Lipid-lipoprotein Profile Research Articles

Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An expert clinical consensus from the national lipid association

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.

Impact of Quantity and Type of Dietary Protein on Cardiovascular Disease Risk Factors Using Standard and Network Meta-analyses of Randomized Controlled Trials.

Higher protein diets (HPDs) have shown favorable outcomes on weight maintenance and body-composition management; however, their protective effects against cardiovascular diseases (CVDs) remain uncertain and contentious. Furthermore, it is important to consider the influence of other macronutrients in the diet and type of dietary protein when studying HPDs, because this aspect has been overlooked in previous studies. We assessed the impacts of quantity and type of dietary protein on CVD risk factors. A database search was conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library and a total of 100 articles met the eligibility criteria. Extracted data from 100 articles were analyzed using standard meta-analysis, and 41 articles were also analyzed using network meta-analysis. In the standard meta-analysis, an HPD had significant favorable effects on systolic blood pressure (SBP) (mean difference [MD] = -1.51 mmHg; 95% CI: -2.77, -0.25), diastolic blood pressure (DBP) (MD = -1.08 mmHg; 95% CI: -1.81, -0.35), and flow-mediated dilation (MD = 0.78%; 95% CI: 0.09, 1.47) compared with lower protein diets. The further network meta-analysis supported that the high-protein, high-carbohydrate, low-fat diet was the most recommended diet to ensure a maximum decrease in SBP, DBP, total cholesterol (TC), and low-density-lipoprotein cholesterol (LDL-C). In comparison to animal-protein-rich diets, plant-protein-rich diets (PPRs) exhibited a significant favorable effects on improving TC (MD = -0.12 mmol/L; 95% CI: -0.19, -0.05), triglyceride (MD = -0.05 mmol/L; 95% CI: -0.09, -0.01), LDL-C (MD = -0.11 mmol/L; 95% CI: -0.18, -0.04), and high-density-lipoprotein cholesterol (MD = 0.03 mmol/L; 95% CI: 0.02, 0.04) levels. Consumption of HPDs and PPRs supports improvements in vascular health and lipid-lipoprotein profiles, respectively. Furthermore, macronutrient composition should be carefully designed in the dietary approach to maximize the effectiveness of HPDs in improving CVD risk factors. PROSPERO registration no. CRD42022369931.

Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Resistance training and cardiometabolic risk in women with metabolically healthy and unhealthy obesity.

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid-lipoprotein profile, inflammation, and glucose-insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01<p<0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11-1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: -0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: -0.42 to-0.84 (small to large effects), p ˂ 0.05). Glucose-insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype.

Does excess body weight accelerate immune aging?

BackgroundOverweight and obesity in older adults increase the risk of a range of comorbidities by sustaining chronic inflammation and thus enhancing immunosenescence. This study aimed to assess whether excess body mass affected disproportion in T lymphocytes. Therefore, the study was designed to explain whether excess body mass in older individuals affected the disproportion in numbers of T lymphocytes and whether anthropometric indices and immune risk profile expressed as CD4/CD8 ratio are diagnostically useful in the analysis of immunosenescence. Materials & methodsOne hundred three individuals aged 73.6 ± 3.1 years were allocated to the normal body mass (body mass index (BMI) 18.5–24.9 kg/m2,n = 39), the pre-obesity (BMI 25.0–29.9 kg/m2, n = 44) or the obesity (BMI ≥30.0 kg/m2, n = 20) group, based on WHO recommendations. Details on the subjects' medical history and lifestyle were obtained by health questionnaire. Anthropometric analysis was performed by bioelectrical impedance method, biochemical analysis was made by the automatic analyzer and ELISA immunoassays, and T and B lymphocyte counts were determined by eight-parameter flow cytometry. Additionally, visceral adiposity index, body adiposity index (BAI), and body shape index (ABSI) were evaluated based on body circumference, BMI and lipid-lipoprotein profile measurements. ResultsThe highest percentage of CD3+CD4+ T lymphocytes (59.4 ± 12.6 %) and the lowest CD3+CD8+ T lymphocytes (31.6 ± 10.0 %) were noted in patients the obesity group. The highest cut-off value of 1.9 for CD4/CD8 ratio was recorded in the normal body mass vs pre-obesity model. CD4/CD8 ratio > 2.5 was recorded in >20 % of our pre-obesity and obesity groups while 64.5 % of the normal body mass group had CD4/CD8 ratio < 1. High diagnostic usefulness was demonstrated for both BAI and lipid accumulation product (LAP) (AUC values of ~0.800 and ~ 0.900 respectively) in three models: normal body mass vs pre-obesity, normal body mass vs obesity, and pre-obesity vs obesity. ConclusionThe odds ratios (OR) for CD4/CD8 ratio in the normal body mass vs obesity model (OR = 16.1, 95%CI 3.8–93.6) indicated a potential diagnostic value of T lymphocytes for clinical prognosis of immune aging in relation to excess body weight in older adults. High values of AUC obtained for the following models: CD4/CD8 + BAI (AUC = 0.927), CD4/CD8 + LAP (AUC = 1.00), CD4/CD8 + ABSI (AUC = 0.865) proved to provide excellent discrimination between older adults with obesity and with normal body mass.

Sex-specific responses in glucose-insulin homeostasis and lipoprotein-lipid components after high-dose supplementation with marine n-3 PUFAs in abdominal obesity: a randomized double-blind crossover study.

Clinical studies on effects of marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) on lipoprotein-lipid components and glucose-insulin homeostasis have shown conflicting results, which may partly be explained by differential responses in females and males. However, we have lacked data on sexual dimorphism in the response of cardiometabolic risk markers following increased consumption of n-3 or n-6 PUFAs. To explore sex-specific responses after n-3 (EPA + DHA) or n-6 (LA) PUFA supplementation on circulating lipoprotein subfractions, standard lipids, apolipoproteins, fatty acids in red blood cell membranes, and markers of glycemic control/insulin sensitivity among people with abdominal obesity. This was a randomized double-blind crossover study with two 7-week intervention periods separated by a 9-week washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we measured lipoprotein particle subclasses, standard lipids, apolipoproteins, fatty acid profiles, and markers of glycemic control/insulin sensitivity. The between-sex difference in relative change scores was significant after n-3 for total high-density lipoproteins (females/males: -11%*/-3.3%, p = 0.036; *: significant within-sex change), high-density lipoprotein particle size (+2.1%*/-0.1%, p = 0.045), and arachidonic acid (-8.3%*/-12%*, p = 0.012), and after n-6 for total (+37%*/+2.1%, p = 0.041) and small very-low-density lipoproteins (+97%*/+14%, p = 0.021), and lipoprotein (a) (-16%*/+0.1%, p = 0.028). Circulating markers of glucose-insulin homeostasis differed significantly after n-3 for glucose (females/males: -2.1%/+3.9%*, p = 0.029), insulin (-31%*/+16%, p < 0.001), insulin C-peptide (-12%*/+13%*, p = 0.001), homeostasis model assessment of insulin resistance index 2 (-12%*/+14%*, p = 0.001) and insulin sensitivity index 2 (+14%*/-12%*, p = 0.001), and quantitative insulin sensitivity check index (+4.9%*/-3.4%*, p < 0.001). We found sex-specific responses after high-dose n-3 (but not n-6) supplementation in circulating markers of glycemic control/insulin sensitivity, which improved in females but worsened in males. This may partly be related to the sex differences we observed in several components of the lipoprotein-lipid profile following the n-3 intervention. https://clinicaltrials.gov/, identifier [NCT02647333].

Comparison of low-density lipoprotein cholesterol estimation methods in individuals with insulin resistance: A cross-sectional study

Background and aimsThe Friedewald, Sampson, and Martin equations were developed to estimate low-density lipoprotein cholesterol levels; however, the validation data of these equations with and without insulin resistance are insufficient. Materials and methodsWe collected data on low-density lipoprotein cholesterol and lipid profiles from the Korea National Health and Nutrition Examination Survey. Using the data on insulin requirement, insulin resistance was calculated for 4,351 participants (median age, 48 [36–59] years; 49.9% male) using the homeostatic model assessment for insulin resistance (n = 2,713) and quantitative insulin-sensitivity check index (n = 2,400). ResultsAccording to the mean and median absolute deviation, the Martin equation yielded more accurate estimates than other equations when the triglyceride level was < 400 mg/dL with insulin resistance; the Sampson equation yielded lower estimates when the direct low-density lipoprotein cholesterol level was < 70 mg/dL and triglyceride level was < 400 mg/dL without insulin resistance. However, the three equations yielded similar estimates when the triglyceride level was < 150 mg/dL with and without insulin resistance. ConclusionThe Martin equation yielded more appropriate estimates than the Friedewald and Sampson equations for triglyceride levels < 400 mg/dL with and without insulin resistance. If the triglyceride level was < 150 mg, the Friedewald equation could also be considered.

Insulin Resistance Is Associated with an Unfavorable Serum Lipoprotein Lipid Profile in Women with Newly Diagnosed Gestational Diabetes

Gestational diabetes (GDM) is associated with various degrees of insulin resistance-a feature related to increased risk of adverse perinatal outcomes. We aimed to determine the previously poorly investigated associations between maternal insulin resistance and serum fasting metabolome at the time of GDM diagnosis. Serum lipoprotein and amino acid profile was analyzed in 300 subjects with newly diagnosed GDM using a validated nuclear magnetic resonance spectroscopy protocol. Associations between insulin resistance (homeostasis model assessment of insulin resistance, HOMA2-IR) and serum metabolites were examined with linear regression. We found insulin resistance to be associated with a distinct lipid pattern: increased concentration of VLDL triglycerides and phospholipids and total triglycerides. VLDL size was positively related and LDL and HDL sizes were inversely related to insulin resistance. Of fatty acids, increased total fatty acids, relative increase in saturated and monounsaturated fatty acids, and relative decrease in polyunsaturated and omega fatty acids were related to maternal insulin resistance. In newly diagnosed GDM, the association between maternal insulin resistance and serum lipoprotein profile was largely as described in type 2 diabetes. Lifestyle interventions aiming to decrease insulin resistance from early pregnancy could benefit pregnancy outcomes via more advantageous lipid metabolism.

Remnant cholesterol levels are associated with severity and death in COVID-19 patients

Coronavirus disease-19 (COVID-19) patients with severe complications present comorbidities like cardiovascular-disease, hypertension and type-2 diabetes mellitus (DM), sharing metabolic alterations like insulin resistance (IR) and dyslipidemia. Our objective was to evaluate the association among different components of the lipid-lipoprotein profile, such as remnant lipoprotein (RLP)-cholesterol, in patients with COVID-19, and to analyze their associations with the severity of the disease and death. We studied 193 patients (68 (29–96) years; 49.7% male) hospitalized for COVID-19 and 200 controls (46 (18–79) years; 52.5% male). Lipoprotein profile, glucose and procalcitonin were assessed. Patients presented higher glucose, TG, TG/HDL-cholesterol and RLP-cholesterol levels, but lower total, LDL, HDL and no-HDL-cholesterol levels (p < 0.001). When a binary logistic regression was performed, age, non-HDL-cholesterol, and RLP-cholesterol were associated with death (p = 0.005). As the COVID-19 condition worsened, according to procalcitonin tertiles, a decrease in all the cholesterol fractions (p < 0.03) was observed with no differences in TG, while levels of RLP-cholesterol and TG/HDL-cholesterol increased (p < 0.001). Lower levels of all the cholesterol fractions were related with the presence and severity of COVID-19, except for RLP-cholesterol levels and TG/HDL-cholesterol index. These alterations indicate a lipid metabolic disorder, characteristic of IR states in COVID-19 patients. RLP-cholesterol levels predicted severity and death in these patients.

Constructing an atlas of associations between polygenic scores from across the human phenome and circulating metabolic biomarkers.

Polygenic scores (PGS) are becoming an increasingly popular approach to predict complex disease risk, although they also hold the potential to develop insight into the molecular profiles of patients with an elevated genetic predisposition to disease. We sought to construct an atlas of associations between 125 different PGS derived using results from genome-wide association studies and 249 circulating metabolites in up to 83,004 participants from the UK Biobank. As an exemplar to demonstrate the value of this atlas, we conducted a hypothesis-free evaluation of all associations with glycoprotein acetyls (GlycA), an inflammatory biomarker. Using bidirectional Mendelian randomization, we find that the associations highlighted likely reflect the effect of risk factors, such as adiposity or liability towards smoking, on systemic inflammation as opposed to the converse direction. Moreover, we repeated all analyses in our atlas within age strata to investigate potential sources of collider bias, such as medication usage. This was exemplified by comparing associations between lipoprotein lipid profiles and the coronary artery disease PGS in the youngest and oldest age strata, which had differing proportions of individuals undergoing statin therapy. Lastly, we generated all PGS-metabolite associations stratified by sex and separately after excluding 13 established lipid-associated loci to further evaluate the robustness of findings. We envisage that the atlas of results constructed in our study will motivate future hypothesis generation and help prioritize and deprioritize circulating metabolic traits for in-depth investigations. All results can be visualized and downloaded at http://mrcieu.mrsoftware.org/metabolites_PRS_atlas. This work is supported by funding from the Wellcome Trust, the British Heart Foundation, and the Medical Research Council Integrative Epidemiology Unit.

The impact of splenectomy on human lipid metabolism.

BackgroundSplenectomy impacts hematological, immunological, and metabolic functions of the patient. Since our understanding of its metabolic effects, in particular effects on lipid metabolism, is limited, this study aims to investigate the effects of splenectomy on lipid metabolism.MethodsThe data from 316 patients undergoing splenectomy between 2009 and 2019 were retrospectively analyzed. Thirty-eight patients whose serum lipid values were measured both preoperatively and 1 year after surgery were included in this study.ResultsSignificantly higher levels of total cholesterol, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) lipid profile were found in the postsplenectomy measurements. However, no significant differences were recorded in levels of triglyceride, HDL, or very-LDL.ConclusionWe determined that splenectomy does impact lipid metabolism, and that the metabolic effects of splenectomy should further be investigated.

Contribution of markers of adiposopathy and adipose cell size in predicting insulin resistance in women of varying age and adiposity

ABSTRACT Adipose tissue (AT) dysfunctions, such as adipocyte hypertrophy, macrophage infiltration and secretory adiposopathy (low plasma adiponectin/leptin, A/L, ratio), associate with metabolic disorders. However, no study has compared the relative contribution of these markers to cardiometabolic risk in women of varying age and adiposity. Body composition, regional AT distribution, lipid-lipoprotein profile, glucose homeostasis and plasma A and L levels were determined in 67 women (age: 40-62 years; BMI: 17-41 kg/m2). Expression of macrophage infiltration marker CD68 and adipocyte size were measured from subcutaneous abdominal (SCABD) and omental (OME) fat. AT dysfunction markers correlated with most lipid-lipoprotein levels. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR, while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Multiple regression analyses including these markers and TAG levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR. The contribution of the A/L ratio was superseded by adipose cell size in the model where the latter replaced TAGs. Finally, leptinemia was a better predictor of IR than adipocyte size and the A/L ratio in our participants sample.

Enhancing the cardiovascular protective effects of a healthy dietary pattern with wolfberry (Lycium barbarum): A randomized controlled trial

The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits. To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore. This is a 16-week, parallel design, randomized controlled trial. All participants (n=40) received dietary counselling to follow healthy dietary pattern recommendations with the wolfberry group given additional instructions to cook and consume 15 g/d whole, dried wolfberry with their main meals. Biomarkers of vascular function (flow-mediated dilation, plasma total nitrate/nitrite, endothelin-1, and intercellular adhesion molecule-1), vascular structure (carotid intima-media thickness) and vascular regeneration (endothelial progenitor cell count, plasma angiopoietin 1 and angiopoietin 2), were assessed at baseline and postintervention. Serum lipid-lipoproteins and blood pressure were evaluated every 4 weeks. All participants showed an improved compliance toward the healthy dietary pattern. This was coupled with marked rises in total nitrate/nitrite concentrations (mean change wolfberry: 3.92±1.73 nmol/mL; control: 5.01±2.55 nmol/L) and reductions in endothelin-1 concentrations (wolfberry: -0.19±0.06 pg/mL; control: -0.15±0.08 pg/mL). Compared with the control which depicted no changes from baseline, the wolfberry group had a significantly higher HDL cholesterol (0.08±0.04 mmol/L), as well as lower Framingham predicted long-term CVD risk (-0.8±0.5%) and vascular age (-1.9±1.0 y) postintervention. No differences were observed in the other vascular health-related outcomes. In middle-aged and older adults, adherence to a healthy dietary pattern improves vascular tone. Incorporating wolfberry to the diet further improves blood lipid-lipoprotein profile and may lower long-term CVD risk. This study was registered at clinicatrials.gov as NCT03535844.

Effects of Low Molecular Weight and Unfractionated Heparin on Lipoprotein Lipase and Lipid Profile in haemodialysis patients

Introduction: In haemodialysis patients, mortality from cardiovascular disease is much greater than in the general population. The current study aimed to evaluate the effects of two different types of heparin, low molecular weight heparins (LMWH) and high molecular weight heparin (HMWH), on lipid profile in patients undergoing haemodialysis.Material &amp; Methods: A total of 60 patients on haemodialysis were selected from two main hospitals of Lahore, Pakistan and were divided into two major groups based on the type of heparin used. A 5 ml blood sample was taken from the dialysis machine to get the serum and was kept frozen at -20ºC for analysis of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein. Comparison of lipoprotein lipase activity between groups were evaluated by using the student t-test. A P-value of ? 0.05 was considered statistically significant.Results: Gender wise distribution of study population (n=60) was 67% (n=40) males and 33% (n=20) females. The age distribution of individuals varied from 39-43 years. Moreover, use of HMWH was high in males (73%) as compared to female (27%) with an average age of 39 ± 12 years where duration of haemodialysis was 4.44 ± 2.83. A significant difference in LPL activity related to different times in all patients was observed. A clearer difference observed in case of LDL where LPL activity was markedly different in both groups. Our data showed that individuals using LMWH had less chances of dyslipidaemia as compared to those using HMWH.Conclusion: LMWH is a useful and safe anticoagulant during haemodialysis as compared to HMWH.

Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice

In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD. LDLr−/−ApoB100/100 male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic LDLr−/− ApoB100/100 mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.

A large-scale observational study linking various kinds of physical exercise to lipoprotein-lipid profile

BackgroundBeing a major cardiovascular risk factor, dyslipidemia is a critical problem in public health. Recommendations in performing regular physical exercise are important to prevent dyslipidemia.MethodsBased on a discovery cohort with 27,735 subjects and a replication cohort with 67,512 subjects, we evaluated the associations of regularly performing 23 exercises with 4 dyslipidemia indices measured from serum, including triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TG/HDL-C ratio. Regular exercise was defined as performing 30 min of “exercise” three times a week. “Exercise” includes leisure-time activities such as jogging, swimming, etc. Sex, age, body mass index, alcohol drinking, cigarette smoking, and education level were adjusted in all statistical analyses.ResultsAmong the 23 exercises, only jogging was associated with a decreased level of TG (95% confidence interval [C.I.] = 5.9–14.5 mg/dL) and TG/HDL-C ratio (95% C.I. = 0.22–0.49). A total of 5 exercises were associated with an increased level of HDL-C, including jogging (95% C.I. = 2.1–3.3 mg/dL), swimming (95% C.I. = 1.6–3.3 mg/dL), dance dance revolution (95% C.I. = 1.5–3.4 mg/dL), international standard dancing (95% C.I. = 1.0–2.7 mg/dL), and cycling (95% C.I. = 0.6–1.8 mg/dL). These significant findings were further well replicated in the cohort of 67,512 subjects.ConclusionRegular jogging was not only associated with an increased level of HDL-C, but also the only one exercise associated with a decreased level of TG and TG/HDL-C ratio. Nonetheless, jogging may be difficult to engage in for subjects with limited exercise capacity. We here found that swimming, dancing, and cycling are also significantly associated with an increased level of HDL-C. People who are seeking exercise to improve their lipoprotein-lipid profiles can have other choices now.

Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer

Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.

Enhancing the Cardiovascular Protective Effects of a Healthy Dietary Pattern with Wolfberry (Lycium barbarum): A Randomized Controlled Trial

Abstract Objectives The study aimed to investigate the impact of wolfberry (Lycium barbarum) consumption as part of a healthy dietary pattern on cardiovascular health in Singaporean middle-aged and older adults. It was hypothesized that the consumption of wolfberry could further enhance the cardiovascular protective effects of a healthy dietary pattern. Methods This was a 16 week, parallel design, randomized controlled trial where 40 Singaporean men and women (aged 50 to 64 years) received dietary counselling to follow a healthy dietary pattern either with or without 15 g/day of dried whole wolfberry, cooked and consumed as part of their meals. Blood pressure, serum lipid-lipoprotein concentrations and dietary compliance using 3-day food records were monitored every 4 weeks. Further evaluation of cardiovascular disease (CVD) biomarkers, broadly classified as serological (total nitrate/nitrite, endothelin-1, intercellular adhesion molecule-1, angiopoietin-1, angiopoietin-2 and von-Willebrand factor), structural (carotid intima-media thickness using B-mode ultrasonography) and functional (flow-mediated dilation using B-mode ultrasonography and circulating endothelial progenitor cells (CD34+/KDR+) by fluorescence-activated cell sorting) were analyzed before and after intervention. Results Adherence to a healthy dietary pattern contributed to a time dependent effect on both the plasma total nitrate/nitrite (P &amp;lt; 0.01) and plasma endothelin-1 (P &amp;lt; 0.005) which were raised and lowered respectively at week 16. However, changes were significant only in the wolfberry group (total nitrate/nitrite: 15.9 ± 1.8 to 19.4 ± 2.2 μmol/L, P &amp;lt; 0.05; endothelin-1: 1.31 ± 0.12 to 1.11 ± 0.10 ng/L, P &amp;lt; 0.01) and not in the control group. Moreover, a significant increase in serum high density lipoprotein (HDL) cholesterol was also detected solely in the wolfberry group (1.56 ± 0.10 to 1.65 ± 0.10 mmol/L, P &amp;lt; 0.05). The other serological, structural and functional biomarkers of cardiovascular health showed no observable change after the intervention. Conclusions Incorporating wolfberry to your daily meals may augment the cardiovascular protective benefits of a healthy dietary pattern by improving the regulation of vascular tone and plasma lipid-lipoprotein profile in Singaporean middle-aged and older adults. Funding Sources Ministry of Education, Singapore.

Ischemic Preconditioning Enhances Aerobic Adaptations to Sprint-Interval Training in Athletes Without Altering Systemic Hypoxic Signaling and Immune Function.

Optimizing traditional training methods to elicit greater adaptations is paramount for athletes. Ischemic preconditioning (IPC) can improve maximal exercise capacity and up-regulate signaling pathways involved in physiological training adaptations. However, data on the chronic use of IPC are scarce and its impact on high-intensity training is still unknown. We investigated the benefits of adding IPC to sprint-interval training (SIT) on performance and physiological adaptations of endurance athletes. In a randomized controlled trial, athletes included eight SIT sessions in their training routine for 4 weeks, preceded by IPC (3 × 5 min ischemia/5 min reperfusion cycles at 220 mmHg, n = 11) or a placebo (20 mmHg, n = 9). Athletes were tested pre-, mid-, and post-training on a 30 s Wingate test, 5-km time trial (TT), and maximal incremental step test. Arterial O2 saturation, heart rate, rate of perceived exertion, and quadriceps muscle oxygenation changes in total hemoglobin (Δ[THb]), deoxyhemoglobin (Δ[HHb]), and tissue saturation index (ΔTSI) were measured during exercise. Blood samples were taken pre- and post-training to determine blood markers of hypoxic response, lipid-lipoprotein profile, and immune function. Differences within and between groups were analyzed using Cohen's effect size (ES). Compared to PLA, IPC improved time to complete the TT (Mid vs. Post: −1.6%, Cohen's ES ± 90% confidence limits −0.24, −0.40;−0.07) and increased power output (Mid vs. Post: 4.0%, ES 0.20, 0.06;0.35), Δ[THb] (Mid vs. Post: 73.6%, ES 0.70, −0.15;1.54, Pre vs. Post: 68.5%, ES 0.69, −0.05;1.43), Δ[HHb] (Pre vs. Post: 12.7%, ES 0.24, −0.11;0.59) and heart rate (Pre vs. Post: 1.4%, ES 0.21, −0.13;0.55, Mid vs. Post: 1.6%, ES 0.25, −0.09;0.60). IPC also attenuated the fatigue index in the Wingate test (Mid vs. Post: −8.4%, ES −0.37, −0.79;0.05). VO2peak and maximal aerobic power remained unchanged in both groups. Changes in blood markers of the hypoxic response, vasodilation, and angiogenesis remained within the normal clinical range in both groups. We concluded that IPC combined with SIT induces greater adaptations in cycling endurance performance that may be related to muscle perfusion and metabolic changes. The absence of elevated markers of immune function suggests that chronic IPC is devoid of deleterious effects in athletes, and is thus a safe and potent ergogenic tool.

APOC3-rs2854116 polymorphism related to hypercholesterolemia in primary school children in Hanoi

APOC3-rs2854116 polymorphism related to hypercholesterolemia in primary school children in Hanoi