Serum Obestatin: A Biomarker of Cardiovascular and All-Cause Mortality in Hemodialysis Patients

2018 ◽  
Vol 47 (4) ◽  
pp. 254-265 ◽  
Author(s):  
Ilia Beberashvili ◽  
Anna Katkov ◽  
Inna Sinuani ◽  
Ada Azar ◽  
Gregory Shapiro ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Experimental Studies ◽  
Cardiovascular Death ◽  
Maintenance Hemodialysis ◽  
Necrosis Factor Alpha ◽  
Markers Of Inflammation ◽  
Gut Hormone ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Acyl Ghrelin

Background: Recent experimental studies have suggested that obestatin, a proposed anorexigenic gut hormone and a physiological opponent of acyl-ghrelin, has protective cardiovascular effects. We tested the hypothesis that obestatin is independent of inflammatory mediators and/or acyl-ghrelin in predicting outcomes of the maintenance hemodialysis (MHD) population. Methods: It was a 6-year cohort study on 261 MHD patients. Obestatin, acyl-ghrelin, adipokines (leptin and adiponectin), markers of inflammation and nutrition, prospective all-cause and cardiovascular mortality were studied. Results: During the follow-up, 160 patients died in total, with 74 deaths due to cardiovascular causes. For each ng/mL increase in baseline obestatin level in fully adjusted models (including malnutrition-inflammation score, Interleukin-6 [IL-6], adipokines and acyl-ghrelin), the hazard for death from all causes was 0.90 (95% CI 0.81–0.99) and for cardiovascular death 0.85 (95% CI 0.73–0.99). However, these associations were more robust in the subgroup of patients aged above 71 years: 0.85 (95% CI 0.73–0.98) for all-cause death and 0.66 (95% CI 0.52–0.85) for cardiovascular death. An interaction between high IL-6 (above median) and low obestatin (below median) levels for increased risk of all-cause mortality (synergy index [SI] 5.14, p = 0.001) and cardiovascular mortality (SI 4.81, p = 0.02) emerged in the development of multivariable adjusted models. Interactions were also observed between obestatin, Tumor necrosis factor-alpha, adipokines and acyl-ghrelin, which were associated with mortality risk. Conclusion: Serum obestatin behaves as a biomarker for cardiovascular and all-cause mortality in MHD patients. The prognostic ability of obestatin in this regard is independent of inflammation, nutritional status, acyl-ghrelin’s and adipokines’ activity and is modified by age being very prominent in patients older than 71 years.

scholarly journals Low Serum Concentration of Obestatin as a Predictor of Mortality in Maintenance Hemodialysis Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ilia Beberashvili ◽  
Inna Sinuani ◽  
Ada Azar ◽  
Hadas Kadoshi ◽  
Gregory Shapiro ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Experimental Studies ◽  
Cross Sectional Study ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
Cross Sectional ◽  
Hazard Ratios ◽  
Gut Hormone ◽  
All Cause Mortality ◽  
Low Serum

Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α[TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-αcategories, the group with low obestatin and high TNF-α(above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-αgroup did not differ from other obestatin-TNF-αcategorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes.

scholarly journals U-shaped Association Between Apolipoprotein B and All-Cause Mortality: Results from the National Health and Nutrition Examination Surveys

2021 ◽  
Author(s):  
mengqi yan ◽  
Xiaocong Liu ◽  
Yuqing Huang ◽  
Yuling Yu ◽  
Dan Zhou ◽  
...  
Keyword(s):  
National Health ◽  
Cardiovascular Mortality ◽  
Proportional Hazards ◽  
Piecewise Linear ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Health And Nutrition ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Non Linear

Abstract BackgroundApolipoprotein B (apoB), a significant component directly reflecting the number of atherogenic lipoprotein particles, gradually becomes a more conducive indicator to control blood lipids. However, epidemiological evidence on its relationship with mortality is limited, especially with all-cause mortality. MethodsParticipants from the National Health and Nutrition Examination Survey during 2007-2014 were grouped according to the apoB quartiles (15-76, 77-92, 93-110, 111-345mg/dL). We performed Cox proportional hazards models and Kaplan-Meier survival curves to evaluate the relationships of apoB with all-cause and cardiovascular mortality. Restricted cubic spline and piecewise linear regression were performed to detect their non-linear relationships. ResultsIn general, we enrolled 10375 participants among United States adults (mean age 46.3 ± 16.9, 47.88% men). On average, participants were followed up for 69.2 months, among whom 533 (5.14%) and 91 (0.88%) deaths were observed due to all -causes and cardiovascular diseases, respectively. After adjusting for confounders, apoB was independently associated with an elevated risk of cardiovascular death (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.03-1.24). However, in the third quartile of apoB, the risk of all-cause death decreased significantly (HR, 0.71; 95% CI, 0.56-0.91). Moreover, the non-linear relationship between apoB and all-cause death demonstrated an increased risk at both low and high level apoB concentrations, divided by the threshold point of 108 mg/dl. ConclusionElevated apoB was significantly associated with an increased risk for cardiovascular mortality, while its association with all-cause mortality was non-linear correlated, with an increased risk at both low and high apoB levels.

scholarly journals Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999–2015

2020 ◽  
Author(s):  
Kosuke Inoue ◽  
Roch Nianogo ◽  
Donatello Telesca ◽  
Atsushi Goto ◽  
Vahe Khachadourian ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Regression Models ◽  
Machine Learning Algorithms ◽  
Logistic Regression Models ◽  
Health And Nutrition ◽  
Increased Risk ◽  
The Us ◽  
All Cause Mortality ◽  
Hba1c Levels

Abstract Objective It is unclear whether relatively low glycated haemoglobin (HbA1c) levels are beneficial or harmful for the long-term health outcomes among people without diabetes. We aimed to investigate the association between low HbA1c levels and mortality among the US general population. Methods This study includes a nationally representative sample of 39 453 US adults from the National Health and Nutrition Examination Surveys 1999–2014, linked to mortality data through 2015. We employed the parametric g-formula with pooled logistic regression models and the ensemble machine learning algorithms to estimate the time-varying risk of all-cause and cardiovascular mortality by HbA1c categories (low, 4.0 to <5.0%; mid-level, 5.0 to <5.7%; prediabetes, 5.7 to <6.5%; and diabetes, ≥6.5% or taking antidiabetic medication), adjusting for 72 potential confounders including demographic characteristics, lifestyle, biomarkers, comorbidities and medications. Results Over a median follow-up of 7.5 years, 5118 (13%) all-cause deaths, and 1116 (3%) cardiovascular deaths were observed. Logistic regression models and machine learning algorithms showed nearly identical predictive performance of death and risk estimates. Compared with mid-level HbA1c, low HbA1c was associated with a 30% (95% CI, 16 to 48) and a 12% (95% CI, 3 to 22) increased risk of all-cause mortality at 5 years and 10 years of follow-up, respectively. We found no evidence that low HbA1c levels were associated with cardiovascular mortality risk. The diabetes group, but not the prediabetes group, also showed an increased risk of all-cause mortality. Conclusions Using the US national database and adjusting for an extensive set of potential confounders with flexible modelling, we found that adults with low HbA1c were at increased risk of all-cause mortality. Further evaluation and careful monitoring of low HbA1c levels need to be considered.

scholarly journals Comorbidity burden may explain adiponectin’s paradox as a marker of increased mortality risk in hemodialysis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilia Beberashvili ◽  
Tamar Cohen-Cesla ◽  
Amin Khatib ◽  
Ramzia Abu Hamad ◽  
Ada Azar ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Maintenance Hemodialysis ◽  
Blood Levels ◽  
Low Concentrations ◽  
Comorbidity Burden ◽  
All Cause Mortality ◽  
Markers Of Oxidative Stress ◽  
Comorbidity Index ◽  
Antiinflammatory Effects ◽  
High Comorbidity

AbstractDespite experimental evidence of beneficial metabolic, antiatherosclerotic and antiinflammatory effects of the 30 kDa adipokine, adiponectin, maintenance hemodialysis (MHD) patients with high adiponectin blood levels have paradoxically high mortality rates. We aimed to examine the direction of the associations between adiponectin and all-cause and cardiovascular mortality as well as with markers of oxidative stress, inflammation and nutrition in MHD patients with varying degrees of comorbidities. A cohort of 261 MHD patients (mean age 68.6 ± 13.6 years, 38.7% women), grouped according to baseline comorbidity index (CI) and serum adiponectin levels, were followed prospectively for six years. High and low concentrations were established according to median CI and adiponectin levels and cross-classified. Across the four CI-adiponectin categories, the group with low comorbidities and high adiponectin exhibited the best outcomes. Conversely, the high comorbidity group with high adiponectin levels had the lowest survival rate in both all-cause mortality (log rankχ2 = 23.74, p < 0.001) and cardiovascular mortality (log rankχ2 = 34.16, p < 0.001). Further data adjustment for case-mix covariates including fat mass index did not substantially affect these results. In conclusion, the direction of adiponectin’s prognostic associations in MHD patients is inverse in those with few comorbidities and direct in those with many comorbidities.

Abstract 3739: The Influence of Albuminuria on Mortality in Patients with Stable Coronary Artery Disease

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Scott D Solomon ◽  
Julie Lin ◽  
Caren G Solomon ◽  
Kathleen Jablonski ◽  
Madeline Murguia Rice ◽  
...  
Keyword(s):  
Coronary Disease ◽  
Systolic Function ◽  
Cardiovascular Death ◽  
Creatinine Ratio ◽  
Normal Range ◽  
Albumin Creatinine Ratio ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
All Cause Mortality

Background: Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and death or cardiovascular events among patients with stable coronary disease. Methods: We studied patients enrolled in the Prevention of Events with an ACE Inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate (eGFR) and outcomes. Results: The majority of patients (73%) had a baseline albumin/creatinine ratio within the normal range. Independent of the eGFR and other baseline covariates, a higher albumin/creatinine ratio even within the normal range was associated with increased risks for all-cause mortality (p < 0.001) and cardiovascular death (p = 0.01). The effect of trandolapril therapy on outcomes was not significantly modified by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 ug/mg vs 14.6 ug/mg, p = 0.0002), after adjusting for baseline ACR, time between collections and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (HR per log ACR 1.74, 95% confidence intervals 1.08–2.82). Conclusions: Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.

scholarly journals Sudden death in patients with sleep apnea: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Emily S. Heilbrunn ◽  
Paddy Ssentongo ◽  
Vernon M. Chinchilli ◽  
Anna E. Ssentongo
Keyword(s):  
Sleep Apnea ◽  
Sudden Death ◽  
Cardiovascular Mortality ◽  
Meta Analysis ◽  
Cardiac Mortality ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
All Cause Mortality

AbstractBackgroundOver 1 billion individuals across the globe experience some form of sleep apnea, and this number is steadily rising. Obstructive sleep apnea (OSA) can negatively influence one’s quality of life and potentially increase the risk of mortality. However, this association between OSA and mortality has not been comprehensively and thoroughly explored. This meta-analysis was conducted to conclusively estimate the risk of death for all-cause mortality and cardiovascular mortality in OSA patients.Study Design4,613 articles from databases including PUBMED, OVID & Joana Briggs, and SCOPUS were comprehensively assessed by two reviewers (AES & ESH) for inclusion criteria. 28 total articles were included, with 22 of them being used for quantitative analysis. Pooled effects of all-cause mortality, cardiac mortality, and sudden death were calculated by utilizing the metaprop function in R Statistical Software and the random-effects model with appropriate 95% confidence intervals.ResultsAnalysis on 42,032 individuals revealed that those with OSA were twice as likely to die from cardiac mortality compared to those without sleep apnea (HR= 1.94, 95%CI 1.39-2.70). Likewise, individuals with OSA were 1.7 times as likely to die from all-cause sudden death compared to individuals without sleep apnea (HR= 1.74, 95%CI 1.40-2.10). There was a significant dose response relationship between severity of sleep apnea and incidence risk of death, where those with severe sleep apnea wereConclusionsIndividuals with obstructive sleep apnea are at an increased risk for all-cause mortality and cardiac mortality. Further research related to appropriate interventions and treatments are necessary in order to reduce this risk and optimize survival in this population.Key MessagesWhat is the key question?Are individuals with sleep apnea at an increased risk for cardiovascular mortality and sudden death?What is the bottom Line?Sleep apnea is associated with an increased risk of cardiovascular mortality and sudden death, with a dose response relationship, where those with severe sleep apnea are at the highest risk of mortality.Why read on?This is the first systematic review and meta-analyses to synthesize and quantify the risk of mortality in those with sleep apnea, highlighting important directions for future research.Prospero Registration IDCRD42020164941

scholarly journals Left Ventricular Mass Regression, All-Cause and Cardiovascular Mortality in Chronic Kidney Disease: A Meta-Analysis

2021 ◽  
Author(s):  
Kevin C. Maki ◽  
Meredith L. Wilcox ◽  
Mary R. Dicklin ◽  
Rahul Kakkar ◽  
Michael H. Davidson
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricular Mass ◽  
Cardiovascular Mortality ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Secondary Outcome ◽  
Ventricular Mass ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥ 12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 38 trials with duration ≥ 12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 8 of other types of interventions. All-cause mortality was reported in 116/2385 (4.86%) subjects in intervention groups and 161/2404 (6.70%) subjects in control groups. The pooled RR estimate of the 24 trials ≥ 12 months with ≥ 1 event in ≥ 1 group was 0.72 (95% CI 0.57 to 0.91, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥ 6 months (31 trials), ≥ 9 months (26 trials), and > 12 months (9 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.66, 95% CI 0.38 to 1.15. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.

Abstract 13619: Major Electrocardiographic Abnormalities in Brazilian Adults: Prognostic Value and Potential Use in Primary Prevention (from the Elsa-Brasil Cohort Study)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Marcelo M Pinto Filho ◽  
Luisa C Brant ◽  
Sandhi M Barreto ◽  
JOSE GERALDO MILL ◽  
Paulo A Andrade Lotufo ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Cardiovascular Mortality ◽  
Risk Model ◽  
Independent Predictor ◽  
Cardiovascular Death ◽  
Noncommunicable Diseases ◽  
Adult Health ◽  
Increased Risk ◽  
Electrocardiographic Abnormality ◽  
Electrocardiogram Ecg

Introduction: Cardiovascular diseases (CVD) are the most preventable noncommunicable diseases. Accurate risk stratification is paramount for identifying patients for whom interventions should be offered. The electrocardiogram (ECG) is a potential tool for CVD primary prevention. Our aim is to evaluate the ECG role as an independent predictor of all-cause and cardiovascular mortality Methods: Participants from the Longitudinal Study of Adult Health (ELSA-Brasil), who were free of known CVD at baseline were included. A 12-lead ECG was obtained at baseline (2008-2010).Participants were followed up to 2018 by annual interviews.Deaths and hospitalizations were independently reviewed. Cox and Fine and Gray competitive risk regressions were applied to evaluate if the presence of any major electrocardiographic abnormality (MEA) at baseline, defined according to de Minnesota Code system (MC), would predict total and cardiovascular deaths in multivariable models Results: The 13,437 participants (mean age 51.8 years, 55% women) were followed for 8±1 years. Baseline prevalence of MEA was 7.2% for men, 5.8% for women. All-cause and cardiovascular mortality occurred in 5.7% and 1.2% of men, and 3.1% and 1.2% of women, respectively. Prevalent MEA was an independent predictor of overall mortality after adjustments for age, race, education and traditional cardiovascular risk factors (HR:2.2; 95%CI 1.6-2.9 for men and HR:2.3; 95%CI 1.6-3.4 for women). [LB1] In the competitive risk model for cardiovascular death, the increased risk attributable to MEA was even higher (HR4.1, 95%CI 2.47-6.81 in men and 5.37, 95%CI 2.54-11.36 in women). Conclusions: Presence of MEA was a strong and independent predictor of overall and cardiovascular death for both sexes. ECG may have a role in improving risk assessment for death in primary care

scholarly journals High Erythropoiesis Resistance Index Is a Significant Predictor of Cardiovascular and All-Cause Mortality in Chinese Maintenance Hemodialysis Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiangxue Lu ◽  
Jialing Zhang ◽  
Shixiang Wang ◽  
Qian Yu ◽  
Han Li
Keyword(s):  
Cardiovascular Mortality ◽  
Resistance Index ◽  
High Sensitivity ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
All Cause Mortality ◽  
Correlated Factors ◽  
Maintenance Hemodialysis Patients

Background. Renal anemia is a common complication of hemodialysis patients. Erythropoietin (EPO) hyporesponsiveness has been recognized as an important factor to poor efficacy of recombinant human erythropoietin in the treatment of renal anemia. More importantly, increased erythropoiesis resistance index (ERI) may be associated with inflammation and increased mortality. Objective. The objective of this research was to investigate correlated factors of EPO responsiveness and to clarify the relationships between EPO hyporesponsiveness and cardiovascular mortality and all-cause mortality among maintenance hemodialysis patients. Methods. This prospective cohort study enrolled 276 maintenance hemodialysis patients for a 55-month follow-up to investigate the factors related to ERI and its relationship to all-cause mortality and cardiovascular mortality. Results. ERI was positively correlated with predialysis serum high-sensitivity C-reactive protein ( r = 0.234 , p < 0.001 ), alkaline phosphatase ( r = 0.134 , p = 0.028 ), and ferritin ( r = 0.155 , p = 0.010 ) and negatively correlated with albumin ( r = − 0.206 , p < 0.001 ) and creatinine ( r = − 0.232 , p < 0.001 ). As multiple linear regression showed, predialysis serum albumin, high-sensitivity C-reactive protein, ferritin, and creatinine were independent correlated factors of ERI ( p < 0.05 ). Kaplan–Meier curves showed that the cumulative incidences of both cardiovascular mortality and all-cause mortality were significantly higher in patients with ERI > 11.04   IU / kg / w / g / dL (both p < 0.01 ). The high ERI group was significantly associated with higher risk for all-cause mortality (OR 1.781, 95% CI 1.091 to 2.910, p = 0.021 ) and cardiovascular mortality (OR 1.972, 95% CI 1.139 to 3.417, p = 0.015 ) after adjusting for confounders. Conclusions. Predialysis serum albumin, high-sensitivity C-reactive protein, ferritin, and creatinine were independent correlated factors of EPO responsiveness among maintenance hemodialysis patients. Patients with higher ERI values had a higher all-cause mortality rate and cardiovascular mortality rate.

scholarly journals Selenoprotein-P Deficiency Predicts Cardiovascular Disease and Death

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1852 ◽  
Author(s):  
Lutz Schomburg ◽  
Marju Orho-Melander ◽  
Joachim Struck ◽  
Andreas Bergmann ◽  
Olle Melander
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Event ◽  
Cardiovascular Mortality ◽  
Cardiovascular Morbidity ◽  
Morbidity And Mortality ◽  
Selenoprotein P ◽  
P Deficiency ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
All Cause Mortality

Selenoprotein-P (SELENOP) is the main carrier of selenium to target organs and reduces tissue oxidative stress both directly and by delivering selenium to protective selenoproteins. We tested if the plasma concentration of SELENOP predicts cardiovascular morbidity and mortality in the primary preventive setting. SELENOP was measured from the baseline exam in 2002–2006 of the Malmö Preventive Project, a population-based prospective cohort study, using a validated ELISA. Quintiles of SELENOP concentration were related to the risk of all-cause mortality, cardiovascular mortality, and a first cardiovascular event in 4366 subjects during a median (interquartile range) follow-up time of 9.3 (8.3–11) years using Cox proportional Hazards Model adjusting for cardiovascular risk factors. Compared to subjects in the lowest quintile of SELENOP, the risk of all three endpoints was significantly lower in quintiles 2–5. The risk (multivariate adjusted hazard ratio, 95% CI) decreased gradually with the lowest risk in quintile 4 for all-cause mortality (0.57, 0.48–0.69) (p < 0.001), cardiovascular mortality (0.52, 0.37–0.72) (p < 0.001), and first cardiovascular event (0.56, 0.44–0.71) (p < 0.001). The lower risk of a first cardiovascular event in quintiles 2–5 as compared to quintile 1 was significant for both coronary artery disease and stroke. We conclude that the 20% with lowest SELENOP concentrations in a North European population without history of cardiovascular disease have markedly increased risk of cardiovascular morbidity and mortality, and preventive selenium supplementation studies stratified for these subjects are warranted.

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