99 results on '"Vega GL"'
Search Results
2. Hypercholesterolemia in post-menopausal women. Metabolic defects and response to low-dose lovastatin
- Author
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Arca, Marcello, Vega, Gl, and Grundy, Sm
- Published
- 1994
Catalog
3. Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length.
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Young, SG, primary, Pullinger, CR, additional, Zysow, BR, additional, Hofmann-Radvani, H, additional, Linton, MF, additional, Farese, RV, additional, Terdiman, JF, additional, Snyder, SM, additional, Grundy, SM, additional, and Vega, GL, additional more...
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- 1993
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4. Physiologic mechanisms for reduced apolipoprotein A-I concentrations associated with low levels of high density lipoprotein cholesterol in patients with normal plasma lipids.
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Gylling, H, primary, Vega, GL, additional, and Grundy, SM, additional
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- 1992
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5. A truncated species of apolipoprotein B, B-83, associated with hypobetalipoproteinemia.
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Farese, RV, primary, Garg, A, additional, Pierotti, VR, additional, Vega, GL, additional, and Young, SG, additional
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- 1992
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6. Evaluation of a method for study of kinetics of autologous apolipoprotein A-I
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Vega, GL, primary, Gylling, H, additional, Nichols, AV, additional, and Grundy, SM, additional
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- 1991
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7. Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia.
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Innerarity, TL, primary, Mahley, RW, additional, Weisgraber, KH, additional, Bersot, TP, additional, Krauss, RM, additional, Vega, GL, additional, Grundy, SM, additional, Friedl, W, additional, Davignon, J, additional, and McCarthy, BJ, additional more...
- Published
- 1990
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8. Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study.
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Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH Jr, and de Lemos JA
- Published
- 2005
9. Ethnic-specific criteria for the metabolic syndrome: evidence from China.
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Liu J, Grundy SM, Wang W, Smith SC Jr., Vega GL, Wu Z, Zeng Z, and Zhao D
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- 2006
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10. Multilevel Mediators on the Associations of Neighborhood Social Environmental Factors and Severity of Metabolic Syndrome: The Jackson Heart Study.
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Moniruzzaman M, Reid LA, Jones KK, Zenk SN, Vega GL, Grundy SM, Sims M, Powell-Wiley TM, and Tamura K
- Abstract
Background: Neighborhood characteristics serve as risk factors for metabolic syndrome (MetS). However, the intermediary factors linking this relationship remain understudied. Thus, we investigated the sex-specific mediating role of C-reactive protein, physical activity (PA), and perceived stress in the associations of perceived neighborhood social environment (PNSE) with MetS severity among Black adults., Methods and Results: This cross-sectional study included 3185 adults (64% women) from exam 1 (2000-2004) of the Jackson Heart Study. MetS severity Z scores were calculated based on the Adult Treatment Panel III criteria formula. PNSE included neighborhood violence, problems, and social cohesion. Men and women were analyzed separately. A bootstrap resampling technique with 95% bias-corrected CI (95% BC CI) was used to evaluate whether C-reactive protein, PA, and perceived stress mediated the association between each PNSE and MetS severity, adjusting for covariates. All PNSE factors were directly related to MetS severity in women but not in men. In women, neighborhood problems were indirectly associated with MetS severity mediated through PA (β=0.02 [95% BC CI, 0.00-0.05]). In men, neighborhood violence, problems, and social cohesion were indirectly associated with MetS severity mediated through PA (β=0.05 [95% BC CI, 0.01-0.10]; β=0.03 [95% BC CI, 0.00-0.06]; and β=-0.04 [95% BC CI, -0.09 to -0.01], respectively). Neither C-reactive protein nor perceived stress mediated such associations in either women or men., Conclusions: All PNSEs (violence, problems, and social cohesion) were directly related to MetS severity in women only. PA mediated the relationship between each PNSE and MetS in a sex-specific manner. Efforts focusing on local conditions are needed to better understand why such disparities exist for at-risk minoritized groups. more...
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- 2024
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11. Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study.
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Neeland IJ, Singh S, McGuire DK, Vega GL, Roddy T, Reilly DF, Castro-Perez J, Kozlitina J, and Scherer PE
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- Adiposity physiology, Adult, Body Mass Index, Chromatography, Liquid, Female, Humans, Magnetic Resonance Spectroscopy, Male, Mass Spectrometry, Middle Aged, Ceramides blood, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 physiopathology, Insulin Resistance physiology, Intra-Abdominal Fat metabolism
- Abstract
Aims/hypothesis: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort., Methods: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed., Results: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m
2 . Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β = -0.14 to -0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (β = -0.06 to -0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors., Conclusions/interpretation: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation. more...- Published
- 2018
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12. Moderate to High Levels of Cardiorespiratory Fitness Attenuate the Effects of Triglyceride to High-Density Lipoprotein Cholesterol Ratio on Coronary Heart Disease Mortality in Men.
- Author
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Farrell SW, Finley CE, Barlow CE, Willis BL, DeFina LF, Haskell WL, and Vega GL
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- Aged, Body Mass Index, Coronary Disease blood, Exercise Test, Humans, Lipoproteins, HDL blood, Male, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Cardiorespiratory Fitness physiology, Cholesterol, HDL blood, Coronary Disease mortality, Physical Fitness, Triglycerides blood
- Abstract
Objective: To examine the prospective relationships among cardiorespiratory fitness (CRF), fasting blood triglyceride to high density lipoprotein cholesterol ratio (TG:HDL-C), and coronary heart disease (CHD) mortality in men., Methods: A total of 40,269 men received a comprehensive baseline clinical examination between January 1, 1978, and December 31, 2010. Their CRF was determined from a maximal treadmill exercise test. Participants were divided into CRF categories of low, moderate, and high fit by age group and by TG:HDL-C quartiles. Hazard ratios for CHD mortality were computed using Cox regression analysis., Results: A total of 556 deaths due to CHD occurred during a mean ± SD of 16.6±9.7 years (669,678 man-years) of follow-up. A significant positive trend in adjusted CHD mortality was shown across decreasing CRF categories (P for trend<.01). Adjusted hazard ratios were significantly higher across increasing TG:HDL-C quartiles as well (P for trend<.01). When grouped by CRF category and TG:HDL-C quartile, there was a significant positive trend (P=.04) in CHD mortality across decreasing CRF categories in each TG:HDL-C quartile., Conclusion: Both CRF and TG:HDL-C are significantly associated with CHD mortality in men. The risk of CHD mortality in each TG:HDL-C quartile was significantly attenuated in men with moderate to high CRF compared with men with low CRF. These results suggest that assessment of CRF and TG:HDL-C should be included for routine CHD mortality risk assessment and risk management., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2017
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13. Metabolic Concomitants of Obese and Nonobese Women With Features of Polycystic Ovarian Syndrome.
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Boumosleh JM, Grundy SM, Phan J, Neeland IJ, Chang A, and Vega GL
- Abstract
Context: Polycystic ovarian syndrome (PCOS) is often associated with obesity and diabetes., Objective: The present study measured body fat distribution and metabolic risk factors in women with features of PCOS., Design: Cross-sectional, multiethnic study of cardiovascular risks., Setting: General community., Study Participants: 145 PCOS and 344 non-PCOS women., Exposure Measures: Body composition by dual x-ray absorptiometry; abdominal fat masses measured by magnetic resonance imaging and hepatic triglyceride by magnetic resonance spectroscopy., Outcomes Measures: Body composition, liver fat content, homeostatic model assessment for insulin resistance (HOMA-IR), revised, and metabolic syndrome components., Results: PCOS women had a higher free androgen index compared with the non-PCOS women. Nonobese PCOS and non-PCOS women had a similar body fat content and distribution, HOMA-IR, and hepatic triglyceride content. Obese PCOS women had a similar total body fat percentage compared with their non-PCOS counterparts (41.4% and 41.4% respectively). Both obese groups had similar intraperitoneal fat (1.4% of total body mass in PCOS vs 1.4% in non-PCOS). However, obese PCOS women had a greater ratio of truncal/lower body fat (1.42 vs 1.27; P < 0.016). They also had greater insulin resistance (HOMA-IR: PCOS, 2.24% vs non-PCOS, 1.91%; P < 0.016), higher liver triglyceride content (6.96% in PCOS vs 4.44% in non-PCOS; P < 0.016), and a greater incidence of hypertension (33% vs 24%; P < 0.05). No differences were observed in other metabolic risk factors., Conclusions: Both obese and nonobese women with PCOS features had a greater free androgen index compared with non-PCOS women, but neither had greater intraperitoneal fat or abnormal lipid levels. Obese, but not nonobese, women with PCOS had a greater truncal/lower extremity fat ratio, HOMA-IR, and liver triglyceride content. more...
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- 2017
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14. An Analysis of Individual Body Fat Depots and Risk of Developing Cancer: Insights From the Dallas Heart Study.
- Author
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Gupta A, Pandey A, Ayers C, Beg MS, Lakoski SG, Vega GL, Grundy SM, Johnson DH, and Neeland IJ
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- Absorptiometry, Photon methods, Adult, Female, Humans, Incidence, Magnetic Resonance Imaging methods, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Statistics as Topic, Texas epidemiology, Breast pathology, Intra-Abdominal Fat pathology, Neoplasms epidemiology, Neoplasms pathology, Obesity diagnosis, Obesity epidemiology, Prostate pathology, Subcutaneous Fat, Abdominal pathology
- Abstract
Objective: To examine the association between specific adipose tissue depots and the risk of incident cancer in the Dallas Heart Study., Patients and Methods: Individuals without prevalent cancer in the Dallas Heart Study underwent quantification of adipose depots: visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and liver fat by magnetic resonance imaging, and subcutaneous lower-body fat (LBF) by dual-energy X-ray absorptiometry from January 1, 2000, through December 31, 2002, and were observed for the development of cancer for up to 12 years. Multivariable Cox proportional hazards modeling was performed to examine the association between fat depots and cancer., Results: Of 2627 participants (median age, 43 years; 69% nonwhite race), 167 (6.4%) developed cancer. The most common primary sites of cancer were the breast (in women) and the prostate (in men). In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy, and body mass index, a 1-SD increase in VAT was not associated with increased risk of cancer (hazard ratio [HR], 0.94; 95% CI, 0.77-1.14). In contrast, each 1-SD increase in LBF was associated with a reduced incidence of cancer (HR, 0.69; 95% CI, 0.52-0.92) in the fully adjusted model., Conclusions: In this study, adiposity-associated cancer risk was heterogeneous and varied by fat depot: VAT was not independently associated with incident cancer, and LBF seemed to protect against cancer development. Further studies of the adiposity-cancer relationship, including serial assessments, are needed to better elucidate this relationship., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2017
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15. Comparison of visceral fat mass measurement by dual-X-ray absorptiometry and magnetic resonance imaging in a multiethnic cohort: the Dallas Heart Study.
- Author
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Neeland IJ, Grundy SM, Li X, Adams-Huet B, and Vega GL
- Subjects
- Adult, Black or African American, Body Composition physiology, Body Mass Index, Female, Hispanic or Latino, Humans, Magnetic Resonance Imaging, Male, Middle Aged, White People, Absorptiometry, Photon, Intra-Abdominal Fat diagnostic imaging, Obesity diagnostic imaging
- Abstract
Background/objectives: Visceral adipose tissue (VAT) mass, a risk factor for cardiometabolic complications of obesity, is usually measured by magnetic resonance imaging (MRI) but this method is not practical in a clinical setting. In contrast, measurement of VAT by dual-x-ray absorptiometry (DXA) appears to circumvent the limitations of MRI. In this study, we compared measurements of VAT mass by MRI and DXA in the large, multiethnic cohort of the Dallas Heart Study (DHS)., Subjects/methods: About 2689 DHS participants underwent paired measurement of VAT by MRI and DXA. Sex-stratified analyses were performed to evaluate the correlation and agreement between DXA and MRI. Model validation was performed using bootstrapping and inter-reader variability was assessed., Results: Mean age of the cohort was 44 years, with 55% female, 48% Black and 75% overweight/obese participants. Regression analysis showed a linear relationship between DXA and MRI with R(2)=0.82 (95% confidence interval (CI) 0.81-0.84) for females and R(2)=0.86 (95% CI 0.85-0.88) for males. Mean difference between methods was 0.01 kg for females and 0.09 kg for males. Bland-Altman analysis showed that DXA tended to modestly underestimate VAT compared with MRI at lower VAT levels and overestimate it compared with MRI at higher VAT levels. Results were consistent in analyses stratified by race, body mass index status, waist girth and body fat. Inter-individual reader correlation among 50 randomly selected scans was excellent (inter-class correlation coefficient=0.997)., Conclusions: VAT mass quantification by DXA was both accurate and valid among a large, multiethnic cohort within a wide range of body fatness. Further studies including repeat assessments over time will help determine its long-term applicability. more...
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- 2016
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16. Body fat distribution and incident cardiovascular disease in obese adults.
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Neeland IJ, Turer AT, Ayers CR, Berry JD, Rohatgi A, Das SR, Khera A, Vega GL, McGuire DK, Grundy SM, and de Lemos JA
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- Adult, Humans, Obesity epidemiology, United States epidemiology, Body Fat Distribution, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Cardiovascular Diseases metabolism, Obesity complications
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- 2015
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17. Association of multiple adiposity exposures and cardiorespiratory fitness with all-cause mortality in men: the Cooper Center Longitudinal Study.
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Farrell SW, Finley CE, Jackson AW, Vega GL, and Morrow JR Jr
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- Adipose Tissue physiology, Adult, Body Mass Index, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Middle Aged, Obesity mortality, Proportional Hazards Models, Waist Circumference physiology, Adiposity physiology, Mortality, Physical Fitness physiology
- Abstract
Objective: To examine the additive effects of an increased number of positive adiposity exposures on all-cause mortality in men before and after stratification by cardiorespiratory fitness (CRF) level., Patients and Methods: A total of 36,836 men underwent a physical examination at the Cooper Clinic from January 1, 1971, through December 31, 2006. Exposures included body mass index, waist circumference, percentage of body fat, and CRF as determined by duration of a maximal exercise test. Participants were identified as being either obese (positive) or nonobese (negative) for each adiposity exposure and then grouped into 4 categories: group 1, negative for all adiposity exposures; group 2, positive for any 1 exposure; group 3, positive for any 2 exposures; and group 4, positive for all exposures. Then CRF was grouped as fit or unfit on the basis of the upper 80% and lower 20% of the age-standardized CRF distribution as previously reported in the Cooper Center Longitudinal Study. Hazard ratios were computed with Cox regression analysis., Results: A total of 2294 deaths occurred during a mean ± SD of 15.5 ± 8.1 years of follow-up. Adjusted hazard ratios across adiposity groups were 1.0 (referent), 1.05, 1.37, and 1.87 for groups 1 through 4, respectively (P for trend <.001). Mortality rates were significantly lower within each of the first 3 adiposity groups in fit compared with unfit men (P<.009 for all comparisons)., Conclusion: An increasing number of positive adiposity exposures were associated with increased mortality in men. Because moderate to high CRF attenuated mortality rates in all adiposity groups, measurement of CRF should be included for identifying men at increased risk for all-cause mortality., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2014
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18. Association of urinary sodium-to-potassium ratio with obesity in a multiethnic cohort.
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Jain N, Minhajuddin AT, Neeland IJ, Elsayed EF, Vega GL, and Hedayati SS
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- Adult, Blood Glucose metabolism, Blood Pressure, Body Mass Index, Ethnicity, Female, Humans, Linear Models, Male, Middle Aged, Nutrition Surveys, Potassium, Dietary analysis, Prospective Studies, Sex Factors, Sodium, Dietary analysis, Triglycerides blood, Adiposity, Obesity ethnology, Obesity urine, Potassium, Dietary urine, Sodium, Dietary urine
- Abstract
Background: Previous studies that reported an association of dietary Na(+) intake with metabolic syndrome were limited by the use of imprecise measures of obesity, Na(+) intake, or exclusion of multiethnic populations. The effect of dietary K(+) intake on obesity is less well described., Objective: We hypothesized that high dietary Na(+) and low K(+), based on the ratio of urinary Na(+) to K(+) (U[Na(+)]/[K(+)]) in a first-void morning urinary sample, is independently associated with total body fat., Design: In a prospective population-based cohort, 2782 participants in the community-dwelling, probability-sampled, multiethnic Dallas Heart Study were analyzed. The primary outcome established a priori was total-body percentage fat (TBPF) measured by dual-energy X-ray absorptiometry. The main predictor was U[Na(+)]/[K(+)]. Robust linear regression was used to explore an independent association between U[Na(+)]/[K(+)] and TBPF. The analyses were stratified by sex and race after their effect modifications were analyzed., Results: Of the cohort, 55.4% were female, 49.8% African American, 30.8% white, 17.2% Hispanic, and 2.2% other races. The mean (±SD) age was 44 ± 10 y, BMI (in kg/m(2)) was 30 ± 7, TBPF was 32 ± 10%, and U[Na(+)]/[K(+)] was 4.2 ± 2.6; 12% had diabetes. In the unadjusted and adjusted models, TBPF increased by 0.75 (95% CI: 0.25, 1.25) and 0.43 (0.15, 0.72), respectively (P = 0.003 for both), for every 3-unit increase in U[Na(+)]/[K(+)]. A statistically significant interaction was found between race and U[Na(+)] /[K(+)], so that the non-African American races had a higher TBPF than did the African Americans per unit increase in U[Na(+)]/[K(+)] (P-interaction < 0.0001 for both). No interaction was found between sex and U[Na(+)]/[K(+)]., Conclusions: The ratio of dietary Na(+) to K(+) intake may be independently associated with TBPF, and this association may be more pronounced in non-African Americans. Future studies should explore whether easily measured spot U[Na(+)]/[K(+)] can be used to monitor dietary patterns and guide strategies for obesity management. more...
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- 2014
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19. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults.
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Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, and de Lemos JA
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- Adiponectin blood, Adult, Atherosclerosis blood, Atherosclerosis pathology, Biomarkers metabolism, C-Reactive Protein metabolism, Cholesterol, HDL blood, Cholesterol, LDL blood, Cholesterol, VLDL blood, Dyslipidemias complications, Female, Heart Diseases blood, Heart Diseases pathology, Humans, Inflammation blood, Inflammation Mediators metabolism, Insulin Resistance, Intra-Abdominal Fat metabolism, Leptin blood, Male, Metabolic Syndrome blood, Metabolic Syndrome pathology, Middle Aged, Multivariate Analysis, Obesity blood, Obesity metabolism, Obesity pathology, Phenotype, Subcutaneous Fat metabolism, Atherosclerosis etiology, Body Fat Distribution, Heart Diseases etiology, Intra-Abdominal Fat pathology, Metabolic Syndrome etiology, Obesity complications, Subcutaneous Fat pathology
- Abstract
Objective: Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults., Design and Methods: Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index., Results: In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment., Conclusion: VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk., (Copyright © 2012 The Obesity Society.) more...
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- 2013
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20. Relation of regional fat distribution to left ventricular structure and function.
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Neeland IJ, Gupta S, Ayers CR, Turer AT, Rame JE, Das SR, Berry JD, Khera A, McGuire DK, Vega GL, Grundy SM, de Lemos JA, and Drazner MH
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- Absorptiometry, Photon, Adult, Cardiac Output, Chi-Square Distribution, Cross-Sectional Studies, Female, Humans, Hypertrophy, Left Ventricular diagnosis, Hypertrophy, Left Ventricular physiopathology, Intra-Abdominal Fat diagnostic imaging, Linear Models, Logistic Models, Magnetic Resonance Imaging, Male, Middle Aged, Multivariate Analysis, Obesity diagnosis, Obesity physiopathology, Predictive Value of Tests, Risk Factors, Subcutaneous Fat diagnostic imaging, Texas, Vascular Resistance, Adiposity, Hemodynamics, Hypertrophy, Left Ventricular etiology, Intra-Abdominal Fat physiopathology, Obesity complications, Subcutaneous Fat physiopathology, Ventricular Function, Left, Ventricular Remodeling
- Abstract
Background: The relation of body fat distribution to left ventricular (LV) structure and function is poorly defined., Methods and Results: A total of 2710 participants without heart failure or LV dysfunction in the Dallas Heart Study underwent dual energy x-ray absorptiometry and MRI assessment of fat distribution, LV morphology, and hemodynamics. Cross-sectional associations of fat distribution with LV structure and function were examined after adjustment for age, sex, race, comorbidities, and lean mass. Mean age was 44 years with 55% women; 48% blacks; and 44% obese. After multivariable adjustment, visceral adipose tissue was associated with concentric remodeling characterized by lower LV end-diastolic volume (β=-0.21), higher concentricity (β=0.20), and wall thickness (β=0.09; P<0.0001 for all). In contrast, lower body subcutaneous fat was associated with higher LV end-diastolic volume (β=0.48), reduced concentricity (β=-0.50), and wall thickness (β=-0.28, P<0.0001 for all). Visceral adipose tissue was also associated with lower cardiac output (β=-0.10, P<0.05) and higher systemic vascular resistance (β=0.08, P<0.05), whereas lower body subcutaneous fat associated with higher cardiac output (β=0.20, P<0.0001) and lower systemic vascular resistance (β=-0.18, P<0.0001). Abdominal subcutaneous fat showed weaker associations with concentric remodeling and was not associated with hemodynamics. Among the subset of obese participants, visceral adipose tissue, but not abdominal subcutaneous fat, was significantly associated with concentric remodeling., Conclusions: Visceral adipose tissue, a marker of central adiposity, was independently associated with concentric LV remodeling and adverse hemodynamics. In contrast, lower body subcutaneous fat was associated with eccentric remodeling. The impact of body fat distribution on heart failure risk requires prospective study. more...
- Published
- 2013
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21. Higher natriuretic peptide levels associate with a favorable adipose tissue distribution profile.
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Neeland IJ, Winders BR, Ayers CR, Das SR, Chang AY, Berry JD, Khera A, McGuire DK, Vega GL, de Lemos JA, and Turer AT
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- Absorptiometry, Photon, Adipokines blood, Adult, Androgens blood, Body Composition, Body Mass Index, Female, Humans, Insulin Resistance, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments blood, Testosterone blood, Adiposity physiology, Natriuretic Peptide, Brain blood
- Abstract
Objectives: The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort., Background: Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans., Methods: A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index., Results: Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = -0.08; p < 0.0001) and liver fat (beta coefficient = -0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations., Conclusions: Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2013
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22. Metabolic risk susceptibility in men is partially related to adiponectin/leptin ratio.
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Vega GL and Grundy SM
- Subjects
- Adult, Apolipoproteins B blood, Blood Pressure, Body Mass Index, Cholesterol, HDL blood, Cross-Sectional Studies, Humans, Insulin Resistance, Male, Middle Aged, Obesity blood, Overweight blood, Risk Factors, Triglycerides blood, Waist Circumference, Adiponectin blood, Leptin blood, Metabolic Syndrome blood
- Abstract
Background: High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance., Methods: This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (<6.5 μ g/mL)and high (≥6.5 μ g/mL)adiponectin levels or a low or high ratio of adiponectin/leptin., Results: Men with high adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol than those with low ratio. Similarly, those with high adiponectin/leptin ratio had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In contrast, levels of adiponectin or the ratio of adiponectin/leptin did not associate with systolic blood pressure. But the ratio of adiponectin/leptin decreased progressively with the increase in the number of risk factors for metabolic syndrome., Conclusion: Adipokine levels may reflect adipose tissue triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat mass, and adiponectin is a biomarker of triglyceride metabolism and insulin sensitivity. Men with high adiponectin/leptin ratios have better triglyceride profile and insulin sensitivity than men with a low ratio regardless of waist girth. more...
- Published
- 2013
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23. Relationship between perceptions about neighborhood environment and prevalent obesity: data from the Dallas Heart Study.
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Powell-Wiley TM, Ayers CR, de Lemos JA, Lakoski SG, Vega GL, Grundy S, Das SR, Banks-Richard K, and Albert MA
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- Adolescent, Adult, Age Factors, Aged, Automobiles, Confidence Intervals, Educational Status, Factor Analysis, Statistical, Female, Humans, Income, Logistic Models, Male, Middle Aged, Obesity psychology, Odds Ratio, Recreation, Risk Factors, Social Environment, Solid Waste, Texas, Violence, Young Adult, Body Mass Index, Environment, Obesity etiology, Perception, Residence Characteristics, Stress, Psychological complications
- Abstract
Objectives: Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment-derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] ≥ 30 kg/m(2) ) among 5,907 participants in the Dallas Heart Study, a multi-ethnic, probability-based sample of Dallas County residents was examined., Design and Methods: Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity., Results: Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors (P trend <0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment (P trend <0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03-1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17-1.64]), trash/litter in neighborhood (OR 1.27, [1.01-1.46]), lack of recreational areas (OR 1.21, [1.01-1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04-1.51])., Conclusions: Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community., (Copyright © 2012 The Obesity Society.) more...
- Published
- 2013
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24. Waist circumference as measure of abdominal fat compartments.
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Grundy SM, Neeland IJ, Turer AT, and Vega GL
- Subjects
- Abdominal Fat metabolism, Adult, Analysis of Variance, Biomarkers blood, Blood Glucose analysis, Ethnicity, Female, Humans, Insulin blood, Insulin Resistance ethnology, Intra-Abdominal Fat physiopathology, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Obesity, Abdominal blood, Obesity, Abdominal ethnology, Obesity, Abdominal physiopathology, Predictive Value of Tests, Sex Factors, Subcutaneous Fat, Abdominal physiopathology, Texas epidemiology, Triglycerides blood, Abdominal Fat physiopathology, Adiposity ethnology, Obesity, Abdominal diagnosis, Waist Circumference ethnology
- Abstract
This study examines intercorrelations among waist circumference (WC), intraperitoneal fat (IPF), and subcutaneous abdominal fat (SAF) in ethnically diverse Dallas Heart Study consisting of 1538 women and 1212 men (50% Black). Correlations between fat depots and triglyceride or HOMA2-IR, biomarkers of metabolic syndrome, are also reported. Total abdominal fat (TAF), ASF, and IPF masses were measured by magnetic resonance imaging. The highest correlations with WC according to ethnicity and gender were noted for TAF (R (2) = 0.81 - 0.88) with progressively lower correlations with ASF (0.65-0.82) and IPF (0.29-0.85). The percentage of IPF relative to TAF was not significantly correlated with WC. For all WC categories, higher IPF/ASF ratios were associated with higher triglyceride levels. In contrast, differences in ratios had little or no association with HOMA2-IR. However, when all data were pooled, IPF was positively correlated with both triglyceride (r = 0.358 (men) and 0.363 (women)) and HOMA2-IR (r = 0.480 (men) and 0.517 (women)); after adjustment for ASF, IPF was still correlated with triglyceride (r = 0.353 (men) and 0.348 (women)) and HOMA2-IR (r = 0.290 (men) and 0.221 (women)). WC measures TAF reliably, but its association with IPF depends on IPF/ASF ratios that vary by gender and ethnicity. more...
- Published
- 2013
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25. Atherogenic low density lipoprotein phenotype in long-term survivors of childhood acute lymphoblastic leukemia.
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Malhotra J, Tonorezos ES, Rozenberg M, Vega GL, Sklar CA, Chou J, Moskowitz CS, Eshelman-Kent DA, Janiszewski P, Ross R, and Oeffinger KC
- Subjects
- Adolescent, Adult, Child, Female, Humans, Lipoproteins, LDL genetics, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Young Adult, Lipoproteins, LDL blood, Phenotype, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Survivors
- Abstract
Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% of LDL-cholesterol (LDL-c) in small dense LDL fractions (LDL(3+4)) were classified as LDL pattern B. Visceral and subcutaneous adipose tissue (VAT, SAT) volumes were also measured by computed tomography. While the mean LDL-c level of ALL survivors was 108.7 ± 26.8 mg/dl, 36% (40/110) of survivors had atherogenic LDL pattern B. This pattern was more common in males (26/47; 55%) than in females (14/63; 22%, P = 0.001) and more common in survivors treated with cranial radiotherapy (15/33; 45%) than in those who were treated with chemotherapy alone (25/77; 33%; P = 0.04, adjusted for age, gender, history of hypertension, and smoking history). VAT was associated with atherogenic lipids: LDL pattern B and LDL(3+4) levels. This association was independent of other measures of body fat. We conclude that a substantial proportion of ALL survivors had an atherogenic LDL phenotype despite normal mean LDL-c levels. An atherogenic LDL phenotype may contribute to the increase in cardiovascular mortality and morbidity in this population. more...
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- 2012
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26. Adipose tissue mass and location affect circulating adiponectin levels.
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Turer AT, Khera A, Ayers CR, Turer CB, Grundy SM, Vega GL, and Scherer PE
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- Absorptiometry, Photon, Adiposity physiology, Adult, Body Composition physiology, Body Mass Index, Body Weight physiology, Female, Humans, Male, Middle Aged, Multivariate Analysis, Obesity blood, Obesity metabolism, Young Adult, Adiponectin blood, Adipose Tissue metabolism
- Abstract
Aims/hypothesis: Plasma levels of adiponectin are inversely associated with body mass. We hypothesised that adipose tissue distribution and body composition influences adiponectin levels., Methods: We assessed plasma adiponectin concentrations and dual-energy X-ray absorptiometry (DEXA) measurements of body composition among 2,820 participants from the Dallas Heart Study., Results: Among both women and men, adiponectin levels were higher in whites than in either Hispanics or African-Americans (for women: median 9.99 μg/ml [25th,75th percentile 7.11, 13.77] vs 7.56 μg/ml [5.05, 9.98] vs 6.39 μg/ml [4.37, 9.41], respectively, p < 0.0001; for men: 6.43 μg/ml [4.66, 9.19] vs 5.55 μg/ml [3.64, 7.50] vs 5.03 μg/ml [3.39, 7.28], p < 0.0001). In univariate analysis, each individual component of body mass was inversely associated with adiponectin. After multivariate analysis, adiponectin levels were found to be positively associated with lower extremity fat, whether expressed in absolute mass (for women: β = 0.055, p < 0.0001; for men: β = 0.061, p < 0.0001), or as a relative proportion (for women: β = 0.035, p < 0.0001; for men: β = 0.034, p < 0.0001). This association was consistent across ethnicities. Conversely, adiponectin was negatively correlated with truncal fat, both in absolute (for women: β = -0.039, p < 0.0001; for men: β = -0.044, p < 0.0001) and relative terms (for women: β = -0.027, p < 0.0001; for men β = -0.033, p < 0.0001). At the extreme of body mass, higher degrees of lower extremity and truncal adiposity were associated with higher levels of adiponectin., Conclusions/interpretation: These data suggest that the location of adipose depots differentially influences circulating adiponectin concentrations-a finding observed across ethnicity and sex. Gross measures of body mass alone do not adequately account for adiponectin levels. This supports a role of adiponectin as a mediator of the positive effects of lower extremity adiposity on improvements in insulin sensitivity. more...
- Published
- 2011
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27. Is intra-abdominal obesity a unique risk factor for metabolic syndrome in non-diabetics?
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Vega GL
- Subjects
- Body Mass Index, Diabetes Mellitus, Type 2 complications, Female, Humans, India epidemiology, Male, Metabolic Syndrome epidemiology, Obesity epidemiology, Risk Factors, Abdominal Fat, Metabolic Syndrome complications, Obesity complications
- Published
- 2010
28. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy.
- Author
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Mehdi UF, Adams-Huet B, Raskin P, Vega GL, and Toto RD
- Subjects
- Adult, Albuminuria drug therapy, Albuminuria urine, Angiotensin II Type 1 Receptor Blockers adverse effects, Angiotensin-Converting Enzyme Inhibitors adverse effects, Bicarbonates blood, Blood Pressure drug effects, Creatinine urine, Diabetic Nephropathies physiopathology, Diabetic Nephropathies urine, Double-Blind Method, Drug Therapy, Combination, Female, Glycated Hemoglobin metabolism, Humans, Hypertension drug therapy, Hypertension physiopathology, Hypertension urine, Lisinopril administration & dosage, Lisinopril adverse effects, Losartan administration & dosage, Losartan adverse effects, Male, Middle Aged, Potassium blood, Renin-Angiotensin System drug effects, Spironolactone administration & dosage, Spironolactone adverse effects, Angiotensin II Type 1 Receptor Blockers administration & dosage, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Diabetic Nephropathies drug therapy, Mineralocorticoid Receptor Antagonists administration & dosage
- Abstract
Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio > or =300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, -51.0%, -11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, -37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial. more...
- Published
- 2009
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29. Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal.
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Periwal V, Chow CC, Bergman RN, Ricks M, Vega GL, and Sumner AE
- Subjects
- Adult, Black or African American, Algorithms, Bayes Theorem, Fatty Acids, Nonesterified blood, Female, Glucose pharmacology, Glucose Tolerance Test, Humans, Hypoglycemic Agents pharmacology, Insulin blood, Insulin Resistance, Likelihood Functions, Male, Middle Aged, Reproducibility of Results, Blood Glucose metabolism, Insulin pharmacology, Lipolysis drug effects, Models, Biological
- Abstract
The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG. more...
- Published
- 2008
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30. Independent associations between metabolic syndrome, diabetes mellitus and atherosclerosis: observations from the Dallas Heart Study.
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Chen K, Lindsey JB, Khera A, De Lemos JA, Ayers CR, Goyal A, Vega GL, Murphy SA, Grundy SM, and McGuire DK
- Subjects
- Adult, Aorta, Abdominal pathology, Aortic Diseases epidemiology, Aortic Diseases pathology, Aortography methods, Atherosclerosis epidemiology, Atherosclerosis pathology, Calcinosis epidemiology, Calcinosis pathology, Coronary Angiography methods, Coronary Artery Disease epidemiology, Coronary Artery Disease pathology, Cross-Sectional Studies, Diabetes Mellitus pathology, Diabetic Angiopathies epidemiology, Diabetic Angiopathies pathology, Female, Humans, Magnetic Resonance Angiography, Male, Metabolic Syndrome epidemiology, Metabolic Syndrome pathology, Middle Aged, Odds Ratio, Population Surveillance, Prevalence, Risk Assessment, Risk Factors, Texas epidemiology, Tomography, X-Ray Computed, Aortic Diseases etiology, Atherosclerosis etiology, Calcinosis etiology, Coronary Artery Disease etiology, Diabetes Mellitus epidemiology, Diabetic Angiopathies etiology, Metabolic Syndrome complications
- Abstract
Diabetes mellitus (DM) has been termed a "coronary disease equivalent", yet data suggest that only those DM subjects with metabolic syndrome (MetS) are at increased coronary risk. Using data from the Dallas Heart Study, a large, probability-based population study, we assessed the individual and joint associations between MetS, DM and atherosclerosis, defined as coronary artery calcium (CAC) detected by electron-beam computerised tomography (EBCT) and abdominal aortic plaque (AAP) detected by magnetic resonance imaging. Among 2,735 participants, the median age was 44 years; 1,863 (68%) were non-white; 1,509 (55%) were women; 697 (25.5%) had MetS without DM; 53 (1.9%) had DM without MetS; and 246 (9.0%) had both DM and MetS. The prevalence of CAC increased from those with neither MetS nor DM (16.6%) to MetS only (24.0%) to DM only (30.2%) to both MetS and DM (44.7%) (ptrend <0.0001). The prevalence of CAC was higher in those with both DM and MetS versus either alone (p<0.0001). After adjustment, MetS and DM were each independently associated with CAC (odds ratio [OR] 1.4, 95% confidence intervals [CI] 1.1-1.8; OR 1.8, 95% CI 1.3-2.5, respectively). Compared with the group without DM or MetS, those with both MetS and DM had the most CAC (adjusted OR 2.3; 95% CI 1.6-3.2). All analyses of AAP yielded qualitatively similar results. In conclusion, both MetS and DM are independently associated with an increased prevalence of atherosclerosis, with the highest observed prevalence in subjects with both DM and MetS. more...
- Published
- 2008
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31. Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis: results from the Dallas Heart Study.
- Author
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Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schönbeck U, Khera A, McGuire DK, Vega GL, Grundy S, Libby P, and de Lemos JA
- Subjects
- Adult, Black or African American, Age Factors, Biomarkers, Cohort Studies, Coronary Artery Disease epidemiology, Female, Humans, Life Style, Male, Metabolic Syndrome epidemiology, Middle Aged, Sex Factors, Texas, White People, Coronary Artery Disease blood, Interleukin-18 blood, Metabolic Syndrome blood
- Abstract
Objective: Although IL-18 promotes atherogenesis in animal studies and predicts cardiovascular risk in humans, it is unknown whether elevated IL-18 levels are associated with coronary atherosclerosis in the general population., Methods and Results: IL-18 plasma levels were determined by ELISA in 2231 subjects from the Dallas Heart Study. In univariable analysis, IL-18 levels associated with traditional cardiovascular risk factors and particularly with components of the metabolic syndrome (MS, P<0.01 for trend across the number of MS components); IL-18 also associated with coronary artery calcium (CAC) scores measured by electron beam computed tomography and aortic plaque measured by MRI (P<0.01 for each). In multivariable analyses, IL-18 remained associated with multiple components of the MS but not with CAC or aortic plaque., Conclusions: In a large population-based sample, elevated IL-18 plasma levels associated with risk factors for atherosclerosis and with the metabolic syndrome. The association between IL-18 and atherosclerosis diminished after accounting for traditional cardiovascular risk factors. These data suggest that IL-18 does not add independently to detection of atherosclerotic burden in asymptomatic individuals. more...
- Published
- 2007
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32. Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.
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Shah SH, Kraus WE, Crossman DC, Granger CB, Haines JL, Jones CJ, Mooser V, Huang L, Haynes C, Dowdy E, Vega GL, Grundy SM, Vance JM, and Hauser ER
- Subjects
- Adult, Coronary Artery Disease diagnosis, Female, Genetic Linkage, Genetic Variation, Humans, Lipoproteins genetics, Lod Score, Male, Middle Aged, Phenotype, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 5, Coronary Artery Disease genetics, Lipoproteins blood, Quantitative Trait Loci
- Abstract
Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease-related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results. We performed ordered subset analysis (OSA) and quantitative trait linkage (QTL) using serum lipoproteins and microsatellite markers in 346 families with early-onset CAD. OSA defined homogeneous subsets and calculated lod scores across a chromosome after ranking families by mean lipoprotein values. QTL used variance components analysis. We found significantly increased linkage to chromosome 3q13 (LOD 5.10, p = 0.008) in families with higher HDL cholesterol, lower LDL and total cholesterol, lower triglycerides, and fewer CAD risk factors, possibly due to a concentrated non-lipoprotein-related genetic effect. OSA identified linkage on chromosome 5q34 in families with higher cholesterol, possibly representing a hereditary lipoprotein phenotype. Multiple QTLs were identified, with the strongest for: total cholesterol on chromosome 5q14 (LOD 4.3); LDL on 20p12 (LOD 3.97); HDL on 3p14 (LOD 1.65); triglycerides on 18q22 (LOD 1.43); and HDL/TC ratio on 3q27-28 (LOD 2.06). Our findings suggest the presence of etiologic heterogeneity in families with early-onset CAD, potentially due to differential effects of lipoprotein phenotypes. Candidate genes are under investigation. more...
- Published
- 2006
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33. Combination of fenofibrate plus low-dose nicotinic acid added to statin treatment in type 2 diabetes: An open-label, crossover study.
- Author
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Vega GL, Vajja M, Palacio N, Caterp NB, and Grundy SM
- Abstract
Background: Plasma lipid abnormalities commonly persist in patients with diabetic dyslipidemia in spite of statin monotherapy., Objective: The aim of this study was to determine whether fenofibrate plus low-dose nicotinic acid adequately improves the lipoprotein profile in patients with diabetic dyslipidemia who are being treated with a statin., Methods: In this open-label, crossover study, patients with type 2 diabetes mellitus who were receiving statin treatment were enrolled at the Lipid Clinic of the Veterans Affairs Medical Center, Dallas, Texas, and administered simvastatin 20 mg/d for 8 weeks. At the end of the 8-week period, fenofibrate 160 mg/d was added for 8 weeks, followed by the addition of extended-release nicotinic acid 1 g/d for an additional 8 weeks. The first subject was recruited on September 25, 2003, and the last subject was recruited on September 28, 2004. Liver function tests, creatine phosphokinase activity, and blood glucose levels were assessed every 4 weeks to assess tolerability. Levels of fasting plasma lipids and lipoprotein cholesterol were measured every 8 weeks on 3 consecutive days in each patient; C-reactive protein, lipoprotein pattern, and glycosylated hemoglobin levels were assessed once every 8 weeks. Plasma levels of total cholesterol, triglycerides, very-low-density lipoprotein plus intermediate-density lipoprotein cholesterol (VLDL+IDL-C), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B were also measured., Results: Twenty-six patients were enrolled in the study and 20 patients (18 men, 2 women; mean [SD] age, 58.8 [6.5] years) completed it. The mean plasma triglyceride level was significantly decreased (-29.2%; P= 0.004) and the mean HDL-C level was significantly increased (+13.5%; P < 0.001) with 3-drug treatment (simvastatin + fenofibrate + extended-release nicotinic acid) compared with simvastatin monotherapy. Significant reductions in plasma levels of VLDL+IDL-C (-35.7%; P = 0.001), VLDL+IDL-apolipoprotein B (-30%; P = 0.005), non-HDL-C (-12.9%; P = 0.001), and total-apolipoprotein B (-17.9%; P < 0.001) were seen with the 3-drug treatment compared with simvastatin alone. Compared with simvastatin monotherapy, simvastatin + fenofibrate-treated (2-drug treatment) patients had significantly lower plasma levels of triglycerides (-24.9%; P = 0.014) and significantly higher levels of HDL-C (+5.4%; P = 0.008). Significant reductions were also seen in levels of VLDL+IDL-C (-28.6%; P = 0.004), VLDL+IDL-apolipoprotein B (-26.7%; P < 0.001), non-HDL-C (-9.1 %; P= 0.004), and total-apolipoprotein B (-12.3%; P < 0.001) in the 2-drug treatment group compared with the simvastatin monotherapy group. The administration of 3-drug treatment was associated with improved responses in all lipoprotein fractions, although only the increase in HDL-C level was statistically significant (+7.7%; P = 0.008) compared with 2-drug treatment., Conclusions: Treatment with the 3-drug regimen was associated with a significant reduction in triglyceride levels compared with simvastatin monotherapy. However, there was not a significant incremental reduction in triglyceride levels when nicotinic acid was added to the 2-drug treatment, suggesting that the triglyceride-lowering effect of fenofibrate + nicotinic acid is not cumulative. To obtain clinically meaningful responses, particularly for the treatment of elevated HDL-C, higher doses of nicotinic acid might be required. more...
- Published
- 2006
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34. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol.
- Author
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Kotowski IK, Pertsemlidis A, Luke A, Cooper RS, Vega GL, Cohen JC, and Hobbs HH
- Subjects
- Alleles, Amino Acid Sequence, Evolution, Molecular, Female, Haplotypes, Humans, Male, Molecular Sequence Data, Mutation, Proprotein Convertase 9, Proprotein Convertases, Cholesterol, LDL blood, Gene Frequency, Hypercholesterolemia genetics, Polymorphism, Single Nucleotide, Serine Endopeptidases genetics
- Abstract
Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma levels of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip-based oligonucleotide hybridization were used to determine whether other sequence variations in PCSK9 contribute to differences in LDL-C levels. The coding regions of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study (n=3,543) who had the lowest (<5th percentile) and highest (>95th percentile) plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F, and A443T) were significantly and reproducibly associated with lower plasma levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low-LDL-C variants were associated with increased hepatic triglyceride content, as measured by proton magnetic resonance spectroscopy. This finding is most consistent with the reduction in LDL-C being caused primarily by accelerating LDL clearance, rather than by reduced lipoprotein production. Association studies with 93 noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3 SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels. These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering. more...
- Published
- 2006
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35. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels.
- Author
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Cohen JC, Pertsemlidis A, Fahmi S, Esmail S, Vega GL, Grundy SM, and Hobbs HH
- Subjects
- Absorption, Adult, Ethnicity genetics, Female, Haplotypes, Humans, Male, Membrane Transport Proteins, Middle Aged, Sterols pharmacokinetics, Texas, Genetic Variation genetics, Lipoproteins, LDL blood, Membrane Proteins genetics, Membrane Proteins metabolism, Proteins genetics, Proteins metabolism, Sterols metabolism
- Abstract
An approach to understand quantitative traits was recently proposed based on the finding that nonsynonymous (NS) sequence variants in certain genes are preferentially enriched at one extreme of the population distribution. The NS variants, although individually rare, are cumulatively frequent and influence quantitative traits, such as plasma lipoprotein levels. Here, we use the NS variant technique to demonstrate that genetic variation in NPC1L1 contributes to variability in cholesterol absorption and plasma levels of low-density lipoproteins (LDLs). The ratio of plasma campesterol (a plant sterol) to lathosterol (a cholesterol precursor) was used to estimate relative cholesterol absorption in a population-based study. Nonsynonymous sequence variations in NPC1L1 were five times more common in low absorbers (n = 26 of 256) than in high absorbers (n = 5 of 256) (P < 0.001). The rare variants identified in low absorbers were found in 6% of 1,832 African-Americans and were associated with lower plasma levels of LDL cholesterol (LDL-C) (96 +/- 36 mg/dl vs. 105 +/- 36 mg/dl; P = 0.005). These data, together with prior findings, reveal a genetic architecture for LDL-C levels that does not conform to current models for quantitative traits and indicate that a significant fraction of genetic variance in LDL-C is due to multiple alleles with modest effects that are present at low frequencies in the population. more...
- Published
- 2006
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36. No association between plasma levels of plant sterols and atherosclerosis in mice and men.
- Author
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Wilund KR, Yu L, Xu F, Vega GL, Grundy SM, Cohen JC, and Hobbs HH
- Subjects
- Adult, Animals, Aorta pathology, Aortic Diseases blood, Arteriosclerosis ethnology, Coronary Disease blood, Coronary Disease ethnology, Exons genetics, Female, Humans, Introns genetics, Male, Mice, Mice, Inbred AKR, Mice, Inbred Strains, Arteriosclerosis blood, Plant Extracts blood, Sterols blood
- Abstract
Objective: Sitosterolemia is characterized by elevated plasma levels of plant sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD develops in some subjects with sitosterolemia, despite having normal plasma cholesterol levels, suggesting that high circulating levels of plant sterols may be atherogenic. We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified mice and in middle-aged men and women., Methods and Results: Wild-type and hypercholesterolemic female mice with >20-fold higher plasma levels of plant sterols because of inactivation of the ATP-binding cassette (ABC) half transporters G5 and G8 (G5G8-/-mice) were fed chow or Western diets for 7 months. No significant differences in aortic lesion area were found when the sitosterolemic mice were compared with littermate controls. To determine whether plasma levels of plant sterols were associated with coronary atherosclerosis in humans, the relationship between plasma plant sterols and coronary calcium (detected by electron beam computer tomography) was examined in 2542 subjects aged 30 to 67 years. Plasma levels of cholesterol, but not sitosterol or campesterol, were significantly higher in subjects with coronary calcium., Conclusions: The results of this study do not support an association between elevated plasma levels of plant sterols and atherosclerosis. more...
- Published
- 2004
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37. African Americans and Caucasians have a similar prevalence of coronary calcium in the Dallas Heart Study.
- Author
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Jain T, Peshock R, McGuire DK, Willett D, Yu Z, Vega GL, Guerra R, Hobbs HH, and Grundy SM
- Subjects
- Coronary Artery Disease diagnostic imaging, Female, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Prevalence, Tomography, X-Ray Computed, United States epidemiology, Black or African American statistics & numerical data, Calcium metabolism, Coronary Artery Disease ethnology, Coronary Vessels chemistry, White People statistics & numerical data
- Abstract
Objectives: We sought to compare the prevalence of coronary atherosclerosis in a cohort of middle-age African American (black) and non-Hispanic Caucasian (white) men and women from a population-based probability sample., Background: Blacks have a higher mortality from coronary heart disease (CHD) than whites, particularly among younger individuals, and yet several studies have reported that coronary atherosclerosis is less prevalent in blacks than in whites. Data from population-based samples comparing coronary atherosclerotic burden between blacks and whites are limited., Methods: The prevalence of coronary atherosclerosis in middle-aged blacks and whites was determined using coronary calcium measured by electron beam computed tomography in 1,289 men and women from a population-based probability sample from Dallas, Texas., Results: The population estimates of the frequency of a positive scan for coronary artery calcium were not statistically different between black and white men (37% vs. 41%, p = 0.36) or between black and white women (29% vs. 23%, p = 0.21). Although the prevalence of most of the coronary risk factors varied significantly between blacks and whites, mean Framingham coronary risk factor scores were identical in black and white men (10 +/- 4) but significantly higher in black women (13 +/- 4) than in white women (12 +/- 4)., Conclusions: Blacks in the general population have a prevalence of coronary atherosclerosis similar to whites. Factors other than coronary atherosclerotic burden, which are not reflected in the Framingham risk score, contribute significantly to the higher CHD mortality rate in blacks. more...
- Published
- 2004
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38. Cardiovascular outcomes for obesity and metabolic syndrome.
- Author
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Vega GL
- Subjects
- Body Constitution, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 etiology, Humans, Hyperlipidemias therapy, Obesity epidemiology, Risk Factors, Cardiovascular Diseases etiology, Metabolic Syndrome complications, Metabolic Syndrome therapy, Obesity complications, Obesity therapy, Outcome Assessment, Health Care
- Published
- 2002
- Full Text
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39. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group IV: lifestyle and medical management of risk factors.
- Author
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Grundy SM, Garber A, Goldberg R, Havas S, Holman R, Lamendola C, Howard WJ, Savage P, Sowers J, and Vega GL
- Subjects
- Cholesterol, LDL blood, Diabetic Angiopathies etiology, Diet, Estrogen Replacement Therapy, Exercise, Female, Humans, Hyperlipidemias blood, Hyperlipidemias complications, Hypertension complications, Hypoglycemic Agents therapeutic use, Life Style, Obesity complications, Risk Factors, Smoking adverse effects, Thrombosis complications, Diabetic Angiopathies prevention & control
- Published
- 2002
- Full Text
- View/download PDF
40. Hepatic lipase (LIPC) promoter polymorphism in men with coronary artery disease. Allele frequency and effects on hepatic lipase activity and plasma HDL-C concentrations.
- Author
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Shohet RV, Vega GL, Anwar A, Cigarroa JE, Grundy SM, and Cohen JC
- Subjects
- Alleles, Cholesterol, HDL blood, Gene Frequency, Heparin blood, Humans, Lipase metabolism, Lipids blood, Male, Multicenter Studies as Topic, Polymorphism, Genetic, Coronary Disease genetics, Lipase genetics, Liver enzymology
- Abstract
Hepatic lipase is an important determinant of plasma HDL concentration and LDL subclass distribution and may therefore influence susceptibility to coronary artery disease (CAD). To assess the effect of genetic variation in hepatic lipase activity on CAD susceptibility, we determined the frequency of the -514T allele of hepatic lipase in white men with CAD and in controls who did not have CAD. In men with CAD, postheparin plasma hepatic lipase activity was 15% to 20% lower in heterozygotes and 30% lower in homozygotes for the -514T allele. Allele frequencies were similar in cases and controls, however, and were consistent with Hardy-Weinberg expectation in both groups. This finding was confirmed in a second group comprising cases with premature symptomatic CAD and controls who were free of disease. These data indicate that a primary decrease in hepatic lipase activity of as much as 30% does not influence susceptibility to CAD in white men. more...
- Published
- 1999
- Full Text
- View/download PDF
41. Effect of lifibrol on the metabolism of low density lipoproteins and cholesterol.
- Author
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Vega GL, von Bergmann K, Grundy SM, Blumenschein S, Carter NB, Laeis P, Lindenthal B, von Bergmann J, Simatupang A, Lutjohann D, and Adams-Huet B
- Subjects
- Adolescent, Adult, Aged, Anticholesteremic Agents pharmacology, Cholesterol, HDL blood, Cholesterol, LDL blood, Cross-Over Studies, Double-Blind Method, Female, Humans, Hypercholesterolemia blood, Hypercholesterolemia urine, Male, Mevalonic Acid urine, Middle Aged, Single-Blind Method, Triglycerides blood, Butanols pharmacology, Cholesterol blood, Hydroxybenzoates pharmacology, Hypercholesterolemia drug therapy, Hypercholesterolemia metabolism, Hypolipidemic Agents pharmacology, Simvastatin pharmacology
- Abstract
Lifibrol is a powerful cholesterol-lowering drug of unknown mechanism of action. This investigation was carried out to determine whether the major action of lifibrol is to enhance clearance of low density lipoproteins (LDL) through the LDL-receptor pathway, and if so, whether the drug exerts its action by altering the excretion of bile acids (acidic steroids), the absorption of cholesterol, or the synthesis of cholesterol. In a first study, in two patients with complete absence of LDL receptors, lifibrol therapy had essentially no effect on plasma LDL concentrations; in two others who had a marked reduction in LDL-receptor activity, response to the drug was attenuated. These findings suggest that lifibrol requires an intact LDL-receptor pathway to exert its action. In a second study, in patients with primary moderate hypercholesterolemia, isotope kinetic studies showed that lifibrol enhanced the fractional catabolic rate of LDL-apolipoprotein B (apo B), but had no effect on transport rates of LDL; these observations likewise support the probability that lifibrol acts mainly to increase the activity of the LDL-receptor pathway. However, in a third study in hypercholesterolemic patients, lifibrol therapy failed to increase acidic steroid excretion, inhibit cholesterol absorption, or reduce net cholesterol balance. Furthermore, lifibrol treatment did not significantly reduce urinary excretion of mevalonic acid. In contrast, in a parallel study, simvastatin therapy, which is known to inhibit cholesterol synthesis, gave the expected decrease in net cholesterol balance and reduction in urinary excretion of mevalonic acid. Thus, lifibrol, like statins, appears to increase the activity of LDL receptors; but in contrast to findings with statins, it was not possible to detect a significant decreased synthesis of cholesterol, either from balance studies or from urinary excretion of mevalonic acid. This finding raises the possibility that lifibrol activates the LDL-receptor pathway through a different mechanisms which remains to be determined. more...
- Published
- 1999
- Full Text
- View/download PDF
42. Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population.
- Author
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Bersot TP, Vega GL, Grundy SM, Palaoglu KE, Atagündüz P, Ozbayrakçi S, Gökdemir O, and Mahley RW
- Subjects
- Adult, Age Factors, Body Mass Index, Female, Humans, Lipoprotein(a) blood, Male, Middle Aged, San Francisco, Statistics, Nonparametric, Triglycerides metabolism, Turkey, Cholesterol, HDL blood, Lipase metabolism, Liver enzymology, Triglycerides blood
- Abstract
Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease and, in the United States, are often associated with hypertriglyceridemia and obesity. In Turkey, low HDL-C levels are highly prevalent, 53% of men and 26% of women having HDL-C levels <35 mg/dl, in the absence of hypertriglyceridemia and obesity. In this study to investigate the cause of low HDL-C levels in Turks, various factors affecting HDL metabolism were assessed in normotriglyceridemic Turkish men and women living in Istanbul and in non-Turkish men and women living in San Francisco. Turkish men and women had significantly lower HDL-C levels than the San Francisco men and women, as well as markedly lower apolipoprotein A-I levels (25 and 39 mg/dl lower, respectively). In both Turkish and non-Turkish subjects, the mean body mass index was <27 kg/m2, the mean triglyceride level was <120 mg/dl, and the mean total cholesterol was 170-180 mg/dl. The mean hepatic triglyceride lipase activity was 21% and 31% higher in Turkish men and women, respectively, than in non-Turkish men and women, and remained higher even after subjects with a body mass index >50th percentile for men and women in the United States were excluded from the analysis. As no dietary or behavioral factors have been identified in the Turkish population that account for increased hepatic triglyceride lipase activity, the elevation most likely has a genetic basis. high density lipoprotein in a normotriglyceridemic, nonobese Turkish population. more...
- Published
- 1999
43. Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men. Genetic and pharmacological evidence.
- Author
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Grundy SM, Vega GL, Otvos JD, Rainwater DL, and Cohen JC
- Subjects
- Cholesterol, HDL classification, Electrophoresis, Polyacrylamide Gel methods, Heterozygote, Homozygote, Humans, Male, Nuclear Magnetic Resonance, Biomolecular, Particle Size, Stanozolol metabolism, Triglycerides genetics, Cholesterol, HDL blood, Lipase genetics, Lipase metabolism, Liver enzymology, Stanozolol pharmacology, Triglycerides blood
- Abstract
Several studies have reported an inverse relationship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distribution of HDL subclasses. Two independent analytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare HDL subclass distributions in 11 homozygotes for the -514C allele of hepatic lipase and in 6 homozygotes for the -514T allele. Mean hepatic lipase activity was 45 +/- 15 mmol. l(-1). hr(-1) in -514C homozygotes and 20 +/- 7 mmol. l(-1). hr(-1) in -514T homozygotes. Both analytical methods indicated that HDL(2b) was significantly higher and HDL(3a) was significantly lower in -514T homozygotes than in -514C homozygotes. No differences were noted in the other HDL fractions (HDL(2a), HDL(3b), and HDL(3c)). To determine the effects of increased hepatic lipase activity, 20 men were given the synthetic anabolic steroid, stanozolol. Stanozolol treatment increased hepatic lipase activity more than two-fold (38 +/- 18 to 85 +/- 25 mmol. l(-1). hr(-1) ), and markedly reduced the plasma concentrations of the larger HDL subclasses (HDL(2b) and HDL(2a)). The plasma concentrations of the smallest HDL subclasses (HDL(3b) and HDL(3c)) were unchanged by stanozolol treatment. Taken together, these genetic and pharmacological data indicate that variation in hepatic lipase activity has highly specific effects on the distribution of HDL subclasses in the circulation.-Grundy, S. M., G. L. Vega, J. D. Otvos, D. L. Rainwater, and J. C. Cohen. Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence. more...
- Published
- 1999
44. Three polymorphisms associated with low hepatic lipase activity are common in African Americans.
- Author
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Nie L, Niu S, Vega GL, Clark LT, Tang A, Grundy SM, and Cohen JC
- Subjects
- Adult, Alleles, Exons, Genotype, Haplotypes, Humans, Introns, Lipase metabolism, Male, Polymerase Chain Reaction, Sequence Analysis, DNA, Black or African American, Black People genetics, Lipase genetics, Liver enzymology, Polymorphism, Restriction Fragment Length
- Abstract
We have shown previously that a hepatic lipase allele (designated -514T) is common among African Americans and contributes to low hepatic lipase activity in this population. To identify other hepatic lipase alleles associated with low hepatic lipase activity in this population, the coding region and intron-exon boundaries of the hepatic lipase gene were sequenced in 20 African American men with low hepatic lipase activity. Two polymorphisms (N193S and L334F) were associated with low post-heparin plasma hepatic lipase activity and were much more common in African Americans than in whites. This finding, together with our previous data on the -514T allele, indicates that at least three different hepatic lipase polymorphisms associated with low hepatic lipase activity are common among African Americans. Analysis of hepatic lipase haplotypes revealed that 97% of African Americans have at least one hepatic lipase allele that is associated with low hepatic lipase activity. more...
- Published
- 1998
45. The -514 polymorphism in the hepatic lipase gene (LIPC) does not influence androgen-mediated stimulation of hepatic lipase activity.
- Author
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Vega GL, Gao J, Bersot TP, Mahley RW, Verstraete R, Grundy SM, White A, and Cohen JC
- Subjects
- Adult, Alleles, Anabolic Agents pharmacology, Female, Genotype, Homozygote, Humans, Lipase blood, Lipase drug effects, Luciferases genetics, Male, Metribolone pharmacology, Middle Aged, Premenopause, Reference Values, Sex Characteristics, Stanozolol pharmacology, Lipase genetics, Liver enzymology, Polymorphism, Genetic, Promoter Regions, Genetic drug effects
- Abstract
The -514T allele of hepatic lipase is associated with increased high density lipoprotein-cholesterol levels in men, but not in women. This observation suggests that the -514C to T polymorphism may diminish the response of hepatic lipase to androgens. To test this hypothesis, five -514T and five -514C homozygous men were treated with the anabolic steroid stanozolol for 6 days. The mean increase in hepatic lipase activity was similar in the two groups (45+/-10 vs. 51+/-10 mmol x hr(-1) x l(-1), P = 0.5). To evaluate the association between the -514 polymorphism and hepatic lipase activity at different physiological androgen concentrations, hepatic lipase genotypes and activities were measured in 44 men and 40 premenopausal women. The effect of the -514T allele on hepatic lipase activity was significant and quantitatively similar in both sexes. These data indicate that the -514 polymorphism does not influence the response of hepatic lipase activity to androgens, and that the effects of this polymorphism on hepatic lipase activity are independent of androgen action. more...
- Published
- 1998
46. Body mass index and hepatic lipase gene (LIPC) polymorphism jointly influence postheparin plasma hepatic lipase activity.
- Author
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Nie L, Wang J, Clark LT, Tang A, Vega GL, Grundy SM, and Cohen JC
- Subjects
- Adolescent, Adult, Genotype, Heparin, Humans, Lipase blood, Male, Body Mass Index, Lipase genetics, Liver enzymology, Polymorphism, Genetic
- Abstract
The -514 polymorphism in the hepatic lipase gene (LIPC) is associated with decreased hepatic lipase activity. In the present study, the interaction between body mass index (BMI), the -514 polymorphism, and hepatic lipase activity was examined in 118 white men and in 51 African American men. BMI was significantly positively correlated with hepatic lipase activity in both populations. BMI was similar in men with genetic differences in hepatic lipase activity, indicating that high hepatic lipase activity did not cause increased BMI. The data therefore suggest that high BMI leads to increased hepatic lipase activity. The actions of BMI and the -514 polymorphism on hepatic lipase activity appear to be additive and independent, rather than synergistic. This finding indicates that hepatic lipase activity is a multifactorial trait, determined in part by polymorphism within the LIPC gene as well as by factors that influence BMI. more...
- Published
- 1998
47. Abnormal metabolism of free fatty acids in hypertriglyceridaemic men: apparent insulin resistance of adipose tissue.
- Author
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Mostaza JM, Vega GL, Snell P, and Grundy SM
- Subjects
- Blood Glucose metabolism, Humans, Male, Middle Aged, Adipose Tissue metabolism, Fatty Acids, Nonesterified metabolism, Hypertriglyceridemia metabolism, Insulin Resistance physiology
- Abstract
Objective: There is growing evidence that endogenous hypertriglyceridaemia is frequently accompanied by a state of insulin resistance. The present study was performed to determine whether patients with primary endogenous hypertriglyceridaemia commonly have abnormalities in plasma concentrations and turnover rates of free fatty acids (FFA), which could reflect a state of insulin resistance in adipose tissue and could account for raised plasma triglycerides., Design: Hypertriglyceridaemic and normotriglyceridemic control patients underwent measurements of plasma concentrations and turnover rates of FFA. Fat weights in both groups were determined by hydrodensitometry, and fat distribution was assessed by skin-folds and measurement of waist and hip circumferences. Other measurements included plasma glucose, insulin, lipids, and lipoproteins., Subjects: Fifteen men with normal plasma triglycerides and 21 men with primary endogenous hypertriglyceridaemia were studied. Men in both groups varied in body weights and total fat weights, but total fat weights were entirely overlapping for the two groups. Waist-to-hip ratios and waist circumferences also were similar for the two groups., Results: For any total body fat content or waist circumference, most hypertriglyceridaemia patients had higher mean plasma concentrations of FFA and higher turnover rates (flux) for FFA than did normotriglyceridemic patients. Hypertriglyceridaemic patients also had higher fasting insulin concentrations for a given body fat content. In general, both FFA flux and plasma insulin levels were positively correlated with plasma concentrations of triglyceride and inversely with high density lipoprotein (HDL) cholesterol., Conclusions: These studies indicate that many patients with primary endogenous hypertriglyceridaemia have increased flux of FFA and hyperinsulinemia that cannot be explained either by increased total body fat content or by greater waist circumferences than observed in normotriglyceridemic patients. more...
- Published
- 1998
- Full Text
- View/download PDF
48. Hepatic lipase activity is lower in African American men than in white American men: effects of 5' flanking polymorphism in the hepatic lipase gene (LIPC).
- Author
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Vega GL, Clark LT, Tang A, Marcovina S, Grundy SM, and Cohen JC
- Subjects
- Adult, Alleles, Cholesterol, HDL blood, Genotype, Heparin blood, Heterozygote, Homozygote, Humans, Male, Polymerase Chain Reaction, United States, Black or African American, Black People genetics, Lipase blood, Lipase genetics, Liver enzymology, Polymorphism, Genetic, White People genetics
- Abstract
Plasma high density lipoprotein cholesterol (HDL-C) concentrations are higher in African American men than in white men, but the mechanism(s) responsible for this ethnic difference has not been elucidated. This study examined the relationship between hepatic lipase activity, plasma HDL-C concentrations, and a hepatic lipase polymorphism (-514T) in African American and white American men. Consistent with previous reports, plasma HDL-C concentrations were significantly higher in African American men than in white American men. Mean post-heparin plasma hepatic lipase activity was significantly lower in African American than in white American men (27 +/- 12 vs. 44 +/- 17 mmol x h(-1) x l(-1), P < 0.001). The -514T hepatic lipase allele was associated with low hepatic lipase activity in both populations, and was 3-fold more common among African Americans than white Americans. Taken together, these data suggest that genetic differences in hepatic lipase activity contribute to the differences in plasma HDL-C concentrations between African American men and white American men. more...
- Published
- 1998
49. Determinants of plasma HDL-cholesterol in hypertriglyceridemic patients. Role of cholesterol-ester transfer protein and lecithin cholesteryl acyl transferase.
- Author
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Tato F, Vega GL, and Grundy SM
- Subjects
- Aged, Cholesterol Ester Transfer Proteins, Humans, Male, Middle Aged, Carrier Proteins analysis, Cholesterol, HDL blood, Glycoproteins, Hypertriglyceridemia blood, Phosphatidylcholine-Sterol O-Acyltransferase analysis
- Abstract
Hypertriglyceridemic patients commonly have low levels of HDL cholesterol. Elevated triglycerides per se may be one cause of low HDL levels, but other factors also may be involved. The current study was designed to define the role of cholesterol-ester transfer protein (CETP) in causation of a low HDL cholesterol in hypertriglyceridemic patients; in addition other factors-lecithin cholesterol acyl transferase (LCAT), hepatic triglyceride lipase (HTGL), and lipoprotein lipase (LPL)-were examined. Plasma activities of CETP and LCAT were measured in 137 male patients with moderate hypertriglyceridemia (plasma triglycerides [TGs] 200 to 500 mg/dL and LDL cholesterol < 160 mg/dL). Results were compared with those from 50 normolipidemic men of similar age and body habitus. In addition, lipase activities in postheparin plasma were measured in 118 of the subjects with hypertriglyceridemia. The activities of CETP and LCAT were 17% (P < .01) and 7% (P < .05), respectively, higher in the hypertriglyceridemic group than in control subjects. By stepwise regression analysis CETP appeared to contribute 15.2% and LCAT 9.8% to variation in HDL-cholesterol levels. Activities of LPL and HTGL together contributed an additional 14.1% to HDL-cholesterol variation. In contrast, levels of plasma TG accounted for only 5.4% of the variation. There were no differences in relative contributions of these parameters in patients with and those without coronary heart disease. This study indicates that several factors contribute to the variation in HDL-cholesterol levels in hypertriglyceridemic patients, and five factors-CETP, LCAT, HTGL, LPL, and triglyceride levels-account for almost half of this variation. more...
- Published
- 1997
- Full Text
- View/download PDF
50. Hypercholesterolemia with cholesterol-enriched LDL and normal levels of LDL-apolipoprotein B. Effects of the step I diet and bile acid sequestrants on the cholesterol content of LDL.
- Author
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Vega GL and Grundy SM
- Subjects
- Aged, Anticholesteremic Agents therapeutic use, Base Sequence, Cholesterol analysis, Cholestyramine Resin therapeutic use, Diet, Fat-Restricted, Humans, Lipoproteins, LDL chemistry, Male, Middle Aged, Molecular Probes genetics, Molecular Sequence Data, Polymerase Chain Reaction, Reference Values, Single-Blind Method, Apolipoproteins B blood, Cholesterol blood, Hypercholesterolemia blood, Hypercholesterolemia therapy, Lipoproteins, LDL blood
- Abstract
One form of hypercholesterolemia is characterized by high levels of LDL cholesterol and normal levels of LDL-apolipoprotein (apo) B. The reason for hypercholesterolemia, therefore, is enrichment of LDL particles with cholesterol. We have reported previously that about one third of patients with primary moderate hypercholesterolemia have this lipoprotein pattern and have no apparent abnormality in LDL-apo B metabolism. The current study was designed to determine whether the combination of the Step I Diet (30% of total calories as fat, <10% saturated fatty acids, and <300 mg per day cholesterol) with or without cholestyramine therapy will correct the hypercholesterolemia in patients of this type. Ten hypercholesterolemic men of this type were identified and recruited into the study. Their LDL cholesterol levels were > or = 160 mg/dL and LDL-apo B levels were <120 mg/dL (LDL cholesterol/apo B ratio >1.60). For patient selection, subjects were challenged with a high fat diet (40% of total calories as fat, 18% saturated fatty acids, and 400 mg per day cholesterol) for 6 weeks to confirm persistence of a high LDL cholesterol/apo B ratio. Thereafter, they were started on a Step I Diet, and lipoprotein analyses were repeated. Finally, cholestyramine (16 g per day) was added to the Step I Diet. The Step I Diet alone significantly reduced the LDL cholesterol/apo B ratios and produced a trend toward lowering LDL cholesterol levels. Cholestyramine therapy further reduced LDL cholesterol levels and maintained a normal LDL cholesterol/apo B ratio. The present investigation thus confirms the existence of a form of moderate hypercholesterolemia that arises from a defect in LDL composition. In addition, it demonstrates that the combination of Step I Diet and cholestyramine therapy corrects this defect and normalizes LDL levels and LDL composition. more...
- Published
- 1996
- Full Text
- View/download PDF
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