Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism.

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

Adherence to UK dietary guidelines is associated with higher dietary intake of total and specific polyphenols compared with a traditional UK diet: further analysis of data from the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach (CRESSIDA) randomised controlled trial.

Adherence to dietary guidelines (DG) may result in higher intake of polyphenols via increased consumption of fruits, vegetables and whole grains. We compared polyphenol dietary intake and urinary excretion between two intervention groups in the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach study: a 12-week parallel-arm, randomised controlled trial (n 161; sixty-four males, ninety-seven females; aged 40-70 years). One group adhered to UK DG, whereas the other group consumed a representative UK diet (control). We estimated polyphenol dietary intake, using a 4-d food diary (4-DFD) and FFQ, and analysed 24-h polyphenol urinary excretion by liquid chromatography-tandem MS on a subset of participants (n 46 control; n 45 DG). A polyphenol food composition database for 4-DFD analysis was generated using Phenol-Explorer and USDA databases. Total polyphenol intake by 4-DFD at endpoint (geometric means with 95 % CI, adjusted for baseline and sex) was significantly higher in the DG group (1279 mg/d per 10 MJ; 1158, 1412) compared with the control group (1084 mg/d per 10 MJ; 980, 1197). The greater total polyphenol intake in the DG group was attributed to higher intake of anthocyanins, proanthocyanidins and hydroxycinnamic acids, with the primary food sources being fruits, cereal products, nuts and seeds. FFQ estimates of flavonoid intake also detected greater intake in DG compared with the control group. 24-h urinary excretion showed consistency with 4-DFD in their ability to discriminate between dietary intervention groups for six out of ten selected, individual polyphenols. In conclusion, following UK DG increased total polyphenol intake by approximately 20 %, but not all polyphenol subclasses corresponded with this finding.

A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores.

Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20-C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40-70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference -67 ms; 95 % CI -130, -3·4, P50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

PURPOSE: Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet). METHODS: A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density). RESULTS: Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control. CONCLUSIONS: Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.

Exploring experiences, barriers, and enablers to home- and class-based exercise in rotator cuff tendinopathy: A qualitative study.

STUDY DESIGN: Qualitative study. INTRODUCTION: Adherence is paramount to the successful outcome of exercise-based treatment. PURPOSE OF STUDY: The barriers and enablers to adherence to a home- and class-based exercise program were explored in this qualitative study. METHODS: Semi-structured interviews were carried out to establish common themes relating to the participants' experiences during a year-long randomized controlled trial. RESULTS/DISCUSSION: Twelve participants were interviewed. The main enablers to exercise were highlighted as equipment, perceived benefit from the exercises, and longer and more intensive monitoring. Barriers included the lack of motivation, lack of equipment, and pain. CONCLUSIONS: Implications for practice are incorporating enablers and addressing barriers including self-discharge from classes; the importance of longer term follow-up and the benefits of adopting exercise into a well-established routine may provide potential benefits. LEVEL OF EVIDENCE: N/A.

Dietary patterns in obese pregnant women; influence of a behavioral intervention of diet and physical activity in the UPBEAT randomized controlled trial.

BACKGROUND: Understanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes. METHODS: In the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15+0-18+6 weeks' gestation), post intervention (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023). RESULTS: Four distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (-0.14; 95% CI -0.19, -0.08, P <0.0001) and Snacks (-0.24; 95% CI -0.31, -0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI 1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI 1.23, 3.41) patterns in the entire cohort were associated with increased risk of gestational diabetes. CONCLUSIONS: In a diverse cohort of obese pregnant women an intensive dietary intervention improved Processed and Snack dietary pattern scores. African/Caribbean and Processed patterns were associated with an increased risk of gestational diabetes, and provide potential targets for future interventions. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

Participation in a Structured Weight Loss Program and All-Cause Mortality and Cardiovascular Morbidity in Obese Patients With Chronic Kidney Disease.

OBJECTIVE: To determine if participation in a weight loss program impacted upon a composite end point of all-cause mortality and cardiovascular morbidity in obese patients with chronic kidney disease (CKD). DESIGN: Retrospective cohort study. SUBJECTS: All patients with a body mass index (BMI) >30 kg/m(2) or >28 kg/m(2) with at least 1 comorbidity (hypertension, diabetes, or dyslipidemia) referred to an established weight management program (WMP) from 2005 to 2009 at a metropolitan tertiary teaching hospital were eligible for inclusion in the study cohort. INTERVENTION: Twelve-month structured weight loss program. MAIN OUTCOME MEASURES: Combined outcome of all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure; kidney transplantation waitlisting. RESULTS: A total of 169 obese patients with CKD commenced the WMP and 169 did not-becoming the observational control group (CON). There were no significant differences between groups for age, BMI, sex, ethnicity, smoking, hypertension, or kidney function at baseline, although CON included more patients with diabetes than WMP (49% vs. 38%, P = .03). Kaplan-Meier survival analysis with log-rank test differed between groups for the combined outcome (P = .03). Cox regression analysis with adjustment for age, sex, ethnicity, hypertension, diabetes, kidney function, baseline BMI, and smoking status, indicated that patients in WMP had a significantly longer event-free period for the combined outcome, than those in CON (adjusted hazard ratio 0.53; 95% confidence interval [CI] 0.29-0.97; P = .04). Participation in the WMP did not increase the likelihood of kidney transplantation waitlisting (odds ratio [OR] 1.06; 95% CI 0.39-2.87; P = .9). Lower baseline BMI and greater weight loss over 12 months were the only factors related to kidney transplantation waitlisting (adjusted R(2) = 0.426). CONCLUSIONS: Participation in a structured weight loss program may be associated with improved outcomes in obese patients with CKD.

Interaction between a CSK gene variant and fish oil intake influences blood pressure in healthy adults.

Blood pressure is a heritable determinant of cardiovascular disease (CVD) risk. Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) associated with blood pressure, including rs1378942 in the c-Src tyrosine kinase (CSK) gene. Fish oil supplementation provides inconsistent protection from CVD, which may reflect genetic variation. We investigated the effect of rs1378942 genotype interaction with fish oil dosage on blood pressure measurements in the MARINA (Modulation of Atherosclerosis Risk by Increasing doses of N-3 fatty Acids) study, a parallel, double-blind, controlled trial in 367 participants randomly assigned to receive treatment with 0.45, 0.9, and 1.8 g/d eicosapentaenoic acid [EPA (20:5n-3)] and docosahexaenoic acid [DHA (22:6n-3)] (1.51:1) or an olive oil placebo for 12 mo. A total of 310 participants were genotyped. There were no significant associations with blood pressure measures at baseline; however, the interaction between genotype and treatment was a significant determinant of systolic blood pressure (SBP) (P = 0.010), diastolic blood pressure (DBP) (P = 0.037), and mean arterial blood pressure (MABP) (P = 0.014). After the 1.8 g/d dose, noncarriers of the rs1378942 variant allele showed significantly lower SBP (P = 0.010), DBP (P = 0.016), and MABP (P = 0.032) at follow-up, adjusted for baseline values, than did carriers. We found no evidence of SNP genotype association with endothelial function (brachial artery diameter and flow-mediated dilatation), arterial stiffness (carotid-femoral pulse wave velocity and digital volume pulse), and resting heart rate. A high intake of EPA and DHA could help protect noncarriers but not carriers of the risk allele. Dietary recommendations to reduce blood pressure in the general population may not necessarily benefit those most at risk. This trial was registered at controlled-trials.com as ISRCTN66664610.

Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement.

Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310), genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with proportions of LC-PUFAs and desaturase activities estimated in plasma and erythrocytes. Minor allele carriage associated with decreased activities of D5D (FADS1) (5.84 × 10(-19) ≤ P ≤ 4.5 × 10(-18)) and D6D (FADS2) (6.05 × 10(-8) ≤ P ≤ 4.20 × 10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 ≤ P ≤ 2.49 × 10(-16)). The significance of haplotype association with D5D activity (P = 2.19 × 10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39 × 10(-28)) was much stronger. In a randomized controlled dietary intervention, increasing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) intake significantly increased D5D (P = 4.0 × 10(-9)) and decreased D6D activity (P = 9.16 × 10(-6)) after doses of 0.45, 0.9, and 1.8 g/day for six months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity estimated in plasma (P = 0.05). In conclusion, different sites at the FADS1-FADS2 locus appear to influence D5D and D6D activity, and rs174537 genotype interacts with dietary EPA+DHA to modulate D5D.

Endothelial function does not relate to haemoglobin or serum erythropoietin concentrations and these do not explain the gender difference in endothelial function in healthy middle-aged men and women.

BACKGROUND: Haemoglobin scavenges nitric oxide, and a previous study has shown a negative association between flow-mediated vasodilation (FMD), a measure of nitric oxide (NO)-dependent vasomotor function and haemoglobin concentrations [Hb]. Circulating erythropoietin (EPO) is also negatively associated with [Hb] and could influence availability of NO. The purpose of this study was to examine the association of FMD with [Hb] and EPO concentrations and to determine whether these contribute to the sex difference in FMD. FMD (by high-resolution ultrasound), [Hb], circulating immunoreactive EPO and cardiovascular risk factors were measured in 317 healthy middle-aged men and women (183 women, 33 premenopausal, mean age ± SD, 55 ± 6·8 years) participating in a dietary study. RESULTS: In the whole mixed-sex group, FMD was negatively correlated with [Hb] (R = -0·23, P < 0·001). However, in a multivariable model, incorporating sex and other confounding factors, FMD was independently negatively correlated only with age, male sex and systolic blood pressure: standardized regression coefficients -0·21 (P < 0·01), -0·17 (P < 0·05) and -0·20 (P < 0·05) respectively and not with [Hb]. Similarly, when the analysis was restricted to men or to postmenopausal women, there was no significant relationship between FMD and Hb. There was no significant correlation between FMD and EPO on either univariate analysis in the whole group, in each sex, or in multivariate analysis. CONCLUSION: These results suggest that in healthy middle-aged subjects, FMD is not influenced by [Hb] or EPO and these do not contribute to the gender difference in FMD.

Adiponectin gene variant interacts with fish oil supplementation to influence serum adiponectin in older individuals.

Marine n3 polyunsaturated fatty acids (PUFAs) activate the transcription factor peroxisome proliferator-activated receptor (PPARγ), which modulates the expression of adiponectin. We investigated the interaction of dietary n3 PUFAs with adiponectin gene (ADIPOQ) single nucleotide polymorphism (SNP) genotypes as a determinant of serum adiponectin concentration. The Modulation of Atherosclerosis Risk by Increasing Doses of n3 Fatty Acids study is a parallel design, double-blind, controlled trial. Serum adiponectin was measured in 142 healthy men and 225 women aged 45-70 y randomized to treatment with doses of 0.45, 0.9, and 1.8 g/d 20:5n3 and 22:6n3 (1.51:1), or placebo for 12 mo. The 310 participants who completed the study were genotyped for 5 SNPs at the ADIPOQ locus: -11391 G/A (rs17300539), -11377 C/G (rs266729), -10066 G/A (rs182052), +45 T/G (rs2241766), and +276 G/T (rs1501299). The -11391 A-allele was associated with a higher serum adiponectin concentration at baseline (n = 290; P < 0.001). The interaction between treatment and age as a determinant of adiponectin was significant in participants aged >58 y after the highest dose (n = 92; P = 0.020). The interaction between +45 T/G and treatment and age was a nominally significant determinant of serum adiponectin after adjustment for BMI, gender, and ethnicity (P = 0.029). Individuals homozygous for the +45 T-allele aged >58 y had a 22% increase in serum adiponectin concentration compared with baseline after the highest dose (P-treatment effect = 0.008). If substantiated in a larger sample, a diet high in n3 PUFAs may be recommended for older individuals, especially those of the +45 TT genotype who have reported increased risk of hypoadiponectinemia, type 2 diabetes, and obesity.

Behavioral interventions for antipsychotic induced appetite changes.

Weight gain remains a well recognized yet difficult to treat adverse effect of many anti-psychotic drugs including agents of the first and second generation. The weight gain liabilities of antipsychotic drugs are partly associated with their ability to increase appetite. Most behavioral interventions for weight control remain of limited efficacy, possibly because they do not specifically target the neuroendocrine factors regulating appetite. Identifying new weight management interventions directly acting on the biochemical and neuroendocrine mechanisms of anti-psychotic induced weight gain may help to improve the efficacy of behavioral weight management programs. Such potentially specific strategies include (1) using diets which do not increase appetite despite calorie restriction; (2) countering thirst as an anticholinergic side-effect; (3) discouraging cannabis use and (4) adding metformin to a behavioral intervention. In view of our currently rather limited treatment repertoire it seems timely systematically to explore such novel options.

Developing a complex intervention for diet and activity behaviour change in obese pregnant women (the UPBEAT trial); assessment of behavioural change and process evaluation in a pilot randomised controlled trial.

BACKGROUND: Complex interventions in obese pregnant women should be theoretically based, feasible and shown to demonstrate anticipated behavioural change prior to inception of large randomised controlled trials (RCTs). The aim was to determine if a) a complex intervention in obese pregnant women leads to anticipated changes in diet and physical activity behaviours, and b) to refine the intervention protocol through process evaluation of intervention fidelity. METHODS: We undertook a pilot RCT of a complex intervention in obese pregnant women, comparing routine antenatal care with an intervention to reduce dietary glycaemic load and saturated fat intake, and increase physical activity. Subjects included 183 obese pregnant women (mean BMI 36.3 kg/m2). RESULTS: Compared to women in the control arm, women in the intervention arm had a significant reduction in dietary glycaemic load (33 points, 95% CI -47 to -20), (p < 0.001) and saturated fat intake (-1.6% energy, 95% CI -2.8 to -0. 3) at 28 weeks' gestation. Objectively measured physical activity did not change. Physical discomfort and sustained barriers to physical activity were common at 28 weeks' gestation. Process evaluation identified barriers to recruitment, group attendance and compliance, leading to modification of intervention delivery. CONCLUSIONS: This pilot trial of a complex intervention in obese pregnant women suggests greater potential for change in dietary intake than for change in physical activity, and through process evaluation illustrates the considerable advantage of performing an exploratory trial of a complex intervention in obese pregnant women before undertaking a large RCT. TRIAL REGISTRATION NUMBER: ISRCTN89971375.

Fortified malted milk drinks containing low-dose ergocalciferol and cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin D concentrations in healthy men and women not exposed to UV-B.

Uncertainty remains regarding the efficacy of low intakes of ergocalciferol (vitamin D2 or D2) and cholecalciferol (vitamin D3 or D3) provided in food to increase serum 25-hydroxy-vitamin D (25-OH-D) metabolite concentrations when UV-B exposure is low. We recruited 40 healthy men and women into a double-blind, parallel design, randomized controlled trial. Participants received placebo or 1 of 4 experimental treatments (D2 or D3 at 5 or 10 µg/d) supplied as a malted milk drink for 4 wk during a period of minimal UV-B exposure in the UK. The primary outcome was a change in serum 25-OH-D2 and 25-OH-D3 concentrations measured by ultra-performance liquid chromatography tandem MS. The secondary outcomes were changes in concentrations of plasma parathyroid hormone and serum calcium (Ca(2+)). Baseline concentrations (geometric mean ± SD) of 25-OH-D2, 25-OH-D3, and total 25-OH-D were 3 ± 4, 32 ± 22, and 37 ± 22 nmol/L, respectively. Both D2- and D3-fortified drinks resulted in dose-dependent increases (P < 0.001) in their respective 25-OH metabolites that did not significantly differ in size. Increments from baseline compared with the placebo group following 5 and 10 µg/d of D2 were (mean ± SEM) 9.4 ± 2.5 and 17.8 ± 2.4 nmol/L for 25-OH-D2 and following 5 and 10 µg/d of D3 were 15.1 ± 4.7 and 22.9 ± 4.6 nmol/L for 25-OH-D3, respectively. There was no difference between D2 and D3 groups in the incremental AUC of their respective metabolites. These findings suggest that D2 and D3 are equipotent in increasing 25-OH-D in healthy men and women with negligible UV-B exposure.

A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA.

Long-chain n-3 PUFA can lower blood pressure (BP) but their acute effects on cardiac output, BP and systemic vascular resistance (SVR) in response to dynamic exercise are uncertain. We compared the effects of high-fat meals rich in EPA (20 : 5n-3), DHA (22 : 6n-3) or oleic acid (control) on cardiac output, BP and SVR in response to exercise stress testing. High-fat meals (50 g fat) containing high-oleic sunflower oil enriched with 4·7 g of either EPA or DHA v. control (high-oleic sunflower oil only) were fed to twenty-two healthy males using a randomised cross-over design. Resting measurements of cardiac output, heart rate and BP were made before and hourly over 5 h following the meal. A standardised 12 min exercise test was then conducted with further measurements made during and post-exercise. Blood samples were collected at fasting, 5 h postprandially and immediately post-exercise for the analysis of lipid, glucose and 8-isoprostane-F2α (8-iso-PGF2α). Plasma concentrations of EPA and DHA increased by 0·22 mmol/l 5 h following the EPA and DHA meals, respectively, compared with the control (P < 0·001). Resting cardiac output and 8-iso-PGF2α increased similarly following all meals and there were no significant differences in cardiac output during exercise between the meals. SVR was lower at 5 h and during exercise following the DHA but not EPA meal, compared with the control meal, by 4·9 % (95 % CI 1·3, 8·4; P < 0·01). Meals containing DHA appear to differ from EPA with regard to their effects on cardiovascular haemodynamics during exercise.

The quality of the evidence for dietary advice given in UK national newspapers.

INTRODUCTION: Newspaper reports advocating dietary intake changes may impact on dietary choice and food related health beliefs. The scientific basis and quality of evidence underpinning these reports is uncertain. OBJECTIVE: To evaluate the scientific quality of newspaper reporting related to dietary advice. DESIGN: Articles offering dietary advice from the top ten selling UK newspapers for a randomly selected week were assessed using two established evidence grading scales: developed by the World Cancer Research Fund (WCRF) and the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Of 111 dietary health claims identified, 72% and 68% (assessed by WCRF and SIGN criteria respectively) had levels of evidence lower than the convincing or probable categories that are recommended for dietary health claims. CONCLUSIONS: Misreporting of dietary advice by UK newspapers is widespread and may contribute to public misconceptions about food and health.

Reproducibility of sequential ambulatory blood pressure and pulse wave velocity measurements in normotensive and hypertensive individuals.

OBJECTIVE: Errors in blood pressure (BP) measurement account for a large proportion of misclassified hypertension diagnoses. Ambulatory blood pressure monitoring (ABPM) is often considered to be the gold standard for measurement of BP, but uncertainty remains regarding the degree of measurement error. The aim of this study was to determine reproducibility of sequential ABPM in a population of normotensive and well controlled hypertensive individuals. METHODS: Individual participant data from three randomized controlled trials, which had recorded ABPM and carotid-femoral pulse wave velocity (PWV) at least twice were combined ( n  = 501). We calculated within-individual variability of daytime and night-time BP and compared the variability between normotensive ( n  = 324) and hypertensive ( n  = 177) individuals. As a secondary analysis, variability of PWV measurements was also calculated, and multivariable linear regression was used to assess characteristics associated with blood pressure variability (BPV). RESULTS: Within-individual coefficient of variation (CoV) for systolic BP was 5.4% (day) and 7.0% (night). Equivalent values for diastolic BP were 6.1% and 8.4%, respectively. No statistically significant difference in CoV was demonstrated between measurements for normotensive and hypertensive individuals. Within-individual CoV for PWV exceeded that of BP measurements (10.7%). BPV was associated with mean pressures, and BMI for night-time measurements. PWV was not independently associated with BPV. CONCLUSION: The variability of single ABPM measurements will still yield considerable uncertainty regarding true average pressures, potentially resulting in misclassification of hypertensive status and incorrect treatment regimes. Repeated ABPM may be necessary to refine antihypertensive therapy.

Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk.

The PPARγ2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. The RISCK Study investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low-fat (LF) diet. At recruitment, there were no significant associations between genotype and plasma lipids; however, P:S × genotype interaction influenced plasma total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and triglyceride (TG) (P = 0.02) concentrations. At P:S ratio ≤ 0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with increasing P:S (respectively, ≤0.33 to >0.65; 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and noncarriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they are not dependent on a reduction in SFA intake.