Diet-sensitive prognostic markers for cardiovascular and renal disease

Diet plays a relevant role in the development and progression of lifestyle-related diseases like hypertension and type 2 diabetes and the subsequent risk of cardiovascular and renal disease. Riphagen used several diet-sensitive biomarkers to further explore the effects of diet on cardiovascular and renal health. Lifestyle measures including dietary sodium restriction and increased potassium intake are recognized to lower blood pressure. Increased potassium intake during sodium restriction, however, was found to have little effect on blood pressure. Riphagen investigated the effects of potassium supplementation on blood pressure and fluid balance in 35 (pre)hypertensive subjects during a fully controlled sodium-restricted diet using a panel of biomarkers. Potassium supplementation was found to have a relatively small blood pressure-lowering effect during sodium restriction. The blood pressure-lowering effects seemed mitigated by activation of several counter regulatory mechanisms involved in regulation of fluid balance and blood pressure (i.e., vasopressin, the renin-angiotensin-aldosterone system [RAAS], and heart rate). Vascular calcification is also an important risk factor for cardiovascular disease. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification. During vitamin K insufficiency, MGP is inactive. Riphagen investigated the prevalence of vitamin K insufficiency and its health consequences through measurement of inactive MGP in a general population-based cohort. Vitamin K insufficiency was found to be a common phenomenon especially among elderly and subjects with chronic diseases and was associated with an increased (cardiovascular) mortality risk. Diet-sensitive biomarkers are a useful tool to further explore the effects of diet on cardiovascular and renal health

Reference intervals for Sysmex XN hematological parameters as assessed in the Dutch Lifelines cohort

Our aim was to derive reference intervals for all Sysmex XN hematology analyzer parameters. The rationale behind the study was the lack of reference intervals for the XN analyzer cell population data (CPD) and functional parameters. Fresh fasting blood samples from 18,484 participants in the Dutch Lifelines study were analyzed using two automated XN analyzers. Structured health questionnaire data were used to select a subgroup of 15,803 apparently healthy individuals for inclusion in the reference population. The Latent Abnormal Values Exclusion (LAVE) approach was used to reduce the influence of latent diseases in the reference population on the resulting reference intervals. We applied analysis of variance to judge the need for partitioning of the reference intervals by sex or age. We report reference intervals for 105 XN analyzer hematological parameters with and without applying LAVE. Sex-related partitioning was required for red blood cells, (RBC, RBC-O), hemoglobin (HGB, HGB-O), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), reticulocyte production index (RPI), and side scattered light intensity of the red blood cell population in the RET channel (RBC-Z). Partitioning for age was not warranted. Body mass index (BMI) and smoking had moderate influence on a minority of the parameters. We provide reference intervals for all Sysmex XN analyzer routine, CPD and functional parameters, using a direct approach in a large cohort in the Netherlands

Separate and combined effects of individual and neighbourhood socio-economic disadvantage on health-related lifestyle risk factors:a multilevel analysis

BACKGROUND: Socio-economic disadvantage at both individual and neighbourhood levels has been found to be associated with single lifestyle risk factors. However, it is unknown to what extent their combined effects contribute to a broad lifestyle profile. We aimed to (i) investigate the associations of individual socio-economic disadvantage (ISED) and neighbourhood socio-economic disadvantage (NSED) in relation to an extended score of health-related lifestyle risk factors (lifestyle risk index); and to (ii) investigate whether NSED modified the association between ISED and the lifestyle risk index. METHODS: Of 77 244 participants [median age (IQR): 46 (40-53) years] from the Lifelines cohort study in the northern Netherlands, we calculated a lifestyle risk index by scoring the lifestyle risk factors including smoking status, alcohol consumption, diet quality, physical activity, TV-watching time and sleep time. A higher lifestyle risk index was indicative of an unhealthier lifestyle. Composite scores of ISED and NSED based on a variety of socio-economic indicators were calculated separately. Linear mixed-effect models were used to examine the association of ISED and NSED with the lifestyle risk index and to investigate whether NSED modified the association between ISED and the lifestyle risk index by including an interaction term between ISED and NSED. RESULTS: Both ISED and NSED were associated with an unhealthier lifestyle, because ISED and NSED were both positively associated with the lifestyle risk index {highest quartile [Q4] ISED beta-coefficient [95% confidence interval (CI)]: 0.64 [0.62-0.66], P < 0.001; highest quintile [Q5] NSED beta-coefficient [95% CI]: 0.17 [0.14-0.21], P < 0.001} after adjustment for age, sex and body mass index. In addition, a positive interaction was found between NSED and ISED on the lifestyle risk index (beta-coefficient 0.016, 95% CI: 0.011-0.021, Pinteraction < 0.001), which indicated that NSED modified the association between ISED and the lifestyle risk index; i.e. the gradient of the associations across all ISED quartiles (Q4 vs Q1) was steeper among participants residing in the most disadvantaged neighbourhoods compared with those who resided in the less disadvantaged neighbourhoods. CONCLUSIONS: Our findings suggest that public health initiatives addressing lifestyle-related socio-economic health differences should not only target individuals, but also consider neighbourhood factors

Associations of 24 h urinary excretions of alpha- and gamma-carboxyethyl hydroxychroman with plasma alpha- and gamma-tocopherol and dietary vitamin E intake in older adults:the Lifelines-MINUTHE Study

Background Urinary metabolites of vitamin E, i.e., alpha- and gamma-carboxyethyl hydroxychroman (alpha- and gamma-CEHC), have gained increasing attention and have been proposed as novel biomarkers of vitamin E intake and status. However, there are insufficient data on the relationship of plasma alpha-tocopherol and gamma-tocopherol and dietary vitamin E intake with 24 h urinary excretions of alpha- and gamma-CEHC. Objectives We aimed to (1) investigate the associations of urinary alpha- and gamma-CEHC/creatinine ratios and 24 h urinary excretions of alpha- and gamma-CEHC with plasma alpha- and gamma-tocopherol, respectively; (2) investigate the associations of urinary alpha- and gamma-CEHC/creatinine ratios and 24 h urinary excretions of alpha- and gamma-CEHC with dietary vitamin E intake, and we hypothesize that 24 h urinary excretions of alpha- and gamma-CEHC will better correlate with vitamin E intake than urinary alpha- and gamma-CEHC/creatinine ratios. Design 24 h Urine and plasma samples were collected from 1519 participants (60-75 years, male: 50%) included in the Lifelines-MINUTHE Study for the assessments of urinary alpha- and gamma-CEHC/creatinine ratios and 24 h urinary excretions of alpha- and gamma-CEHC, and plasma alpha- and gamma-tocopherol. Among those participants, dietary vitamin E intake data from 387 participants were available from an externally validated Flower-Food Frequency Questionnaire (FFQ). The associations of plasma alpha- and gamma-tocopherol, dietary vitamin E intake, with urinary alpha- and gamma-CEHC were assessed using multivariate linear regressions. Results 24 h Urinary excretion of alpha-CEHC (median (IQR): 0.9 (0.3-2.4) mu mol) was less than that of gamma-CEHC (median (IQR): 1.5 (0.5-3.5) mu mol). After adjustment for covariates, we found that 24 h urinary alpha-CEHC excretion and urinary alpha-CEHC/creatinine ratio were both positively associated with plasma alpha-tocopherol (std.beta: 0.06, p = 0.02; std.beta: 0.06, p = 0.01, respectively). Furthermore, the sum of 24 h urinary alpha- and gamma-CEHC excretions was positively associated with dietary vitamin E intake (std.beta: 0.08; p = 0.03), whereas there was no relation between urinary alpha- and gamma-CEHC/creatinine ratios and vitamin E intake. No association was observed neither between plasma alpha- and gamma-tocopherol and dietary vitamin E intake, nor between urinary gamma-CEHC and plasma gamma-tocopherol. Conclusion Our study confirmed our hypothesis that 24 h urinary alpha- and gamma-CEHC excretions would be a better marker for dietary vitamin E intake than urinary alpha- and gamma-CEHC/creatinine ratios. Considering that both 24 h urinary alpha- and gamma-CEHC excretions and alpha- and gamma-CEHC/creatinine ratios were also associated with plasma alpha-tocopherol status, we suggest that 24 h urinary alpha- and gamma-CEHC excretions could be used to assess overall vitamin E status

Circulating de novo lipogenesis fatty acids and all-cause mortality in a prospective Dutch population cohort

Background: Circulating fatty acids (FA) from de novo lipogenesis (DNL) are associated with all-cause mortality in individuals with elevated CVD risk. However, compared to FA early in the DNL synthetic pathway, cis-vaccenic acid, one of the FA distal in the DNL synthetic pathway, has rarely been studied in a general population cohort. We hypothesized that circulating cis-vaccenic acid is more strongly related to all-cause mortality than other circulating DNL-related FA. Objectives: The primary and secondary objectives of this study were to investigate the prospective associations of plasma levels of cis-vaccenic acid and other DNL-related FA with all-cause mortality in a general population, respectively. Methods: We included 850 participants (mean ± SD age 53 ± 15 years) from the Dutch Lifelines cohort study. Circulating levels of palmitic (C16:0), palmitoleic (C16:1n7), cis-vaccenic (cis-C18:1n7), stearic (C18:0), oleic acid (C18:1n9) in plasma phospholipids (PL) and triglycerides (TG) were measured by gas chromatography. The associations of circulating cis-C18:1n7 and other DNL-related FA with all-cause mortality were assessed using Cox regression analyses. Results: During a median follow-up of 9.3 (IQR: 5.4–10.8) years, 34 (4.0%) participants had died. In plasma PL, a 1-SD increase in cis-C18:1n7 was associated with an increased risk of all-cause mortality in univariate and multivariate models (p<0.02 for all), with a HR [95% CI] of 1.60 [1.13–2.25] after adjustment for age and sex. Conclusions: Circulating plasma PL cis-C18:1n7 was associated with a higher risk for all-cause mortality. More studies are needed in different cohorts to verify and validate our results

Plasma phospholipid fatty acid profile, estimated desaturase activities and prevalence of the metabolic syndrome in a general population cohort:A cross-sectional study

BACKGROUND: An altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic diseases, including the MetS, but studies in the general populations are lacking, and only few studies have investigated a broad spectrum of FA in plasma phospholipids (PL). OBJECTIVE: We investigated, cross-sectionally, the relationship of the FA profile and desaturase activities in plasma PL with the prevalence of MetS in a general population in The Netherlands. METHODS: Baseline characteristic data from 850 participants (Male: 50.2%) aged 38-68 years recruited in the Lifelines Cohort study were obtained. The FA profile was determined in fasting plasma PL, and desaturase activities were estimated from product/precursor ratios. The MetS was defined according to International Diabetes Federation. Logistic regressions were used to examine the relation of the FA profile with the prevalence of MetS, and Bonferroni correction was applied to account for multiple testing. RESULTS: 151 participants (17.7%) had the MetS. After adjustment for several confounders and Bonferroni correction, higher tertiles of C18 : 0 (the early precursor of de novo lipogenesis pathway), C18 : 3n6 and C20 : 3n6 (both consistent with a high Δ 6 desaturase (D6D) activity), and D6D activity itself were associated with a higher prevalence of MetS, while higher tertiles of C18 : 1n7, C24 : 0, and C24 : 1n9 (very-long-chain FA) as well as stearoyl-CoA desaturase (SCD)-18 were inversely associated with the MetS. CONCLUSIONS: This study shows that a wide-ranging plasma PL FA profile and estimated desaturase activities were different between adults with and without the MetS in a general representative population and implicates the importance of monitoring individual FAs and desaturase activities as novel modifiable biomarkers for the MetS