Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies

REVIEW PURPOSE: This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). FINDINGS: Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. SUMMARY: Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future

Exploring absolute and relative measures of exposure to food environments in relation to dietary patterns among European adults.

OBJECTIVE: To explore the associations of absolute and relative measures of exposure to food retailers with dietary patterns, using simpler and more complex measures. DESIGN: Cross-sectional survey. SETTING: Urban regions in Belgium, France, Hungary, the Netherlands and the UK.ParticipantsEuropean adults (n 4942). Supermarkets and local food shops were classified as 'food retailers providing healthier options'; fast-food/takeaway restaurants, cafés/bars and convenience/liquor stores as 'food retailers providing less healthy options'. Simpler exposure measures used were density of healthy and density of less healthy food retailers. More complex exposure measures used were: spatial access (combination of density and proximity) to healthy and less healthy food retailers; density of healthier food retailers relative to all food retailers; and a ratio of spatial access scores to healthier and less healthy food retailers. Outcome measures were a healthy or less healthy dietary pattern derived from a principal component analysis (based on consumption of fruits, vegetables, fish, fast foods, sweets and sweetened beverages). RESULTS: Only the highest density of less healthy food retailers was significantly associated with the less healthy dietary pattern (β = -129·6; 95 % CI -224·3, -34·8). None of the other absolute density measures nor any of the relative measures of exposures were associated with dietary patterns. CONCLUSIONS: More complex measures of exposure to food retailers did not produce stronger associations with dietary patterns. We had some indication that absolute and relative measures of exposure assess different aspects of the food environment. However, given the lack of significant findings, this needs to be further explored

Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: a randomised, crossover trial

Aims/hypothesis To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods In a randomised, open-label, crossover trial conducted in the Netherlands, 36 apparently healthy postmenopausal women who were habitual alcohol consumers, received 250 ml white wine (~25 g alcohol/day) or 250 ml of white grape juice (control) daily during dinner for 6 weeks. Randomisation to treatment allocation occurred according to BMI. Insulin sensitivity and ADIPOQ mRNA and plasma adiponectin levels were measured at the end of both periods. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Levels of ADIPOQ mRNA in subcutaneous adipose tissue were determined by RT-PCR. Results All subjects completed the study. Six weeks of white wine consumption reduced fasting insulin (mean¿±¿SEM 40.0¿±¿3.4 vs 46.5¿±¿3.4 pmol/l; p

Development of an objectively measured walkability index for the Netherlands

Background Walkability indices have been developed and linked to behavioural and health outcomes elsewhere in the world, but not comprehensively for Europe. We aimed to 1) develop a theory-based and evidence-informed Dutch walkability index, 2) examine its cross-sectional associations with total and purpose-specific walking behaviours of adults across socioeconomic (SES) and urbanisation strata, 3) explore which walkability components drive these associations. Methods Components of the index included: population density, retail and service density, land use mix, street connectivity, green space, sidewalk density and public transport density. Each of the seven components was calculated for three Euclidean buffers: 150 m, 500 m and 1000 m around every 6-digit postal code location and for every administrative neighbourhood in GIS. Componential z-scores were averaged, and final indices normalized between 0 and 100. Data on self-reported demographic characteristics and walking behaviours of 16,055 adult respondents (aged 18–65) were extracted from the Dutch National Travel Survey 2017. Using Tobit regression modelling adjusted for individual- and household-level confounders, we assessed the associations between walkability and minutes walking in total, for non-discretionary and discretionary purposes. By assessing the attenuation in associations between partial indices and walking outcomes, we identified which of the seven components drive these associations. We also tested for effect modification by urbanization degree, SES, age and sex. Results In fully adjusted models, a 10% increase in walkability was associated with a maximum increase of 8.5 min of total walking per day (95%CI: 7.1–9.9). This association was consistent across buffer sizes and purposes of walking. Public transport density was driving the index’s association with walking outcomes. Stratified results showed that associations with minutes of non-discretionary walking were stronger in rural compared to very urban areas, in neighbourhoods with low SES compared to high SES, and in middle-aged (36–49 years) compared to young (18–35 years old) and older adults (50–65 years old). Conclusions The walkability index was cross-sectionally associated with Dutch adult’s walking behaviours, indicating its validity for further use in research

Exploring the relationship between perceived barriers to healthy eating and dietary behaviours in European adults.

Dietary behaviours may be influenced by perceptions of barriers to healthy eating. Using data from a large cross-European study (N = 5900), we explored associations between various perceived barriers to healthy eating and dietary behaviours among adults from urban regions in five European countries and examined whether associations differed across regions and socio-demographic backgrounds. Frequency of consumption of fruit, vegetables, fish, fast food, sugar-sweetened beverages, sweets, breakfast and home-cooked meals were split by the median into higher and lower consumption. We tested associations between barriers (irregular working hours; giving up preferred foods; busy lifestyle; lack of willpower; price of healthy food; taste preferences of family and friends; lack of healthy options and unappealing foods) and dietary variables using multilevel logistic regression models. We explored whether associations differed by age, sex, education, urban region, weight status, household composition or employment. Respondents who perceived any barrier were less likely to report higher consumption of healthier foods and more likely to report higher consumption of fast food. 'Lack of willpower', 'time constraints' and 'taste preferences' were most consistently associated with consumption. For example, those perceiving lack of willpower ate less fruit [odds ratio (OR) 0.57; 95% confidence interval (CI) 0.50-0.64], and those with a busy lifestyle ate less vegetables (OR 0.54; 95% CI 0.47-0.62). Many associations differed in size, but not in direction, by region, sex, age and household composition. Perceived 'lack of willpower', 'time constraints' and 'taste preferences' were barriers most strongly related to dietary behaviours, but the association between various barriers and lower intake of fruit and vegetables was somewhat more pronounced among younger participants and women

Evaluating compliance to a low glycaemic index (GI) diet in women with polycystic ovary syndrome (PCOS)

<p>Abstract</p> <p>Background</p> <p>A low Glycaemic Index (GI) diet may decrease some long-term health risks in Polycystic Ovary Syndrome (PCOS) such as endometrial cancer. This study was performed to assess compliance to a low GI diet in women with PCOS. Food diaries prospectively collected over 6 months from women on a low GI diet or healthy eating diet were analysed retrospectively. The women were recruited for a pilot randomised control trial investigating whether a low GI diet decreased the risk of Endometrial Cancer. Nine women with PCOS completed 33 food diaries (17 from women on a low GI diet and 16 from women on a healthy eating diet) recording 3023 food items (low GI group:n = 1457; healthy eating group:n = 1566). Data was analysed using Foster-Powell international values inserted into an SPSS database as no scientifically valid established nutrition software was found. The main outcome measures were mean item GI and Glyacemic Load (GL), mean meal GL, percentage high GI foods and mean weight loss.</p> <p>Findings</p> <p>Women allocated the low GI diet had a statistically significant lower GI of food items (33.67 vs 36.91, p < 0.05), lower percentage of high GI foods (4.3% vs 12.1%, p < 0.05) and lower GL of food items and meals.</p> <p>Conclusion</p> <p>Women with PCOS on a low GI diet consumed food items with a significantly lower mean GI and GL compared to the healthy eating diet group. Longer term compliance needs evaluation in subsequent studies to ascertain that this translates to reduced long term health risks.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN86420258">ISRCTN86420258</a></p

Heterogeneity of associations between total and types of fish intake and the incidence of type 2 diabetes: Federated meta-analysis of 28 prospective studies including 956,122 participants

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of con-founders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction (p = 0.002) on the association between fish and type 2 diabe-tes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01–1.03, I = 61%) for total fish, 1.04 (1.01–1.07, I = 46%) for fatty fish, and 1.02 (1.00–1.04, I = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02–1.04, I = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pol-lutants, but meanwhile, existing dietary regional, national, or international guidelines should con-tinue to guide fish consumption within overall healthy dietary patterns

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Innovations in personalised diabetes care and risk management.

Type 2 diabetes is associated with an increased risk of developing macro and microvascular complications. Nevertheless, there is substantial heterogeneity between people with type 2 diabetes in their risk of developing such complications. Personalised medicine for people with type 2 diabetes may aid in efficient and tailored diabetes care for those at increased risk of developing such complications. Recently, progress has been made in the development of personalised diabetes care in several areas. Particularly for the risk prediction of cardiovascular disease, retinopathy and nephropathy, innovative methods have been developed for prediction and tailored monitoring or treatment to prevent such complications. For other complications or subpopulations of people with type 2 diabetes, such as the frail elderly, efforts are currently ongoing to develop such methods. In this review, we discuss the recent developments in innovations of personalised diabetes care for different complications and subpopulations of people with type 2 diabetes, their performance and modes of application in clinical practice