Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Metaanalysis

Ellervik, Christina; Marott, Jacob Louis; Tybjærg‐Hansen, Anne; Schnohr, Peter; Nordestgaard, Børge G.

doi:10.1373/clinchem.2014.229013

Cited by 50 publications

(39 citation statements)

References 38 publications

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“…In fact, in pilot experiments on a few hundred of the frozen samples, we attempted to measure high-sensitivity CRP, but the quality of the measurements was very poor, in contrast to the ferritin measurements. Thus, as we were not able to adjust for CRP (or any other marker of acute phase/inflammation), we agree that this is a limitation of our study (1 ). However, we find it unlikely that the associations in our paper are mediated only by inflammation, as the P values are extremely significant, and both moderately and markedly increased ferritin concentrations were associated with early death.…”

Section: In Replymentioning

confidence: 60%

“…to compare its accuracy performance to such thresholds. Next, glucose sensor accuracy thresholds do depend on the robustness of the control algorithm and should be specified (using simulations) for each individual glucose controller (1,5 ). Generalization of these thresholds will underestimate errors for less robust glucose controllers and potentially harm patients; it should be avoided, accordingly.…”

mentioning

confidence: 99%

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Is Ferrotoxicity a New Great Public Health Challenge?

Breimer

Nilsson

2015

Clinical Chemistry

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Section: In Replymentioning

confidence: 60%

mentioning

confidence: 99%

Is Ferrotoxicity a New Great Public Health Challenge?

Breimer

Nilsson

2015

Clinical Chemistry

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“…S-ferritin er en vanlig analyse i allmennpraksis, og moderat hyperferritinemi er et relativt hyppig funn (1). Forbigående økning ses ved akutt inflammatorisk sykdom med økt syntese av ferritin og andre akuttfaseproteiner, og ved tilstander som gir levercelleskade med lekkasje av ferritin, saelig hepatitt og sporadisk overdrevet inntak av alkohol (2).…”

Section: G/ 100 Ml) Han Hadde Vaert Blodgiver Og Gitt Blod Sju Gangeunclassified

“…Forbigående økning ses ved akutt inflammatorisk sykdom med økt syntese av ferritin og andre akuttfaseproteiner, og ved tilstander som gir levercelleskade med lekkasje av ferritin, saelig hepatitt og sporadisk overdrevet inntak av alkohol (2). Varig hyperferritinemi ses ved kroniske tilstander som alkoholisme, infeksjon, inflammatorisk sykdom, fettlever, diabetes, enkelte kreftsykdommer, hemolyse og jernoverskudd på grunn av arvelig hemokromatose (1,3).…”

Section: G/ 100 Ml) Han Hadde Vaert Blodgiver Og Gitt Blod Sju Gangeunclassified

En mann i 50-årene med høyt ferritinnivå og økende kognitiv svikt

Bjørk¹,

Gjerde²,

Tzoulis³

et al. 2015

Tidsskriftet

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“…In this issue of Clinical Chemistry, Ellervik et al (1 ) report relationships between baseline ferritin concentrations and risk of all-cause and cause-specific mortality in 8988 individuals enrolled in the Copenhagen City Heart Study. Median follow-up was 23 years, during which 6364 individuals died.…”

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confidence: 99%

Ferrotoxic Disease: The Next Great Public Health Challenge

Zacharski

2014

Clinical Chemistry

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In this issue of Clinical Chemistry, Ellervik et al. (1 ) report relationships between baseline ferritin concentrations and risk of all-cause and cause-specific mortality in 8988 individuals enrolled in the Copenhagen City Heart Study. Median follow-up was 23 years, during which 6364 individuals died. Multifactorially adjusted hazard ratios for total mortality in individuals with ferritin values below vs above 200 g/L showed significantly lower mortality overall (P ϭ 0.0008) and separately for men (P ϭ 0.02) and women (P ϭ 0.03) with lower ferritin concentrations. Cause-specific mortality below vs above the 200 g/L threshold was significantly lower for cancer (P ϭ 0.005), metabolic disease (P ϭ 0.002) and cardiovascular disease (P ϭ 0.00006). A highly significant progressive decrease in median survival occurred with increasing ferritin concentrations. The hazard ratio for total mortality increased by 13% for each 100 g/L increase in ferritin concentration. The median survival was 79 years with concentrations Ͻ200 g/L, 76 years with ferritin concentrations between 200 and 399 g/L, 72 years with ferritin concentrations between 400 and 599 g/L, and 55 years with ferritin concentrations in excess of 600 g/L. A stepwise increase in mortality with increasing ferritin concentrations was found for each disease category. Adjusted hazard ratios for increased disease-specific mortality for ferritin concentrations above 600 g/L vs below 200 g/L were significant for malignant (P ϭ 0.01), endocrine (P ϭ 0.0001), and cardiovascular (P ϭ 0.01) disease. The conclusion was that "increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population." Increased ferritin concentrations were interpreted by the authors "as a biological marker of pathogenic processes that reflects severity and presence of a variety of disease states leading to premature death." They stated that "causality may be difficult to claim in this study, since, unlike transferrin saturation, increased ferritin is associated with many diseases other than hereditary iron overload."Readers may be challenged by the interpretation of ferritin concentrations reported from this study. Ferritin values in the range of 200 g/L, which were found to be disadvantageous, are common in practice. Reluctance to assign cause-and-effect relationships, or to test the relationship between ferritin concentrations and outcomes at all, may be based on the assumption that high ferritin values might in some sense be "nonspecific" (perhaps "acute phase") in this context. It might also be thought that high ferritin concentrations occur too commonly and in too many different diseases to be useful in terms of determining diagnosis or prognosis or designing treatment strategies. The seemingly discontinuous association between increased ferritin concentrations and clinical outcomes for commonly observed increases in ferritin vs the larger increases seen with hereditary iron overload may lead to the presumptio...

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Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Metaanalysis

Abstract: BACKGROUND: Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population.

Cited by 50 publications

References 38 publications

Is Ferrotoxicity a New Great Public Health Challenge?

Is Ferrotoxicity a New Great Public Health Challenge?

En mann i 50-årene med høyt ferritinnivå og økende kognitiv svikt

Ferrotoxic Disease: The Next Great Public Health Challenge

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