494 results on '"Rohatgi, Anand"'
Search Results
152. Assessing Clinical Utility of Carotid Intima-Media Thickness on the Basis of Reclassification
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Rohatgi, Anand, primary and Berry, Jarett D., additional
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- 2010
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153. Separating the Contenders From the Pretenders
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de Lemos, James A., primary and Rohatgi, Anand, additional
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- 2010
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154. Associations of Four Circulating Chemokines with Multiple Atherosclerosis Phenotypes in a Large Population-Based Sample: Results from the Dallas Heart Study
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Castillo, Leticia, primary, Rohatgi, Anand, additional, Ayers, Colby R., additional, Owens, Andrew W., additional, Das, Sandeep R., additional, Khera, Amit, additional, McGuire, Darren K., additional, and de Lemos, James A., additional
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- 2010
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155. Differential Associations Between Soluble Cellular Adhesion Molecules and Atherosclerosis in the Dallas Heart Study
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Rohatgi, Anand, primary, Owens, Andrew W., additional, Khera, Amit, additional, Ayers, Colby R., additional, Banks, Kamakki, additional, Das, Sandeep R., additional, Berry, Jarett D., additional, McGuire, Darren K., additional, and de Lemos, James A., additional
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- 2009
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156. The Report Card on Growth Differentiation Factor 15
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Rohatgi, Anand, primary and de Lemos, James A., additional
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- 2009
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157. The association between peptidoglycan recognition protein-1 and coronary and peripheral atherosclerosis: Observations from the Dallas Heart Study
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Rohatgi, Anand, primary, Ayers, Colby R., additional, Khera, Amit, additional, McGuire, Darren K., additional, Das, Sandeep R., additional, Matulevicius, Susan, additional, Timaran, Carlos H., additional, Rosero, Eric B., additional, and de Lemos, James A., additional
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- 2009
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158. Abstract 4990: Multi-Marker Approach Using Novel Biomarkers Improves Prediction of Subclinical Atherosclerosis: Observations from the Dallas Heart Study
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Rohatgi, Anand, primary, Matulevicius, Susan, additional, Das, Sandeep R, additional, Khera, Amit, additional, McGuire, Darren K, additional, Ayers, Colby R, additional, and de Lemos, James A, additional
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- 2008
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159. Abstract 5544: Lymphotoxin β Receptor is Associated with Atherosclerosis in the Dallas Heart Study
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Owens, Andrew W, primary, Matulevicius, Susan, additional, Rohatgi, Anand, additional, Ayers, Colby R, additional, Das, Sandeep, additional, Khera, Amit, additional, McGuire, Darren K, additional, and De Lemos, James A, additional
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- 2008
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160. Hyperthyroidism-Associated Coronary Vasospasm with Myocardial Infarction and Subsequent Euthyroid Angina
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Patel, Rupa, primary, Peterson, Gail, additional, Rohatgi, Anand, additional, Ghayee, Hans K., additional, Keeley, Ellen C., additional, Auchus, Richard J., additional, and Chang, Alice Y., additional
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- 2008
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161. HDL Cholesterol: Physiology, Pathophysiology, and Management
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Link, Jeffrey J., primary, Rohatgi, Anand, additional, and de Lemos, James A., additional
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- 2007
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162. Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?
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Mani, Preethi and Rohatgi, Anand
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High-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of niacin, AIM-HIGH and HPS2-THRIVE, have shown that despite its effects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverse effects. Studies of other classes of agents such as cholesteryl ester transfer protein (CETP) inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events. While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction. Increasing ApoA-I, the primary apolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C and LDL particle measures. Cholesterol efflux, the mechanism by which macrophages in vessel walls secrete cholesterol outside cells, correlates with both surrogate end points and clinical events. The effects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits. Although the HDL cholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested. [ABSTRACT FROM AUTHOR]
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- 2015
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163. The association of abnormal findings on transthoracic echocardiography with 2011 Appropriate Use Criteria and clinical impact.
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Koshy, Thomas, Rohatgi, Anand, Das, Sandeep, Price, Angela, deLuna, Andres, Reimold, Nicholas, Willett, Kyle, Reimold, Sharon, and Matulevicius, Susan
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Transthoracic echocardiography (TTE) Appropriate Use Criteria (AUC) were developed to promote high-value care. We describe the prevalence of clinically significant abnormal TTE findings overall and in subgroups defined by appropriate and inappropriate AUC, and their association with clinical impact. 548 consecutive TTEs at an academic medical center were retrospectively reviewed for AUC, clinical impact, and TTE abnormalities. TTE reports within 1 year of the index TTE were reviewed to determine if abnormalities were new, unchanged, or resolved. Clinical impact was classified into no change, active change, or continuation of care. 91 % of TTEs were appropriate, 5 % were inappropriate, and 4 % were uncertain by AUC. 46 % of all TTEs and 57 % of first-time TTEs had no significant TTE abnormalities. Appropriate TTEs had a higher prevalence of ≥1 TTE abnormality than inappropriate TTEs (56 vs. 33 %, p = 0.029). Among repeat TTEs, 72 % had ≥1 TTE abnormality, however only 25 % had a new abnormality. The prevalence of a new abnormality was similar between inappropriate and appropriate repeat TTEs (25 vs. 26 %, p = 1.0). The prevalence of ≥1 abnormality was similar between TTEs that resulted in active change and no change in care (70 vs. 64 %, p = 0.06). Although most TTEs were appropriate as defined by AUC, the majority had no significant abnormalities. Although most TTEs were appropriate by AUC, >50 % of all TTEs and 25 % of repeat TTEs had no significant abnormalities. Appropriate TTEs had a higher prevalence of abnormalities, however the prevalence of abnormalities was similar between TTEs that resulted in active change versus no change in care. [ABSTRACT FROM AUTHOR]
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- 2015
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164. Resistin Is an Inflammatory Marker of Atherosclerosis in Humans
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Reilly, Muredach P., primary, Lehrke, Michael, additional, Wolfe, Megan L., additional, Rohatgi, Anand, additional, Lazar, Mitchell A., additional, and Rader, Daniel J., additional
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- 2005
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165. GlycA, hsCRP differentially associated with MI, ischemic stroke: In the Dallas Heart Study and Multi-Ethnic Study of Atherosclerosis
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Riggs, Kayla A., Joshi, Parag H., Khera, Amit, Otvos, James D., Greenland, Philip, Ayers, Colby R., and Rohatgi, Anand
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•GlycA more strongly predicted incident MI.•hsCRP more strongly predicted incident ischemic stroke.•GlycA may detect other inflammatory risk not captured by hsCRP
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- 2022
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166. Abstract 13404: Novel Sized-Based HDL Subspecies Demonstrate Inverse Associations With Incident Vascular Events
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Deets, Austin, Singh, Kavisha, Chandra, Alvin, Joshi, Parag H, Khera, Amit, Virani, Salim S, Ballantyne, Christie M, Otvos, James D, Dullaart, Robin, Gruppen, Eke G, Connelly, Margery A, Ayers, Colby, and Rohatgi, Anand
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Recent studies suggest that total high-density lipoprotein particle concentration (HDL-P) outperforms HDL cholesterol (HDL-C) in predicting atherosclerotic cardiovascular disease (ASCVD). Whether specific size-based HDL subspecies contribute to the atheroprotective effects of HDL-P remains unknown. Our objective was to assess size-based HDL subspecies for association with both incident myocardial infarction (MI) and ischemic stroke in a large, diverse cohort, expecting heterogeneous associations regarding subspecies and vascular endpoints.Participants without prior ASCVD enrolled in the Dallas Heart Study, MESA, ARIC, and PREVEND were included as a single pooled cohort (N=15,371). Seven HDL size-based subspecies were quantified by NMR (LP4 algorithm; H1=smallest; H7=largest). The primary adjudicated outcomes over an average of 8-10 years of follow up were first MI and first ischemic stroke. Cox proportional hazards models included traditional ASCVD risk factors (except HDL-C) and all seven HDL subspecies.As continuous variables, higher H1, H2 and H4 concentrations were associated with lower risk of MI (Panel A), whereas higher H2 and H4 concentrations were associated with lower risk of ischemic stroke (Panel B). The top vs bottom quartiles of H2 and H4 had 27-32% lower incidence of MI (HR Q4 vs. Q1 [95% CI]: H1 0.73 [0.58-0.91]; H2 0.69 [0.54-0.89]; H4 0.68 [0.54-0.86]) and no significant associations with ischemic stroke. Serial adjustment for HDL-C attenuated all associations with ischemic stroke. However, H1 and H4 retained significant inverse associations with MI adjusted for HDL-C (HR/SD [95% CI]: H1 0.88 [0.81-0.94]; H4 0.89 [0.82-0.97]).H1 (small HDL) and H4 (medium HDL), but no large subspecies, demonstrated inverse associations with MI in a large multi-ethnic pooled cohort. Next steps include assessment of interactions by sex and race as well as incremental clinical utility of H1 and H4 compared to both HDL-C and total HDL-P in predicting MI.
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- 2022
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167. High‐Density Lipoprotein is Independently Associated with Muscle Mitochondrial Function in Healthy Humans.
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Giacona, John M., Petric, Ursa B., Saldanha, Suzanne, Smith, Scott A., Rohatgi, Anand, and Vongpatanasin, Wanpen
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- 2022
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168. Soluble ST2 Is Associated with All-Cause and Cardiovascular Mortality in a Population-Based Cohort: The Dallas Heart Study.
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Lu Q. Chen, de Lemos, James A., Das, Sandeep R., Ayers, Colby R., and Rohatgi, Anand
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- 2013
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169. Abstract 498: HDL Containing Specific Proteins Blunts The Association With Cholesterol Efflux Capacity: Observations From The Dallas Heart Study
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Gangwar, Anamika, Saldanha, Suzanne, Deodhar, Sneha, Wu, Elaine, Lee, MinJae, Pahlavani, Mandana, Thenayan, Lydia, Furtado, Jeremy D, Sacks, Frank M, and Rohatgi, Anand
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Cholesterol efflux (CE) is a major athero-protective function of high density lipoproteins (HDL). HDL is a heterogeneous mixture of lipoproteins that contain apoA1, the prime protein of HDL, and may contain one or more of >200 other proteins. These other proteins cluster on subpopulations of HDL particles to form HDL subspecies. It is not entirely clear by simply measuring individual protein abundances what drives HDL function. We aimed to study the differential association of 7 HDL subspecies defined by presence or absence of a functional protein with extreme and persistent cholesterol efflux capacity (CEC). From ~3000 individuals in the multi-ethnic population-based DHS (Dallas Heart Study) cohort, people at the bottom 10% and top 90% of CEC were reassessed after 15 years resulting in 36 participants with extreme persistent high or low CEC for the present study. HDL with and without 7 individual proteins potentially relevant to HDL function were quantified using ELISA. Differences in association with CEC between HDL subspecies that contain or lack a defining protein were examined by heterogeneity test. In the low CEC group, HDL lacking apolipoprotein C3 (apoC3), complement C3, apoE (apolipoprotein E) and PLMG (plasminogen) were each associated positively with CEC while HDL subspecies containing these proteins were not positively associated with CEC. (Pearson correlation coefficient range 0.55369 to 0.66562 vs -0.08432 to -0.25198; p <0.05 for heterogeneity). In the high CEC group, no significant heterogeneity was found in association with CEC between HDL subspecies that contain or lack the same proteins. In people with extreme and persistent low CEC, HDL subspecies containing apoC3, complement C3, apoE and PLMG blunt the overall positive association between HDL and CEC. Our findings suggest that CEC of HDL in individuals with persistent and extreme low CEC is determined by the presence/absence of apoC3, complement C3, apoE and PLMG in HDL subspecies. Future studies involving manipulation of these proteins in HDL to investigate the effect on CE will provide deeper insight into functional speciation of HDL. This knowledge can be further applied to define biomarkers for altered CE in atherosclerotic cardiovascular diseases (ASCVD).
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- 2022
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170. Abstract 427: Extreme Low Cholesterol Efflux Is Linked More Strongly To Worse Anti-oxidative Function Than With Systemic Inflammation
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Pahlavani, Mandana, Saldanha, Suzanne, Deodhar, Sneha, Thenayan, Lydia, Haley, Robert, Wu, Elaine, Gangwar, Anamika, and Rohatgi, Anand
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Reverse cholesterol transport is a main anti-atherosclerotic function of high-density lipoprotein (HDL), and cholesterol efflux capacity (CEC) is a key first step of this function. Inflammation and oxidation are metabolically linked to cholesterol transport but the relationships between these functions have not been well characterized. The objective of this study was to determine if extreme high or low CEC also had differences in inflammation and anti-oxidative functions. We hypothesized that inflammation and anti-oxidative functions of HDL are worse in those with extreme low vs. high CEC. Cholesterol efflux capacity was previously measured in 2,924 participants in the Dallas Heart Study, a multi-ethnic population-based cohort. Those below the 10thand above the 90thpercentile were recruited 15-17 years later, and those with persistent extreme high and low CEC were studied (N=36). Several inflammatory markers such as interleukin-1(IL-1), IL-6, IL-10, tumor necrosis factor α (TNF- α), vascular cell adhesion protein 1(VCAM-1), and serum amyloid A (SAA) were measured using MAGPIX instrument on whole EDTA plasma. The antioxidant levels of paraoxonase-1 (PON1) were measured based on arylesterase activity using ELISA kit on whole citrated plasma. We analyzed data in whole group and stratified by sex, race/ethnicity, and diabetes status. Despite a two-fold difference in CEC, there were no significant differences in inflammatory markers between extreme high vs. low CEC. In those with diabetes, SAA levels were significantly higher in those with low vs. high efflux (P=0.02). High CEC group showed the inverse association with inflammatory marker (IL-1) while direct association with anti-inflammatory marker (IL-10) performing Pearson Correlation Coefficient, R=1, P<0.0001. Activity of PON1 was lower in those with extreme low vs. high CEC, median (IQR) low vs. high: 76.7 (62.2-104.5) vs. 90.1 (82.6-102.0) U/L, (P=0.03). In conclusion, these findings suggest that a key measure of reverse cholesterol transport is more strongly related to anti-Oxidative function than systemic inflammation. Future studies are warranted to determine the complementary information these metabolic markers contribute for cardiovascular risk.
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- 2022
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171. Abstract 400: Cardiometabolic Profile Of Haptoglobin Genotype In A Multi-Ethnic Diabetes Cohort
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Duvalyan, Angela, Gangwar, Anamika, Joshi, Parag H, Khera, Amit, Navar, Ann M, Wu, Elaine, and Rohatgi, Anand
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Background:Haptoglobin has three common genotypes: Hp 1-1, Hp 2-1, and Hp 2-2. The Hp 2-2 genotype, known to have poorer antioxidizing capacity, is associated with worse cardiovascular outcomes in select patients with diabetes. In this study, we explore the association between various cardiometabolic biomarker profiles and the three Hp genotypes in a multiethnic population.Methods:A cross-sectional analysis was performed for all participants with diabetes in the Dallas Heart Study and Multi-Ethnic Study of Atherosclerosis cohorts. Hp genotype was measured in 1,158 participants (399 from DHS and 759 from MESA) using ELISA technique (Savyon Diagnostics, Ltd). Associations between Hp genotype and 26 cardiometabolic circulating and imaging biomarkers were assessed by ANOVA and stratified by ethnicity.Results:The study included 51% women, 44% Black (513 of 1,158: Hp 1-1=45%, Hp 2-1=35%, Hp 2-2=20%), 26% Hispanic (300 of 1,158: Hp 1-1=25%, Hp 2-1=49%, Hp 2-2=26%), 20% White (237 of 1,158: Hp 1-1=16%, Hp 2-1=56%, Hp 2-2=28%), and 9.2% Asian/Pacific Islander/East Indian (107 of 1,158: Hp 1-1=15%, Hp 2-1=36%, Hp 2-2=49%) participants. Significant differences were seen in lipid metabolism as well as atherosclerosis, inflammatory, structural, and endothelial markers with no significant differences seen in imaging biomarkers. In White participants, Hp 1-1 was associated with elevated total cholesterol (p=0.016), LDL-p (p=0.001), and LDL-C (p=0.004). In Asian/Pacific Islander/East Indian participants, Hp 2-2 was associated with elevated systolic blood pressure (p=0.029), BMI (p=0.029), and inflammatory markers such as IL-6 (p=0.018) and D-dimer (p=0.027). In Black participants, Hp 2-2 was associated with elevated ICAM (p=0.048) and BMI (p=0.007). Lastly, in Hispanic participants, no significant associations were seen. In exploratory analysis, when comparing Hp 1-1 and Hp 2-1 with Hp 2-2, there was greater magnitude effect size of certain biomarkers in Black and Asian participants, suggesting potential differential effects by ethnicity.Conclusion:Associations between Hp genotype and various cardiometabolic biomarkers are varied and ethnicity dependent with further studies needed to investigate the underlying physiologic mechanisms.
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- 2022
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172. 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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173. The Relationship of Body Mass and Fat Distribution With Incident Hypertension Observations From the Dallas Heart Study
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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.
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obesity ,hypertension ,visceral fat ,body fat distribution - Abstract
BackgroundObesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear.ObjectivesThis study sought to determine the relationship between adipose tissue distribution and incident hypertension.MethodsNormotensive 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).ResultsAmong 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m2), 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).ConclusionsIncreased 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.
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174. 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
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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.
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exercise testing ,cardiovascular disease ,epidemiology ,cardiovascular diseases ,lifetime risk - Abstract
ObjectivesThe purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).BackgroundHigher 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.MethodsWe 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.ResultsDifferences 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.ConclusionsA 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.
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175. 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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176. 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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177. 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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ABAC1 ,HDL functionality ,CETP ,cholesterol efflux - Full Text
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178. Abstract 14129: Association of Coronary Artery Calcium With Atherosclerotic Cardiovascular Disease versus Bleeding Risk- Implications for Aspirin Use: The Dallas Heart Study
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Ajufo, Ezimamaka, Ayers, Colby R, Vigen, Rebecca, Joshi, Parag H, Rohatgi, Anand, de Lemos, James A, and Khera, Amit
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Introduction:The 2019 Primary Prevention Guideline suggests selective use of low-dose aspirin (ASA) for primary prevention of ASCVD given increased bleeding risk. Higher coronary calcium (CAC) may identify those more likely to benefit from ASA, but whether higher CAC also associates with more bleeding is unclear.Methods:Participants of the Dallas Heart Study, free from ASCVD and not on ASA at baseline were included. Fatal and non-fatal major bleeding events (gastrointestinal, intracranial, major other) were identified from ICD9 and 10 codes. Adjudicated ASCVD events (non-fatal MI, coronary heart disease death, non-fatal and fatal stroke) were identified using ICD codes and phone surveys. Multivariable Cox models were used to assess the independent association of CAC with incident bleeding and ASCVD events.Results:The cohort included 2184 participants (mean age 44y, 57% female, 33% black) with 109 major bleeding events and 123 ASCVD events over a median follow-up of 17 years. Older age, black race, diabetes, smoking, blood pressure, peptic ulcer disease, corticosteroid and antacid use were associated with bleeding. Higher CAC categories (0, 1-100, >100) were associated with both ASCVD and bleeding events (p<0.001 each; Figure). CAC better discriminated ASCVD risk (c-statistic 0.79, 95% CI 0.74 to 0.83) than bleeding risk (c-statistic 0.61, 95% CI 0.55 to 0.66), and CAC ?100 (vs. CAC=0) remained associated with ASCVD [HR, 95%CI 3.98 (2.07-7.64)], but not bleeding [HR-1.24 (0.68-2.27)] after multivariable adjustment . In exploratory analyses applying meta-analysis estimates of the effect of ASA, the absolute 10-year reduction of ASCVD would be 1.7% and absolute increased bleeding 2.2% in those with CAC ?100.Conclusions:Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. Additional studies are warranted to determine if there are CAC thresholds with favorable net benefit of ASA for primary prevention of ASCVD.
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- 2019
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179. Abstract 13076: Impact of Haptoglobin Genotype and Diabetes Status on Anacetrapib-Mediated Increase in Cholesterol Efflux Capacity
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Gulati, Jaskeerat, Metzinger, Mark, Saldanha, Suzanne, El-Ghazali, Ayea, Deodhar, Sneha, Chindah, Aseruchi, Ayers, Colby R, and Rohatgi, Anand
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Introduction:Impaired cholesterol efflux (CEC) from macrophages to apolipoprotein A-I is linked to coronary heart disease (CHD). Haptoglobin (Hp) binds to apolipoprotein A-I, and the Hp copy number variant designated by allele ?2? is linked to CEC and HDL dysfunction in diabetics. However, the direct effect of allele ?2? on CEC remains unknown. Given the effects of anacetrapib (ANA) on increased HDL-C, increased CEC, and reduced CHD, we hypothesized that allele ?2? would blunt the effect of ANA on CEC in diabetic patients.Objective:To determine how Hp CNV status impacts the effect of ANA on CEC in diabetics.Methods:This study included 332 participants with CHD and diabetes randomized to ANA 100mg vs. placebo in the DEFINE trial. BODIPY CEC from J774 macrophages to apo B-depleted plasma was measured at baseline and at 24 weeks. Hp CNV status was determined using a commercially available ELISA assay (Savyon Diagnostics, Ltd., St. Ashdod, Israel).Results:Among the 332 participants with diabetes, 51 had the 1-1, 162 had the 2-1, and 119 had the 2-2 Hp allele (194 Men and 138 Women). In unadjusted analyses, ANA was associated with a significant increase in CEC in those with the ?1? allele (18%; std beta = 0.42; p=0.0026) but not in those with the ?2? allele (11%; std beta = 0.08; p=0.16; p for interaction = 0.02; Figure). These findings remained significant adjusting for baseline risk factors and serial changes in lipids including apo AI and apo B (?1? allele: std beta = 0.55; p=0.05; ?2? allele: std beta = 0.19; p=0.18; p for interaction = 0.08). This effect modification by Hp genotype was consistent in both diabetic men and women but was not present in non-diabetics (p for interaction = 0.36).Conclusion:Among diabetic patients with CHD, the effect of ANA on raising CEC was blunted in those with a Hp CNV linked to dysfunctional HDL. These findings warrant validation and suggest a strategy to identify those most likely to benefit from interventions targeting reverse cholesterol transport.
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- 2019
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180. Abstract 11929: Lipoprotein(a) and Family History of Coronary Heart Disease Are Additive for Predicting Long-Term Cardiovascular Risk: The Atherosclerosis Risk in Communities (ARIC) Study.
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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
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- 2018
181. Abstract 15986: GlycA: A Novel Marker of Inflammation and Potential Link Between Obesity and Cardiovascular Disease.
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Riggs, Kayla A, Rocha, Natalia A, Patel, Kershaw V, Khera, Amit, Ayers, Colby R, Neeland, Ian J, and Rohatgi, Anand
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- 2018
182. Abstract 15297: High-Density Lipoprotein Function Associates With GlycA, a Novel Inflammation Marker, but Does Not Explain the Association Between GlycA and Incident Cardiovascular Events.
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Riggs, Kayla A, Joshi, Parag H, Khera, Amit, Singh, Kavisha, Akinmolayemi, Oludamilola, Ayers, Colby R, and Rohatgi, Anand
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- 2018
183. 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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- 2018
184. 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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185. Proteomic characterization of high-density lipoprotein particles in patients with non-alcoholic fatty liver disease.
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Rao, Prahlad K., Merath, Kate, Drigalenko, Eugene, Jadhav, Avinash Y. L., Komorowski, Richard A., Goldblatt, Matthew I., Rohatgi, Anand, Sarzynski, Mark A., Gawrieh, Samer, and Olivier, Michael
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THERAPEUTICS ,FATTY liver ,HIGH density lipoproteins ,ANTITHROMBIN III ,CARDIOTONIC agents ,PROTEOMICS - Abstract
Background: Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications. Methods: From a cohort of morbidly obese females who were diagnosed with simple steatosis (SS), NASH, or normal liver histology, we selected five matched individuals from each condition for a preliminary pilot HDL proteome analysis. HDL particles were enriched using size-exclusion chromatography, and the proteome of the resulting fraction was analyzed by liquid chromatography tandem mass spectrometry. Differences in the proteomes between the three conditions (normal, SS, NASH) were assessed using label-free quantitative analysis. Gene ontology term analysis was performed to assess the potential impact of proteomic changes on specific functions of HDL particles. Results: Of the 95 proteins identified, 12 proteins showed nominally significant differences between the three conditions. Gene ontology term analysis revealed that severity of the liver pathology may significantly impact the anti-thrombotic functions of HDL particles, as suggested by changes in the abundance of HDL-associated proteins such as antithrombin III and plasminogen. Conclusions: The pilot data from this study suggest that changes in the HDL proteome may impact the functionality of HDL particles in NAFLD and NASH patients. These proteome changes may alter cardio-protective properties of HDL, potentially contributing to the increased cardiovascular disease risk in affected individuals. Further validation of these protein changes by orthogonal approaches is key to confirming the role of alterations in the HDL proteome in NAFLD and NASH. This will help elucidate the mechanistic effects of the altered HDL proteome on cardioprotective properties of HDL particles. [ABSTRACT FROM AUTHOR]
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- 2018
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186. Novel and Emerging Biomarkers with Risk Predictive Utility for Atherosclerotic Cardiovascular Disease.
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Shah, Nimish N. and Rohatgi, Anand
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Purpose of Review: Since the release of the American Heart Association and American College of Cardiology’s 2013 pooled cohort equations and the European Cardiology Society’s 2016 SCORE, numerous studies have better characterized the predictive ability of emerging and novel biomarkers for atherosclerotic cardiovascular disease (ASCVD). Here, we review these emerging ASCVD biomarkers, with a focus on those that have been assessed using risk discrimination and reclassification performance indices in large population studies.Recent Findings: These biomarkers include genetic risk scores (GRS) based on a growing number of risk alleles, inflammatory and thrombotic markers, lipid components and functional measures, protein metabolites, microRNAs, and a variety of subclinical atherosclerosis imaging measures. While most of these markers have demonstrated some degree of association with and predictive utility for ASCVD, only coronary artery calcium (CAC) has demonstrated consistent risk prediction improvement across multiple population and risk profiles.Summary: Although CAC has garnered evidence to merit inclusion in modern risk prediction algorithms, large population studies and high-throughput genetic and protein technologies have shown promise for the risk prediction utility of several emerging biomarkers that may warrant consideration in future multimodality ASCVD risk prediction algorithms. [ABSTRACT FROM AUTHOR]
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- 2018
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187. The association between HDL particle concentration and incident metabolic syndrome in the multi-ethnic Dallas Heart Study.
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Mani, Preethi, Ren, Hao-Yu, Neeland, Ian J., McGuire, Darren K., Ayers, Colby R., Khera, Amit, and Rohatgi, Anand
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Aims Metabolic syndrome (MetS) increases atherosclerotic cardiovascular disease (ASCVD) risk. Low HDL cholesterol (HDL-C) is a diagnostic criterion of MetS and a major ASCVD risk factor. HDL particle concentration (HDL-P) associates with incident ASCVD independent of HDL-C, but its association with incident MetS has not been studied. We hypothesized that HDL-P would be inversely associated with incident metabolic syndrome independent of HDL-C and markers of adiposity and insulin resistance. Materials and methods HDL-P was measured by NMR and visceral fat by MRI in participants of the Dallas Heart Study, a probability-based population sample of adults age 30–65. Participants with prevalent MetS, DM, CVD, and any systemic illlness were excluded. Incident MetS as defined by NCEP ATPIII criteria was determined in all participants after median follow-up period of 7.0 years. Results Among 1120 participants without DM or MetS at baseline (57% women, 45% Black, mean age 43), 22.8% had incident MetS at follow-up. HDL-P and HDL-C were modestly correlated (r = 0.54, p < 0.0001). In models adjusted for traditional risk factors and MetS risk factors including visceral fat, HS-CRP, triglyceride to HDL-C ratio, and HOMA-IR, the lowest quartile of HDL-P was associated with a 2-fold increased risk of incident MetS (OR 2.1, 95%CI 1.4–3.1; p = 0.0003). Conclusions Low HDL-P is independently associated with incident MetS after adjustment for traditional risk factors, lipid parameters, adiposity, inflammation, and markers of insulin resistance. Further studies are warranted to validate these findings and elucidate the mechanisms underpinning this association. [ABSTRACT FROM AUTHOR]
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- 2017
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188. 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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189. 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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190. Abstract 87
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deLuna, Andres, Price, Angela L, Rohatgi, Anand, Das, Sandeep R, Reimold, Sharon C, and Matulevicius, Susan A
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- 2012
191. Abstract 299
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Enriquez, Jonathan R, Lemos, James A de, Farzaneh-Far, Ramin, Rohatgi, Anand, Peng, S. A, Spertus, John A, Holper, Elizabeth M, Roe, Matthew T, and Das, Sandeep R
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- 2012
192. 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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193. 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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194. 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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195. 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 , *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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196. 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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197. 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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198. 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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199. HDL in the 21st Century A Multifunctional Roadmap for Future HDL Research
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Alan T. Remaley, Anand Rohatgi, Marit Westerterp, Arnold von Eckardstein, Kerry-Anne Rye, Center for Liver, Digestive and Metabolic Diseases (CLDM), Translational Immunology Groningen (TRIGR), University of Zurich, and Rohatgi, Anand
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Proteomics ,Apolipoprotein B ,Inflammasomes ,030204 cardiovascular system & hematology ,Bioinformatics ,DISEASE ,chemistry.chemical_compound ,0302 clinical medicine ,2737 Physiology (medical) ,Risk Factors ,540 Chemistry ,ENDOTHELIAL INFLAMMATION ,MACROPHAGES ,10038 Institute of Clinical Chemistry ,0303 health sciences ,INSULIN-RESISTANCE ,biology ,Reverse cholesterol transport ,Cholesterol ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Lipoproteins, HDL ,SERUM PARAOXONASE ,HDL ,CARDIOVASCULAR-RISK ,Inflammation ,610 Medicine & health ,History, 21st Century ,2705 Cardiology and Cardiovascular Medicine ,Article ,Proinflammatory cytokine ,03 medical and health sciences ,Physiology (medical) ,Diabetes mellitus ,Mendelian randomization ,medicine ,Humans ,030304 developmental biology ,APOLIPOPROTEIN-A-I ,business.industry ,CHOLESTEROL EFFLUX CAPACITY ,Research ,nutritional and metabolic diseases ,biomarkers ,medicine.disease ,PARTICLE-SIZE ,lipoproteins ,Oxidative Stress ,chemistry ,inflammation ,biology.protein ,atherosclerosis ,business ,HIGH-DENSITY-LIPOPROTEIN ,Lipoprotein - 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 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 even further. 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 anti-diabetic properties. HDLs can be anti-inflammatory, which may protect against atherosclerosis and diabetes, as well as pro-inflammatory, which may help clear pathogens in sepsis. In addition, the molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and non-coding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A-I) have revealed non-linear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus non-coronary 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 remain research tools thus far. Ultimately, therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None thus far have 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 here 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.
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- 2021
200. 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]
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- 2015
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