Association of Lipoprotein-Associated Phospholipase A2 Mass and Activity with Coronary and Aortic Atherosclerosis: Findings from the Dallas Heart Study

Abstract Background: Our aim was to characterize the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with coronary and aortic atherosclerosis in a large population-based study. Methods: Lp-PLA2 mass and activity were measured in 2171 subjects 30–65 years old participating in the Dallas Heart Study. We examined the association of Lp-PLA2 levels with 3 atherosclerosis phenotypes: coronary artery calcium (CAC) measured by electron-beam computed tomography and abdominal aortic plaque (AAP) and aortic wall thickness (AWT) measured by magnetic resonance imaging. Results: CAC and AAP were detected in 21% and 40% of subjects, respectively, and mean AWT (SD) was 1.70 (0.32) mm. In univariable analyses, Lp-PLA2 mass (but not activity) was higher in both men (P = 0.04) and women (P = 0.02) with detectable CAC. Lp-PLA2 mass and activity were higher (P = 0.004 and P = 0.01, respectively) and AWT was greater (P < 0.001 and P = 0.02, respectively) in women with aortic atheroma, but not in men. After adjustment for traditional atherosclerosis risk factors and C-reactive protein concentrations, Lp-PLA2 mass and activity were not associated with AAP or AWT in either sex, but Lp-PLA2 mass remained modestly associated with detectable CAC only in men (odds ratio 1.20 per 1 standard deviation increase, 95% CI 1.01–1.42, P = 0.04). Conclusions: Although Lp-PLA2 mass was independently associated with CAC in men, it was not associated with AAP or AWT in men or with any of the atherosclerosis phenotypes in women. These findings suggest that if Lp-PLA2 independently influences clinical events, it does so by promoting atherosclerotic plaque instability rather than by stimulating atherogenesis.

Download Full-text

Associations of Four Circulating Chemokines with Multiple Atherosclerosis Phenotypes in a Large Population-Based Sample: Results from the Dallas Heart Study

Journal of Interferon & Cytokine Research ◽

10.1089/jir.2009.0045 ◽

2010 ◽

Vol 30 (5) ◽

pp. 339-347 ◽

Cited By ~ 22

Author(s):

Leticia Castillo ◽

Anand Rohatgi ◽

Colby R. Ayers ◽

Andrew W. Owens ◽

Sandeep R. Das ◽

...

Keyword(s):

Large Population ◽

Population Based ◽

Heart Study ◽

Dallas Heart Study

Download Full-text

Abdominal Aortic Atherosclerosis at MR Imaging Is Associated with Cardiovascular Events: The Dallas Heart Study

Radiology ◽

10.1148/radiol.13122707 ◽

2013 ◽

Vol 269 (1) ◽

pp. 84-91 ◽

Cited By ~ 28

Author(s):

Christopher D. Maroules ◽

Eric Rosero ◽

Colby Ayers ◽

Ronald M. Peshock ◽

Amit Khera

Keyword(s):

Mr Imaging ◽

Cardiovascular Events ◽

Aortic Atherosclerosis ◽

Abdominal Aortic ◽

Heart Study ◽

Dallas Heart Study

Download Full-text

INTERACTIONS BETWEEN SMOKING, CIRCULATING PULMONARY SURFACTANT PROTEIN-B AND AORTIC ATHEROSCLEROSIS IN THE DALLAS HEART STUDY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(11)61463-0 ◽

2011 ◽

Vol 57 (14) ◽

pp. E1463

Author(s):

Ann B. Nguyen ◽

Anand Rohatgi ◽

Christine K. Garcia ◽

Colby R. Ayers ◽

Sandeep Das ◽

...

Keyword(s):

Pulmonary Surfactant ◽

Surfactant Protein ◽

Aortic Atherosclerosis ◽

Surfactant Protein B ◽

Heart Study ◽

Dallas Heart Study ◽

Pulmonary Surfactant Protein B ◽

Pulmonary Surfactant Protein ◽

Protein B

Download Full-text

Abstract 171: CRP, IL-18, and BNP are Associated with Regional Brain Atrophy: Results from the Dallas Heart Study

Stroke ◽

10.1161/str.44.suppl_1.a171 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Richard T Lucarelli ◽

Amit Khera ◽

Ronald M Peshock ◽

Roderick McColl ◽

Colby Ayers ◽

...

Keyword(s):

Brain Atrophy ◽

Linear Regression Analysis ◽

Brain Regions ◽

Population Based ◽

Multivariate Linear Regression Analysis ◽

Brain Images ◽

Brain Volumes ◽

Heart Study ◽

Total Brain ◽

Dallas Heart Study

Purpose: Multiple biomarkers have been associated with total brain atrophy. However, little is known about their relationship to segmental atrophy in a large, multi-ethnic, population-based sample. Materials and Methods: 3D-MPRAGE brain images obtained at 3T from 2082 participants of the Dallas Heart Study (DHS) 2 were analyzed with Freesurfer and outlier analysis was performed. Divisive eigenvalue clustering of 89 brain segments yielded 24 groups with linked atrophy patterns. Plasma C-reactive protein (CRP), IL-18, homocsysteine and B-type natriuretic peptide (BNP) obtained 7 years prior during DHS 1 were available for 1343, 840, 1333 and 1331 participants, respectively. Multivariate linear regression analysis with adjustments for age, ethnicity, and gender were used to demonstrate associations between biomarkers and atrophy clusters. Results: Nine atrophy clusters were associated with CRP, three atrophy clusters were associated with IL-18, and six atrophy clusters were associated with BNP (Table 1). Homocysteine did not have any significant correlations. Conclusions: The markers studied had associations with distinct patterns of segmental atrophy indicating they may have unique interactions in different brain regions. This suggests that distinct inflammatory and other pathways may be at work in specific regions of the brain and that their localized effects may be obscured by approaches evaluating solely total brain volumes. Table 1:

Download Full-text

Soluble ST2 Is Associated with All-Cause and Cardiovascular Mortality in a Population-Based Cohort: The Dallas Heart Study

Clinical Chemistry ◽

10.1373/clinchem.2012.191106 ◽

2013 ◽

Vol 59 (3) ◽

pp. 536-546 ◽

Cited By ~ 42

Author(s):

Lu Q Chen ◽

James A de Lemos ◽

Sandeep R Das ◽

Colby R Ayers ◽

Anand Rohatgi

Keyword(s):

Risk Factors ◽

African Americans ◽

Cardiovascular Mortality ◽

Population Based ◽

Low Risk ◽

Cardiac Events ◽

Risk Population ◽

Soluble St2 ◽

Heart Study ◽

Dallas Heart Study

BACKGROUND ST2, part of the interleukin-1 receptor family, is released from cardiac myocytes under mechanical strain. Soluble ST2 (sST2) concentrations are associated with adverse cardiac events in high-risk cohorts. We evaluated the association of sST2 with all-cause and cardiovascular mortality in a large, low-risk population–based cohort. METHODS Plasma sST2 was measured in 3294 subjects from the Dallas Heart Study, a probability-based population cohort. We categorized participants into undetectable (reference group) or quartiles of detectable sST2 concentrations. Associations with all-cause and cardiovascular mortality were assessed over a median 8.3 years of follow-up. RESULTS sST2 concentrations were not significantly associated with most traditional risk factors, prevalent subclinical cardiovascular disease, or nonfatal cardiac events. However, a higher proportion of African Americans had detectable concentrations of sST2 than non–African Americans (44% vs 21%, respectively, P < 0.0001). In addition, sST2 concentrations were significantly associated with markers of inflammation. Increased sST2 was associated with increased all-cause mortality (Ptrend ≤ 0.0001) and cardiovascular mortality (Ptrend = 0.0004). In fully adjusted models, those in the highest quartile of detectable sST2 were at increased risk for all-cause death compared to those with undetectable sST2 concentrations (adjusted hazard ratio 2.1, 95% CI 1.4–3.2, P = 0.0009). CONCLUSIONS In a low-risk population, sST2 does not associate with traditional cardiovascular risk factors or nonfatal cardiovascular events but is higher in African Americans and is associated with increased all-cause and cardiovascular mortality. Further investigation is needed regarding the role of sST2 in risk prediction, particularly among African Americans.

Download Full-text

Influence of race and sex on lipoprotein-associated phospholipase A2 levels: Observations from the Dallas Heart Study

Atherosclerosis ◽

10.1016/j.atherosclerosis.2007.10.010 ◽

2008 ◽

Vol 199 (1) ◽

pp. 110-115 ◽

Cited By ~ 38

Author(s):

Emmanouil S. Brilakis ◽

Amit Khera ◽

Darren K. McGuire ◽

Raphael See ◽

Subhash Banerjee ◽

...

Keyword(s):

Phospholipase A2 ◽

Heart Study ◽

Dallas Heart Study

Download Full-text

Association of adiponectin in patatin-like phospholipase domain-containing 3 (PNPLA3) associated hepatic steatosis.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.184 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 184-184

Author(s):

Muhammad Shaalan Beg ◽

Amit G. Singal ◽

Colby Ayers ◽

Sadia Saleem ◽

Jorge A. Marrero ◽

...

Keyword(s):

Risk Factors ◽

Hepatic Steatosis ◽

Hepatocellular Cancer ◽

Population Based ◽

Linear Regression Models ◽

Nonalcoholic Fatty Liver ◽

Heart Study ◽

Qualitative Effect ◽

Dallas Heart Study ◽

The Impact

184 Background: The I148M polymorphism (rs738409) of the patatin-like phospholipase domain-containing 3 (PNPLA3) gene is strongly associated with hepatic triglyceride content (HTGC) and the development of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), which are themselves risk factors for hepatocellular cancer (HCC). Serum adiponectin affects insulin resistance and carcinogenesis and has also been associated with HTGC. Whether these risk factors are additive in predisposing to HTGC is unknown. We evaluated the impact of adiponectin and PNPLA3 genotypes on HTGC in a large community cohort. Methods: The Dallas Heart Study (DHS) is a multi-ethnic population based study of Dallas County residents. HTGC was quantified using H-MR spectroscopy. Univariate and multivariable logistic and linear regression models were generated to test the association between HTGC and log adiponectin stratified by PNPLA3 genotype (CC, CG and GG). Models were adjusted for age, gender, race, hypertension, diabetes, HOMA-IR and BMI. Results: There were 2,259 patients who had complete clinical, biochemical, imaging, and genotyping data and were included in this analysis. Median age was 44 and 47% were male. Race distribution was 48% Black, 32% White, and 18% Hispanic. The prevalences of PNPLA3 genotypes were 61% CC (wild type), 32% GC and 7% GG. The median concentration of adiponectin was 6.6 ug/ml. Adiponectin was an independent predictor HTCG across all genotypes after adjusting for covariates (CC b=-0.34, GC b=-0.42, GG b=-0.38, p<0.005 for each). HTGC decreased across gender and race-stratified quartiles of adiponectin for each PNPLA3 genotype, and the qualitative effect was greatest in the I148M homozygotes (table). Conclusions: Adiponectin is independently associated with hepatic steatosis across all three PNPLA3 genotypes. The combination of at-risk PNPLA3 genotypes and hypoadiponectemia is associated with a high risk of hepatic steatosis. Future studies will need to address downstream HCC risk and whether manipulation of adiponectin level may be of clinical benefit. [Table: see text]

Download Full-text