera, Amit, McGuire, Darren, Grundy, Scott, and de Lemos, James
- Published
- 2012
- Full Text
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45. Circulating levels of matrix metalloproteinase-9 and abdominal aortic pathology: From the Dallas Heart Study.
- Author
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Grodin, Justin L, Powell-Wiley, Tiffany M, Ayers, Colby R, Kumar, Darpan S, Rohatgi, Anand, Khera, Amit, McGuire, Darren K, de Lemos, James A, and Das, Sandeep R
- Subjects
- *
METALLOPROTEINASES , *ABDOMINAL aorta , *PATHOLOGY , *AORTIC aneurysm treatment , *MAGNETIC resonance imaging , *DISEASE risk factors - Abstract
Prior reports have associated increased circulating levels of matrix metalloproteinase-9 (MMP-9), an endopeptidase active in the extracellular matrix, with the formation and rupture of aortic aneurysms, raising the possibility that MMP-9 may be a useful diagnostic or therapeutic target for aortic pathology. However, associations between MMP-9 and pathological abdominal aortic phenotypes in the general population have not been reported. In the Dallas Heart Study, a population-based sample of Dallas County residents (n = 2304), we measured MMP-9 and performed magnetic resonance imaging (MRI) of the abdominal aorta, measuring aortic compliance, plaque, wall thickness and luminal diameter. After adjustment for traditional cardiac risk factors and body size, higher MMP-9 quartiles were independently associated with higher aortic wall thickness and larger luminal diameter (p < 0.0001 for each), but not abdominal aortic plaque (p = 0.08), coronary artery calcium (p = 0.20) or the aortic luminal diameter/aortic wall thickness ratio (p = 0.37), supporting the hypothesis that therapies targeting MMP-9 may affect the abdominal aortic wall and modify aortic pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
46. Lifetime risks for cardiovascular disease mortality by cardiorespiratory fitness levels measured at ages 45, 55, and 65 years in men. The Cooper Center Longitudinal Study.
- Author
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Berry JD, Willis B, Gupta S, Barlow CE, Lakoski SG, Khera A, Rohatgi A, de Lemos JA, Haskell W, Lloyd-Jones DM, Berry, Jarett D, Willis, Benjamin, Gupta, Sachin, Barlow, Carolyn E, Lakoski, Susan G, Khera, Amit, Rohatgi, Anand, de Lemos, James A, Haskell, William, and Lloyd-Jones, Donald M
- Abstract
Objectives: The purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).Background: Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.Methods: We followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event.Results: Differences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors.Conclusions: A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
47. Lifetime Risks for Cardiovascular Disease Mortality by Cardiorespiratory Fitness Levels Measured at Ages 45, 55, and 65 Years in Men: The Cooper Center Longitudinal Study
- Author
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Berry, Jarett D., Willis, Benjamin, Gupta, Sachin, Barlow, Carolyn E., Lakoski, Susan G., Khera, Amit, Rohatgi, Anand, de Lemos, James A., Haskell, William, and Lloyd-Jones, Donald M.
- Subjects
- *
CARDIOVASCULAR diseases risk factors , *PHYSICAL fitness , *EXERCISE tests , *MORTALITY , *EPIDEMIOLOGY , *METABOLIC equivalent , *CARDIOPULMONARY system - Abstract
Objectives: The purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD). Background: Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD. Methods: We followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event. Results: Differences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors. Conclusions: A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
48. Association of Troponin T Detected With a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population.
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de Lemos, James A., Drazner, Mark H., Omland, Torbjorn, Ayers, Colby R., Khera, Amit, Rohatgi, Anand, Hashim, Ibrahim, Berry, Jarett D., Das, Sandeep R., Morrow, David A., and McGuire, Darren K.
- Subjects
- *
FIRE assay , *MORTALITY , *PHENOTYPES , *HEALTH outcome assessment ,HEART disease research ,CARDIOVASCULAR disease related mortality - Abstract
The article presents information on a study which investigated the incidence and predictors of detectable cardiac troponin T (cTnT) in the general population using a highly sensitive assay. Likewise, the study identified whether cTnT levels quantified with the new assay relate to pathological cardiac phenotypes and subsequent mortality. The primary outcome measure of the research is explained. It discusses in detail the research findings. The association between detected cTnT and structural heart disease and subsequent risk for all-cause mortality is presented.
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- 2010
- Full Text
- View/download PDF
49. Association Between Peptidoglycan Recognition Protein-1 and Incident Atherosclerotic Cardiovascular Disease Events: The Dallas Heart Study.
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Brownell, Nicholas K., Khera, Amit, de Lemos, James A., Ayers, Colby R., and Rohatgi, Anand
- Subjects
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ATHEROSCLEROTIC plaque , *PEPTIDOGLYCANS , *NATURAL immunity , *VASCULITIS , *DISEASE prevalence , *ATHEROSCLEROSIS , *CARRIER proteins , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *EVALUATION research - Published
- 2016
- Full Text
- View/download PDF
50. USING READILY AVAILABLE CLINICAL INFORMATION TO IDENTIFY INDIVIDUALS WITH HIGH LIPOPROTEIN A LEVELS: THE DALLAS HEART STUDY.
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Ustunkaya, Tuna, Ajufo, Ezimamaka, Ayers, Colby, Mauricio, Rina, Rohatgi, Anand, Joshi, Parag, and Khera, Amit
- Subjects
- *
HEART - Published
- 2021
- Full Text
- View/download PDF
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