Dataset Information

Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands.

ABSTRACT: Importance:Higher plasma concentrations of vitamin B12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B12 with mortality in the general population remains unclear. Objective:To investigate the association of plasma concentrations of vitamin B12 with all-cause mortality. Design, Setting, and Participants:This longitudinal cohort study used post hoc analysis to examine data from participants of the Prevention of Renal and Vascular End-stage Disease Study in Groningen, the Netherlands. Participants included individuals who completed the second screening visit beginning January 1, 2001, excluding those who were missing values of vitamin B12 plasma concentrations or used vitamin B12 supplementation. Follow-up time was defined between the beginning of the second screening round to end of follow-up on January 1, 2011. Data analysis was conducted from October 2, 2018, to February 22, 2019. Exposures:Plasma vitamin B12 concentration level. Main Outcomes and Measures:Death as recorded by the Central Bureau of Statistics of Groningen, the Netherlands. Results:A total of 5571 participants (mean [SD] age, 53.5 [12.0] years; 2830 [50.8%] men) were included in analyses. Median (interquartile range) plasma concentration of vitamin B12 was 394.42 (310.38-497.42) pg/mL. During the median (interquartile range) of 8.2 (7.7-8.9) years of follow-up, 226 participants (4.1%) died. According to quartiles of the distribution of plasma vitamin B12 concentration levels, mortality rates were 33.8 deaths per 10?000 person-years for the quartile with the lowest plasma concentration of vitamin B12 and 65.7 deaths per 10?000 person-years for the quartile with the highest plasma concentration of vitamin B12. After adjustment for multiple clinical and laboratory variables, Cox regression analyses found a significant association between higher vitamin B12 plasma concentration level and increased risk of all-cause mortality (hazard ratio per 1-SD increase, 1.25 [95% CI, 1.06-1.47]; P?=?.006). Conclusions and Relevance:These findings suggest that higher levels of plasma concentrations of vitamin B12 were associated with increased risk of all-cause mortality after adjusting for age, sex, renal function, and other clinical and laboratory variables. The mechanisms underlying this association remain to be established.

SUBMITTER: Flores-Guerrero JL

PROVIDER: S-EPMC6991261 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands.

Flores-Guerrero Jose L JL Minovic Isidor I Groothof Dion D Gruppen Eke G EG Riphagen Ineke J IJ Kootstra-Ros Jenny J Muller Kobold Anneke A Hak Eelko E Navis Gerjan G Gansevoort Ron T RT de Borst Martin H MH Dullaart Robin P F RPF Bakker Stephan J L SJL

JAMA network open 20200103 1

<h4>Importance</h4>Higher plasma concentrations of vitamin B12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B12 with mortality in the general population remains unclear.<h4>Objective</h4>To investigate the association of plasma concentrations of vitamin B12 with all-cause mortality.<h4>Design, setting, and participants</h4>This longitudinal cohort study used pos ...[more]

PMID: 31940038

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Project description:ImportanceSeveral lines of evidence support low plasma transthyretin concentration as an in vivo biomarker of transthyretin tetramer instability, a prerequisite for the development of both wild-type transthyretin cardiac amyloidosis (ATTRwt) and hereditary transthyretin cardiac amyloidosis (ATTRm). Both ATTRm and ATTRwt cardiac amyloidosis may manifest as heart failure (HF). However, whether low plasma transthyretin concentration confers increased risk of incident HF in the general population is unknown.ObjectiveTo evaluate whether low plasma transthyretin concentration is associated with incident HF in the general population.Design, setting, and participantsThis study included data from 2 similar prospective cohort studies of the Danish general population, the Copenhagen General Population Study (CGPS; n = 9582) and the Copenhagen City Heart Study (CCHS; n = 7385). Using these data, first, whether low concentration of plasma transthyretin was associated with increased risk of incident HF was tested. Second, whether genetic variants in TTR associated with increasing tetramer instability were associated with lower transthyretin concentration and with higher risk of HF was tested. Data were collected from November 2003 to March 2017 in the CGPS and from November 1991 to June 1994 in the CCHS; participants from both studies were observed for survival time end points until March 2017. Data were analyzed from March to June 2019.ExposuresTransthyretin concentration at or below the 5th percentile, between the 5th and 95th percentile (reference), and greater than the 95th percentile; genetic variants in TTR.Main outcome and measureIncident HF identified using the Danish National Patient Registry.ResultsOf 9582 individuals in the CGPS, 5077 (53.0%) were women, and the median (interquartile range [IQR]) age was 56 (47-65) years. Of 7385 individuals in the CCHS, 4452 (60.3%) were women, and the median (IQR) age was 59 (46-70) years. During a median (IQR) follow-up of 12.6 (12.3-12.9) years and 21.7 (11.6-23.8) years, 441 individuals (4.6%) in the CGPS and 1122 individuals (15.2%) in the CCHS, respectively, developed HF. Baseline plasma transthyretin concentrations at or below the 5th percentile were associated with incident HF (CGPS: hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; CCHS: HR, 1.4; 95% CI, 1.1-1.7). Risk of HF was highest in men with low transthyretin levels. Compared with p.T139M, a transthyretin-stabilizing variant, TTR genotype was associated with stepwise lower transthyretin concentrations for wild-type TTR (-16.5%), p.G26S (-18.1%), and heterozygotes for other variants (p.V142I, p.H110N, and p.D119N; -30.8%) (P for trend <.001). The corresponding HRs for incident HF were 1.14 (95% CI, 0.57-2.28), 1.29 (95% CI, 0.64-2.61), and 2.04 (95% CI, 0.54-7.67), respectively (P for trend = .04).Conclusions and relevanceIn this study, lower plasma and genetically determined transthyretin concentrations were associated with a higher risk of incident HF, suggesting a potential mechanistic association between low transthyretin concentration as a marker of tetramer instability and incident HF in the general population.

Dataset Information

Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands.

Publications

Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands.

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