Improvement in Visceral Adipose Tissue and LDL Cholesterol by High PUFA Intake: 1-Year Results of the NutriAct Trial.

We assessed the effect of a dietary pattern rich in unsaturated fatty acids (UFA), protein and fibers, without emphasizing energy restriction, on visceral adipose tissue (VAT) and cardiometabolic risk profile. Within the 36-months randomized controlled NutriAct trial, we randomly assigned 502 participants (50-80 years) to an intervention or control group (IG, CG). The dietary pattern of the IG includes high intake of mono-/polyunsaturated fatty acids (MUFA/PUFA 15-20% E/10-15% E), predominantly plant protein (15-25% E) and fiber (≥30 g/day). The CG followed usual care with intake of 30% E fat, 55% E carbohydrates and 15% E protein. Here, we analyzed VAT in a subgroup of 300 participants via MRI at baseline and after 12 months, and performed further metabolic phenotyping. A small but comparable BMI reduction was seen in both groups (mean difference IG vs. CG: -0.216 kg/m2 [-0.477; 0.045], partial η2 = 0.009, p = 0.105). VAT significantly decreased in the IG but remained unchanged in the CG (mean difference IG vs. CG: -0.162 L [-0.314; -0.011], partial η2 = 0.015, p = 0.036). Change in VAT was mediated by an increase in PUFA intake (ß = -0.03, p = 0.005) and induced a decline in LDL cholesterol (ß = 0.11, p = 0.038). The NutriAct dietary pattern, particularly due to high PUFA content, effectively reduces VAT and cardiometabolic risk markers, independent of body weight loss.

Effect of unsaturated fat and protein intake on liver fat in people at risk of unhealthy aging: 1-year results of a randomized controlled trial.

BACKGROUND: Short-term trials indicate improvement of intrahepatic lipids (IHLs) and metabolism by dietary protein or unsaturated fatty acids (UFAs) beyond weight loss. OBJECTIVES: We aimed to assess the effect of a dietary intervention high in protein and UFAs on IHLs and metabolic outcome after 12 mo, as long-term effects of such a combined intervention are unknown. METHODS: Within a 36-mo randomized controlled trial, eligible subjects (aged 50 to 80 y, ≥1 risk factor for unhealthy aging) were randomly assigned to either intervention group (IG) with high intake of mono-/poly-UFAs [15-20 percent of total energy (%E)/10%-15%E, respectively], plant protein (15%-25%E), and fiber (≥30 g/d), or control group [CG, usual care, dietary recommendations of the German Nutrition Society (fat 30%E/carbohydrates 55%E/protein 15%E)]. Stratification criteria were sex, known cardiovascular disease, heart failure, arterial hypertension, type 2 diabetes, and cognitive or physical impairment. Nutritional counseling and supplementation of foods mirroring the intended dietary pattern were performed in the IG. Diet-induced effects on IHLs, analyzed by magnetic resonance spectroscopy, as well as on lipid and glucose metabolism were predefined secondary endpoints. RESULTS: IHL content was analyzed in 346 subjects without significant alcohol consumption at baseline and in 258 subjects after 12 mo. Adjusted for weight loss, sex, and age, we observed a comparable decline of IHLs in IG and CG (-33.3%; 95% CI: -49.3, -12.3%; n = 128 compared with -21.8%; 95% CI: -39.7, 1.5%; n = 130; P = 0.179), an effect that became significant by comparing adherent IG subjects to adherent CG subjects (-42.1%; 95% CI: -58.1, -20.1%; n = 88 compared with -22.2%; 95% CI: -40.7, 2.0%; n = 121; P = 0.013). Compared with the CG, decline of LDL cholesterol (LDL-C) and total cholesterol (TC) was stronger in the IG (for LDL-C P = 0.019, for TC P = 0.010). Both groups decreased in triglycerides and insulin resistance (P for difference between groups P = 0.799 and P = 0.124, respectively). CONCLUSIONS: Diets enriched with protein and UFAs have beneficial long-term effects on liver fat and lipid metabolism in adherent older subjects. This study was registered at the German Clinical Trials Register, https://www.drks.de/drks_web/setLocale_EN.do, DRKS00010049. Am J Clin Nutr 20XX;xx:xx-xx.

Long-term impact of the metabolic status on weight loss-induced health benefits.

BACKGROUND: While short-term effects of weight loss on quality of life and metabolic aspects appear to be different in metabolically healthy (MHO) and metabolically unhealthy obese (MUO), respective long-term data is still missing. Given the high relevance of long-term changes, we aimed to address these in this post-hoc analysis of the MAINTAIN trial. METHODS: We analyzed 143 overweight/obese subjects (BMI ≥ 27 kg/m2, age ≥ 18 years) before and after a 3-month weight loss program (≥ 8% weight loss), after a 12-month period of a randomized weight maintenance intervention (n = 121), and after another 6 months without intervention (n = 112). Subjects were retrospectively grouped into MHO and MUO by the presence of metabolic syndrome and secondarily by estimates of insulin sensitivity (HOMA-IR and ISIClamp). Quality of life (QoL), blood pressure, lipids, HOMA-IR, and ISIClamp were assessed and evaluated using mixed model analyses. RESULTS: Despite similar short- and long-term weight loss, weight loss-induced improvement of HOMA-IR was more pronounced in MUO than MHO after 3 months (MHO: 2.4[95%-CI: 1.9-2.9] vs. 1.6[1.1-2.1], p = 0.004; MUO: 3.6[3.2-4.0] vs. 2.0[1.6-2.4], p < 0.001; p = 0.03 for inter-group comparison). After 21 months, the beneficial effect was no longer seen in MHO (2.0[1.5-2.6], p = 1.0), while it remained partially preserved in MUO (2.9[2.4-3.3], p = 0.002). QueryShort-term improvements of lipid parameters were similar in both groups. However, long-term improvements of HDL-cholesterol and triglycerides were only seen in MUO (44.4[41.5-47.4] vs. 49.3[46.2, 52.3] mg/dl, p < 0.001; 176.8[158.9-194.8] vs. 138.8[119.4-158.3] mg/dl, p < 0.001, respectively) but not in MHO. Weight loss-induced improvements in the QoL and particularly the physical health status were maintained in MUO until the end of the trial, while benefits disappeared over time in MHO. Group allocation by HOMA-IR and ISIClamp revealed higher benefits for MUO mainly in parameters of the glucose metabolism and QoL. CONCLUSIONS: Our data demonstrates stronger and longer-lasting improvements of metabolism and QoL in MUO after weight loss. Trial registration (ClinicalTrials.gov): NCT00850629. Registered 25 February 2009, https://clinicaltrials.gov/ct2/show/NCT00850629 .

Nutritional counseling frequency and baseline food pattern predict implementation of a high-protein and high-polyunsaturated fatty acid dietary pattern: 1-year results of the randomized NutriAct trial.

BACKGROUND & AIMS: NutriAct is a 36-month randomized controlled multi-center trial designed to analyze the effects of a food pattern focusing on a high-protein and high-unsaturated fatty acids (UFA) intake on healthy aging. We aimed to determine factors associated with a successful modulation of dietary pattern after 12 months in elderly participants. METHODS: 502 participants were randomized into either usual care control group including dietary recommendations of the German Nutrition Society (DGE) or an intervention group, which used supplementation of rapeseed oil and specifically designed foods as well as repetitive advices to implement a food pattern based on high intake of predominantly plant proteins, UFA and fiber (NutriAct pattern). Food intake was repeatedly assessed by 3-day food records at months 0, 3, 6 and 12. Linear regression models were used to investigate determinants of basal food intake and modulation of dietary pattern during the intervention. RESULTS: Food records of 242 intervention and 246 control participants (median age 66 y, 37% males) were available at baseline and were included. At baseline, high BMI was related to higher protein and saturated fatty acids and lower fiber intake. The intervention resulted in higher intake of protein, mono- and polyunsaturated fatty acids (MUFA and PUFA) and fiber, and lower carbohydrate and saturated fatty acid consumption (all p < 0.001). While individuals who were already at baseline closer to the NutriAct pattern also achieved a diet closer to the proposed pattern at month 12, the strongest absolute changes (%E) of dietary behavior were seen in those with dietary patterns further away from the proposed pattern at baseline. Attendance to nutritional sessions was crucial to change MUFA, PUFA, fiber and carbohydrate intake. CONCLUSIONS: A successful modification of dietary pattern was achieved by the performed intervention within 12 months. Baseline dietary habits and attendance to nutritional sessions were substantial determinants predicting changes in dietary pattern. CLINICAL TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.

Vascular injury biomarkers and stroke risk: A population-based study.

OBJECTIVE: Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study. METHODS: A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk. RESULTS: Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; p linear trend < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; p linear trend < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; p linear trend = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; p linear trend = 0.05). CONCLUSIONS: In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.

Biomarkers of Vascular Injury and Type 2 Diabetes: A Prospective Study, Systematic Review and Meta-Analysis.

Data on biomarkers of vascular injury and type 2 diabetes (T2D) risk from prospective studies are lacking. We evaluated seven biomarkers of vascular injury in relation to T2D. Additionally, a meta-analysis was performed. From the EPIC-Heidelberg cohort, 2224 participants were followed-up from baseline for 16 (median) years. E-Selectin, P-Selectin, intercellular adhesion molecule 3 (ICAM3), thrombomodulin, thrombopoietin, glycoprotein IIb/IIIa and fibrinogen levels were measured in baseline blood samples. The systematic review and meta-analysis included prospective studies identified through MEDLINE and Web of Science that investigated the association between mentioned biomarkers and T2D. The study population included 55% women, median age was 50 years, and 163 developed T2D. ICAM3 was associated with lower T2D risk (fully adjusted HRhighest vs. lowest tertile 0.62 (95% CI: 0.43, 0.91)), but no other studies on ICAM3 were identified. Overall, fifteen studies were included in the systematic review and meta-analysis (6,171 cases). E-Selectin was associated with higher T2D risk HRper SD: 1.34 (95% CI: 1.16, 1.54; I2 = 63%, n = 9 studies), while thrombomodulin was associated with lower risk HRper SD: 0.82 (95% CI: 0.71, 0.95; I2 = 0%, n = 2 studies). In the EPIC-Heidelberg, ICAM3 was associated with lower T2D risk. The meta-analysis showed a consistent positive association between E-Selectin and T2D. It was also suggestive of an inverse association between thrombomodulin and T2D, although further studies are needed to corroborate this finding.

Thrombomodulin and Thrombopoietin, Two Biomarkers of Hemostasis, Are Positively Associated with Adherence to the World Cancer Research Fund/American Institute for Cancer Research Recommendations for Cancer Prevention in a Population-Based Cross-Sectional Study.

A pro-coagulative state is related to increased risk of cardiovascular diseases but also certain cancers. Since experimental and smaller human studies suggest that diet, physical activity, and body weight may all affect coagulation, we evaluated associations between these lifestyle factors and hemostatic biomarkers in a population-based study. Cross-sectional baseline data from 2267 randomly selected participants of EPIC-Heidelberg (age range 35-65 years) was used. Fibrinogen, glycoprotein IIb/IIIa, P-selectin, thrombomodulin (TM), and thrombopoietin (TPO) were measured in baseline plasma samples. A score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention was created. Associations between the WCRF/AICR score as well as its individual components and hemostatic biomarkers were analyzed by linear regression models. Multivariable-adjusted geometric means (95% confidence intervals) of TM and TPO were higher with greater adherence to the WCRF/AICR recommendations (TM, lowest vs. highest score category: 2.90 (2.7,3.1) vs. 3.10 (2.9,3.3) ng/mL, plinear trend = 0.0001; TPO: 328 (302,356) vs. 348 (321,378) pg/mL, plinear trend = 0.0007). These associations were driven by lower alcohol and meat consumption among persons with higher WCRF/AICR scores. Our results indicate that lifestyle factors favorably affect TM and TPO, two hemostatic factors implicated in chronic disease development.

Author Correction: Biomarkers of vascular injury in relation to myocardial infarction risk: A population-based study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Plasma Fibrinogen and sP-Selectin are Associated with the Risk of Lung Cancer in a Prospective Study.

BACKGROUND: While enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether prediagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case-cohort design. METHODS: Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of lung cancer (n = 190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain HRs of lung cancer across quartiles of biomarker levels. RESULTS: Fibrinogen [HR highest vs. lowest quartile: 1.91 (95% confidence interval: 1.09-3.34)] and sP-Selectin [HR: 2.51 (1.39-4.52)] were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814. CONCLUSION: Our findings indicate that enhanced platelet activation and a procoagulative state contribute to lung carcinogenesis. IMPACT: The current prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.

Biomarkers of vascular injury in relation to myocardial infarction risk: A population-based study.

Little is known about circulating biomarkers of vascular injury in relation to cardiovascular disease risk. Thus, we evaluated associations between six novel markers (E-Selectin, P-Selectin, thrombomodulin, thrombopoietin, intercellular adhesion molecule 3 and GPIIb/IIIa) and established cardiovascular risk factors as well as the risk of myocardial infarction (MI) in a population-based study. Biomarkers were measured in pre-diagnostic plasma samples of a case-cohort subset of EPIC-Heidelberg (incident MI cases: n = 369, random sub-cohort: n = 2,418). Generalized Linear models were used to analyse cross-sectional associations between biomarkers and cardiovascular risk factors. Multivariable Cox Regression analyses were carried out to obtain Hazard Ratios (HRs) of MI across quartiles of biomarkers levels. Cross-sectional analyses showed that sex, smoking, alcohol consumption, diabetes and exogenous hormone use were associated with biomarker levels. However, while fibrinogen was associated with MI risk (HR per standard deviation: 2.97 [95% confidence interval: 1.61, 5.46]), none of the six novel biomarkers was associated with MI risk after multivariable adjustment. In a population-based cohort, biomarkers of vascular injury were associated with established cardiovascular risk factors, but not MI risk. The tested biomarkers may reflect pathophysiological alterations in cardiovascular disease development rather than constituting independent MI risk factors.

Pre-diagnostic plasma concentrations of Fibrinogen, sGPIIb/IIIa, sP-selectin, sThrombomodulin, Thrombopoietin in relation to cancer risk: Findings from a large prospective study.

While enhanced platelet activation may drive cancer progression and metastases, less is known about its role in early cancer development. Thus, we evaluated whether pre-diagnostic biomarkers of platelet activation and coagulation are related to the risks of common cancers in the prospective EPIC-Heidelberg Study using a case-cohort design. Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of breast (n = 605), prostate (n = 543), and colorectal cancer (n = 249). Multivariable Cox regression models revealed no statistically significant associations between biomarker concentrations and any of the cancer endpoints. Subgroup analyses showed a significant inverse relationship between TPO and colorectal cancer among men, with a hazard ratio (HR, highest vs. lowest quartile) of 0.60 (95% confidence interval: 0.37,0.95), whereas no significant association was observed among women. With regard to fibrinogen levels and breast cancer risk, there was a significant positive association among nulliparous women (HR: 2.53 [95% CI: 1.21, 5.30]), but not among parous women. Overall, our data suggest that enhanced platelet activation and a pro-coagulative state may not be related to increased risks of common cancers, although studies on other potential biomarkers of platelet activation and further cancer types are needed. Findings from our subgroup analyses require further investigation, as potential underlying mechanisms are not known.

Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.

BACKGROUND: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. METHODS: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. RESULTS: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. CONCLUSIONS: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.

Change in Carotid Plaque Components: A 4-Year Follow-Up Study With Serial MR Imaging.

OBJECTIVES: The goal of this study was to determine how carotid plaque components (e.g., intraplaque hemorrhage [IPH], calcification, lipid core) change over time and which cardiovascular risk factors are associated with the development of each component. BACKGROUND: Carotid atherosclerotic plaque components are important markers of plaque vulnerability. How these components change and which factors lead to the development and changes in the components remain unclear. METHODS: A total of 198 participants (mean age 67.5 ± 10.6 years) from the population-based Rotterdam Study, all with carotid wall thickening on ultrasound, underwent 2 magnetic resonance imaging scans for carotid plaque characterization (mean interscan interval 4.1 ± 0.2 years). Presence of IPH, calcification, and lipid-rich necrotic core was assessed on both sides on the baseline and follow-up scans. The association between cardiovascular risk factors and incident carotid plaque components was assessed. RESULTS: In the 396 arteries, all plaque components significantly changed over time. Incidence of IPH, calcification, and lipid core was, respectively, 18.5%, 59.2%, and 39.6%. The factor most strongly associated with the incidence of IPH was use of antihypertensive drugs (multivariate adjusted odds ratio [OR]: 3.87; 95% confidence interval [CI]: 1.90 to 7.90) and severe hypertension (multivariate adjusted OR: 4.70; 95% CI: 1.50 to 14.80). The incidence of calcification was associated with hypertension (OR: 2.20; 95% CI: 1.07 to 4.40). Higher cholesterol levels were associated with incidence of lipid cores (multivariate adjusted OR per unit increase in cholesterol: 1.40; 95% CI: 1.10 to 1.70). CONCLUSIONS: In these community-dwelling subjects, characteristics of plaque composition changed dramatically within a few years, and cardiovascular risk factors played a major role in these changes. Hypertension and its treatment and serum cholesterol levels were the main risk factors for the development of atherosclerotic plaque components over time.