Prevention Of Renal And Vascular End-Stage Disease Research Articles

Sex differences in new-onset heart failure.

Sex differences in patients with established heart failure have been well described, but much less is known in the development of heart failure. We studied sex-specific incidence and risk of new-onset heart failure in 8592 subjects (mean age 49.2 ± 12.7 years; 50.1 % women) of the Prevention of REnal and Vascular ENdstage Disease (PREVEND) study and distinguished reduced and preserved ejection fraction (HFrEF <40 % and HFpEF >50 %). Of 374 cases with incident heart failure, 241 (64.4 %) occurred in men and 133 (35.6 %) in women (median follow-up 12.5 years; 96,550 person-years). Men developed heart failure earlier (7.0 vs. 8.6 years; P < 0.001). Incidence rates per 1,000 person-years in women compared to men were lower for HFrEF (1.2 vs. 3.0 %; P < 0.001), but higher for HFpEF (1.2 vs. 0.7 %; P < 0.001). Women developed HFpEF later in life than HFrEF (75.1 vs. 69.7 years; P = 0.033), while men showed no significant difference (72.2 vs. 69.5 years; P = 0.116). Multivariable competing risks analyses showed that women had lower risk for HFrEF (subhazard ratio = 0.47; 95 % CI 0.29-0.76, P = 0.002) but higher risk for HFpEF (subhazard ratio = 2.16; 95 % CI 1.21-3.83, P = 0.009) than men. Among all risk factors, only atrial fibrillation had a sex-specific predictive value and increased risk specifically for women (P-for interaction = 0.016). In a middle-aged population, men developed heart failure more frequently and at a younger age than women. However, women had higher risk for HFpEF, with atrial fibrillation being a specific female risk factor.

Should non-cardiovascular mortality be considered in the SCORE model? Findings from the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort.

Competing non-cardiovascular related deaths were not accounted for in the Systematic COronary Risk Evaluation (SCORE) model. In this study we assessed the impact of non-cardiovascular related deaths on the prognostic performance and yield of the SCORE model. 5,752 participants from the Prevention of Renal and Vascular End stage Disease cohort aged 40 years and older who were free of atherosclerotic cardiovascular disease (CVD) at baseline were included. A cause-specific hazards (CSH) CVD-related mortality prediction model that accounted for non-CVD-related deaths was developed. The prognostic performance of this model was then compared with a refitted SCORE model. During a median follow-up period of 12.5 years, 139 CVD and 495 non-CVD-related deaths were reported. Discriminatory performance was comparable between the models (C-index = 0.64). The models showed good calibration although the CSH model underestimated risk in the highest decile while the refitted SCORE model showed overestimation. The CSH model classified more non-events into the low risk group compared to the refitted SCORE model (n = 51), yet it was accompanied by a misclassification of six events into the low risk group. The refitted SCORE model classified more individuals as high risk. However, the potential overtreatment that may result from utilizing the refitted SCORE model, when compared with the CSH model, still falls within acceptable limits. Our findings do not support the incorporation of non-cardiovascular mortality into the estimation of total cardiovascular risk in the SCORE model.

Urinary potassium excretion and risk of developing hypertension: the prevention of renal and vascular end-stage disease study.

Previous prospective cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake, may provide a more objective and quantitative estimate of this association. Risk of hypertension (defined as blood pressure ≥140/90 mm Hg or initiation of blood pressure-lowering drugs) was prospectively studied in 5511 normotensive subjects aged 28 to 75 years not using blood pressure-lowering drugs at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Potassium excretion was measured in two 24-hour urine specimens at baseline (1997-1998) and midway during follow-up (2001-2003). Baseline median potassium excretion was 70 mmol/24 h (interquartile range, 57-85 mmol/24 h), which corresponds to a dietary potassium intake of ≈91 mmol/24 h. During a median follow-up of 7.6 years (interquartile range, 5.0-9.3 years), 1172 subjects developed hypertension. The lowest sex-specific tertile of potassium excretion (men: <68 mmol/24 h; women: <58 mmol/24 h) had an increased risk of hypertension after multivariable adjustment (hazard ratio, 1.20; 95% confidence interval, 1.05-1.37), compared with the upper 2 tertiles (Pnonlinearity=0.008). The proportion of hypertension attributable to low potassium excretion was 6.2% (95% confidence interval, 1.7%-10.9%). No association was found between the sodium to potassium excretion ratio and risk of hypertension after multivariable adjustment. Low urinary potassium excretion was associated with an increased risk of developing hypertension. Dietary strategies to increase potassium intake to the recommended level of 90 mmol/d may have the potential to reduce the incidence of hypertension.

Pleiotropic Effects of Lipid Genes on Plasma Glucose, HbA1c, and HOMA-IR Levels

Dyslipidemia is strongly associated with raised plasma glucose levels and insulin resistance (IR), and genome-wide association studies have identified 95 loci that explain a substantial proportion of the variance in blood lipids. However, the loci's effects on glucose-related traits are largely unknown. We have studied these lipid loci and tested their association collectively and individually with fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and IR in two independent cohorts: 10,995 subjects from LifeLines Cohort Study and 2,438 subjects from Prevention of Renal and Vascular Endstage Disease (PREVEND) study. In contrast to the positive relationship between dyslipidemia and glucose traits, the genetic predisposition to dyslipidemia showed a pleiotropic lowering effect on glucose traits. Specifically, the genetic risk score related to higher triglyceride level was correlated with lower levels of FPG (P = 9.6 × 10(-10) and P = 0.03 in LifeLines and PREVEND, respectively), HbA1c (P = 4.2 × 10(-7) in LifeLines), and HOMA of estimated IR (P = 6.2 × 10(-4) in PREVEND), after adjusting for blood lipid levels. At the single nucleotide polymorphism level, 15 lipid loci showed a pleiotropic association with glucose traits (P < 0.01), of which eight (CETP, MLXIPL, PLTP, GCKR, APOB, APOE-C1-C2, CYP7A1, and TIMD4) had opposite allelic directions of effect on dyslipidemia and glucose levels. Our findings suggest a complex genetic regulation and metabolic interplay between lipids and glucose.

Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

Aims/hypothesisOxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population.MethodsWe analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28–75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes.ResultsDuring a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1–Q3) Prx4 level was 0.84 (0.53–1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43–1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05–1.29) in the whole population; by sex, it was 1.31 (1.14–1.50) for men and 1.03 (0.87–1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p = 0.002 for reclassification improvement).Conclusions/interpretationOur findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3278-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Abstract MP24: Urinary Potassium Excretion and Risk of Developing Hypertension

Background: Potassium supplementation lowers blood pressure (BP) in randomized controlled trials, but the long-term effect of dietary potassium intake on risk of hypertension has not yet been established. Objective: To examine the association of 24h urinary excretions of potassium, reflecting dietary uptake, with risk of hypertension. Methods: We used data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, community-based, observational cohort of Dutch men and women aged 28-75 years. Potassium excretion was measured at baseline (1997-98) and during follow-up (2001-03) in two consecutive 24h urine specimens. Risk of hypertension (defined as BP ≥140/90 mmHg, or initiation of BP-lowering drugs) was studied in 5,511 normotensive subjects not using BP-lowering drugs at baseline. We used Cox proportional hazards regression analysis with time-dependent covariates. Results: Baseline median potassium excretion was 72 mmol/24h (Q1-Q3: 57-85 mmol/24h). During a median follow-up of 7.6 years (Q1-Q3: 5.0-9.3 years), 1172 subjects developed hypertension. We observed a nonlinear association between potassium excretion and risk of hypertension (P=0.005; Figure ). This association was in such a way that the lowest sex-specific tertile of potassium excretion (men: &lt;68 mmol/24h; women: &lt;58 mmol/24h) had an increased risk of hypertension (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.08-1.37) after adjustment for age and sex, compared to the upper two tertiles. Further adjustment for body mass index, smoking status, alcohol intake, parental history of hypertension (HR, 1.25; 95% CI, 1.11-1.41), and additionally for 24h urinary excretions of sodium, magnesium, and calcium (HR, 1.23; 95% CI, 1.08-1.40) did not materially affect the association. Conclusions: In this population-based cohort, low potassium excretion was associated with an increased risk of developing hypertension. Figure: Association between 24h urinary potassium excretion and risk of hypertension.

Sodium Excretion and Risk of Developing Coronary Heart Disease

Despite compelling evidence for sodium's adverse effects on blood pressure, it remains uncertain whether excess sodium intake is a risk factor for coronary heart disease (CHD) in the overall population and in potentially more susceptible subgroups. We prospectively followed 7543 adults aged 28 to 75 years and free of cardiovascular and kidney disease in 1997/1998 of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Sodium excretion was measured in two 24-hour urine collections at baseline. Potential susceptibility factors were blood pressure and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median 24-hour sodium excretion was 137 mmol (Q1-Q3, 106-171 mmol). During a median follow-up of 10.5 (Q1-Q3: 9.9-10.8) years, 452 CHD events occurred. In the entire cohort, there was no association between each 1-g/d (43 mmol/24 h) increment in sodium excretion and CHD risk (adjusted hazard ratio, 1.07; 95% confidence interval, 0.98-1.18; P=0.15). However, the association of sodium excretion with CHD risk tended to be modified by mean arterial pressure (Pinteraction=0.08) and was modified by NT-proBNP (Pinteraction=0.002). When stratified, each 1-g/d increment in sodium excretion was associated with an increased risk for CHD in subjects with hypertension (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; n=2363) and in subjects with NT-proBNP concentrations above the sex-specific median (adjusted hazard ratio, 1.16; 95% confidence interval, 1.03-1.30; n=3771). Overall, there was no association between sodium excretion and risk of CHD. The association between sodium excretion and CHD risk was modified by NT-proBNP. Higher sodium excretion was associated with an increased CHD risk among subjects with increased NT-proBNP concentrations or with hypertension.

Estimated Albumin Excretion Rate Versus Urine Albumin-Creatinine Ratio for the Assessment of Albuminuria: A Diagnostic Test Study From the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study

Albumin-creatinine ratio (ACR) in spot urine samples is recommended for albuminuria screening instead of measured albumin excretion rate (mAER) in 24-hour urine collections. In patients with extremes of muscle mass, differences in spot urine creatinine values may lead to under- or overestimation of mAER by ACR. We hypothesized that calculating estimated AER (eAER) using spot ACR and estimated creatinine excretion rate (eCER) may improve albuminuria assessment. Diagnostic test study. 2,711 community-living individuals from the general population of the Netherlands participating in the PREVEND (Prevention of Renal and Vascular Endstage Disease) Study. eAER was computed as the product of ACR and eCER. eCER was computed using 3 previously validated methods (Ix, Ellam, and Walser). mAER, based on two 24-hour urine collections. Accuracy of the eAER and ACR were defined as the percentage of participants falling within 30% (P30) of mAER. Mean age was 49 years, 46% were men, mean estimated glomerular filtration rate was 84 ± 15 mL/min/1.73 m(2), and median mAER was 7.2 (IQR, 5.4-11.0) mg/d. Mean measured CER was 1,381 mg/d, and median ACR was 4.9 mg/g. Using the Ix equation, median eAER was 6.4 mg/d. In the full cohort, eAER was more accurate and less biased compared to ACR (P30, 48.9% vs 33.6%; bias, -34.2% vs -14.1%, respectively). In subgroup analysis, improvement was most notable in the middle and highest weight tertiles and in men. Using the other methods for eCER produced similar results. Little ethnic heterogeneity and a generally healthy cohort make extension of findings to other races and the chronically ill uncertain. In a large community-dwelling cohort, eAER was more accurate than ACR in assessing albuminuria.

Telomere length loss due to smoking and metabolic traits

Human age-dependent telomere attrition and telomere shortening are associated with several age-associated diseases and poorer overall survival. The aim of this study was to determine longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length. Leucocyte telomere length was measured by quantitative polymerase chain reaction in 8074 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community-based prospective cohort study initiated in 1997. Follow-up data were available at two time-points up to 2007. Leucocyte telomere length was measured, on between one and three separate occasions, in a total of 16 783 DNA samples. Multilevel growth models were created to identify the factors that influence leucocyte telomere dynamics. We observed an average attrition rate of 0.47 ± 0.16 relative telomere length units (RTLUs) per year in the study population aged 48 (range 39-60) years at baseline. Annual telomere attrition rate increased with age (P < 0.001) and was faster on average in men than in women (P for interaction 0.043). The major independent factors determining telomere attrition rate were active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and multiple traits of the metabolic syndrome (waist-hip ratio, P = 0.007; blood glucose level, P = 0.045, and HDL cholesterol level, P < 0.001). Smoking and variables linked to the metabolic syndrome are modifiable lifestyle factors that accelerate telomere attrition in humans. The higher rate of cellular ageing may mediate the link between smoking and the metabolic syndrome to an increased risk of several age-associated diseases.

Lowered Magnesium in Hypertension

We read with interest the article by Joosten et al1 dealing with urinary magnesium excretion and risk of hypertension—the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study. The authors examined 5511 participants. A total of 1172 developed hypertension. The urinary magnesium excretion was associated with risk of hypertension in an inverse log-linear fashion, and this association remained after adjustment for age, sex, body …

Twenty-four hour urinary urea excretion and 9-year risk of hypertension

It is not yet clear whether dietary protein could help maintaining a healthy blood pressure (BP). We investigated the association between total protein intake, estimated from 24-h urinary urea excretion, and incident hypertension in Dutch men and women. We analyzed data of 3997 men and women (aged 28-75 years) who participated in the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, a prospective cohort study. Urea excretion was assessed in two consecutive 24-h urine collections at baseline and approximately 4 years later, from which total protein intake was estimated using the Maroni method. Participants were followed for 9 years for hypertension incidence, defined as BP at least 140/90 mmHg or initiation of antihypertensive medication. Hazard ratios (HR) were obtained in sex-specific quintiles of protein intake using time-dependent Cox regression, adjusted for age, sex, BMI, smoking, alcohol use, and 24-h urinary excretions of sodium and potassium. Baseline BP was on average 119/70 mmHg and 976 participants developed hypertension during follow-up. Mean protein intake (in g/kg ideal body weight) was 1.18 ± 0.26 for men and 1.12 ± 0.25 for women. Estimated protein intake was nonlinearly inversely associated with incident hypertension in the fully adjusted model, with nonsignificant HR of 0.77, 0.75, 0.82, and 0.83 in consecutive quintiles compared with the lowest quintile (P-trend: 0.52). Protein intake, as assessed by urinary urea excretion, was not significantly associated with 9-year hypertension incidence in Dutch men and women.

Role of HDL Cholesterol and Estimates of HDL Particle Composition in Future Development of Type 2 Diabetes in the General Population: The PREVEND Study

High-density lipoproteins (HDLs) may directly stimulate β-cell function and glucose metabolism. We determined the relationships of fasting high-density lipoprotein cholesterol (HDL-C), plasma apolipoprotein (apo) A-I and apoA-II, and HDL-C-to-apoA-I and HDL-C-to-apoA-II ratios, as estimates of HDL particle composition, with incident type 2 diabetes mellitus. A prospective study was carried out in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort after exclusion of subjects with diabetes at baseline (n = 6820; age, 28-75 years). The association of HDL-related variables with incident type 2 diabetes was determined by multivariate logistic regression analyses. After a median follow-up of 7.7 years, 394 incident cases of type 2 diabetes mellitus were ascertained (5.8%). After adjustment for age, sex, family history of diabetes, body mass index, hypertension, alcohol, and smoking, odd ratios (ORs) for diabetes were 0.55 (95% confidence interval [CI], 0.47-0.64; P < .001), 0.81 (0.71-0.93; P = .002), 0.02 (0.01-0.06; P < .001), and 0.03 (0.01-0.060; P < .001) per 1-SD increase in HDL-C and apoA-I and in the HDL-C-to-apoA-I and the HDL-C-to-apoA-II ratios, respectively. In contrast, apoA-II was not related to incident diabetes (OR = 1.02; 95% CI, 0.90-1.16; P=0.71). The relationships of HDL-C and the ratios of HDL-C to apoA-I and HDL-C to apoA-II remained significant after further adjustment for baseline glucose and triglycerides (OR(HDL) = 0.74 [95% CI, 0.61-0.88], OR(HDL/APO A-I) = 0.14 [0.04-0.44], and OR(HDL/APOA-II) = 0.12 [0.04-0.36]; all P ≤ .001). Higher HDL-C, as well as higher HDL-C-to-apoA-I and HDL-C-to-apoA-II ratios are strongly and independently related to a lower risk of future type 2 diabetes.

Urinary and plasma magnesium and risk of ischemic heart disease

Previous studies on dietary magnesium and risk of ischemic heart disease (IHD) have yielded inconsistent results, in part because of a lack of direct measures of actual magnesium uptake. Urinary excretion of magnesium, an indicator of dietary magnesium uptake, might provide more consistent results. The objective was to investigate whether urinary magnesium excretion and plasma magnesium are associated with IHD risk. We examined 7664 adult participants free of known cardiovascular disease in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study-a prospective population-based cohort study. Urinary magnesium excretion was measured in 2 baseline 24-h urine collections. Mean ± SD urinary magnesium excretion was 4.24 ± 1.65 mmol/24 h for men and 3.54 ± 1.40 mmol/24 h for women. During a median follow-up of 10.5 y (IQR: 9.9-10.8 y), 462 fatal and nonfatal IHD events occurred. After multivariable adjustment, urinary magnesium excretion had a nonlinear relation with IHD risk (P-curvature = 0.01). The lowest sex-specific quintile (men: <2.93 mmol/24 h; women: <2.45 mmol/24 h) had an increased risk of fatal and nonfatal IHD (multivariable HR: 1.60; 95% CI: 1.28, 2.00) compared with the upper 4 quintiles of urinary magnesium excretion. A similar increase in risk of the lowest quintile was observed for mortality related to IHD (HR: 1.70; 95% CI: 1.10, 2.61). No associations were observed between circulating magnesium and risk of IHD. Low urinary magnesium excretion was independently associated with a higher risk of IHD incidence. An increased dietary intake of magnesium, particularly in those with the lowest urinary magnesium, could reduce the risk of IHD.

Urinary Magnesium Excretion and Risk of Hypertension

Observational studies on dietary or circulating magnesium and risk of hypertension have reported weak-to-modest inverse associations, but have lacked measures of actual dietary uptake. Urinary magnesium excretion, an indicator of intestinal magnesium absorption, may provide a better insight in this association. We examined 5511 participants aged 28 to 75 years free of hypertension in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective population–based cohort study. Circulating magnesium was measured in plasma and urinary magnesium in two 24-hour urine collections, both at baseline. Incident hypertension was defined as blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic, or initiation of antihypertensive medication. During a median follow-up of 7.6 years (interquartile range, 5.0–9.3 years), 1172 participants developed hypertension. The median urinary magnesium excretion was 3.8 mmol/24 hour (interquartile range, 2.9–4.8 mmol/24 hour). Urinary magnesium excretion was associated with risk of hypertension in an inverse log-linear fashion, and this association remained after adjustment for age, sex, body mass index, smoking status, alcohol intake, parental history of hypertension, and urinary excretion of sodium, potassium, and calcium. Each 1-unit increment in ln-transformed urinary magnesium excretion was associated with a 21% lower risk of hypertension after multivariable adjustment (adjusted hazard ratio, 0.79; 95% confidence interval, 0.71–0.88). No associations were observed between circulating magnesium and risk of hypertension. In conclusion, in this cohort of men and women, urinary magnesium excretion was inversely associated with risk of hypertension across the entire range of habitual dietary intake.

Heart failure with preserved and reduced ejection fraction: different risk profiles for different diseases

This editorial refers to ‘Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND’, by F.P. Brouwers et al. , doi:10.1093/eurheartj/eht066 Approximately 15 million Europeans and 6 million Americans suffer from heart failure (HF), with annual direct and indirect costs in the billions.1 About half of patients have a preserved ejection fraction (HFpEF), while the others display a reduced EF (HFrEF).2,3 Clinical trials have unequivocally shown that treatments such as neurohormonal antagonists improve outcome in HFrEF, while similar trials in HFpEF have been neutral.1,2 Several reasons have been proposed for this differential response, including unique pathophysiologies in HFpEF and HFrEF, differing degrees of neurohormonal activation, significant pathophysiological heterogeneity within the broad population of HFpEF patients, and higher non-cardiovascular mortality in HFpEF.1,2 It is also possible that the heart in HFrEF displays greater plasticity and amenability to reverse remodelling, while changes in the mechanical properties of the heart and vasculature in HFpEF might be less reversible by the time symptoms develop. Thus, interventions designed to prevent HFpEF might be more effective to reduce the global disease burden. To better inform strategies to prevent HFpEF (and HFrEF), detailed insight is needed into disease-specific risk factors. Brouwers and colleagues have now presented exciting new data identifying common and distinct risk profiles for incident HFpEF and HFrEF.4 As part of the community-based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8592 subjects living in Groningen, The Netherlands, underwent baseline medical examination along with blood testing and 24 h urine sampling. After a median follow-up duration of 11.5 years, the authors undertook the ambitious enterprise of carefully reviewing all medical records to identify subjects developing incident HF. The HF diagnosis was established …

Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND

Differences in clinical characteristics and outcome of patients with established heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are well established. Data on epidemiology and prediction of new onset HFpEF, compared with HFrEF, have not been described. In 8592 subjects of the Prevention of Renal and Vascular End-stage Disease (PREVEND), a community-based, middle-aged cohort study, we performed cause-specific hazard analyses to study the predictive value of risk factors and established cardiovascular biomarkers on new onset HFrEF vs. HFpEF (left ventricular ejection fraction ≤ 40 and ≥ 50%, respectively). A P-value for competing risk (Pcr) <0.10 between HFrEF and HFpEF was considered statistically significant. All potential new onset heart failure cases were reviewed and adjudicated to HFrEF or HFpEF by an independent committee. During a median follow-up of 11.5 years, 374 (4.4%) subjects were diagnosed with heart failure, of which 125 (34%) with HFpEF and 241 (66%) with HFrEF. The average time to diagnosis of new onset HFrEF was 6.6 ± 3.6 years; it was 8.3 ± 3.3 years for HFpEF (P < 0.001). Male gender was associated with new onset HFrEF, whereas female gender with new onset HFpEF (Pcr < 0.001). Higher age and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased the risk for both HFpEF and HFrEF, although for age this was stronger for HFpEF (Pcr = 0.018), whereas NT-proBNP was stronger associated with risk for HFrEF (Pcr = 0.083). Current smokers, increased highly sensitive troponin T, and previous myocardial infarction conferred a significantly increased risk for HFrEF, but not for HFpEF (Pcr = 0.093, 0.091, and 0.061, respectively). Conversely, a history of atrial fibrillation, increased urinary albumin excretion (UAE), and cystatin C were significantly more associated with the risk for HFpEF, but not for HFrEF (Pcr < 0.001, 0.061, and 0.033, respectively). The presence of obesity at baseline was associated with comparable prognostic information for both HFpEF and HFrEF. Higher age, UAE, cystatin C, and history of atrial fibrillation are strong risk factors for new onset HFpEF. This underscores differential pathophysiological mechanisms for both subtypes of heart failure.

Targeting albuminuria in arterial hypertension and diabetes

Targeting albuminuria in arterial hypertension and diabetes

A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus

Microalbuminuria is considered the first clinical sign of kidney dysfunction and is associated with a poor renal and cardiovascular prognosis in type 2 diabetes. Detection of patients who are prone to develop micro- or macroalbuminuria may represent an effective strategy to start or optimise therapeutic intervention. Here we assessed the value of a urinary proteomic-based risk score (classifier) in predicting the development and progression of microalbuminuria. We conducted a prospective case-control study. Cases (n = 44) and controls (n = 44) were selected from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study and from the Steno Diabetes Center (Gentofte, Denmark). Cases were defined by transition from normo- to microalbuminuria or from micro- to macroalbuminuria over a follow-up of 3years. Controls with no transitions in albuminuria were pair-matched for age, sex and albuminuria status. A model for the progression of albuminuria was built using a proteomic classifier based on 273 urinary peptides. The proteomic classifier was independently associated with transition to micro- or macroalbuminuria (OR 1.35 [95% CI 1.02, 1.79], p = 0.035). The classifier predicted the development and progression of albuminuria on top of albuminuria and estimated GFR (eGFR, area under the receiver operating characteristic [ROC] curve increase of 0.03, p = 0.002; integrated discrimination index [IDI]: 0.105, p = 0.002). Fragments of collagen and α-2-HS-glycoprotein showed significantly different expression between cases and controls. Although limited by the relatively small sample size, these results suggest that analysis of a urinary biomarker set enables early renal risk assessment in patients with diabetes. Further work is required to confirm the role of urinary proteomics in the prevention of renal failure in diabetes.

Increased risk of arterial thromboembolism after a prior episode of venous thromboembolism: results from the Prevention of REnal and Vascular ENd stage Disease (PREVEND) Study

Large population-based studies are needed to establish the magnitude and duration of the recently suggested association between arterial and venous thromboembolism. In 1997-98, all inhabitants of Groningen, the Netherlands, aged 28-75years (n=85421), were invited to participate in a study that followed and monitored responding subjects (n=40856) for venous and arterial thromboembolism until 2009. Thromboembolism was verified with national registries of hospital discharge diagnoses and death certificates, anticoagulation clinic and medical records. During a median follow-up of 10·7years, 549 participants developed venous thromboembolism and 3283 developed arterial thromboembolism. Annual incidence of arterial thromboembolism after venous thromboembolism was 2·03% [95% confidence interval (CI), 1·48-2·71], compared to 0·87% (95% CI, 0·84-0·90) in subjects without venous thromboembolism. The hazard ratio (HR) of arterial thromboembolism after venous thromboembolism was 1·40 (95% CI, 1·04-1·88) after adjustment for age, sex and cardiovascular risk factors. This risk was highest during the first year after venous thromboembolism [annual incidence, 3·00% (95% CI, 1·64-5·04); adjusted HR, 2·01 (95% CI, 1·19-3·40)] and after an unprovoked event [annual incidence, 2·53% (95% CI, 1·68-3·66); adjusted HR, 1·62 (95% CI, 1·11-2·34)]. This study showed that subjects with venous thromboembolism are at increased risk for arterial thromboembolism, particularly in the first year after venous thromboembolism and after an unprovoked event.

Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population

ObjectiveExperimental studies have shown that adrenomedullin (ADM) has an important role in circulatory homeostasis. Mid-regional pro-ADM (MR-proADM) is a stable form of ADM. Observational studies found an important association with...