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Apolipoprotein B discordance with low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in relation to coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).
Cao, J, Nomura, SO, Steffen, BT, Guan, W, Remaley, AT, Karger, AB, Ouyang, P, Michos, ED, Tsai, MY
Journal of clinical lipidology. 2020;(1):109-121.e5
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BACKGROUND Discordant levels of apolipoprotein B (apo B) relative to low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) may be associated with subclinical atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE The present study investigated whether discordance between apo B and LDL-C or non-HDL-C levels was associated with subclinical ASCVD measured by coronary artery calcium (CAC). METHODS This study was conducted in a subpopulation of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, aged 45 to 84 years, free of ASCVD, and not taking lipid-lowering medications at the baseline (2000-2002) (prevalence analytic N = 4623; incidence analytic N = 2216; progression analytic N = 3947). Apo B discordance relative to LDL-C and non-HDL-C was defined using residuals and percentile rankings (>5/10/15 percentile). Associations with prevalent and incident CAC (CAC > 0 vs CAC = 0) were assessed using prevalence ratio/relative risk regression and CAC progression (absolute increase/year) using multinomial logistic regression. RESULTS Higher apo B levels were associated with CAC prevalence, incidence, and progression. Apo B discordance relative to LDL-C or non-HDL-C was inconsistently associated with CAC prevalence and progression. Discordantly high apo B relative to LDL-C and non-HDL-C was associated with CAC progression. Associations for apo B discordance with non-HDL-C remained after further adjustment for metabolic syndrome components. CONCLUSION Apo B was associated with CAC among adults aged ≥45 years not taking statins, but provided only modest additional predictive value of apo B for CAC prevalence, incidence, or progression beyond LDL-C or non-HDL-C. Apo B discordance may still be important for ASCVD risk assessment and further research is needed to confirm findings.
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Choline Intake as Supplement or as a Component of Eggs Increases Plasma Choline and Reduces Interleukin-6 without Modifying Plasma Cholesterol in Participants with Metabolic Syndrome.
DiBella, M, Thomas, MS, Alyousef, H, Millar, C, Blesso, C, Malysheva, O, Caudill, MA, Fernandez, ML
Nutrients. 2020;(10)
Abstract
Metabolic syndrome (MetS) is characterized by low-grade inflammation and insulin resistance, which increase the risk of heart disease. Eggs have numerous nutrients including choline, carotenoids, and fat-soluble vitamins that may protect against these conditions. Egg phosphatidylcholine (PC) is a major contributor of dietary choline in the American diet. However, uncertainty remains regarding eggs due to their high concentration of cholesterol. In this study, we evaluated the effect of two sources of choline, whole eggs (a source of PC) and a choline supplement (choline bitartrate, CB), on plasma lipids, glucose, insulin resistance, and inflammatory biomarkers. We recruited 23 subjects with MetS to participate in this randomized cross-over intervention. After a 2-week washout, with no choline intake, participants were randomly allocated to consume three eggs/day or CB (~400 mg choline/d for both) for 4 weeks. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records indicated higher concentrations of vitamin E and selenium during the egg period (p < 0.01). Interestingly, there were no changes in plasma total, low density lipoprotein (LDL)- or high density lipoprotein (HDL)-cholesterol, triglycerides, or glucose, compared either to baseline or between treatments. In contrast, interleukin-6 was reduced, with both sources of choline compared to baseline, while eggs also had an effect on lowering C-reactive protein, insulin, and insulin resistance compared to baseline. This study demonstrates that in a MetS population, intake of three eggs per day does not increase plasma LDL cholesterol, and has additional benefits on biomarkers of disease compared to a choline supplement, possibly due to the presence of other antioxidants in eggs.
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The Effect of Ramadan Fasting on Body Composition and Metabolic Syndrome in Apparently Healthy Men.
Al-Barha, NS, Aljaloud, KS
American journal of men's health. 2019;(1):1557988318816925
Abstract
There are few studies investigating the role of Ramadan fasting on body composition and the characteristics of metabolic syndrome, especially in hot environments. The main aim of the study was to investigate the effect of Ramadan fasting on body composition and the characteristics of metabolic syndrome in apparently healthy men. In a randomized design, 44 college students aged 27.6 ± 5.8 years were selected to participate in the present study. Lifestyle was assessed by a developed questionnaire, body composition was measured using a bioelectrical impedance analyzer, and blood parameters were evaluated by taking a vein blood sample (10 ml) after fasting 10 hr. All measurements were taken 2-3 days before the month of Ramadan, at the end of Week 2 and end of Week 3, and 6 weeks later. The results identified no significant changes in any of the body composition parameters before, during, or after the month of Ramadan. The only significant change in blood parameters was recorded as a positive reduction in low-density lipoprotein (LDL) during the month of Ramadan, compared to before and after Ramadan. No major changes in metabolic syndrome factors were seen except in fasting blood glucose and systolic blood pressure as both factors were slightly but significantly elevated during the month of Ramadan and even after Ramadan, though both of them were within normal levels. This study concludes that Ramadan fasting could be one of the factors that reduce LDL. More studies are needed to clarify the role of Ramadan fasting on different populations such as obese and diabetic patients.
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Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies.
Stroes, E, Robinson, JG, Raal, FJ, Dufour, R, Sullivan, D, Kassahun, H, Ma, Y, Wasserman, SM, Koren, MJ
Clinical cardiology. 2018;(10):1328-1335
Abstract
BACKGROUND Evolocumab significantly lowers low-density lipoprotein cholesterol (LDL-C) when dosed 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) subcutaneously. HYPOTHESIS LDL-C changes are comparable among different patient subgroups in a pooled analysis of data from phase 3 trials. METHODS A total of 3146 patients received ≥1 dose of evolocumab or control in four 12-week phase 3 studies. Percent change from baseline in LDL-C for evolocumab 140 mg Q2W or 420 mg QM vs control was reported as the average of week 10 and 12 values. Quantitative and qualitative interactions between treatment group and subgroup by dose regimen were tested. RESULTS In the pooled analysis, treatment differences vs placebo or ezetimibe were similar for both 140 mg Q2W and 420 mg QM doses across ages (<65 years, ≥65 years); gender; race (Asian, black, white, other); ethnicity (Hispanic, non-Hispanic); region (Europe, North America, Asia Pacific); glucose tolerance status (type 2 diabetes mellitus, metabolic syndrome, neither); National Cholesterol Education Program risk categories (high, moderately high, moderate, low); and European Society of Cardiology/European Atherosclerosis Society risk categories (very high, high, moderate, or low). Certain low-magnitude variations in LDL-C lowering among subgroups led to significant quantitative interaction P values that, when tested by qualitative interaction, were not significant. The incidences of adverse events were similar across groups treated with each evolocumab dosing regimen or control. CONCLUSIONS Consistent reductions in LDL-C were observed in the evolocumab group regardless of demographic and disease characteristics.
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High intake of regular-fat cheese compared with reduced-fat cheese does not affect LDL cholesterol or risk markers of the metabolic syndrome: a randomized controlled trial.
Raziani, F, Tholstrup, T, Kristensen, MD, Svanegaard, ML, Ritz, C, Astrup, A, Raben, A
The American journal of clinical nutrition. 2016;(4):973-981
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BACKGROUND Regular-fat cheese contains a high amount of saturated fat. Therefore, dietary guidelines in many countries recommend the consumption of reduced-fat cheese as opposed to regular-fat cheese. However, the negative effect of regular-fat cheese is still under debate. OBJECTIVES The aim was to compare the effects of regular-fat cheese with an equal amount of reduced-fat cheese and an isocaloric amount of carbohydrate-rich foods on LDL cholesterol and risk factors for the metabolic syndrome (MetS). DESIGN The study was a 12-wk randomized parallel intervention preceded by a 2-wk run-in period. A total of 164 subjects with ≥2 MetS risk factors were randomly allocated to 1 of 3 intervention groups: regular-fat cheese (REG), reduced-fat cheese (RED), or a no-cheese, carbohydrate control (CHO) group. Subjects in the REG and RED groups replaced part of their daily habitual diet with 80 g cheese/10 MJ, whereas subjects in the CHO group did the same with bread and jam corresponding to 90 g and 25 g/10 MJ, respectively. RESULTS A total of 139 subjects completed the intervention. The primary outcome, LDL cholesterol, was not significantly different between the REG and RED diets or between the REG and CHO diets. There was no significant difference in HDL cholesterol between the REG and RED diets, but HDL cholesterol tended to be higher with the REG diet than with the CHO diet (0.06 ± 0.03 mmol/L; P = 0.07). Insulin, glucose, and triacylglycerol concentrations as well as blood pressure and waist circumference did not differ significantly between the 3 diets. CONCLUSION A high daily intake of regular-fat cheese for 12 wk did not alter LDL cholesterol or MetS risk factors differently than an equal intake of reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods. This trial was registered at www.clinicaltrials.gov as NCT02616471.
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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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Partly replacing meat protein with soy protein alters insulin resistance and blood lipids in postmenopausal women with abdominal obesity.
van Nielen, M, Feskens, EJ, Rietman, A, Siebelink, E, Mensink, M
The Journal of nutrition. 2014;(9):1423-9
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Increasing protein intake and soy consumption appear to be promising approaches to prevent metabolic syndrome (MetS). However, the effect of soy consumption on insulin resistance, glucose homeostasis, and other characteristics of MetS is not frequently studied in humans. We aimed to investigate the effects of a 4-wk, strictly controlled, weight-maintaining, moderately high-protein diet rich in soy on insulin sensitivity and other cardiometabolic risk factors. We performed a randomized crossover trial of 2 4-wk diet periods in 15 postmenopausal women with abdominal obesity to test diets with 22 energy percent (En%) protein, 27 En% fat, and 50 En% carbohydrate. One diet contained protein of mixed origin (mainly meat, dairy, and bread), and the other diet partly replaced meat with soy meat analogues and soy nuts containing 30 g/d soy protein. For our primary outcome, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of both periods. Plasma total, LDL, and HDL cholesterol, triglycerides, glucose, insulin, and C-reactive protein were assessed, and blood pressure, arterial stiffness, and intrahepatic lipid content were measured at the start and end of both periods. Compared with the mixed-protein diet, the soy-protein diet resulted in greater insulin sensitivity [FSIGT insulin sensitivity, 34 ± 29 vs. 22 ± 17 (mU/L)(-1) · min(-1), P = 0.048; disposition index, 4974 ± 2543 vs. 2899 ± 1878, P = 0.038; n = 11]. Total cholesterol was 4% lower after the soy-protein diet than after the mixed-protein diet (4.9 ± 0.7 vs. 5.1 ± 0.6 mmol/L, P = 0.001), and LDL cholesterol was 9% lower (2.9 ± 0.7 vs. 3.2 ± 0.6 mmol/L, P = 0.004; n = 15). Thus, partly replacing meat with soy in a moderately high-protein diet has clear advantages regarding insulin sensitivity and total and LDL cholesterol. Therefore, partly replacing meat products with soy products could be important in preventing MetS. This trial was registered at clinicaltrials.gov as NCT01694056.
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The effect of rosuvastatin on incident pneumonia: results from the JUPITER trial.
Novack, V, MacFadyen, J, Malhotra, A, Almog, Y, Glynn, RJ, Ridker, PM
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2012;(7):E367-72
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BACKGROUND Evidence from observational studies have raised the possibility that statin treatment reduces the incidence of certain bacterial infections, particularly pneumonia. We analyzed data from a randomized controlled trial of rosuvastatin to examine this hypothesis. METHODS We analyzed data from the randomized, double-blind, placebo-controlled JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). In this trial, 17,802 healthy participants (men 50 years and older and women 60 and older) with a low-density lipoprotein (LDL) cholesterol level below 130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level of 2.0 mg/L or greater were randomly assigned to receive either rosuvastatin or placebo. We evaluated the incidence of pneumonia on an intention-to-treat basis by reviewing reports of adverse events from the study investigators, who were unaware of the treatment assignments. RESULTS Among 17,802 trial participants followed for a median of 1.9 years, incident pneumonia was reported as an adverse event in 214 participants in the rosuvastatin group and 257 in the placebo group (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.69-1.00). In analyses restricted to events occurring before a cardiovascular event, pneumonia occurred in 203 participants given rosuvastatin and 250 given placebo (HR 0.81, 95% CI 0.67-0.97). Inclusion of recurrent pneumonia events did not modify this effect (HR 0.81, 95% CI 0.67-0.98), nor did adjustment for age, sex, smoking, metabolic syndrome, lipid levels and C-reactive protein level. INTERPRETATION Data from this randomized controlled trial support the hypothesis that statin treatment may modestly reduce the incidence of pneumonia. (ClinicalTrials.gov trial register no. NCT0023968.).
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A plant stanol yogurt drink alone or combined with a low-dose statin lowers serum triacylglycerol and non-HDL cholesterol in metabolic syndrome patients.
Plat, J, Brufau, G, Dallinga-Thie, GM, Dasselaar, M, Mensink, RP
The Journal of nutrition. 2009;(6):1143-9
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We evaluated the effects of 2 commonly available strategies (plant stanol ester drink and 10 mg simvastatin) on coronary heart disease (CHD) risk variables in participants with metabolic syndrome. Metabolic syndrome patients are at increased risk to develop CHD, partly due to high triacylglycerol (TAG) and low HDL cholesterol (HDL-C) concentrations and a low-grade inflammatory profile. Effects of plant stanol esters on TAG concentrations in these participants are unknown. After a 3-wk run-in period in which individuals consumed placebo yogurt drinks and placebo capsules, participants were randomly divided into 4 groups: placebo (n = 9), simvastatin + placebo drink (n = 10), placebo + stanol drink (n = 9), and simvastatin + stanol drink (n = 8). After 9 wk, we evaluated the effects on serum lipids, low-grade inflammation, and endothelial dysfunction markers. In metabolic syndrome patients, stanol esters (2.0 g/d), simvastatin, or the combination lowered non-HDL-C by 12.8% (P = 0.011), 30.7% (P < 0.001), and 35.4% (P < 0.001), respectively, compared with placebo. TAG were lowered by 27.5% (P = 0.044), 21.7% (P = 0.034), and 32.7% (P < 0.01), respectively. The total-:HDL-C ratio was significantly lowered in all 3 intervention groups. We found no treatment effects on the apolipoprotein CII:CIII ratio, cholesterol ester transfer protein mass, FFA concentrations, and markers for low-grade inflammation or endothelial dysfunction. This study shows that in metabolic syndrome patients, plant stanol esters lower not only non-HDL-C, but also TAG. Effects on TAG were also present in combination with statin treatment, illustrating an additional benefit of stanol esters in this CHD risk population.
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Comparative effects of three popular diets on lipids, endothelial function, and C-reactive protein during weight maintenance.
Miller, M, Beach, V, Sorkin, JD, Mangano, C, Dobmeier, C, Novacic, D, Rhyne, J, Vogel, RA
Journal of the American Dietetic Association. 2009;(4):713-7
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Although popular diets focus on weight loss and their favorable biochemical and physiological effects, fewer investigations have evaluated the biological impact of these diets during weight maintenance. To study this issue, three popular diets-Atkins, South Beach, and Ornish-were tested in a randomized and counterbalanced crossover study between January and December 2006. Participants completed each of the three 4-week isocaloric dietary intervention phases followed by a 4-week washout period. They were weighed weekly and caloric adjustments made if weight change exceeded 1 kg. At the completion of each dietary phase, 3-day food records were analyzed, fasting blood sampled, and brachial artery reactivity testing performed. Eighteen adults completed all three isocaloric dietary phases. During the South Beach and Ornish maintenance phase, there were significant reductions in low-density lipoprotein cholesterol (11.8%; P=0.01, 16.6%; P=0.0006, respectively) compared to prediet baseline. In addition, in contrast to the Atkins maintenance phase, significant reductions in low-density lipoprotein cholesterol and apolipoprotein B levels were observed after the South Beach (P=0.003, P=0.05; repeated measures analyses of variance) and Ornish maintenance phases (P=0.0004, P=0.006, repeated measures analyses of variance). Brachial artery testing revealed an inverse correlation between flow-mediated vasodilatation and intake of saturated fat (r=-0.33; P=0.016). These data suggest that during weight maintenance, less favorable biological effects are observed during a simulated, high-fat Atkins diet when compared to the South Beach and Ornish diet. The findings support additional study in subjects with visceral obesity and the metabolic syndrome, in whom an increased risk of coronary disease at baseline may be accentuated with chronic consumption of a diet that exhibits unfavorable effects on lipids and endothelial function.