Macronutrient intake and prevalence of markers of metabolic syndrome in white UK adult males in the National Diet and Nutrition Survey Rolling Programme 2008–2014

The amount of carbohydrates recommended for consumption by current dietary guidelines has been challenged in relation to their suitability to prevent or manage cardiometabolic (CM) diseases with suggestions that they should be decreased and replaced by protein or fat( 1 , 2 ). Others have argued that a more personalised approach is required( 3 ). Aim of this investigation was to assess the potential impact of lower versus higher consumption of dietary macronutrients and prevalence of CM risk markers in a representative sample of the UK male white population. Unweighted data from 642 white adult males aged 19 and over in the National Diet and Nutrition Survey Rolling Programme( 4 ) (NDNS RP) 2008–2014 with or without metabolic syndrome (MetS)( 5 ) were analysed for associations of dietary macronutrient intake as percentage food energy (%FE) with CM risk markers. Logistic regression analysis (adjusted for age group and smoking status) was used to compare the odds ratios [OR] of prevalence of individual markers of MetS between the lowest and highest quartiles of dietary macronutrient intake as %FE (⩽44 vs. ≥52 for carbohydrates; ⩽31 vs. ≥39 for fats; ⩽15. vs. ≥19 for protein). There was a significant (p < 0·05) reduction in likelihood of MetS (OR, .55; 95 % confidence interval [CI], .34 to .84), and elevated waist circumference (OR, .50; 95 % CI, .30 to .83) and glucose levels (OR, .51; 95 % CI, .30 to .87) for those in the highest quartile of carbohydrate %FE intake compared to the lowest quartile, whereas those in the highest quartile of protein %FE intake had a significantly (p < 0·05) increased risk of presenting with the same markers of MetS (OR, 1·75; 95 % CI, 1·05 to 2·93; OR, 2·12; 95 % CI, 1·24 to 3·63; and OR, 2·15; 95 % CI, 1·25 to 3·70 respectively). Those with the highest compared to the lowest total dietary fat intake also presented with elevated CM risk markers, albeit these findings were not significant. *Metabolic Syndrome (MetS) definition: 3 out of 5 of the following: triglycerides (TRIG) ≥1·7 mmol/L; High-density lipoprotein cholesterol (HDL-C) ⩽1·03 mmol/L for males; Waist circumference (WC) ≥94 cm for white males; Glucose (GLUC) ≥5·6 mmol/L; Blood pressure (BP) ≥130 mmHg systolic or ≥85 mmHg diastolic respectively; CHO%FE – total carbohydrates percentage food energy; FAT%FE – total fats food energy; PROT%FE– total protein food energy; OR – odds ratio (adjusted for age group and smoking status), 1st vs. 4th quartile of intake; CI – confidence interval; a p < 0·05 Further investigations need to confirm whether the quality of the macronutrients consumed and overall diet quality( 6 ) has had an impact on these results. In the context of a personalised approach to nutrition future cohort studies should also provide data that allow for examining inter-individual variations in responses to dietary macronutrients, especially carbohydrates, to achieve optimum CM health for a larger proportion of the population

The association between dietary macronutrient intake and fibrogen growth factor 21 in a sample of White UK adults with elevated cardiometabolic risk markers

Increased levels of Fibrogen growth factor 21 (FGF21) is an emerging risk marker for cardiometabolic (CM) disease(1). Little detail is known about the impact of the human diet on FGF21 levels. The aim of this investigation was to assess potential associations between mean daily dietary macronutrient intake and FGF21 levels in a sample of 10 healthy normal-weight and overweight Caucasian adults aged 32–60 (80 % male) at increased CM risk(2). This pilot study received ethical approval from Liverpool John Moores University Research Ethics Committee (16/ELS/029) and was registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly allocated to one of two groups and asked to either consume 50 % energy from CHO for a duration of 8 weeks. Blood plasma samples were col- lected at baseline (BL), interim point (IP) and endpoint (EP) after a 12-hour overnight fast, immediately processed and frozen at −80°C. Thawed plasma samples were analysed via Quantikine® enzyme-linked immunosorbent assay (ELISA) (R&D Systems) for FGF21 levels. Two-way mixed ANOVA and Pearson’s partial correlation adjusted for estimated weekly moderate and vigorous activity was undertaken using IBM SPSS 24®. There were no effects for diet between groups or over time (data not shown). Significant correlations between macronutrient intakes and FGF21 levels were found for both groups at IP, but not at BL or EP. Moderate and significant positive correlations were found in the overall group for intake (g/d) for glucose (rpartial = ·699, p = ·04) and fructose (rpartial = ·686, p = ·04) and strong and significant positive correlations for non-milk extrinsic sugars (rpartial = ·742, p = ·02). Strong and significant positive correlations were also found in the LC group for glucose intake (g/d) (rpartial = ·980, p = ·02) and fructose (rpartial = ·967, p = ·03) and for protein (rpartial =·998, p=·002) after adjusting for physical activity. Mean carbohydrate intake (g/d) was 160·0 (s.d. 124·5) overall and 44·2 (s.d. 14·9) in the LC group at IP. Mean protein intake (g/d) was 113·2 (21·4) 130·0 (s.d. 15·9) overall and in the LC group at IP. Mean FGF21 levels were 179·9 pg/mL (s.d. 144·9) in the overall group and 94.4 pg/ML (s.d. 48.6) in the LC group at IP. %TE Intake (g/d) PROT FAT CHO GLU FRU NMES PROT FAT rrrrrrrrrrr −·214 ·623 ·635 −·326 −·491 ·448 ·699* ·686* ·742* −·606 −·496 ·143 ·637 ·937 ·427 −·059 ·722 ·980* ·967* ·919 ·998** −·080 Total kcal CHO NMES T LC CHO-Total carbohydrates, FAT-Total fat, FRU-Fructose, GLUC-Glucose, LC-low-carbohydrate, high-fat group, NMES-non-milk extrinsic sugars, PROT-protein, T – total, %TE – percentage total energy, *p < ·05 **p < ·005. In conclusion, low-carbohydrate diets provide the opportunity to assess responses to even small amounts of CHO, which are likely to be replaced in part by proteins. Despite low overall intakes of fructose and glucose in the LC group, strong and positive correlations with FGF21 levels were observed. The lower levels of FGF21 in the LC compared to the overall group are in line with findings that FGF21 levels are elevated with high-carbohydrate, low-protein diets with dietary fats having only minor impact(3). However, the majority of studies have still been undertaken using rodent models. The impact of dietary macronutrients on FGF21 levels as novel CMR marker in humans and the mechanism behind this relationship warrant further investigation. 1. Lakhani I, Gong M, Wong W et al. (2018) Metabolism 2018 Feb 1. pii: S0026-0495(18)30023-4. [Epub ahead of print]. 2. Jebb S, Lovegrove J, Griffin B et al. (2010) Am J Clin Nutr 92, 748–58. 3. Solon-Biet S, Cogger V, Pulpitel T et al. (2016) Cell Metab 24, 555–565

Dietary carbohydrate intake, visceral adipose tissue and associated markers of cardiometabolic risk

Risk of cardiometabolic (CM) disease is characterised by elevated visceral adipose tissue (VAT) and a number of associated biomar- kers(1). Some dietary carbohydrates (CHO) have been found to contribute to VAT accumulation(2). Little is known about the impact of following a low-carbohydrate diet versus a high-carbohydrate diet on VAT, adiponectin (ADPN), leptin (LEPT) and leptin:adipo- nectin ratio (LAR). The aim of this investigation was to assess the impact of dietary carbohydrates (CHO) on VAT and emerging CM risk markers in a sample of 10 healthy normal-weight and overweight Caucasian adults aged 32–60 (80 % male) at increased CM risk(3). This pilot study received ethical approval from Liverpool John Moores University Research Ethics Committee (16/ELS/ 029) and was registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly allocated to one of two groups and asked to either consume 50 % energy from CHO (high-carb (HC)) for a duration of 8 weeks. VAT was ana- lysed via bioelectrical impedance (SECA mBCA 515). Blood plasma samples were collected at baseline (BL), interim point (IP) and endpoint (EP) after a 12-hour overnight fast, immediately processed and frozen at -80°C. Thawed plasma samples were analysed via immunoassay technology (Randox Evidence InvestigatorTM Metabolic Syndrome Arrays I and II) for ADPN and LEPT levels. Statistical analysis was undertaken using IBM SPSS 24®. Parametric data was analysed via two-way mixed ANOVA; non-parametric data was analysed via Mann-Whitney U test and Friedman test. Average daily carbohydrate intake in the LC group was 44·2 g at IP and 48·9 g at EP. There were no significant differences between groups at any time point for ADPN, LEPT, LAR or VAT and no significant inter- actions for time or group*time for ADPN, LEPT or LAR. However, in the LC group VAT decreased significantly between baseline and endpoint by 15 % (p = ·015) Over the course of the intervention ADPN and LEPT decreased non- significantly (by 4 % and 70 % respectively) in the LC group, whilst increasing non-significantly in the HC group (9 % and 65 % respectively). LAR increased in the HC group throughout the study, whilst LAR in the LC group decreased albeit not significantly. VAT (litre) ADPN (ng/mL) LEPT (ng/mL) LAR BL IP EP Median Median Median M SD M SD M SD BL IP EP BL IP EP BL IP EP LC 4·1a 1·2 3·8 1·3 3·5a 1·2 8·9 8·6 8·5 3·96 1·64 1·20 0·45 0·19 0·14 HC 2·7 0·1 1·6 0·3 2·5 0·1 11·3 13·4 12·3 0·97 1·1 1·60 0·07 0·07 0·46 ADPN = adiponectin, BL = baseline, EP = endpoint, HC = high-carbohydrate, moderate fat diet, IP = interim point, LAR = leptin:adiponectin ratio, LEPT = leptin, LC = low-carbohydrate, high-fat diet, VAT = visceral adipose tissue, ap = ·015. NB: interquartile ranges not provided for median values due to missing data. Higher LAR has been found to be a marker of increased CM risk(4). In conclusion, while the significant reduction in VAT in the LC group corresponds with the reduction of LAR further evidence is required to corroborate these findings. Previous evidence for LC is supportive for improved CM health from various biomarkers(5); LAR should be considered as a useful endocrine addition for future LC studies. 1. Krasimira A, Mozaffarian D & Pischon T (2018) Clin Chem 64, 142–153. 2. Rüttgers D, Fischer K, Koch M et al. (2015) Br J Nutr 114, 1929–1940. 3. Jebb S, Lovegrove J, Griffin B et al. (2010) Am J Clin Nutr 92, 748–58. 4. López-Jaramillo P, Gómez-Arbeláez D, López-López J et al. (2014) Horm Mol Biol Clin Investig 18, 37–45. 5. Bazzano L, Hi T, Reynolds K et al. (2014) Ann Intern Med 161, 309–318

Real-world applicability and impact of early rhythm control for European patients with atrial fibrillation: a report from the ESC-EHRA EORP-AF Long-Term General Registry

Background: Use of rate/rhythm control is essential to control symptoms in patients with atrial fibrillation (AF). Recently, the EAST-AFNET 4 trial described how early rhythm control strategy was associated with a lower risk of adverse clinical outcomes. Objectives: The aim was to evaluate the real-world applicability and impact of an early rhythm control strategy in patients with AF. Methods: Use of an early rhythm control strategy was assessed in a European cohort of AF patients derived from the EHRA-ESC EORP-AF General Long-Term Registry. Early rhythm control was defined as use of antiarrhythmic drugs or cardioversion/catheter ablation. The primary outcome included cardiovascular death, stroke, acute coronary syndrome, and worsening of heart failure. Quality of life and health-care resource usage were also assessed as outcomes. Results: Among the 10,707 patients evaluated for eligibility to EAST-AFNET 4, a total of 3774 (34.0%) were included. Early rhythm control was associated with better quality of life, but with greater use of health-care resources. During follow-up, the primary outcome occurred less often in early rhythm control patients than in those with no rhythm control (13.6% vs. 18.5%, p &lt; 0.001). In the multivariate adjusted Cox regression model, no significant difference was found between no rhythm control and early rhythm control, for the primary outcome. No difference in the primary outcome between early rhythm control and ‘no rhythm control patients’ adherent to Atrial fibrillation Better Care (ABC) pathway’ was evident (p = 0.753) Conclusions: Use of an early rhythm control strategy was associated with a lower rate of major adverse events, but this difference was non-significant on multivariate analysis, being mediated by differences in baseline characteristics and clinical risk profile. Early rhythm control was associated with a higher use of health-care resources and risk of hospital admission, despite showing better quality of life. Graphic abstract: [Figure not available: see fulltext.

The Effect of Carbohydrate Restriction on Lipids, Lipoproteins, and Nuclear Magnetic Resonance-Based Metabolites: CALIBER, a Randomised Parallel Trial

Low-carbohydrate high-fat (LCHF) diets can be just as effective as high-carbohydrate, lower-fat (HCLF) diets for improving cardiovascular disease risk markers. Few studies have compared the effects of the UK HCLF dietary guidelines with an LCHF diet on lipids and lipoprotein metabolism using high-throughput NMR spectroscopy. This study aimed to explore the effect of an ad libitum 8-week LCHF diet compared to an HCLF diet on lipids and lipoprotein metabolism and CVD risk factors. For 8 weeks, n = 16 adults were randomly assigned to follow either an LCHF (n = 8, <50 g CHO p/day) or an HCLF diet (n = 8). Fasted blood samples at weeks 0, 4, and 8 were collected and analysed for lipids, lipoprotein subclasses, and energy-related metabolism markers via NMR spectroscopy. The LCHF diet increased (p < 0.05) very small VLDL, IDL, and large HDL cholesterol levels, whereas the HCLF diet increased (p < 0.05) IDL and large LDL cholesterol levels. Following the LCHF diet alone, triglycerides in VLDL and HDL lipoproteins significantly (p < 0.05) decreased, and HDL phospholipids significantly (p < 0.05) increased. Furthermore, the LCHF diet significantly (p < 0.05) increased the large and small HDL particle concentrations compared to the HCLF diet. In conclusion, the LCHF diet may reduce CVD risk factors by reducing triglyceride-rich lipoproteins and improving HDL functionality

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

Inter-examiner reliability of the diagnosis of cervical pillar hyperplasia (CPH) and the correlation between CPH and spinal degenerative joint disease (DJD)

BACKGROUND: Cervical pillar hyperplasia (CPH) is a recently described phenomenon of unknown aetiology. Its clinical importance is poorly understood at the present time; therefore, the objective of this study was to determine (1) the inter-examiner reliability of detecting CPH and (2) if there is a clinically important correlation (r > 0.4) between the number of cervical spine levels showing signs of degenerative joint disease (DJD) and CPH. METHODS: The sample consisted of 320 radiographs of human male and female subjects who ranged from 40 to 79 years of age. The inter-examiner reliability of assessing the presence/absence of pillar hyperplasia was evaluated on 50 neutral lateral radiographs by two examiners using line drawings and it was quantified using the kappa coefficient of concordance. To determine the presence/absence of hyperplastic pillars as well as the presence/absence of DJD at each intervertebral disc and zygapophysial joint, 320 AP open mouth, AP lower cervical and neutral lateral radiographs were then examined. The unpaired t-test at the 5% level of significance was performed to test for a statistically significant difference between the number of levels affected by DJD in patients with and without hyperplasia. The Spearman's rho at the 5% level of significance was performed to quantify the correlation between DJD and age. RESULTS: The inter-examiner reliability of detecting cervical pillar hyperplasia was moderate with a kappa coefficient of 0.51. The unpaired t-test indicated that there was no statistically significant difference (p > 0.05) between the presence/absence of cervical pillar hyperplasia and the number of levels affected by DJD in an age-matched population, regardless of whether all elements were considered together, or the discs and facets were analyzed separately. A Spearman correlation rank of 0.67 (p < 0.05) suggested a moderately strong correlation between the number of elements (i.e. discs/facets) affected, and the age of the individual. CONCLUSION: Cervical pillar hyperplasia is a reasonable concept that requires further research. Its evaluation is easy to learn and acceptably reliable. Previous research has suggested that CPH may affect the cervical lordosis, and therefore, alter biomechanics which may result in premature DJD. This current study, however, indicates that, globally, CPH does not appear to be related to the development of DJD

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services

Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, &lt;50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p &lt; 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p &lt; 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation