The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of ...multiple days is considered to be an accurate method.
We included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis.
Among 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval CI, 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94).
Higher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).
Metabolic-associated fatty liver disease (MAFLD) is characterized by hepatic steatosis, metabolic dysregulation, and neutrophilic inflammation. In this study, we hypothesized that systemic levels of ...plasma calprotectin, as a biomarker of neutrophilic inflammation, may be associated with suspected MAFLD. Plasma calprotectin levels were measured in subjects (n = 5446) participating in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort study. Suspected MAFLD was defined by the fatty liver index (FLI ≥ 60) and hepatic steatosis index (HSI ≥ 36) as proxies. Plasma calprotectin levels were significantly higher in subjects with FLI ≥ 60 (0.57 IQR: 0.42−0.79 mg/L, n = 1592) (p < 0.001) compared to subjects with FLI < 60 (0.46 0.34−0.65 mg/L, n = 3854). Multivariable logistic regression analyses revealed that plasma calprotectin levels were significantly associated with suspected MAFLD (FLI ≥ 60), even after adjustment for potential confounding factors, including current smoking, alcohol consumption, hypertension, diabetes, cardiovascular diseases, insulin resistance (HOMA-IR), hs-CRP, eGFR, and total cholesterol levels (OR 1.19 95% CI: 1.06−1.33, p = 0.003). Interaction analyses revealed significant effect modifications for the association between plasma calprotectin and suspected MAFLD by BMI (p < 0.001) and hypertension (p = 0.003), with the strongest associations in subjects with normal BMI and without hypertension. Prospectively, plasma calprotectin levels were significantly associated with all-cause mortality after adjustment for potential confounding factors, particularly in subjects without suspected MAFLD (FLI < 60) (hazard ratio (HR) per doubling: 1.34 (1.05−1.72), p < 0.05). In conclusion, higher plasma calprotectin levels are associated with suspected MAFLD and with the risk of all-cause mortality, the latter especially in subjects without suspected MAFLD.
Abstract
Background
The longitudinal association between low education and chronic kidney disease (CKD) and its underlying mechanisms is poorly characterized. We therefore examined the association of ...low education with incident CKD and change in kidney function, and explored potential mediators of this association.
Methods
We analysed data on 6078 participants from the community-based Prevention of Renal and Vascular End-stage Disease study. Educational level was categorized into low, medium and high (< secondary, secondary/equivalent, > secondary schooling, respectively). Kidney function was assessed by estimating glomerular filtration rate (eGFR) by serum creatinine and cystatin C at five examinations during ∼11 years of follow-up. Incident CKD was defined as new-onset eGFR <60 mL/min/1.73 m2 and/or urinary albumin ≥30 mg/24 h in those free of CKD at baseline. We estimated main effects with Cox regression and linear mixed models. In exploratory causal mediation analyses, we examined mediation by several potential risk factors.
Results
Incident CKD was observed in 861 (17%) participants. Lower education was associated with higher rates of incident CKD low versus high education; hazard ratio (HR) (95% CI) 1.25 (1.05–1.48), Ptrend = 0.009 and accelerated eGFR decline B (95% CI) −0.15 (−0.21 to −0.09) mL/min/1.73 m2/year, Ptrend < 0.001. The association between education and incident CKD was mediated by smoking, potassium excretion, body mass index (BMI), waist-to-hip ratio (WHR) and hypertension. Analysis on annual eGFR change in addition suggested mediation by magnesium excretion, protein intake and diabetes.
Conclusions
In the general population, we observed an inverse association of educational level with CKD. Diabetes and the modifiable risk factors smoking, poor diet, BMI, WHR and hypertension are suggested to underlie this association. These findings provide support for targeted preventive policies to reduce socioeconomic disparities in kidney disease.
Research into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on ...blood pressure. This study aims to separate the specific effects of chloride and sodium intake on blood pressure.
We studied 5673 participants from the Prevention of Renal and Vascular End-Stage Disease(PREVEND) study. Urinary chloride(uCl) and sodium(uNa) were measured in two 24-hour collections. We used generalized-linear-regression to evaluate the relation of uCl and uNa with baseline blood pressure and Cox-proportional-hazards-analysis to assess the association with hypertension. Multicollinearity was assessed with Ridge regression.
Baseline 24-hour uCl was 135±39mmol and uNa was 144±54mmol. The correlation between uCl and uNa was high (Pearson's r = 0.96). UCl and uNa had similar non-significant positive and linear associations with blood pressure. In 3515 normotensive patients, 1021 patients developed hypertension during a median follow-up of 7.4 years. UCl and uNa had a comparable but non-significant J-shaped effect on the risk of hypertension. Adding both uCl and uNa to the same model produced instability, demonstrated by Ridge coefficients that converged or changed sign. The single index of uNa minus uCl showed a non-significant higher risk of hypertension of 2% per 10mmol/24-hour difference (HR1.02, 95%CI 0.98-1.06).
UCl and uNa had similar positive but non-significant associations with blood pressure and risk of hypertension and their effects could not be disentangled. Hence, the alleged adverse effects of high salt intake could be due to sodium, chloride or both. This encourages further study into the effect of chloride in order to complement dietary recommendations currently focused on sodium alone.
Body-mass index (BMI), waist circumference, and waist-hip ratio are commonly used anthropometric indices of adiposity. However, over the past 10 years, several new anthropometric indices were ...developed, that more accurately correlated with body fat distribution and total fat mass. They include relative fat mass (RFM), body-roundness index (BRI), weight-adjusted-waist index and body-shape index (BSI). In the current study, we included 8295 adults from the PREVEND (Prevention of Renal and Vascular End-Stage Disease) observational cohort (the Netherlands), and sought to examine associations of novel as well as established adiposity indices with incident heart failure (HF). The mean age of study population was 50 ± 13 years, and approximately 50% (n = 4134) were women. Over a 11 year period, 363 HF events occurred, resulting in an overall incidence rate of 3.88 per 1000 person-years. We found that all indices of adiposity (except BSI) were significantly associated with incident HF in the total population (P < 0.001); these associations were not modified by sex (P interaction > 0.1). Amongst adiposity indices, the strongest association was observed with RFM hazard ratio (HR) 1.67 per 1 SD increase; 95% confidence interval (CI) 1.37-2.04. This trend persisted across multiple age groups and BMI categories, and across HF subtypes HR: 1.76, 95% CI 1.26-2.45 for HF with preserved ejection fraction; HR 1.61, 95% CI 1.25-2.06 for HF with reduced ejection fraction. We also found that all adiposity indices (except BSI) improved the fit of a clinical HF model; improvements were, however, most evident after adding RFM and BRI (reduction in Akaike information criteria: 24.4 and 26.5 respectively). In conclusion, we report that amongst multiple anthropometric indicators of adiposity, RFM displayed the strongest association with HF risk in Dutch community dwellers. Future studies should examine the value of including RFM in HF risk prediction models.
Background The cause of heart failure with preserved ejection fraction (HFpEF) is poorly understood, and specific therapies are lacking. Previous studies suggested that inflammation plays a role in ...the development of HFpEF. Herein, we aimed to investigate in community-dwelling individuals whether a higher plasma interleukin 6 (IL-6) level is associated with an increased risk of developing new-onset heart failure (HF) over time, and specifically HFpEF. Methods and Results We performed a case-cohort study based on the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study, a prospective general population-based cohort study. We included 961 participants, comprising 200 participants who developed HF and a random group of 761 controls. HF with reduced ejection fraction or HFpEF was defined on the basis of the left ventricular ejection fraction of ≤40% or >40%, respectively. In Cox proportional hazard regression analyses, IL-6 levels were statistically significantly associated with the development of HF (hazard ratio HR, 1.28; 95% CI, 1.02-1.61;
=0.03) after adjustment for key risk factors. Specifically, IL-6 levels were significantly associated with the development of HFpEF (HR, 1.59; 95% CI, 1.16-2.19;
=0.004), whereas the association with HF with reduced ejection fraction was nonsignificant (HR, 1.05; 95% CI, 0.75-1.47;
=0.77). In sensitivity analyses, defining HFpEF as left ventricular ejection fraction ≥50%, IL-6 levels were also significantly associated with the development of HFpEF (HR, 1.47; 95% CI, 1.04-2.06;
=0.03) after adjustment for key risk factors. Conclusions IL-6 is associated with new-onset HFpEF in community-dwelling individuals, independent of potential confounders. Our findings warrant further research to investigate whether IL-6 might be a novel treatment target to prevent HFpEF.
Chronic kidney disease (CKD) is a rising public health problem that may progress to kidney failure, requiring kidney replacement therapy. It is also associated with an increased incidence of ...cardiovascular disease (CVD). Because of its asymptomatic nature, CKD is often detected in a late stage. Population screening for albuminuria could allow early detection of people with CKD who may benefit from preventive treatment. In case such screening is performed in a general practitioner (GP) setting, this will result in relatively high costs. Home-based screening might be an effective and cost-effective alternative.
The THOMAS study (Towards HOMe-based Albuminuria Screening) is designed to prospectively investigate two methods for home-based population screening for increased albuminuria to detect yet undiagnosed CKD and risk factors for progression and CVD.
This investigator initiated, randomized population-based study will include 15.000 individuals aged 45-80 years, who will be randomly assigned to be invited for a home-based screening test for albuminuria with a more conventional urine collection device or an innovative smartphone application. If the test result is positive upon confirmation (i.e., elevated albuminuria), participants are invited to a central screening facility for an elaborate screening for CKD and CVD risk factors. Participants are referred to their GP for appropriate treatment, if abnormalities are found. Primary endpoints are the participation rate, yield, and cost-effectiveness of the home-based screening and elaborate screening.
The THOMAS study will evaluate the effectiveness and cost-effectiveness of home-based albuminuria screening in the general population for the early detection of CKD and CVD risk factors. It will provide insight into the willingness to participate in population screening for CKD and into the compliance of the general population to a corresponding screening protocol and compliance to participate. Thus, it may help to develop an attractive novel screening strategy for the early detection of CKD.
ClinicalTrials.gov, registration number NCT04295889, registered 05 March 2020. https://www.google.com/search?client=firefox-b-d&q=NCT04295889.
Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally ...associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality.
Participants (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality.
The mean protein-adjusted serum free thiol level was 5.05 ± 1.02 μmol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio HR per doubling 0.68 95% confidence interval CI 0.47-1.00, P = 0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 95% CI 0.44-1.00, P = 0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria.
In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.
ContextHigh-density lipoproteins (HDL) may be protective against type 2 diabetes (T2D) development, but HDL particles vary in size and function, which could lead to differential associations with ...incident T2D. A newly developed nuclear magnetic resonance (NMR)-derived algorithm provides concentrations for 7 HDL subspecies.
ObjectiveWe aimed to investigate the association of HDL particle subspecies with incident T2D in the general population.
MethodsAmong 4828 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline, HDL subspecies with increasing size from H1P to H7P were measured by NMR (LP4 algorithm of the Vantera NMR platform).
ResultsA total of 265 individuals developed T2D (median follow-up of 7.3 years). In Cox regression models, HDL size and H4P (hazard ratio HR per 1 SD increase 0.83 95% CI, 0.69-0.99 and 0.85 95% CI, 0.75-0.95, respectively) were inversely associated with incident T2D, after adjustment for relevant covariates. In contrast, levels of H2P were positively associated with incident T2D (HR 1.15 95% CI, 1.01-1.32). In secondary analyses, associations with large HDL particles and H6P were modified by body mass index (BMI) in such a way that they were particularly associated with a lower risk of incident T2D, in subjects with BMI < 30 kg/m2.
ConclusionGreater HDL size and lower levels of H4P were associated with a lower risk, whereas higher levels of H2P were associated with a higher risk of developing T2D. In addition, large HDL particles and H6P were inversely associated with T2D in nonobese subjects.
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