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Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.
Boden, WE, Miller, MG, McBride, R, Harvey, C, Snabes, MC, Schmidt, J, McGovern, ME, Fleg, JL, Desvigne-Nickens, P, Anderson, T, et al
American heart journal. 2020;:65-76
Abstract
BACKGROUND Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.
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Addition of oat bran reduces HDL-C and does not potentialize effect of a low-calorie diet on remission of metabolic syndrome: A pragmatic, randomized, controlled, open-label nutritional trial.
Leão, LSCS, Aquino, LA, Dias, JF, Koifman, RJ
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:126-130
Abstract
OBJECTIVES It is unclear whether addition of soluble fiber to a low-calorie diet potentializes weight loss and amelioration of metabolic syndrome (MetS). The aim of this study was to analyze the effects of oat bran on prevalence of MetS and associated disorders. METHODS A pragmatic, randomized controlled, 6-wk nutritional trial was carried out with 154 outpatients (mean age 47.6 ± 12.6 y of age). The intervention group (n = 83) received a low-calorie diet plus 40 g/d of oat bran; the control group (n = 71) received a low-calorie diet only. MetS parameters and prevalence were calculated and compared (using two-tailed statistical tests) before and after follow-up. RESULTS After follow-up, a significant but similar reduction was observed in MetS prevalence (40% reduction, 63% and 64.8% prevalence in intervention and control groups, respectively; P = 0.226), body mass index, body weight, waist circumference, systolic and diastolic blood pressures, triacylglycerides, and blood glucose levels in both groups (P < 0.05). Mean high-density lipoprotein cholesterol (HDL-C) was reduced in the intervention group (43.6 ± 9.6 to 41.2 ± 9.5 mg/dL; P = 0.025), but not in the control group (44.6 ± 10.5 to 44.5 ± 12.1 mg/dL; P = 0.890). There was no significant difference in any of the variables between the groups, although the P-value for HDL-C was almost significant (P = 0.078). Calorie and dietetic fiber intake during the 6-wk period were similar in both groups. CONCLUSIONS Daily consumption of oat bran did not potentialize the beneficial effects of a traditional low-calorie diet on the prevalence of MetS and associated disorders. Additionally, it reduced HDL-C.
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Effect of rosuvastatin on dyslipidemia and other parameters associated with metabolic syndrome in Saudi patients.
Rafeeq, MM, Habib, HS, Murad, H, Gari, MA, Gazzaz, ZJ
Nigerian journal of clinical practice. 2017;(4):445-453
Abstract
CONTEXT Metabolic syndrome (MS) is a constellation of metabolic irregularities consisting of dyslipidemia, hypertension, hyperglycemia, chronic inflammatory, and hypercoagulable state predisposing to diabetes and cardiovascular events. Statins are first-line drugs to treat the associated atherogenic dyslipidemia. AIM: Effect of rosuvastatin on MS in Saudi patients was studied. SETTINGS AND DESIGN Prospective, open label, randomized clinical study. MATERIALS AND METHODS Patients of either sex ≥18 years (n = 153) having MS as per modified National Cholesterol Education Program Adult Treatment Panel III criteria were prescribed rosuvastatin 10 mg OD for 24 weeks. Serum lipids, biochemical, clinical, and anthropometric parameters were studied before and after treatment. STATISTICAL ANALYSIS USED Statistical Package for Social Sciences version17 was used. Descriptive analysis was used for all variables and documented as mean ± SD. Normality checked by Shapiro-Wilk test, Kurtosis and Skewness Z-score, and visualization of histograms. Lipid levels and other parameters before and after treatment were evaluated by paired t-test for parametric data and Wilcoxon signed rank test for nonparametric data. Pre- and post-test values were correlated by Pearson's correlation coefficient. Multiple regression analysis was performed to see effect of other variables. RESULTS Highly significant reduction was observed in low density lipoprotein cholesterol, total cholesterol, triglycerides; very low density lipoprotein cholesterol, non-high density lipoprotein cholesterol and atherosclerotic index with an elevation in high density lipoprotein cholesterol. A total of 86% patients reached low density lipoprotein cholesterol goal of ≤ 100 mg/dL. Beneficial response was observed on other associated parameters. There was strong correlation between pre- and post values. No significant effect was observed for any of the variables on cholesterol reduction. No serious/severe adverse effect was observed. CONCLUSION Rosuvastatin markedly improved atherogenic dyslipidemia of MS.
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Fenofibrate and extended-release niacin improve the endothelial protective effects of HDL in patients with metabolic syndrome.
Gomaraschi, M, Ossoli, A, Adorni, MP, Damonte, E, Niesor, E, Veglia, F, Franceschini, G, Benghozi, R, Calabresi, L
Vascular pharmacology. 2015;:80-86
Abstract
BACKGROUND Fibrates and niacin are at present the most effective therapies to increase plasma levels of high density lipoprotein-cholesterol (HDL-C); to date, limited data are available on their effects on HDL protective functions. METHODS AND RESULTS Within a multicenter, randomized, open-label, cross-over study, 37 patients with metabolic syndrome received 6weeks' treatment with fenofibrate or extended-release niacin (ER niacin), with a 4weeks' wash-out period. HDL ability to preserve endothelial cell homeostasis was assessed by incubating cultured endothelial cells with HDL isolated from patients at baseline and after each treatment. HDL isolated from patients at baseline were as effective as control HDL in inhibiting vascular cell adhesion molecule-1 (VCAM-1) expression, but less efficient in promoting endothelial cell nitric oxide (NO) release. Both fenofibrate and ER niacin increased HDL ability to inhibit TNFα-induced VCAM-1 expression (+7% and +11%, respectively). Fenofibrate and ER niacin also improved the impaired HDL ability to induce the expression of endothelial nitric oxide synthase and NO production (+10% and +8%, respectively). Interestingly, HDL isolated after treatment showed an ability to promote endothelial NO release similar to HDL isolated from controls. No differences were observed between the two drugs. With both drugs, HDL function was improved irrespective of baseline HDL-C levels. CONCLUSION Treatment with fenofibrate or ER niacin in patients with metabolic syndrome not only increased HDL-C levels but also improved the endothelial protective effects of HDL.
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Effects of niacin and omega-3 fatty acids on the apolipoproteins in overweight patients with elevated triglycerides and reduced HDL cholesterol.
Savinova, OV, Fillaus, K, Harris, WS, Shearer, GC
Atherosclerosis. 2015;(2):520-5
Abstract
OBJECTIVE Prescription omega-3 acid ethyl esters (P-OM3) and extended release niacin (ERN) both have beneficial effects on plasma lipids and lipoproteins. The purpose of this study was to describe the effects of mono- and combination (Combo) therapy of these agents in patients with the metabolic syndrome. METHODS Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) were isolated from 56 overweight patients with elevated triglyceride/HDL-C ratios at baseline and after 16 weeks of treatment with placebo, ERN (2g/day), P-OM3 (4g/day), or Combo and then analyzed by quantitative electrophoresis for apolipoproteins (apo) A1, A2, B, C2, C3 and E. Total plasma concentrations and the ratios of each apo with apoB (in VLDL and LDL) and with apoA1 (in HDL) were calculated. An apoC3 glycosylation index (a ratio between di- and mono-sialylated isoforms) was also determined in plasma and in each lipoprotein fraction. RESULTS ERN reduced plasma apoB (-11%, p < 0.05). Combo increased LDL apoE/apoB ratio (64%, p < 0.01) and LDL apoA1/apoB (91%, p < 0.05). ERN increased the apoC3 glycosylation index only in HDL (37%, p < 0.05), whereas P-OM3 and Combo increased the index in whole plasma (48% and 49%, respectively, p < 0.05 for both) and in every lipoprotein class (VLDL: 26%, p < 0.01 and 26%, p < 0.05; LDL: 55%, p < 0.01 and 61%, p < 0.01; HDL: 43%, p < 0.001 and 44%, p < 0.001, respectively). All findings were significant after adjustment for age, sex, body mass index (BMI), smoking, medications, and baseline apo value. CONCLUSIONS ERN produced a beneficial reduction in plasma apoB. The enrichment of LDL with apoE and apoA1 was unique to the Combo group and might be beneficial owing to the atheroprotective properties of apoE and HDL2 (a likely source of apoA1 in LDL fraction). The effect of therapies on the apoC3 glycosylation index is a novel finding, the implications of which will require further study.
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Elevated interleukin-10: a new cause of dyslipidemia leading to severe HDL deficiency.
Moraitis, AG, Freeman, LA, Shamburek, RD, Wesley, R, Wilson, W, Grant, CM, Price, S, Demosky, S, Thacker, SG, Zarzour, A, et al
Journal of clinical lipidology. 2015;(1):81-90
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Abstract
BACKGROUND Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. Investigating mechanisms underlying acquired severe HDL deficiency in noncritically ill patients ("disappearing HDL syndrome") could provide new insights into HDL metabolism. OBJECTIVE To determine the cause of low HDL-C in patients with severe acquired HDL deficiency. METHODS AND RESULTS Patients with intravascular large B-cell lymphoma (n = 2), diffuse large B-cell lymphoma (n = 1), and autoimmune lymphoproliferative syndrome (n = 1) presenting with markedly decreased HDL-C, low low-density lipoprotein cholesterol (LDL-C), and elevated triglycerides were identified. The abnormal lipoprotein profile returned to normal after therapy in all 4 patients. All patients were found to have markedly elevated serum interleukin-10 (IL-10) levels that also normalized after therapy. In a cohort of autoimmune lymphoproliferative syndrome patients (n = 93), IL-10 showed a strong inverse correlation with HDL-C (R(2) = 0.3720, P < .0001). A direct causal role for increased serum IL-10 in inducing the observed changes in lipoproteins was established in a randomized, placebo-controlled clinical trial of recombinant human IL-10 in psoriatic arthritis patients (n = 18). Within a week of initiating subcutaneous recombinant human IL-10 injections, HDL-C precipitously decreased to near-undetectable levels. LDL-C also decreased by more than 50% (P < .0001) and triglycerides increased by approximately 2-fold (P < .005). All values returned to baseline after discontinuing IL-10 therapy. CONCLUSION Increased IL-10 causes severe HDL-C deficiency, low LDL-C, and elevated triglycerides. IL-10 is thus a potent modulator of lipoprotein levels, a potential new biomarker for B-cell disorders, and a novel cause of disappearing HDL syndrome.
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Potent peroxisome proliferator-activated receptor-α agonist treatment increases cholesterol efflux capacity in humans with the metabolic syndrome.
Khera, AV, Millar, JS, Ruotolo, G, Wang, MD, Rader, DJ
European heart journal. 2015;(43):3020-2
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AIMS: Fibrate medications weakly stimulate the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) and are currently employed clinically in patients with dyslipidaemia. The potent and selective agonist of PPAR-α LY518674 is known to substantially increase apolipoprotein A-I (apoA-I) turnover without major impact on steady-state levels of apoA-I or high-density lipoprotein-cholesterol (HDL-C). We sought to determine whether therapy with a PPAR-α agonist impacts cholesterol efflux capacity, a marker of HDL function. METHODS AND RESULTS Cholesterol efflux capacity was measured at baseline and after 8 weeks of therapy in a randomized, placebo-controlled trial involving participants with metabolic syndrome treated with either LY518674 100 μg daily (n = 13) or placebo (n = 15). Efflux capacity assessment was quantified using a previously validated ex vivo assay that measures the ability of apolipoprotein-B depleted plasma to mobilize cholesterol from macrophages. LY518674 led to a 15.7% increase from baseline (95% CI 3.3-28.1%; P = 0.02, P vs. placebo = 0.01) in efflux capacity. The change in apoA-I production rate in the active treatment arm was strongly linked to change in cholesterol efflux capacity (r = 0.67, P = 0.01). CONCLUSIONS Potent stimulation of PPAR-α leads to accelerated turnover of apoA-I and an increase in cholesterol efflux capacity in metabolic syndrome patients despite no change in HDL-C or apoA-I levels. This finding reinforces the notion that changes in HDL-C levels may poorly predict impact on functionality and thus has implications for ongoing pharmacologic efforts to enhance apoA-I metabolism.
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Resistant starch type 4-enriched diet lowered blood cholesterols and improved body composition in a double blind controlled cross-over intervention.
Nichenametla, SN, Weidauer, LA, Wey, HE, Beare, TM, Specker, BL, Dey, M
Molecular nutrition & food research. 2014;(6):1365-9
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A metabolic health crisis is evident as cardiovascular diseases (CVD) remain the leading cause of mortality in the United States. Effects of resistant starch type 4 (RS4), a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of RS4-enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double blind (participants-investigators), placebo-controlled, cluster cross-over intervention (n = 86, age≥18, 2-12 week interventions, 2-week washout) in the United States, individuals were classified as having MetS (With-MetS) or not (No-MetS) following International Diabetes Federation (IDF)-criteria. RS4 consumption compared with CF resulted in 7.2% (p = 0.002) lower mean total cholesterol, 5.5% (p = 0.04) lower non-HDL, and a 12.8% (p < 0.001) lower HDL cholesterol in the With-MetS group. No-MetS individuals had a 2.6% (p = 0.02) smaller waist circumference and 1.5% (p = 0.03) lower percent body fat following RS4 intervention compared to CF. A small but significant 1% increase in fat-free mass was observed in all participants combined (p = 0.02). No significant effect of RS4 was observed for glycemic variables and blood pressures. RS4 consumption improved dyslipidemia and body composition. Incorporation of RS4 in routine diets could offer an effective strategy for public cardio-metabolic health promotion.
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Smoking associates with visceral fat accumulation especially in women.
Nakanishi, K, Nishida, M, Ohama, T, Moriyama, T, Yamauchi-Takihara, K
Circulation journal : official journal of the Japanese Circulation Society. 2014;(5):1259-63
Abstract
BACKGROUND Smoking and metabolic syndrome (MetS) are major public health problems in modern society and are important risk factors of cardiovascular disease (CVD). The association of smoking, MetS, and CVD is widely reported, but reports targeted to women are few. In the present study, we evaluated risk factors, including visceral fat area (VFA), for CVD and development of subclinical atherosclerosis in female smokers especially. METHODS AND RESULTS Subjects consisted of 162 apparent healthy female and male smokers, and 315 age-matched never-smokers who underwent a health examination in the Osaka University Health Care Center. For female smokers, lifestyle and carotid intima-media thickness (IMT) were evaluated. Triglycerides were significantly higher and high-density lipoprotein-cholesterol significantly lower in smokers than in never-smokers for both men and women. However, VFA was significantly high only in smoking women when compared with never-smokers. Multivariate analysis revealed that age, body mass index, and smoking were the independent predictors of high VFA in women. In addition, annual IMT increase was significantly higher in smokers than never-smokers in women. CONCLUSIONS VFA was notably high in female smokers, but the difference was not observed in men. Smoking habit is an important risk factor of visceral fat accumulation and progression of subclinical atherosclerosis in women.
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Postpartum weight retention is associated with elevated ratio of oxidized LDL lipids to HDL-cholesterol.
Puhkala, J, Luoto, R, Ahotupa, M, Raitanen, J, Vasankari, T
Lipids. 2013;(12):1227-35
Abstract
Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox-LDL and serum lipids. The study is a nested comparative research of a cluster-randomized controlled trial, NELLI (lifestyle and counselling during pregnancy). During early pregnancy (8-12 weeks) and 1 year postpartum, 141 women participated in measurements for determining of plasma lipids: total cholesterol (T-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triacylglycerols (TAG) and ox-LDL. Subjects were stratified into tertiles (weight loss, unaltered weight and weight gain groups) based on their weight change from baseline to follow-up. Ox-LDL was determined by baseline level of conjugated dienes in LDL lipids. Among the group of weight gainers, concentration of TAG reduced less (-0.14 vs. -0.33, p = 0.002), HDL-C reduced more (-0.31 vs. -0.16, p = 0.003) and ox-LDL/HDL-C ratio increased (3.0 vs. -0.2, p = 0.003) when compared to group of weight loss. Both T-C and LDL-C elevated more (0.14 vs. -0.21, p = 0.008; 0.31 vs. 0.07, p = 0.015) and TAG and ox-LDL reduced less (-0.33 vs. 0.20, p = 0.033; -3.33 vs. -0.68, p = 0.026) in unaltered weight group compared to weight loss group. The women who gained weight developed higher TAG and ox-LDL/HDL-C ratio as compared to those who lost weight. Postpartum weight retention of 3.4 kg or more is associated with atherogenic lipid profile.