80 results on '"Anuurad E"'
Search Results
2. Ethnic differences in the formation of small LDL particles in Asians: a comparison of Koreans, Japanese and Mongolians
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Anuurad, E., Shiwaku, K., Enkhmaa, B., Nogi, A., Kitajima, K., Yamasaki, M., and Yamane, Y.
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- 2004
3. Overweight Japanese with body mass indexes of 23.0-24.9 have higher risks for obesity-associated disorders: a comparison of Japanese and Mongolians
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Shiwaku, K, Anuurad, E, Enkhmaa, B, Nogi, A, Kitajima, K, Shimono, K, Yamane, Y, and Oyunsuren, T
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- 2004
4. Difficulty in losing weight by behavioral intervention for women with Trp64Arg polymorphism of the β3-adrenergic receptor gene
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Shiwaku, K, Nogi, A, Anuurad, E, Kitajima, K, Enkhmaa, B, Shimono, K, and Yamane, Y
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- 2003
5. Overweight Japanese with body mass indexes of 23.0–24.9 have higher risks for obesity-associated disorders: a comparison of Japanese and Mongolians
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Shiwaku, K, primary, Anuurad, E, additional, Enkhmaa, B, additional, Nogi, A, additional, Kitajima, K, additional, Shimono, K, additional, Yamane, Y, additional, and Oyunsuren, T, additional
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- 2003
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6. 2P-0408 Development and evaluation of interventional program for metabolic syndrome based on health education and self-determination
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Nogi, A., primary, Shiwaku, K., additional, Kitajima, K., additional, Shimono, K., additional, Anuurad, E., additional, Enkhmaa, B., additional, and Yamane, Y., additional
- Published
- 2003
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7. 3P-0820 Ethnical differences in the prevalence of small low-density lipoprotein particles; A comparison of Japanese and Mongolians
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Anuurad, E., primary, Shiwaku, K., additional, Enkhmaa, B., additional, Nogi, A., additional, Kitajima, K., additional, Shimono, K., additional, Oyunsuren, T., additional, and Yamane, Y., additional
- Published
- 2003
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8. 2P-0406 Difficulty in losing weight and improving metabolic parameters by behavioral intervention for women with Trp64 Arg polymorphism of the β3-adrenergic receptor gene
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Shiwaku, K., primary, Nogi, A., additional, Anuurad, E., additional, Kitajima, K., additional, Enkhmaa, B., additional, Shimono, K., additional, and Yamane, Y., additional
- Published
- 2003
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9. HIV protease inhibitors and obesity.
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Anuurad E, Bremer A, Berglund L, Anuurad, Erdembileg, Bremer, Andrew, and Berglund, Lars
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- 2010
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10. Difficulty in losing weight by behavioral intervention for women with Trp64Arg polymorphism of the β3-adrenergic receptor gene.
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Shiwaku, K, Nogi, A, Anuurad, E, Kitajima, K, Enkhmaa, B, Shimono, K, and Yamane, Y
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- 2003
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11. Role of lipoprotein(a) in cardiovascular disease current and future perspectives.
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Berglund L, Anuurad E, Berglund, Lars, and Anuurad, Erdembileg
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- 2008
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12. Attenuated age-impact on systemic inflammatory markers in the presence of a metabolic burden.
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Anuurad Erdembileg, Annie Mirsoian, Byambaa Enkhmaa, Wei Zhang, Laurel A Beckett, William J Murphy, and Lars F Berglund
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Medicine ,Science - Abstract
The overall burden of chronic disease, inflammation and cardiovascular risk increases with age. Whether the relationship between age and inflammation is impacted by presence of an adverse metabolic burden is not known.We determined inflammatory markers in humans (336 Caucasians and 224 African Americans) and in mice, representing a spectrum of age, weight and metabolic burden.In humans, levels of inflammatory markers increased significantly with age in subjects without the metabolic syndrome, (P=0.009 and P=0.037 for C-reactive protein, P
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- 2015
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13. Appropriate BMI for Asian populations.
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Shiwaku K, Anuurad E, Enkhmaa B, Kitajima K, and Yamane Y
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- 2004
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14. Lp(a)-Associated Oxidized Phospholipids in Healthy Black and White Participants in Relation to apo(a) Size, Age, and Family Structure.
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Berglund L, Kim K, Zhang W, Prakash N, Truax K, Anuurad E, and Enkhmaa B
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- Adolescent, Adult, Aged, Apoprotein(a) genetics, Child, Humans, Middle Aged, Oxidation-Reduction, Young Adult, Black People genetics, Lipoprotein(a) genetics, Phospholipids, White People genetics
- Abstract
Background Lp(a) (lipoprotein(a)) is the major lipoprotein carrier of oxidized phospholipids (OxPL) and this function mediates Lp(a) atherogenicity. However, the relationship between OxPL, Lp(a), and genetic and biological characteristics remains poorly understood. We assessed the relationship between Lp(a)-bound OxPL, apolipoprotein(a) (apo(a)) size, age, and family structure in 2 racial groups. Methods and Results Healthy Black and White families were recruited from the general population (age: 6-74 years, n=267). OxPL and Lp(a) levels were assayed enzymatically; apo(a) isoform, LPA allele sizes, and allele-specific Lp(a) levels were determined. Lp(a)-OxPL levels did not differ significantly by racial and age groups. Lp(a)-OxPL levels were associated with total plasma Lp(a) in all participants and in race-specific analyses. Further, OxPL levels were significantly associated with allele-specific Lp(a) levels carried by the smaller apo(a) size in all participants (β=0.33, P =0.0003) as well as separately for Black (β=0.50, P =0.0032) and White (β=0.26, P =0.0181) participants. A significant association of OxPL with allele-specific Lp(a) levels for larger apo(a) sizes was seen only in Black participants (β=0.53, P =0.0076). In this group, Lp(a)-OxPL levels were also heritable (h
2 =0.29, P =0.0235), resulting in a significant interracial difference in heritability between Black and White people ( P =0.0352). Conclusions Lp(a)-OxPL levels were associated with allele-specific Lp(a) level carried on smaller apo(a) sizes and among Black participants also for larger apo(a) sizes. The heritability estimates for Lp(a)-bound OxPL differed by race.- Published
- 2021
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15. Building an institutional K awardee program at UC Davis through utilization of CTSA resources.
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Guo BP, Rainwater J, Neves S, Anuurad E, Wun T, and Berglund L
- Abstract
NIH offers multiple mentored career development award mechanisms. By building on the UC Davis Clinical and Translational Science Center (CTSC) from its initial NIH funding in 2006, we created an institution-wide K scholar resource. We investigated subsequent NIH funding for K scholars and to what extent CTSC research resources were used. Using NIH RePORTER, we created a database of UC Davis investigators who obtained K01, K08, K23, K25, or K99, as well as institutional KL2 or K12 awards and tracked CTSC research resource use and subsequent funding success. Overall, 94 scholars completed K training between 2007 and 2020, of which 70 participated in one of four institutional, NIH-funded K programs. An additional 103 scholars completed a mentored clinical research training program. Of 94 K awardees, 61 (65%) later achieved NIH funding, with the majority receiving a subsequent individual K award. A higher proportion (73%) of funded scholars used CTSC resources compared to unfunded (48%). Biostatistics and Biomedical Informatics were most commonly used and 55% of scholars used one or more CTSC resource. We conclude that institutional commitment to create a K scholar platform and use of CTSC research resources is associated with high NIH funding rates for early career investigators., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2021.)
- Published
- 2021
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16. PCSK9 in African Americans and Caucasians in Relation to Lp(a) Level, Apo(a) Size and Heritability.
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Enkhmaa B, Kim K, Zhang W, Prakash N, Truax K, Anuurad E, and Berglund L
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Context: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces lipoprotein(a) [Lp(a)] levels, but the association of PCSK9 with Lp(a) level and its major determinant, apolipoprotein(a) [apo(a)] size, is not fully understood., Objective: To assess the relationship between PCSK9, Lp(a) level, apo(a) size, age, and ethnicity/race., Design: Cross-sectional., Setting: General population., Participants: Healthy African Americans and Caucasians (n = 267); age range: 6 to 74 years., Interventions: None., Main Outcome Measures: PCSK9 levels, apo(a) isoform and LPA allele sizes, and isoform-specific Lp(a) levels., Results: Plasma PCSK9 levels were significantly higher in African Americans vs Caucasians, in females vs males, and in adults vs children. PCSK9 levels were not associated with total plasma Lp(a) levels either in all participants or in ethnicity-specific analyses. However, PCSK9 levels were significantly positively associated with isoform-specific Lp(a) levels carried by the larger apo(a) size in all participants ( r = 0.139, P = 0.0361). In ethnicity/race analyses, a significant association was seen for African Americans ( r = 0.268, P = 0.0199), but not for Caucasians. In contrast, there were no significant associations of PCSK9 with isoform-specific Lp(a) levels for the smaller apo(a) sizes in all participants nor in ethnic-specific analyses. Furthermore, heritability (h
2 ) analyses revealed a significant heritability for PCSK9 level in both ethnic groups, with a higher estimate in Caucasians than in African Americans (47% vs 22%, respectively)., Conclusions: Among African Americans, but not Caucasians, PCSK9 levels were associated with isoform-specific Lp(a) levels carried on larger, but not smaller, apo(a) sizes. The findings illustrate a diverging relationship of PCSK9 with isoform-specific Lp(a) levels across ethnicity., (© Endocrine Society 2020.)- Published
- 2020
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17. Heritability of apolipoprotein (a) traits in two-generational African-American and Caucasian families.
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Enkhmaa B, Anuurad E, Zhang W, Kim K, and Berglund L
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- Adolescent, Adult, Black or African American, Aged, Alleles, Child, Female, Genetic Variation genetics, Humans, Inheritance Patterns, Male, Middle Aged, White People, Young Adult, Apoprotein(a) genetics
- Abstract
Heritability of LPA allele, apo(a) isoform sizes, and isoform-associated lipoprotein(a) [Lp(a)] levels was studied in 82 Caucasian and African-American families with two parents and two children (age: 6-74 years). We determined: 1 ) Lp(a) levels; 2 ) LPA allele sizes; 3 ) apo(a) isoform sizes; and 4 ) isoform-specific apo(a) levels (ISLs), the amount of Lp(a) carried by an individual apo(a) isoform. Trait heritability was estimated by mid-parent-offspring analysis. The ethnicity-adjusted heritability estimate for Lp(a) level was 0.95. Heritability for ISLs corresponding to the smaller LPA allele in a given allele-pair was higher than that corresponding to the larger LPA allele (0.91 vs. 0.59, P = 0.017). Although not statistically different, heritability for both apo(a) isoforms (0.90 vs. 0.70) and LPA alleles (0.98 vs. 0.82) was higher for the smaller versus larger sizes. Heritability was generally lower in African-Americans versus Caucasians with a 4-fold difference for the larger LPA allele (0.25 vs. 0.94, P = 0.001). In Caucasians, an overall higher heritability pattern was noted for the older (≥47 years) versus younger (<47 years) families. In conclusion, Lp(a) level and traits associated with the smaller LPA alleles were strongly determined by genetics, although with a varying ethnic influence. Ethnic differences in heritability of the larger LPA allele warrant further investigations., (Copyright © 2019 Enkhmaa et al.)
- Published
- 2019
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18. Effect of antiretroviral therapy on allele-associated Lp(a) level in women with HIV in the Women's Interagency HIV Study.
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Enkhmaa B, Anuurad E, Zhang W, Li CS, Kaplan R, Lazar J, Merenstein D, Karim R, Aouizerat B, Cohen M, Butler K, Pahwa S, Ofotokun I, Adimora AA, Golub E, and Berglund L
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- Adult, Anti-HIV Agents therapeutic use, Apoprotein(a) blood, Cohort Studies, Female, HIV Seropositivity complications, HIV Seropositivity genetics, Hepatitis C complications, Humans, Phenotype, Risk, Treatment Outcome, Alleles, Anti-HIV Agents pharmacology, HIV Seropositivity blood, HIV Seropositivity drug therapy, Lipoprotein(a) blood
- Abstract
We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women. ART effects were tested by a mixed-effects model across pre-ART and post-ART first and third visits. Data from 120 HIV-seronegative women were used. The mean age was 38 years; most were African-American (∼70%). Pre-ART ASLs associated with the larger (4.6 mg/dl vs. 8.0 mg/dl, P = 0.024) or smaller (13 mg/dl vs. 19 mg/dl, P = 0.041) apo(a) sizes were lower in the HIV-seropositive versus HIV-seronegative group, as was the prevalence of a high Lp(a) level ( P = 0.013). Post-ART ASL and prevalence of high Lp(a) or apo(a) sizes and frequency of small size apo(a) (22 kringles) did not differ between the two groups. ART increased Lp(a) level (from 18 to 24 mg/dl, P < 0.0001) and both ASLs ( P < 0.001). In conclusion, regardless of genetic control, Lp(a) can be modulated by HIV and its treatment. ART initiation abrogates HIV-induced suppression of Lp(a) levels and ASLs, contributing to promote CVD risk in HIV-seropositive individuals., (Copyright © 2018 Enkhmaa et al.)
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- 2018
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19. The roles of apo(a) size, phenotype, and dominance pattern in PCSK9-inhibition-induced reduction in Lp(a) with alirocumab.
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Enkhmaa B, Anuurad E, Zhang W, Yue K, Li CS, and Berglund L
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- Antibodies, Monoclonal, Humanized, Gene Expression Regulation drug effects, Humans, Protein Isoforms chemistry, Protein Isoforms metabolism, Antibodies, Monoclonal pharmacology, Apoprotein(a) chemistry, Apoprotein(a) metabolism, PCSK9 Inhibitors, Phenotype, Protease Inhibitors pharmacology
- Abstract
An elevated level of lipoprotein (a) [Lp(a)] is a risk factor for CVD. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a) reduction with apo(a) size polymorphism, phenotype, and dominance pattern and LDL cholesterol (LDL-C) reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from two clinical trials. Alirocumab significantly reduced total Lp(a) (pooled median: -21%, P = 0.0001) and allele-specific apo(a), an Lp(a) level carried by the smaller (median: -18%, P = 0.002) or the larger (median: -37%, P = 0.0005) apo(a) isoform, at week 8 versus baseline. The percent reduction in Lp(a) level with alirocumab was similar across apo(a) phenotypes (single vs. double bands) and carriers and noncarriers of a small size apo(a) (≤22 kringles). The percent reduction in LDL-C correlated significantly with the percent reduction in Lp(a) level ( r = 0.407, P < 0.0001) and allele-specific apo(a) level associated with the smaller ( r = 0.390, P < 0.0001) or larger ( r = 0.270, P = 0.0183) apo(a) sizes. In conclusion, alirocumab-induced Lp(a) reduction was independent of apo(a) phenotypes and the presence or absence of a small size apo(a)., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2017
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20. Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.
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Enkhmaa B, Anuurad E, Zhang W, Li CS, Kaplan R, Lazar J, Merenstein D, Karim R, Aouizerat B, Cohen M, Butler K, Pahwa S, Ofotokun I, Adimora AA, Golub E, and Berglund L
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- Adult, Biomarkers blood, Carotid Artery Diseases blood, Carotid Artery Diseases diagnostic imaging, Carotid Artery Diseases genetics, Case-Control Studies, Female, HIV Infections blood, HIV Infections diagnosis, HIV Infections genetics, Humans, Linear Models, Predictive Value of Tests, Prospective Studies, Risk Assessment, Risk Factors, United States, Young Adult, Alleles, Apoprotein(a) blood, Apoprotein(a) genetics, Carotid Artery Diseases etiology, Carotid Artery, Common diagnostic imaging, Carotid Intima-Media Thickness, HIV Infections complications
- Abstract
Objective: In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear., Approach and Results: The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4
+ T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness., Conclusions: Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection., (© 2017 American Heart Association, Inc.)- Published
- 2017
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21. Lipid Lowering with Soluble Dietary Fiber.
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Surampudi P, Enkhmaa B, Anuurad E, and Berglund L
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- Animals, Blood Pressure drug effects, Cardiovascular Diseases prevention & control, Humans, Risk Reduction Behavior, Dietary Fiber, Lipids blood
- Abstract
Consumption of dietary soluble fibers has been associated with health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, weight loss, improved immune function, and reduced inflammation. Many of these health benefits relate to a reduced risk of developing cardiovascular disease. In this paper, we have reviewed recent studies on the hypocholesterolemic effects of dietary soluble fibers as well as fiber-rich foods. Findings include the following: (a) consumption of water-soluble, viscous-forming fibers can reduce total and low-density lipoprotein cholesterol levels by about 5-10 %; (b) minimal changes of high-density lipoprotein cholesterol or triglyceride levels were observed; (c) cholesterol-lowering properties of soluble fibers depend on their physical and chemical properties; and (d) medium to high molecular weight fibers are more effective in reducing lipid levels. Hypocholesterolemic benefits were also observed with some fiber-rich foods, such as whole oats, whole barley, legumes, peas, beans, flax seeds, apples, and citrus foods.
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- 2016
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22. Lipoprotein (a): impact by ethnicity and environmental and medical conditions.
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Enkhmaa B, Anuurad E, and Berglund L
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- Age Factors, Apolipoproteins A blood, Apolipoproteins B blood, Ethnicity genetics, Female, Genetic Variation, Humans, Lipoprotein(a) blood, Male, Polymorphism, Single Nucleotide, Risk Factors, Sex Characteristics, Apolipoproteins A genetics, Apolipoproteins B genetics, Kringles genetics, Lipoprotein(a) genetics
- Abstract
Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases.
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- 2016
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23. The unresolved mystery of high-density lipoprotein: time for a paradigm shift?
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Enkhmaa B, Anuurad E, and Berglund L
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- Humans, Lipoproteins, HDL, Triglycerides
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- 2016
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24. Lipoprotein(a) and apolipoprotein(a) in polycystic ovary syndrome.
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Enkhmaa B, Anuurad E, Zhang W, Abbuthalha A, Kaur P, Visla J, Karakas S, and Berglund L
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Objective: Levels of lipoprotein(a), Lp(a), an independent risk factor for cardiovascular disease (CVD), are affected by sex hormones. Women with polycystic ovary syndrome (PCOS) have elevated androgen levels and are at increased CVD risk. We investigated the impact of PCOS-related hormonal imbalance on Lp(a) levels in relation to apo(a) gene size polymorphism, a major regulator of Lp(a) level., Design: Cross-sectional., Patients: Forty-one Caucasian women with PCOS based on the NIH criteria., Measurements: (1) Apo(a) gene size polymorphism measured as Kringle (K) 4 repeat number; (2) total plasma Lp(a) level; (3) allele-specific apo(a) level assessing the amount of Lp(a) carried by an individual apo(a) allele/isoform; and (4) sex hormone levels., Results: The mean age was 32 ± 6 years, and the mean BMI was 35 ± 8 with 66% of women classified as obese (BMI >30 kg/m
2 ). LDL cholesterol was borderline high (3·37 mmol/l), and HDL cholesterol was low (1·06 mmol/l). The distribution of Lp(a) level was skewed towards lower levels with a median level of 22·1 nmol/l (IQR: 6·2-66·5 nmol/l). Lp(a) levels were not correlated with age, body weight or BMI. The median allele-specific apo(a) level was 10·6 nmol/l (IQR: 3·1-31·2 nmol/l), and the median apo(a) size was 27 (IQR: 23-30) K4 repeats. Allele-specific apo(a) levels were significantly and inversely correlated with K4 repeats (r = -0·298, P = 0·007). Neither Lp(a) nor allele-specific apo(a) levels were significantly associated with testosterone or dehydroepiandrosterone sulphate levels., Conclusions: The apo(a) genetic variability remains the major regulator of plasma Lp(a) levels in women with PCOS., (© 2015 John Wiley & Sons Ltd.)- Published
- 2016
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25. Combined High-Density Lipoprotein Proteomic and Glycomic Profiles in Patients at Risk for Coronary Artery Disease.
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Krishnan S, Huang J, Lee H, Guerrero A, Berglund L, Anuurad E, Lebrilla CB, and Zivkovic AM
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- Adult, Aged, Atherosclerosis blood, Case-Control Studies, Coronary Angiography, Coronary Artery Disease diagnosis, Female, Gangliosides analysis, Glycomics methods, Humans, Lipoproteins, HDL analysis, Lipoproteins, HDL chemistry, Male, Middle Aged, Principal Component Analysis, Proteomics methods, Random Allocation, Risk Factors, Coronary Artery Disease blood, Lipoproteins, HDL blood
- Abstract
Objectives: To test whether recently developed methods for comprehensive profiling of the high-density lipoprotein (HDL) glycome combined with the HDL proteome can distinguish individuals with coronary artery disease (CAD) from those without., Methods: Twenty subjects at risk for CAD, who underwent diagnostic coronary arteriography, were analyzed. Ten subjects had CAD, and ten did not. HDL was extracted from fasting plasma samples by ultracentrifugation, followed by shotgun proteomic, glycomic, and ganglioside analyses using LC-MS. CAD vs non-CAD subjects' data were compared using univariate and multivariate statistics., Results: Principal components analysis showed a clear separation of CAD and non-CAD subjects, confirming that combined HDL proteomic and glycomic profiles distinguished at-risk subjects with atherosclerosis from those without. CAD patients had lower HDL apolipoprotein content (specifically ApoA-I, A-II, and E, p < 0.05), and lower serum amyloid A2 (SAA2, p = 0.020) and SAA4 (p = 0.007) but higher sialylated glycans (p < 0.05)., Conclusion: Combined proteomic and glycomic profiling of isolated HDL was tested as a novel analytical approach for developing biomarkers of disease. In this pilot study we found that HDL proteome and glycome distinguished between individuals who had CAD from those who did not within a group of individuals equally at risk for heart disease.
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- 2015
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26. Mediterranean diet and cardiovascular disease: a step closer to mechanisms using a precision animal model?
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Enkhmaa B, Anuurad E, and Berglund L
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- Animals, Female, Humans, Apolipoprotein A-I blood, Clusterin blood, Coronary Vessels physiology, Lipoproteins, HDL blood, Solanum lycopersicum
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- 2015
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27. Rhesus monkey (Macaca mulatta) lipoprotein(a) and apolipoprotein(a): high frequency of small size apolipoprotein(a) isoforms.
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Enkhmaa B, Abbuthalha A, Anuurad E, Zhang W, Tarantal AF, and Berglund L
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- Alleles, Animals, Apolipoprotein A-I genetics, Genetic Variation, Humans, Lipoprotein(a) genetics, Macaca mulatta genetics, Protein Isoforms, Species Specificity, Apolipoprotein A-I blood, Lipoprotein(a) blood, Macaca mulatta blood
- Abstract
Background: Levels of lipoprotein(a), Lp(a), a genetically regulated independent cardiovascular risk factor present in humans and Old World monkeys, are impacted by the apolipoprotein(a), apo(a), gene. Allele-specific apo(a) levels, taking both the apo(a) genotypic and phenotypic characteristics into account, are useful markers to determine atherosclerotic cardiovascular risk., Methods: We determined (i) the genetic variability of apo(a), (ii) Lp(a) levels, and (iii) allele-specific apo(a) levels in rhesus monkeys (n = 95)., Results: Lp(a) levels differed substantially between animals (range: 4-247 nmol/l) with a skewed distribution toward lower levels. Lp(a) and allele-specific apo(a) levels were inversely related to the number of apo(a) Kringle 4 (K4) repeats. The median apo(a) size was 23 K4 repeats, and the prevalence of a small size apo(a) (≤22 K4) was 43%., Conclusions: Distribution of Lp(a) and allele-specific apo(a) levels in rhesus monkeys reflected the corresponding human patterns, but with a high prevalence of smaller apo(a) sizes., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
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28. Diverging trajectory patterns of systemic versus vascular inflammation over age in healthy Caucasians and African-Americans.
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Enkhmaa B, Anuurad E, Zhang W, Kim K, and Berglund L
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- Adolescent, Adult, Age Distribution, Age Factors, Biomarkers blood, California epidemiology, Child, Cross-Sectional Studies, Female, Healthy Volunteers, Humans, Inflammation blood, Inflammation diagnosis, Inflammation Mediators blood, Male, Middle Aged, Prognosis, Risk Factors, Time Factors, Vasculitis blood, Vasculitis diagnosis, Black or African American, Health Status Disparities, Inflammation ethnology, Vasculitis ethnology, White People
- Abstract
Objective: Age and inflammation are risk factors for cardiovascular disease but the impact of inflammation on cardiovascular risk across the lifespan is not understood. We investigated whether an inflammatory burden is modulated by age in healthy subjects., Methods: Caucasian and African-American families were recruited from the general population (age range: 6-74 years, n = 267). Systemic inflammation was assessed by C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, haptoglobin and α-acid glycoprotein, and vascular inflammation was assessed by pentraxin-3 (PTX-3), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM). To collectively assess systemic or vascular factors across the age spectrum, a composite z-score for each marker category was calculated., Results: There was a contrasting pattern in systemic versus vascular inflammatory burden over age with an increase in systemic but a decrease in vascular markers in both ethnic groups. The results remained unchanged after adjustments for the covariates and covariance. When looking at individual markers to examine which markers are most contributing factors to the composite scores, CRP and SAA were significantly and positively associated with age, while PTX-3 and sVCAM were significantly and negatively associated with age in both ethnic groups., Conclusions: The composite z-score for systemic inflammation increased with age, while the composite z-score for vascular inflammation declined with age, irrespective of ethnicity. The findings illustrate a regulatory relationship between age and inflammation, and suggest that a perceived elevation of vascular markers among the very young may be an indication of physiological changes rather than reflecting a disease process., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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29. Significant associations between lipoprotein(a) and corrected apolipoprotein B-100 levels in African-Americans.
- Author
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Enkhmaa B, Anuurad E, Zhang W, and Berglund L
- Subjects
- Aged, Alleles, Apolipoprotein B-100 genetics, Atherosclerosis blood, Atherosclerosis genetics, Cholesterol blood, Cholesterol, LDL blood, Female, Humans, Lipoprotein(a) genetics, Male, Middle Aged, Protein Isoforms, Risk Assessment, Risk Factors, White People, Black or African American genetics, Apolipoprotein B-100 blood, Atherosclerosis ethnology, Lipoprotein(a) blood
- Abstract
Objectives: Lipoprotein(a), Lp(a), represents an apolipoprotein (apo) B-carrying lipoprotein, yet the relationship between Lp(a) and apoB levels has not been fully explored., Methods: We addressed the relationship between Lp(a) and apoB-containing lipoprotein levels in 336 Caucasians and 224 African-Americans. Our approach takes unique molecular properties of Lp(a) as well as contribution of Lp(a) to the levels of these lipoproteins into account., Results: Levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apoB and apoB/apoA-1 did not differ across ethnicity. African-Americans had higher levels of Lp(a) and high-density lipoprotein cholesterol and lower triglyceride levels compared to Caucasians. Lp(a) levels were correlated with levels of TC (p < 0.005), LDL-C (p < 0.001), apoB (p < 0.05) or apoB/apoA-1 (p < 0.05) in both ethnic groups. These associations remained significant only in African-Americans after adjustments for the contribution of Lp(a)-cholesterol or Lp(a)-apoB. Furthermore, taking Lp(a)-apoB into account, allele-specific apo(a) levels were significantly associated with apoB levels and the apoB/apoA-1 ratio in African-Americans. The latter associations in African-Americans remained significant for allele-specific apo(a) levels for smaller apo(a) sizes (<26 K4 repeats), after controlling for the effects of age, sex, and BMI., Conclusions: Although TC, LDL-C, and apoB levels were comparable between African-Americans and Caucasians, the associations of these parameters with Lp(a) and allele specific apo(a) levels differed between these two ethnic groups. In African-Americans, apoB and apoB/apoA-1 remained consistently and positively associated with both Lp(a) and allele-specific apo(a) levels after adjustments for the contribution of Lp(a)-apoB. The findings suggest an interethnic difference with a closer relationship between Lp(a) and apoB among African-Americans., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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30. HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels.
- Author
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Enkhmaa B, Anuurad E, Zhang W, Abbuthalha A, Li XD, Dotterweich W, Pollard RB, Asmuth DM, and Berglund L
- Subjects
- Adult, Black or African American genetics, Apoprotein(a) genetics, Biomarkers blood, CD4 Lymphocyte Count, California epidemiology, Cardiovascular Diseases blood, Cardiovascular Diseases ethnology, Cardiovascular Diseases virology, Cross-Sectional Studies, Female, HIV genetics, HIV immunology, HIV Infections complications, HIV Infections diagnosis, HIV Infections ethnology, HIV Infections virology, Humans, Lipoprotein(a) genetics, Male, Middle Aged, Particle Size, Prognosis, RNA, Viral blood, Risk Factors, Viral Load, White People legislation & jurisprudence, Apoprotein(a) blood, HIV Infections blood, Lipoprotein(a) blood
- Abstract
Objective: Mechanisms underlying the cardiovascular risk of lipoprotein(a) are poorly understood. We investigated the relationship of apolipoprotein(a) (apo(a)) size, lipoprotein(a), and allele-specific apo(a) levels with HIV disease activity parameters in a biethnic population., Methods and Results: Lipoprotein(a) and allele-specific apo(a) levels were determined in 139 white and 168 black HIV-positive patients. Plasma HIV RNA viral load and CD4+ T-cell count were used as surrogates for disease activity. Lipoprotein(a) and allele-specific apo(a) levels were higher in blacks than whites (for both P<0.001). Apo(a) allele size distribution was similar between the 2 ethnic groups, with a median apo(a) size of 28 kringle 4 repeats. Allele-specific apo(a) levels were positively associated with CD4+ T-cell count (P=0.027) and negatively with plasma HIV RNA viral load (P<0.001). Further, allele-specific apo(a) levels associated with smaller (<28 kringle 4) atherogenic apo(a) sizes were higher in subjects with CD4+ T-cell counts of ≥350 (P=0.002)., Conclusions: Allele-specific apo(a) levels were higher in subjects with high CD4+ T-cell count or low plasma HIV RNA viral load. The findings suggest that HIV disease activity reduced allele-specific apo(a) levels. Higher allele-specific apo(a) levels associated with atherogenic small apo(a) sizes might contribute to increased cardiovascular risk in HIV-positive subjects with improved disease status.
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- 2013
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31. Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase cardiovascular risk.
- Author
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Gungor Z, Anuurad E, Enkhmaa B, Zhang W, Kim K, and Berglund L
- Subjects
- 1-Alkyl-2-acetylglycerophosphocholine Esterase, Black or African American genetics, Analysis of Variance, Biomarkers blood, C-Reactive Protein analysis, Coronary Angiography, Coronary Artery Disease blood, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease ethnology, Cross-Sectional Studies, Fibrinogen analysis, Gene Frequency, Genetic Predisposition to Disease, Humans, Inflammation blood, Inflammation ethnology, Phenotype, Risk Assessment, Risk Factors, Serum Amyloid A Protein analysis, Serum Amyloid P-Component analysis, United States epidemiology, White People genetics, Apolipoprotein E4 genetics, Coronary Artery Disease genetics, Coronary Artery Disease immunology, Inflammation genetics, Inflammation immunology, Inflammation Mediators blood, Phospholipases A2 blood
- Abstract
Objective: Apolipoprotein E (apoE) has been implicated as conveying increased risk for coronary artery disease (CAD). Previous studies suggest a role of apoE as a modulator of immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD., Methods: ApoE genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA]) and vascular inflammatory markers (Lipoprotein-associated phospholipase A(2) [Lp-PLA(2)] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography., Results: For both ethnic groups, Lp-PLA(2) index, an integrated measure of Lp-PLA(2) mass and activity, increased significantly and stepwise across apoE isoforms (P = 0.009 and P = 0.026 for African Americans and Caucasians respectively). No differences were found for other inflammatory markers tested (CRP, fibrinogen, SAA and PTX-3). For the top cardiovascular score tertile, apo E4 carriers had a significantly higher level of Lp-PLA(2) index in both ethnic groups (P = 0.027 and P = 0.010, respectively)., Conclusion: The presence of the apo E4 isoform was associated with a higher level of Lp-PLA(2) index, a marker of vascular inflammation. Our results suggest that genetic variation at the apoE locus may impact cardiovascular disease risk through enhanced vascular inflammation., (Published by Elsevier Ireland Ltd.)
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- 2012
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32. Lipoprotein(a): genotype-phenotype relationship and impact on atherogenic risk.
- Author
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Enkhmaa B, Anuurad E, Zhang W, Tran T, and Berglund L
- Subjects
- Alleles, Atherosclerosis genetics, Coronary Disease blood, Coronary Disease genetics, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Lipoprotein(a) blood, Models, Biological, Polymorphism, Genetic physiology, Risk Factors, Atherosclerosis etiology, Lipoprotein(a) genetics, Lipoprotein(a) physiology
- Abstract
In 2010, more than 45 years after the initial discovery of lipoprotein(a) [Lp(a)] by Kare Berg, an European Atherosclerosis Society Consensus Panel recommended screening for elevated Lp(a) in people at moderate to high risk of atherosclerotic cardiovascular disease (CVD). This recommendation was based on extensive epidemiological findings demonstrating a significant association between elevated plasma Lp(a) levels and coronary heart disease, myocardial infarction, and stroke. In addition to those patients considered to be at moderate to high risk of heart disease, statin-treated patients with recurrent heart disease were also identified as targeted for screening of elevated Lp(a) levels. Taken together, recent findings have significantly strengthened the notion of Lp(a) as a causal risk factor for CVD. It is well established that Lp(a) levels are largely determined by the size of the apolipoprotein a [apo(a)] gene; however, recent studies have identified several other LPA gene polymorphisms that have significant associations with an elevated Lp(a) level and a reduced copy number of K4 repeats. In addition, the contribution of other genes in regulating Lp(a) levels has been described. Besides the strong genetic regulation, new evidence has emerged regarding the impact of inflammation as a modulator of Lp(a) risk factor properties. Thus, oxidized phospholipids that possess a strong proinflammatory potential are preferentially carried on Lp(a) particles. Collectively, these findings point to the importance of both phenotypic and genotypic factors in influencing apo(a) proatherogenic properties. Therefore, studies taking both of these factors into account determining the amount of Lp(a) associated with each individual apo(a) size allele are valuable tools when assessing a risk factor role of Lp(a).
- Published
- 2011
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33. Age as a modulator of inflammatory cardiovascular risk factors.
- Author
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Anuurad E, Enkhmaa B, Gungor Z, Zhang W, Tracy RP, Pearson TA, Kim K, and Berglund L
- Subjects
- Black or African American, Age Factors, Biomarkers, C-Reactive Protein analysis, Cardiovascular Diseases ethnology, Female, Fibrinogen analysis, Humans, Inflammation ethnology, Male, Middle Aged, Phospholipases A2 metabolism, Risk Factors, Serum Amyloid A Protein analysis, Serum Amyloid P-Component analysis, White People, Cardiovascular Diseases etiology, Inflammation etiology
- Abstract
Objective: Levels of acute phase reactants are affected by age. The extent to which cardiovascular risk associated with aging is due to an increase in the inflammatory burden is not known. We assessed the relationship with age of inflammatory markers, representing (1) systemic (C-reactive protein, fibrinogen, and serum amyloid-A) and (2) vascular (lipoprotein-associated phospholipase A(2) and pentraxin-3) inflammation., Methods and Results: We determined lipoprotein-associated phospholipase A(2) mass and activity, C-reactive protein, fibrinogen, serum amyloid-A, and pentraxin-3 levels and other cardiovascular disease risk factors in 336 whites and 224 African Americans. Levels of systemic inflammatory markers increased significantly with age in both ethnic groups (P<0.05 for all), whereas trend patterns of vascular inflammatory markers did not change significantly with age for either group. In multivariate regression models adjusting for confounding variables, age remained independently associated with a composite Z score for systemic but not vascular inflammation (β=0.250, P<0.001, and β=0.276, P<0.001, for whites and African Americans, respectively)., Conclusions: We report an increase in the systemic but not vascular inflammatory burden with age. Levels of both categories of inflammatory markers with age were similar across ethnicity after adjustment for confounders. Our results underscore the importance of age in evaluating inflammatory markers to assess cardiovascular risk.
- Published
- 2011
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34. Differential associations of serum amyloid A and pentraxin-3 with allele-specific lipoprotein(a) levels in African Americans and Caucasians.
- Author
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Enkhmaa B, Anuurad E, Ozturk Z, Zhang W, Pearson TA, and Berglund L
- Subjects
- 1-Alkyl-2-acetylglycerophosphocholine Esterase blood, Black or African American, Alleles, Cardiovascular Diseases etiology, Female, Humans, Interleukin-1beta pharmacology, Interleukin-6 physiology, Lipoprotein(a) genetics, Male, Tumor Necrosis Factor-alpha physiology, White People, C-Reactive Protein analysis, Lipoprotein(a) blood, Serum Amyloid A Protein analysis, Serum Amyloid P-Component analysis
- Abstract
Lipoprotein(a) [Lp(a)] is a cardiovascular disease (CVD) risk factor, where inflammation impacts levels differentially across ethnicity. We investigated the effect of systemic [serum amyloid A (SAA)] and vascular [pentraxin-3 (PTX-3)] inflammation on Lp(a) levels across different apolipoprotein(a) [apo(a)] sizes in a biethnic population. Lp(a) and allele-specific apo(a) levels, apo(a) sizes, SAA, and PTX-3 levels were determined in 336 Caucasians and 224 African Americans. We dichotomized subjects into 2 groups using the respective median SAA (29.8 and 41.5 mg/dL for Caucasians and African Americans, respectively) or PTX-3 levels (1.6 and 1.1 ng/mL for Caucasians and African Americans, respectively). Among African Americans, but not in Caucasians, Lp(a) levels were increased (146 vs 117 nmol/L, P = 0.024) in the high versus low SAA group. No difference was observed across PTX-3 groups. Furthermore, among African Americans with smaller (<26 K4 repeats) apo(a) sizes, allele-specific apo(a) levels (111 vs 79 nmol/L, P = 0.020) were increased in the high versus low SAA group. Again, no difference was observed for PTX-3. We did not find any significant associations between allele-specific apo(a) and SAA or PTX-3 levels among Caucasians with smaller (<26 K4) apo(a) sizes. In conclusion, increased levels of SAA, but not PTX-3, were associated significantly with higher Lp(a) levels for smaller (<26 K4) apo(a) sizes in African Americans. Our results implicate that a proinflammatory stimulus may result in an increased cardiovascular risk through a selective increase in Lp(a) levels among African Americans who carry a smaller apo(a) size., (Copyright © 2011 Mosby, Inc. All rights reserved.)
- Published
- 2011
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35. Integrated role of two apoliprotein E polymorphisms on apolipoprotein B levels and coronary artery disease in a biethnic population.
- Author
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Ozturk Z, Enkhmaa B, Shachter NS, Berglund L, and Anuurad E
- Subjects
- Adult, Aged, Apolipoproteins E physiology, Case-Control Studies, Epistasis, Genetic physiology, Female, Gene Frequency, Genetic Predisposition to Disease genetics, Genotype, Humans, Male, Middle Aged, Population, Protein Isoforms genetics, Apolipoproteins B blood, Apolipoproteins E genetics, Coronary Artery Disease blood, Coronary Artery Disease ethnology, Coronary Artery Disease genetics, Polymorphism, Single Nucleotide physiology
- Abstract
Background: Apolipoprotein E (ApoE) plays a major role in lipoprotein metabolism and genetic variability of ApoE confers susceptibility to coronary artery disease (CAD). Beyond variability in the coding region, promoter polymorphisms in the ApoE gene impact on ApoE transcription., Methods: We determined the ApoE - 491 A/T promoter polymorphism, ApoE isoforms, lipid and lipoprotein levels, and CAD risk factors in 313 Caucasians and 215 African Americans., Results: Caucasians had a lower ApoE T allele frequency compared to African Americans (18.1% vs. 32.3%, P < 0.05). Among T/* carriers, ApoB levels were significantly lower in Caucasians, but significantly higher among African Americans, in both cases compared to A/A homozygotes (P = 0.017, and P = 0.012). For a given -491A/T genotype, levels of atherogenic lipoproteins differed across ApoE2/E3/E4 isoforms among African Americans, but not Caucasians, as T/* carriers with ApoE4 had significantly higher ApoB levels compared to T/* carriers with ApoE2 (P = 0.010). Among patients with CAD, Caucasian A/A homozygotes and African American T/* carriers had higher ApoB levels compared to the same genotype without CAD (P = 0.007, P = 0.049, respectively)., Conclusions: We observed an ethnicity-specific variability in ApoB levels across the ApoE - 491 A/T polymorphism and a modulatory impact on this pattern by ApoE2/E3/E4 isoforms.
- Published
- 2010
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36. Enigmatic role of lipoprotein(a) in cardiovascular disease.
- Author
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Anuurad E, Enkhmaa B, and Berglund L
- Subjects
- Alleles, Apolipoproteins A blood, Atherosclerosis blood, Atherosclerosis pathology, Atherosclerosis therapy, Cardiovascular Diseases blood, Cardiovascular Diseases pathology, Cardiovascular Diseases therapy, Humans, Inflammation metabolism, Inflammation pathology, Lipoprotein(a) blood, Risk Factors, Cardiovascular Diseases metabolism, Lipoprotein(a) metabolism
- Abstract
Lipoprotein (a), [Lp(a)] has many properties in common with low-density lipoprotein, (LDL) but contains a unique protein apolipoprotein(a), linked to apolipoprotein B-100 by a single disulfide bond. There is a substantial size heterogeneity of apo(a), and generally smaller apo(a) sizes tend to correspond to higher plasma Lp(a) levels, but this relation is far from linear, underscoring the importance to assess allele-specific apo(a) levels. The presence of apo(a), a highly charged, carbohydrate-rich, hydrophilic protein may obscure key features of the LDL moiety and offer opportunities for binding to vessel wall elements. Recently, interest in Lp(a) has increased because studies over the past decade have confirmed and more robustly demonstrated a risk factor role of Lp(a) for cardiovascular disease. In particular, levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with coronary artery disease (CAD). Other studies suggest that proinflammatory conditions may modulate risk factor properties of Lp(a). Further, Lp(a) may act as a preferential acceptor for proinflammatory oxidized phospholipids transferred from tissues or from other lipoproteins. However, at present only a limited number of agents (e.g., nicotinic acid and estrogen) has proven efficacy in lowering Lp(a) levels. Although Lp(a) has not been definitely established as a cardiovascular risk factor and no guidelines presently recommend intervention, Lp(a)-lowering therapy might offer benefits in subgroups of patients with high Lp(a) levels., (© 2010 Wiley Periodicals, Inc.)
- Published
- 2010
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37. Postprandial metabolic responses to dietary glycemic index in hypercholesterolemic postmenopausal women.
- Author
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Bukkapatnam RN, Berglund L, Anuurad E, Devaraj S, Hyson D, Rafii F, Malmstein C, and Villablanca AC
- Subjects
- Area Under Curve, Blood Glucose, Cross-Over Studies, Female, Humans, Hyperglycemia, Life Style, Middle Aged, Nutritional Status, Prospective Studies, Risk Factors, Time Factors, Diet, Glucose Intolerance, Glycemic Index, Hypercholesterolemia metabolism, Postmenopause, Postprandial Period
- Abstract
Cardiovascular disease is the leading cause of death in postmenopausal women. While diet and lifestyle remain the cornerstones of prevention, a low-fat/high-carbohydrate diet is associated with hyperglycemia and hyperlipemia-atherosclerotic risk factors affected by postprandial conditions. The objective of this study was to examine the acute response of lipids and insulin to a low-fat/high-carbohydrate meal with either a high-glycemic or a low-glycemic index in healthy postmenopausal women. Fifteen healthy postmenopausal women were enrolled in a randomized crossover dietary intervention study. Levels of glucose, triglyceride, free fatty acids (FFAs), and insulin were measured preprandially and for 240 minutes after consumption of the test meals. In response to the high-glycemic compared with the low-glycemic index meal, postprandial insulin levels had a higher peak (65.4 vs 48.1 microU/mL, respectively), the homeostasis model assessment-insulin resistance (HOMA-IR) was significantly higher (P=.014), serum triglyceride levels declined significantly (P<.001), and there was a small reduction in FFA levels, although the difference did not reach statistical significance. The results suggest a postprandial impact of glycemic index on cardiovascular metabolic biomarkers in postmenopausal women and may have implications for dietary glycemic modification of cardiovascular risk in women., (2009 Wiley Periodicals, Inc.)
- Published
- 2010
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38. Usefulness of apolipoprotein B/apolipoprotein A-I ratio to predict coronary artery disease independent of the metabolic syndrome in African Americans.
- Author
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Enkhmaa B, Anuurad E, Zhang Z, Pearson TA, and Berglund L
- Subjects
- Chi-Square Distribution, Coronary Angiography, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease ethnology, Female, Humans, Logistic Models, Male, Metabolic Syndrome ethnology, Middle Aged, Predictive Value of Tests, Risk Assessment, White People, Black or African American, Apolipoprotein A-I blood, Apolipoproteins B blood, Coronary Artery Disease blood, Metabolic Syndrome blood
- Abstract
Studies have demonstrated that the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio predicts cardiovascular risk better than any of the cholesterol indexes. A number of factors that define the metabolic syndrome (MS) differ across African-American and European-American ethnicities. We assessed the relation of the apoB/apoA-I ratio to MS and coronary artery disease (CAD) in 224 African Americans and 304 European Americans. The MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and CAD was assessed as ≥50% stenosis or a continuous cardiovascular score (0 to 75). The European Americans had a greater apoB/apoA-I ratio than the African Americans (1.15 vs 1.07, p = 0.008). The apoB/apoA-I ratio was associated with presence of the MS in both European Americans (odds ratio 5.9, 95% confidence interval 2.53 to 13.57, p <0.001) and African Americans (odds ratio 8.3, 95% confidence interval 3.52 to 19.25, p <0.001) and was greater in subjects with the MS than in those without the MS (1.21 vs 1.04, p <0.001, for European Americans and 1.20 vs 0.94, p <0.001, for African Americans). A stepwise increase was seen in the prevalence of the MS across the apoB/apoA-I ratio tertiles in both ethnic groups (chi-square = 13.1, p <0.001, for European Americans and chi-square = 19.6, p <0.001, for African Americans). On multiple regression analyses, the apoB/apoA-I ratio independently predicted CAD in African Americans (β = 0.242, p = 0.011). The cardiovascular score was significantly increased across the apoB/apoA-I ratio tertiles in the European-American subjects with the MS (p = 0.001). However, this association was seen in the African-American subjects without the MS (p = 0.023). In conclusion, the apoB/apoA-I ratio differed across ethnicities and was associated with presence of the MS in both groups. Among African Americans, an elevated apoB/apoA-I ratio independently predicted a greater risk of CAD., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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39. Association of Lp-PLA(2) activity with allele-specific Lp(a) levels in a bi-ethnic population.
- Author
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Enkhmaa B, Anuurad E, Zhang W, Pearson TA, and Berglund L
- Subjects
- 1-Alkyl-2-acetylglycerophosphocholine Esterase biosynthesis, Black or African American, Aged, Apolipoprotein B-100 blood, Black People, Cholesterol, HDL blood, Cholesterol, LDL blood, Ethnicity, Female, Humans, Male, Middle Aged, Triglycerides blood, White People, 1-Alkyl-2-acetylglycerophosphocholine Esterase genetics, Alleles, Lipoprotein(a) genetics
- Abstract
Objectives: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and lipoprotein(a) [Lp(a)] have been implicated as cardiovascular disease risk factors, and are differentially regulated across ethnicity. We investigated the association between Lp-PLA(2) activity and allele-specific apolipoprotein(a) [apo(a)] levels in a bi-ethnic population., Methods: Lp-PLA(2) activity, Lp(a) and allele-specific apo(a) levels were determined in 224 African Americans and 336 Caucasians., Results: Lp-PLA(2) activity level was higher among Caucasians compared to African Americans (173 + or - 41 nmol/min/ml vs. 141 + or - 39 nmol/min/ml, P<0.001), and positively associated with Lp(a), total and LDL cholesterol, triglyceride, apolipoprotein B-100, and negatively with HDL cholesterol levels in both ethnic groups. The association between Lp-PLA(2) activity and Lp(a) was stronger among African Americans compared to Caucasians (R=0.238, beta(1)=3.48, vs. R=0.111, beta(1)=1.93, respectively). The Lp-PLA(2) activity level was significantly associated with allele-specific apo(a) levels for smaller (<26 K4 repeats) apo(a) sizes in both ethnic groups (P=0.015 for African Americans, P=0.038 for Caucasians). In contrast, for larger (>26 K4 repeats) apo(a) sizes, high Lp-PLA(2) activity levels were associated with higher allele-specific apo(a) levels in African Americans (P=0.009), but not in Caucasians., Conclusion: The association between Lp-PLA(2) activity and allele-specific apo(a) levels differs across African American-Caucasian ethnicity., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2010
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40. Association of lipoprotein-associated phospholipase A2 with coronary artery disease in African-Americans and Caucasians.
- Author
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Anuurad E, Ozturk Z, Enkhmaa B, Pearson TA, and Berglund L
- Subjects
- Black People, Coronary Angiography, Coronary Disease diagnostic imaging, Enzyme-Linked Immunosorbent Assay, Humans, Insulin Resistance, Predictive Value of Tests, Regression Analysis, Risk Factors, White People, Black or African American, 1-Alkyl-2-acetylglycerophosphocholine Esterase blood, Coronary Disease blood
- Abstract
Context: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is bound predominately to low-density lipoprotein and has been implicated as a risk factor for coronary artery disease (CAD)., Objective: We investigated the association between Lp-PLA(2) and CAD in a biethnic African-American and Caucasian population., Design: Lp-PLA(2) mass, activity, and index, an integrated measure of mass and activity, and other cardiovascular risk factors were determined in 224 African-Americans and 336 Caucasians undergoing coronary angiography., Main Outcome Measures: We assessed the distribution of Lp-PLA(2) levels and determined the predictive role of Lp-PLA(2) as a risk factor for CAD., Results: Levels of Lp-PLA(2) mass and activity were higher among Caucasians compared with African-Americans (293 +/- 75 vs. 232 +/- 76 ng/ml, P < 0.001 for mass and 173 +/- 41 vs. 141 +/- 39 nmol/min/ml, P < 0.001 for activity, respectively). However, Lp-PLA(2) index was similar in the two groups (0.61 +/- 0.17 vs. 0.64 +/- 0.19, P = NS). In both ethnic groups, Lp-PLA(2) activity and index was significantly higher among subjects with CAD. African-American subjects with CAD had significantly higher Lp-PLA(2) index than corresponding Caucasian subjects (0.69 +/- 0.20 vs. 0.63 +/- 0.18, P = 0.028). In multivariate regression analyses, after adjusting for other risk factors, Lp-PLA(2) index was independently (odds ratio 6.7, P = 0.047) associated with CAD in African-Americans but not Caucasians., Conclusions: Lp-PLA(2) activity and index was associated with presence of CAD among African-Americans and Caucasians undergoing coronary angiography. The findings suggest an independent impact of vascular inflammation among African-Americans as contributory to CAD risk and underscore the importance of Lp-PLA(2) as a cardiovascular risk factor.
- Published
- 2010
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41. Postprandial lipoproteins and cardiovascular disease risk in diabetes mellitus.
- Author
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Enkhmaa B, Ozturk Z, Anuurad E, and Berglund L
- Subjects
- Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 physiopathology, Humans, Risk Factors, Cardiovascular Diseases complications, Diabetes Complications metabolism, Diabetes Complications physiopathology, Lipoproteins metabolism, Postprandial Period physiology
- Abstract
Diabetes mellitus is associated with increased risk for atherosclerotic cardiovascular disease (CVD). Recent prospective studies in healthy individuals suggest that the postprandial triglyceride (TG) level is a better independent predictor for assessing future CVD events than fasting TG levels. In contrast, results have been more controversial among diabetic patients, as some studies report a positive association between postprandial TG and CVD. This raises the issue of to what extent postprandial TG levels may be of predictive value in the diabetic population. One possibility impacting on the predictive power of postprandial TG in identifying CVD risk may be the presence of other risk factors, including alterations in lipid and lipoprotein metabolism, which could make it more difficult to identify the impact of postprandial lipemia on cardiovascular risk. The findings provide a challenge to develop a better approach to assess the impact of postprandial lipemia on CVD risk under diabetic conditions.
- Published
- 2010
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42. Human immunodeficiency virus and highly active antiretroviral therapy-associated metabolic disorders and risk factors for cardiovascular disease.
- Author
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Anuurad E, Semrad A, and Berglund L
- Subjects
- Antiretroviral Therapy, Highly Active adverse effects, Bone Density, Bone Remodeling, Cardiovascular Diseases chemically induced, Cardiovascular Diseases metabolism, Cardiovascular Diseases virology, Endocrine System Diseases etiology, HIV Infections complications, HIV Infections metabolism, HIV Infections virology, HIV-Associated Lipodystrophy Syndrome etiology, Humans, Lipid Metabolism, Metabolic Diseases chemically induced, Metabolic Diseases metabolism, Metabolic Diseases virology, Metabolic Syndrome etiology, Risk Assessment, Risk Factors, Anti-Retroviral Agents adverse effects, Cardiovascular Diseases etiology, HIV Infections drug therapy, Metabolic Diseases etiology
- Abstract
The successful introduction of highly active antiretroviral therapy (HAART), a combination of potent antiretroviral agents, including protease inhibitors, nucleoside reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors, has impacted positively on morbidity and mortality among human immunodeficiency virus (HIV)-positive patients. Over time, HAART has been associated with a number of metabolic and anthropometric abnormalities, including dyslipidemia and insulin resistance as well as subcutaneous fat loss and abdominal obesity, potentially contributing to cardiovascular risk. Recent studies have more firmly established that both HIV infection and HAART might increase the risk of clinical cardiovascular events. Furthermore, whereas HIV/HAART is associated with multiple aspects of endocrine dysfunction, there has been less focus on bone disease, although some studies indicate a higher prevalence of osteoporosis among HIV-positive subjects compared to HIV-negative controls. The relationship between bone and fat metabolism under HIV-positive conditions deserves further attention, and available data suggest the possibility of an intriguing connection. In the future, an increasing population of aging HIV-positive patients with a spectrum of antiretroviral therapies and accumulation of endocrine abnormalities and conventional cardiovascular risk factors will present preventive and therapeutic challenges to our health-care system.
- Published
- 2009
- Full Text
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43. Synergistic role of inflammation and insulin resistance as coronary artery disease risk factors in African Americans and Caucasians.
- Author
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Anuurad E, Tracy RP, Pearson TA, Kim K, and Berglund L
- Subjects
- Adult, Black or African American, Aged, Black People, Coronary Artery Disease ethnology, Female, Fibrinogen metabolism, Glucose metabolism, Humans, Male, Middle Aged, Risk Factors, White People, Coronary Artery Disease diagnosis, Inflammation diagnosis, Insulin Resistance
- Abstract
The separate roles of inflammation and insulin resistance (IR) in the pathogenesis of cardiovascular disease (CVD) are well recognized. We investigated whether presence of inflammation would modify coronary artery disease (CAD) risk prediction in subjects with or without IR. Insulin, glucose, CRP and fibrinogen levels were determined in 317 Caucasians and 222 African Americans undergoing diagnostic coronary angiography. Extent of CAD was defined by a composite score (0-75). The overall prevalence of IR (HOMA-IR>or=3.0) in Caucasians and African Americans was 32.5% and 22.9%, respectively (P<0.05). The degree of CAD (composite score) was higher in subjects with IR (20.7 vs. 14.5, P=0.014 and 20.1 vs. 13.1, P=0.031 for Caucasians and African Americans, respectively), and in a multiple regression model IR was an independent predictor for CAD in both groups. In both ethnic groups, subjects with a combination of IR and high CRP (>or=3mg/l) had significantly higher composite score compared to those with no IR and low CRP (<3mg/l) (21.2 vs. 13.9, P<0.05 and 20.9 vs. 10.2, P<0.05 for Caucasians and African Americans, respectively). Similarly, the composite score was significantly higher in subjects with IR and high fibrinogen (>or=340 mg/dl) compared to those with no IR and low fibrinogen. In conclusion, elevated levels of inflammatory markers were positively associated with IR. Further, a combination of IR and inflammation resulted in a higher degree of CAD in both Caucasians and African Americans. The results suggest that inflammation may potentiate the cardiovascular risk factor role of IR.
- Published
- 2009
- Full Text
- View/download PDF
44. ApoE and ApoC-I polymorphisms: association of genotype with cardiovascular disease phenotype in African Americans.
- Author
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Anuurad E, Yamasaki M, Shachter N, Pearson TA, and Berglund L
- Subjects
- Apolipoprotein C-I blood, Apolipoproteins E blood, Cardiovascular Diseases blood, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Phenotype, Black or African American genetics, Apolipoprotein C-I genetics, Apolipoproteins E genetics, Cardiovascular Diseases genetics, Polymorphism, Genetic
- Abstract
Apolipoproteins (apo) E and C-I are components of triglyceride (TG)-rich lipoproteins and impact their metabolism. Functional polymorphisms have been established in apoE but not in apoC-I. We studied the relationship between apoE and apoC-I gene polymorphisms and plasma lipoproteins and coronary artery disease (CAD) in 211 African Americans and 306 Caucasians. In African Americans but not in Caucasians, apoC-I H2-carriers had significantly lower total and LDL cholesterol and apoB levels, and higher glucose, insulin, and HOMA-IR levels compared with H1 homozygotes. Differences across CAD phenotypes were seen for the apoC-I polymorphism. African-American H2-carriers without CAD had significantly lower total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and apoB (P < 0.001) levels compared with H1 homozygotes, whereas no differences were found across apoC-I genotypes for African Americans with CAD. Among African-American apoC-I H1 homozygotes, subjects with CAD had a profile similar to the metabolic syndrome (i.e., higher triglyceride, glucose, and insulin) compared with subjects without CAD. For African-American H2-carriers, subjects with CAD had a pro-atherogenic lipid pattern (i.e., higher LDL cholesterol and apoB levels), compared with subjects without CAD. ApoC-I genotypes showed an ethnically distinct phenotype relationship with regard to CAD and CAD risk factors.
- Published
- 2009
- Full Text
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45. Relationship of postprandial nonesterified fatty acids, adipokines, and insulin across gender in human immunodeficiency virus-positive patients undergoing highly active antiretroviral therapy.
- Author
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Lu G, Thomas-Geevarghese A, Anuurad E, Raghavan S, Minolfo R, Ormsby B, Karmally W, El-Sadr WM, Albu J, and Berglund L
- Subjects
- Adiponectin blood, Adult, Eating physiology, Fasting blood, Female, Humans, Insulin Resistance physiology, Leptin blood, Male, Middle Aged, Postprandial Period physiology, Sex Characteristics, Adipokines blood, Antiretroviral Therapy, Highly Active, Fatty Acids, Nonesterified blood, HIV Infections blood, HIV Infections drug therapy, Insulin blood
- Abstract
Background: Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions., Methods: We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART)., Results: For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r(2) = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r(2) = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed., Conclusions: In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase.
- Published
- 2009
- Full Text
- View/download PDF
46. Comparison of C-reactive protein and metabolic syndrome as cardiovascular risk factors in African-Americans and European-Americans.
- Author
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Anuurad E, Tracy RP, Pearson TA, Beckett L, and Berglund L
- Subjects
- Adult, Black or African American, Coronary Angiography, Coronary Artery Disease diagnostic imaging, Female, Humans, Male, Risk Factors, White People, C-Reactive Protein analysis, Coronary Artery Disease blood, Coronary Artery Disease ethnology, Metabolic Syndrome blood, Metabolic Syndrome ethnology
- Abstract
The aim of this study was to investigate the association of C-reactive protein (CRP) with the metabolic syndrome (MS) and its components, and their association with coronary artery disease (CAD) in African Americans and European Americans. MS was defined using revised National Cholesterol Education Program Adult Treatment Panel III criteria in 224 African Americans and 304 European Americans who underwent coronary angiography; CAD was defined as > or =50% stenosis in any segment or as a composite cardiovascular score (0 to 75). The relative frequencies of MS and CAD were significantly higher in African Americans with high (> or =3 mg/L) versus low (<3 mg/L) CRP levels (76% vs 24%, p <0.001, for MS and 70% vs 30%, p = 0.001, for CAD). Composite scores were higher in subjects with high (> or =3 mg/L) versus low (<3 mg/L) CRP levels in African Americans (16.9 vs 11.2, p = 0.038) and European Americans (18.5 vs 14.5, p = 0.002). Furthermore, in the 2 ethnic groups, cardiovascular scores were higher in subjects with MS, irrespective of CRP levels. Adjusting for other risk factors, multiple regression analysis demonstrated an association of MS, but not CRP, with CAD in European Americans but not African Americans (r(2) = 0.533, p <0.001). In conclusion, MS was independently associated with CAD in European Americans and African Americans, whereas CRP did not add prognostic information beyond established cardiovascular risk factors in either ethnic group.
- Published
- 2009
- Full Text
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47. Increased lipoprotein remnant cholesterol levels in HIV-positive patients during antiretroviral therapy.
- Author
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Anuurad E, Thomas-Geevarghese A, Devaraj S, Albu J, Minolfo R, El-Sadr WM, Lu G, Karmally W, and Berglund L
- Subjects
- Adult, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Humans, Hyperlipidemias blood, Male, Middle Aged, Postprandial Period, Protease Inhibitors administration & dosage, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active methods, Cholesterol blood, HIV Infections drug therapy, HIV Infections metabolism, Lipoproteins blood, Reverse Transcriptase Inhibitors administration & dosage, Triglycerides blood
- Abstract
Increased levels of postprandial triglycerides (TG) and remnant like particles (RLP) are associated with cardiovascular disease. We evaluated whether postprandial lipemia differed in HIV-positive patients with or without different antiretroviral regimens. A standardized high fat load was administered to 28 subjects: 11 HIV-positive subjects receiving protease inhibitors (PI), 10 HIV-positive subjects receiving non-nucleoside reverse transcriptase inhibitors (NNRTI) and 7 HIV-positive subjects not receiving highly active antiretroviral therapy, HAART (Naïve). Baseline TG levels and TG area under the curve (AUC) did not differ among the three groups. The postprandial TG concentration curves were similar in the NNRTI and Naïve groups, peaking at 3-5-h. Baseline RLP cholesterol was higher in the NNRTI group compared to other two groups (P=0.035). Both HAART groups (NNRTI and PI) had higher postprandial RLP cholesterol AUC than the Naïve group (P=0.024, ANOVA). In conclusion, during HIV conditions, HAART resulted in a pro-atherogenic pattern with accumulation of remnant lipoproteins.
- Published
- 2008
- Full Text
- View/download PDF
48. High levels of inflammatory biomarkers are associated with increased allele-specific apolipoprotein(a) levels in African-Americans.
- Author
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Anuurad E, Rubin J, Chiem A, Tracy RP, Pearson TA, and Berglund L
- Subjects
- Biomarkers, Female, Humans, Male, White People, Black or African American genetics, Alleles, Apoprotein(a) blood, C-Reactive Protein analysis, Fibrinogen analysis, Inflammation ethnology
- Abstract
Background: A role of inflammation for cardiovascular disease (CVD) is established. Lipoprotein(a) [Lp(a)] is an independent CVD risk factor where plasma levels are determined by the apolipoprotein(a) [apo(a)] gene, which contains inflammatory response elements., Design: We investigated the effect of inflammation on allele-specific apo(a) levels in African-Americans and Caucasians. We determined Lp(a) levels, apo(a) sizes, allele-specific apo(a) levels, fibrinogen and C-reactive protein (CRP) levels in 167 African-Americans and 259 Caucasians., Results: Lp(a) levels were increased among African-Americans with higher vs. lower levels of CRP [<3 vs. > or =3 mg/liter (143 vs. 108 nmol/liter), P = 0.009] or fibrinogen (<340 vs. > or =340 mg/liter, P = 0.002). We next analyzed allele-specific apo(a) levels for different apo(a) sizes. No differences in allele-specific apo(a) levels across CRP or fibrinogen groups were seen among African-Americans or Caucasians for small apo(a) sizes (<22 kringle 4 repeats). Allele-specific apo(a) levels for medium apo(a) sizes (22-30 kringle 4 repeats) were significantly higher among African-Americans, with high levels of CRP or fibrinogen compared with those with low levels (88 vs. 67 nmol/liter, P = 0.014, and 91 vs. 59 nmol/liter, P < 0.0001, respectively). No difference was found for Caucasians., Conclusions: Increased levels of CRP or fibrinogen are associated with higher allele-specific medium-sized apo(a) levels in African-Americans but not in Caucasians. These findings indicate that proinflammatory conditions result in a selective increase in medium-sized apo(a) levels in African-Americans and suggest that inflammation-associated events may contribute to the interethnic difference in Lp(a) levels between African-Americans and Caucasians.
- Published
- 2008
- Full Text
- View/download PDF
49. Apolipoprotein E and cardiovascular diseases.
- Author
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Anuurad E and Berglund L
- Subjects
- Humans, Polymorphism, Genetic, Apolipoproteins E genetics, Cardiovascular Diseases genetics
- Published
- 2008
50. Metabolic syndrome components in african-americans and European-american patients and its relation to coronary artery disease.
- Author
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Anuurad E, Chiem A, Pearson TA, and Berglund L
- Subjects
- Age Factors, Blood Glucose analysis, Blood Pressure physiology, Body Fat Distribution, Cholesterol, HDL blood, Coronary Angiography, Coronary Artery Disease blood, Female, Humans, Hypertension ethnology, Male, Metabolic Syndrome blood, New York epidemiology, New York City epidemiology, Prevalence, Risk Factors, Sex Factors, Triglycerides blood, Black or African American, Coronary Artery Disease ethnology, Metabolic Syndrome ethnology, White People
- Abstract
A number of factors used to define the metabolic syndrome (MS) differ between African-American and European-American patients, which raises the question whether the individual constellation of MS components would impact cardiovascular risk. Our objectives were to assess the association between the MS and coronary artery disease (CAD) across ethnicities and to explore whether the constellation used to define the syndrome would impact any such association. We studied the distribution of the MS and its relation to CAD in 304 European-American subjects and 224 African-American subjects undergoing diagnostic coronary angiography. The overall prevalence of the MS in European-American and African-American subjects were 65.5% and 49.1%, respectively. Compared with European-American subjects, the lipid components of the syndrome were less frequent among African-American subjects (44% vs 64% [p <0.001] for high-density lipoprotein [HDL] cholesterol and 21% vs 51% [p <0.001] for triglyceride, respectively). The prevalence of CAD was significantly higher in subjects with MS across ethnicity (71.1% of European-American subjects and 56.6% of African-American subjects, p = 0.017 and p = 0.046, respectively). Multiple regression analyses demonstrated an association of blood pressure and HDL cholesterol with CAD among European-American subjects, which remained significant taking other risk factors into account (r(2) = 0.542, p <0.001). In conclusion, presence of CAD was more common among subjects with MS independently of ethnicity. Of the MS components, blood pressure was associated with CAD among European-American subjects. Although our findings may not be directly extrapolated to the population at large, they illustrate the importance of a high-risk metabolic environment as a cardiovascular risk factor.
- Published
- 2007
- Full Text
- View/download PDF
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