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The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort.
Roumie CL, Huizinga MM, Liu X, Greevy RA, Grijalva CG, Murff HJ, Hung AM, Griffin MR
(2011) Pharmacoepidemiol Drug Saf 20: 36-44
MeSH Terms: Blood Glucose, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Type 2, Drug Interactions, Dyslipidemias, Female, Humans, Hypoglycemic Agents, Insulin, Lipid Metabolism, Lipids, Male, Retrospective Studies, Sulfonylurea Compounds, Thiazolidinediones, Treatment Outcome, Veterans
Show Abstract · Added February 24, 2014
OBJECTIVE - Effects of oral antidiabetic drugs (OADs) on lipids may influence cardiovascular outcomes. Our aim was to compare time to initiation of lipid lowering medication (LLM) and 12-month lipid profiles among new OAD users.
METHODS - We identified a retrospective cohort of 17,774 veterans who received care at Veterans Administration (VA) Mid-South Network with a first OAD from 1 January 2000 to 31 December 2007. There were 6917 patients (38.9%) not on a LLM at baseline, and 3871 (56%) had complete covariates. Incident users of sulfonylurea and combination metformin + sulfonylurea were compared to metformin users for time to LLM initiation. Incident users of these OADs and thiazolidendiones were included in comparison of 12-month low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and total cholesterol. All analyses adjusted for demographics, lipids, HbA1C, healthcare utilization, and cardiovascular disease at baseline.
RESULTS - The median time to starting LLM was 2.35 years (interquartile range 0.96, 4.6) following metformin initiation and not statistically different for users of sulfonylureas, or combination OADs. Compared to metformin users, 12-month HDL was 1.35 mg/dl (95%CI: -2.01, -0.72) lower and TGs were 5.7% higher (95%CI: 1.5%, 10.0%) for sulfonylurea users; TGs were 24.8% (95%CI: 0.7%, 54.5%) higher for thiazolidinedione users. Statin users had LDL and total cholesterol 16.7 mg/dl (95%CI: -19.9, -13.5) and 18.6 mg/dl (95%CI: -22.1, -15.1) lower than non-statin users, respectively.
CONCLUSIONS - Time to LLM initiation was similar between OADs. Metformin use resulted in more favorable lipids at 12 months compared to sulfonylureas or thiazolidinediones.
Copyright © 2010 John Wiley & Sons, Ltd.
0 Communities
4 Members
0 Resources
18 MeSH Terms
Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia.
Wang ET, Calderon-Margalit R, Cedars MI, Daviglus ML, Merkin SS, Schreiner PJ, Sternfeld B, Wellons M, Schwartz SM, Lewis CE, Williams OD, Siscovick DS, Bibbins-Domingo K
(2011) Obstet Gynecol 117: 6-13
MeSH Terms: Adult, Diabetes Mellitus, Dyslipidemias, Female, Humans, Hypertension, Polycystic Ovary Syndrome, Prospective Studies, United States, Young Adult
Show Abstract · Added March 14, 2014
OBJECTIVE - To estimate whether women aged 20-32 years who fulfilled National Institutes of Health criteria for polycystic ovary syndrome (PCOS) would be at higher risk for subsequent development of incident diabetes, dyslipidemia, and hypertension, and to estimate whether normal-weight women with PCOS would have the same degree of cardiovascular risk as overweight women with PCOS.
METHODS - We estimated the association of PCOS with incident diabetes, dyslipidemia, and hypertension over a period of 18 years among 1,127 white and African-American women in the Coronary Artery Risk Development in Young Adults cohort. We classified women at baseline (ages 20-32 years) based on self-reported symptoms and serum androgen measures using National Institutes of Health PCOS criteria. We estimated the association of PCOS and subsequent cardiovascular risk factors, independent of baseline body mass index (BMI), using multivariable logistic regression. Additionally, among 746 women with a second assessment of PCOS at ages 34-46 years, we estimated the association of persistent PCOS with cardiovascular risk factors.
RESULTS - Of 1,127 women, 53 (4.7%) met criteria for PCOS at ages 20-32 years. Polycystic ovary syndrome was associated with a twofold higher odds of incident diabetes (23.1% compared with 13.1%, adjusted odds ratio [AOR] 2.4, confidence interval [CI] 1.2-4.9) and dyslipidemia (41.9% compared with 27.7%, AOR 1.9, CI 1.0-3.6) over the course of 18 years; the association with incident hypertension was not significant (26.9% compared with 26.3%, AOR 1.7, CI 0.8-3.3). Normal-weight women with PCOS (n=31) had a threefold higher odds of incident diabetes compared with normal-weight women without PCOS (AOR 3.1, CI 1.2-8.0). Compared with those without PCOS, women with persistent PCOS (n=11) had the highest odds of diabetes (AOR 7.2, CI 1.1-46.5).
CONCLUSION - Polycystic ovary syndrome is associated with subsequent incident diabetes and dyslipidemia, independent of BMI. Diabetes risk may be greatest for women with persistent PCOS symptoms.
LEVEL OF EVIDENCE - II.
0 Communities
1 Members
0 Resources
10 MeSH Terms
High-density lipoprotein (HDL) cholesterol: leveraging practice-based biobank cohorts to characterize clinical and genetic predictors of treatment outcome.
Wilke RA
(2011) Pharmacogenomics J 11: 162-73
MeSH Terms: Apolipoprotein A-I, Atorvastatin, Cholesterol, HDL, Cholesterol, LDL, Databases, Nucleic Acid, Dose-Response Relationship, Drug, Dyslipidemias, Electronic Health Records, Genetic Association Studies, Genetic Markers, Heptanoic Acids, Humans, Obesity, Pravastatin, Pyrroles, Risk Assessment, Simvastatin, Treatment Outcome
Show Abstract · Added February 12, 2015
Over the past decade, large multicenter trials have unequivocally demonstrated that decreasing low-density lipoprotein (LDL) cholesterol can reduce both primary and secondary cardiovascular events in patients at risk. However, even in the context of maximal LDL lowering, there remains considerable residual cardiovascular risk. Some of this risk can be attributed to variability in high-density lipoprotein (HDL) cholesterol. As such, there is tremendous interest in defining determinants of HDL homeostasis. Risk prediction models are being constructed based upon (1) clinical contributors, (2) known molecular determinants and (3) the genetic architecture underlying HDL cholesterol levels. To date, however, no single resource has combined these factors within the context of a practice-based data set. Recently, a number of academic medical centers have begun constructing DNA biobanks linked to secure encrypted versions of their respective electronic medical record. As these biobanks combine resources, the clinical community is in a position to characterize lipid-related treatment outcome on an unprecedented scale.
0 Communities
1 Members
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18 MeSH Terms
Prepregnancy lipids related to preterm birth risk: the coronary artery risk development in young adults study.
Catov JM, Ness RB, Wellons MF, Jacobs DR, Roberts JM, Gunderson EP
(2010) J Clin Endocrinol Metab 95: 3711-8
MeSH Terms: Adult, African Americans, Cholesterol, Dyslipidemias, European Continental Ancestry Group, Female, Humans, Odds Ratio, Pregnancy, Premature Birth, Prospective Studies, Risk, Risk Factors
Show Abstract · Added February 28, 2014
CONTEXT - Preterm birth is associated with maternal cardiovascular risk, but mechanisms are unknown.
OBJECTIVE - We considered that dyslipidemia may predispose women to both conditions and that prepregnancy lipids may be related to preterm birth risk. We hypothesized that low or high prepregnancy plasma lipids would be associated with preterm birth.
DESIGN, SETTING, AND PARTICIPANTS - A total of 1010 women (49% black) enrolled in the multicenter, prospective Coronary Artery Risk Development in Young Adults study with at least one singleton birth during 20 yr of follow-up were evaluated.
MAIN OUTCOME MEASURE - Postbaseline preterm births less than 34 wk or 34 to less than 37 wk vs. greater than 37 wk gestation.
RESULTS - We detected a U-shaped relationship between prepregnancy cholesterol concentrations and preterm birth risk. Women with prepregnancy cholesterol in the lowest quartile compared with the second quartile (<156 vs. 156-171 mg/dl) had an increased risk for preterm birth 34 to less than 37 wk (odds ratio 1.86; 95% confidence interval 1.10, 3.15) and less than 34 wk (odds ratio 3.04; 1.35, 6.81) independent of race, age, parity, body mass index, hypertension during pregnancy, physical activity, and years from measurement to birth. Prepregnancy cholesterol in the highest quartile (>195 mg/dl) was also associated with preterm birth less than 34 wk among women with normotensive pregnancies (odds ratio 3.80; 95% confidence interval 1.07, 7.57). There were no associations between prepregnancy triglycerides, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol and preterm birth.
CONCLUSIONS - Both low and high prepregnancy cholesterol were related to preterm birth risk. These may represent distinct pathways to the heterogeneous outcome of preterm birth. Additional studies are needed to elucidate mechanisms that link low or high cholesterol to preterm birth and later-life sequelae.
0 Communities
1 Members
0 Resources
13 MeSH Terms
NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids.
Ferguson JF, Phillips CM, McMonagle J, Pérez-Martínez P, Shaw DI, Lovegrove JA, Helal O, Defoort C, Gjelstad IM, Drevon CA, Blaak EE, Saris WH, Leszczyńska-Gołabek I, Kiec-Wilk B, Risérus U, Karlström B, Lopez-Miranda J, Roche HM
(2010) Atherosclerosis 211: 539-44
MeSH Terms: Aged, Biomarkers, Cardiovascular Diseases, Dyslipidemias, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Female, Genotype, Humans, Male, Metabolic Syndrome, Middle Aged, Nitric Oxide Synthase Type III, Polymorphism, Genetic, Risk, Risk Factors, Triglycerides
Show Abstract · Added January 20, 2015
OBJECTIVE - Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene-nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS).
METHODS - Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene-nutrient interactions.
RESULTS - Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene-nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC+AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes.
CONCLUSIONS - Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Natural killer T cells and atherosclerosis: form and function meet pathogenesis.
Braun NA, Covarrubias R, Major AS
(2010) J Innate Immun 2: 316-24
MeSH Terms: Adaptive Immunity, Animals, Arteriosclerosis, Chronic Disease, Cytokines, Dyslipidemias, Glycolipids, Humans, Immunity, Innate, Inflammation, Mice, Natural Killer T-Cells
Show Abstract · Added February 11, 2014
Atherosclerosis is a chronic inflammatory disease characterized by dyslipidemia and accumulation of lipids in the arterial intima, with activation of both innate and adaptive immunity. Reciprocally, dyslipidemia associated with atherosclerosis can perturb normal immune function. Natural killer T (NKT) cells are a specialized group of immune cells that share characteristics with both conventional T cells and natural killer cells. However, unlike these cells, NKT cells recognize glycolipid antigens and produce both pro- and anti-inflammatory cytokines upon activation. Because of these unique characteristics, NKT cells have recently been ascribed a role in the regulation of immunity and inflammation, including cardiovascular disease. In addition, NKT cells represent a bridge between dyslipidemia and immune regulation. This review summarizes the current knowledge of NKT cells and discusses the interplay between dyslipidemia and the normal functions of NKT cells and how this might modulate inflammation and atherosclerosis.
(c) 2010 S. Karger AG, Basel.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community.
Lieb W, Zachariah JP, Xanthakis V, Safa R, Chen MH, Sullivan LM, Larson MG, Smith HM, Yang Q, Mitchell GF, Vita JA, Sawyer DB, Vasan RS
(2010) Circ Cardiovasc Genet 3: 300-6
MeSH Terms: Adult, Angiopoietin-2, Biomarkers, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Dyslipidemias, Female, Genetic Linkage, Humans, Male, Metabolic Syndrome, Middle Aged, Obesity, Receptor, TIE-2, Risk Factors
Show Abstract · Added March 11, 2014
BACKGROUND - Experimental studies suggest that endothelial growth factors play an important role in angiogenesis and vascular remodeling. The clinical and genetic correlates of circulating angiopoietin-2 (Ang-2) and its soluble receptor/regulator Tie-2 (sTie-2) have not been determined in a community-based sample.
METHODS AND RESULTS - Serum Ang-2 and sTie-2 were assayed in 3778 third-generation cohort participants of the Framingham Heart Study (mean age, 40+/-9 years; 53% women). Clinical correlates and heritability of both biomarkers were assessed using generalized estimating equations and variance-component analyses. Ang-2 levels were higher and sTie-2 levels were lower in women than in men. Ang-2 was positively related to age, smoking, systolic blood pressure, hypertension treatment, and diabetes (P<0.05 for all) but was inversely associated with total cholesterol and diastolic blood pressure (P<0.0001 for both), and sTie-2 was positively associated with body mass index, diabetes, and triglycerides but was inversely related to age, alcohol consumption, and glomerular filtration rate (P<0.05 for all). Both Ang-2 and sTie-2 were higher in participants with metabolic syndrome (P<0.005), with stronger associations of Ang-2 with blood pressure traits and of sTie-2 with obesity-dyslipidemia components. Heritability estimates for Ang-2 and sTie-2 were 27% and 56%, respectively (P<0.0001). A region on chromosome 9 was significantly linked to circulating sTie-2 levels (logarithm of the odds score, 8.31).
CONCLUSION - Circulating levels of Ang-2 and sTie-2 are heritable traits associated with cardiovascular disease risk factors, including the metabolic syndrome. These observations are consistent with the notion that angiogenesis and vascular remodeling are determined in part by genetic influences and associated with metabolic risk factors.
1 Communities
2 Members
0 Resources
16 MeSH Terms
Increased oxidative stress and altered substrate metabolism in obese children.
Oliver SR, Rosa JS, Milne GL, Pontello AM, Borntrager HL, Heydari S, Galassetti PR
(2010) Int J Pediatr Obes 5: 436-44
MeSH Terms: Carbohydrate Metabolism, Cardiovascular Diseases, Case-Control Studies, Child, Dyslipidemias, Female, Glucose, Humans, Hydrocortisone, Insulin, Interleukin-6, Leukocyte Count, Lipid Metabolism, Male, Obesity, Oxidative Stress, Risk Factors, Sex Characteristics
Show Abstract · Added March 26, 2014
OBJECTIVE - Pediatric obesity, a major risk factor for cardiovascular diseases and diabetes, has steadily increased in the last decades. Although excessive inflammation and oxidation are possible biochemical links between obesity and cardiovascular events in adults, little information is available in children. Furthermore, effects of gender and fitness on the interaction between dyslipidemia and oxidative/inflammatory stress in children are mostly unknown.
METHODS - Therefore, we measured systemic markers of oxidation (F(2)-isoprostanes [F(2)-IsoP] and antioxidants) and inflammation (interleukin-6 [IL-6] and leukocyte counts) and metabolic variables in 113 peripubertal children (55 obese [Ob] age and gender-adjusted BMI% ≥ 95(th), 25 Females [F]; 15 overweight [OW] BMI% 85(th)-95(th), 8 F; 43 normoweight [NW] 25 F).
RESULTS - When compared with NW, Ob displayed elevated F(2)-IsoP (99 ± 7 vs. 75 ± 4 pg/mL, p<0.005), IL-6 (2.2 ± 0.2 vs. 1.5 ± 0.3 pg/mL, p<0.005), elevated total leukocytes and neutrophils, altered levels of total cholesterol , low- and high-density-lipoprotein cholesterol, triglycerides, free fatty acids, glucose, and insulin (all p<0.005). This pattern was present in both genders and over a broad range of fitness in Ob.
CONCLUSIONS - Our data indicate that alterations in metabolic control and a concomitant increase in inflammation and oxidative stress occur early in life in obese children, likely exposing both genders to a similar degree of increased risk of future cardiovascular diseases.
1 Communities
1 Members
0 Resources
18 MeSH Terms
Nonpharmacologic treatment of dyslipidemia.
Houston MC, Fazio S, Chilton FH, Wise DE, Jones KB, Barringer TA, Bramlet DA
(2009) Prog Cardiovasc Dis 52: 61-94
MeSH Terms: Animals, Antioxidants, Aquaculture, Cardiovascular Diseases, Cholesterol, LDL, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diet, Dyslipidemias, Eicosanoids, Exercise, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Fatty Acids, Unsaturated, Fishes, Herbal Medicine, Humans, Hypolipidemic Agents, Life Style, Niacin, Nutrition Therapy, Oxygen Consumption, Seafood, Soybean Proteins, Tocotrienols
Added December 10, 2013
0 Communities
1 Members
0 Resources
25 MeSH Terms
Mechanisms for increased cardiovascular disease in chronic kidney dysfunction.
Yamamoto S, Kon V
(2009) Curr Opin Nephrol Hypertens 18: 181-8
MeSH Terms: Animals, Cardiovascular Diseases, Dyslipidemias, Homeostasis, Humans, Kidney Failure, Chronic, Macrophages, Risk Factors
Show Abstract · Added January 24, 2012
PURPOSE OF REVIEW - Patients with chronic kidney disease (CKD) have the highest risk for atherosclerotic cardiovascular disease (CVD). Current interventions have been insufficiently effective in lessening excess incidence and mortality from CVD in patients with CKD versus other high-risk groups. This review focuses on traditional and CKD-related risks as well as key mechanisms of macrophage foam cell formation that underlie the excess CVD in the setting of CKD.
RECENT FINDINGS - Hyperlipidemia, particularly increased low-density lipoprotein (LDL) cholesterol, is the key factor in atherogenesis in the general population, but has not been found to be the overriding risk for greater CVD in CKD, especially as renal damage progresses. Although higher incidence of CVD in CKD is not due to higher serum lipids per se, CKD is associated with abnormal lipid metabolism that is proatherogenic. CKD-related risks, including inflammation and disturbances in mineral metabolism, have been implicated. In addition, perturbations of the macrophage, a cell that is central in atherogenesis, may be important.
SUMMARY - The mechanisms underlying the heightened risk for CVD in CKD have been the focus of intense study and may relate to the combined effects of traditional and CKD-specific risks involving inflammation and lipid metabolism, especially perturbation of macrophage cholesterol homeostasis.
0 Communities
1 Members
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8 MeSH Terms