Appetite-regulating hormones in early life and relationships with type of feeding and body composition in healthy term infants

Introduction: Body composition in early life influences development of obesity during childhood and beyond. Appetite-regulating hormones (ARH) play a role in regulation of food intake and might thus influence body composition in later life. Studies on associations between ARH and body composition in early life are limited. Methods: In 197 healthy term infants, we measured serum fasting levels of ghrelin, leptin, insulin, glucose-dependent insulinotropic peptide (GIP), pancreatic polypeptide (PP) and peptide YY (PYY) at 3 months and in 41 infants also at 6 months and their associations with type of feeding and longitudinal fat mass percentage (FM%) measured by air displacement plethysmography at 1, 3 and 6 months and abdominal visceral and subcutaneous fat, measured by ultrasound, at 3 and 6 months. Results: Infants with formula feeding for 3 months had significantly higher serum levels of ghrelin, leptin, insulin, GIP and PP (p = 0.026, p = 0.018, p = 0.002, p < 0.001, resp.) and lower serum levels of PYY (p = 0.002) at 3 months than breastfed infants. Leptin and ghrelin correlated positively with FM% at 3 months and insulin with change in FM% between 1 and 3 months (r = 0.40, p < 0.001, r = 0.23, p < 0.05, r = 0.22, p < 0.01, resp.). Leptin at 3 months correlated with subcutaneous fat at 3 months (r = 0.23, p < 0.001), but not with visceral fat. Other ARH did not correlate with body composition. Conclusion: Formula-fed infants had a different profile of ARH than breastfed infants, suggesting that lower levels of ghrelin, leptin and insulin in breastfed infants contribute to the protective role of breastfeeding against obesity development. Leptin, ghrelin and insulin were associated with fat mass percentage or its changes

Determinants of quality of life in acute heart failure patients with and without comorbidities:a prospective, observational study

AIMS: The relation between non-cardiac comorbidities and health-related quality of life (HRQoL) in patients with heart failure (HF) has been studied to a limited extent. To investigate the HRQoL and their determinants among HF patients with and without comorbidities. METHODS AND RESULTS: TRIUMPH (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure) is a Dutch prospective, multicentre study enrolling 496 acute HF patients between 2009 and 2014. We included 334 patients who had completed the HRQoL questionnaires at baseline. The HRQoL was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) en EuroQuality-of-life five Dimensions (EQ-5D). Comorbidity was defined as having a history of at least one of the following comorbidities: chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and/or cerebrovascular accident. Patients with comorbidity (n = 205, 61%) had lower scores on the physical limitation scale and clinical summary score of the KCCQ (P = 0.03 and P = 0.01, respectively). Female sex, COPD, previous HF, increasing body mass index (BMI), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), high systolic blood pressure, and the presence of anxiety and/or depression negatively influenced the HRQoL among HF patients with comorbidity. Besides anxiety and depression, we hardly found any other determinant of HRQoL in patients without comorbidity. CONCLUSION: Heart failure patients without comorbidity had better HRQoL than patients with comorbidity. Sex, previous HF, BMI, COPD, systolic blood pressure, NT-proBNP levels, and also anxiety and depression were determinants of HRQoL in patients with comorbidity. In those without comorbidity, apart from anxiety and depression, no further determinants of HRQoL were found

Appetite-regulating hormone trajectories and relationships with fat mass development in term-born infants during the first 6 months of life

BACKGROUND: The first 6 months of life are a critical window for adiposity programming. Appetite-regulating hormones (ARH) are involved in food intake regulation and might, therefore, play a role in adiposity programming. Studies examining ARH in early life are limited. PURPOSE: To investigate ghrelin, peptide YY (PYY) and leptin until 6 months and associations with fat mass percentage (FM%), infant feeding and human milk macronutrients. PROCEDURES: In 297 term-born infants (Sophia Pluto Cohort), ghrelin (acylated), PYY and leptin were determined at 3 and 6 months, with FM% measurement by PEAPOD. Exclusive breastfeeding (BF) was classified as BF ≥ 3 months. Human milk macronutrients were analyzed (MIRIS Human Milk Analyzer). MAIN FINDINGS: Ghrelin increased from 3 to 6 months (p < 0.001), while PYY decreased (p < 0.001), resulting in increasing ghrelin/PYY ratio. Leptin decreased. Leptin at 3 months was higher in girls, other ARH were similar between sexes. Leptin at 3 and 6 months correlated with FM% at both ages(R ≥ 0.321, p ≤ 0.001) and gain in FM% from 1 to 6 months(R ≥ 0.204, p = 0.001). In BF infants, also ghrelin and ghrelin/PYY ratio correlated with this gain in FM%. Exclusively BF infants had lower ghrelin and higher PYY compared to formula fed infants at 3 months (p ≤ 0.039). ARH did not correlate with macronutrients. CONCLUSIONS: Increasing ghrelin and decreasing PYY, thus increasing ghrelin/PYY ratio, suggests an increasing orexigenic drive until 6 months. ARH were different between BF and FF infants at 3 months, but did not correlate with human milk macronutrients. Ghrelin and leptin, but not PYY, correlated with more FM development during the first 6 months, suggesting that they might be involved in adiposity programming. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02533-z

Individualized angiotensin-converting enzyme (ACE)-inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants: The PERindopril GENEtic (PERGENE) risk model

Background-Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. Methods and Results-Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 t

Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure

Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates

Biomarkers to Improve Prognostication in Heart Failure

The course of heart failure is difficult to predict. Biomarkers could help us to improve predicting outcome. Therefore, we initiated the TRIUMPH study in which nearly 500 patients with acute heart failure from 14 Dutch hospitals were followed for one year. During this period we collected clinical data and seven blood samples to evaluate known and unknown biomarkers. We found that repeated measurements of both ST2 and galectin-3 were independent predictors of heart failure re-admission and death, independent of known risk factors and repeated NT-proBNP measurements, which is currently a widely used biomarker in patients with heart failure. In the second part of this thesis, the TRIUMPH population investigated whether there is a relationship between the quality of life and different comorbidities, the presence of other diseases such as previous stroke, renal dysfunction, diabetes mellitus and COPD. We saw that patients with co-morbidities experience a poorer quality of life. In addition, it was noted that patients with heart failure often suffer from symptoms and that this is even more common in heart failure patients with depressive complaints. Finally, we performed a meta-analysis to see whether RAAS inhibitors, a blood pressure lowering agent, improve survival in patients with hypertension. Data from nearly 160,000 patients were collected for an average of four years. During this period, there was a 5% decrease in death compared to using other contemporary blood pressure lowering medication or placebo. This is an important finding as hypertension is one of the most common diseases worldwide