31.03.2014 UL researchers find simple blood iron test predicts fatal outcomes in the general population

Study finds extreme levels of Transferrin Saturation Ratio reflecting blood iron levels linked to increased risk of death

A new study led by researchers at the Graduate Entry Medical School (GEMS), University of Limerick (UL) has found that people with low levels and very high levels of a commonly measured laboratory test, the "transferrin saturation ratio" are at an increased risk of death. The test is a measure of the amount of available iron in the bloodstream with low levels generally reflecting a state of iron deficiency and high levels suggesting a relative excess.

The study found that subjects with extremely low transferrin saturation levels (less that 17.5%) were at a 45% higher risk of death. On the other hand, the risk of death was also significantly higher for subjects with very high levels of transferrin saturation above 31.3 %.

According to primary author, Professor Austin Stack, Foundation Chair of Medicine at University of Limerick Graduate Entry Medical School, and Consultant Nephrologist at University Hospital Limerick, "the transferrin saturation ratio" is a commonly used blood test to assess the amount of iron in a patient. Low levels of transferrin saturation ratio generally indicate iron deficiency, while high levels;-traditionally > 50% indicate an excess of iron, which can be detrimental to health. High levels usually occur in states of iron overload like haemochromatosis, multiple blood transfusions and cirrhosis. There is some uncertainly as to what the optimal levels of transferrin saturation ratio are to maintain normal health, and while some studies to date have shown that low levels are associated with elevated death risk, others have suggested the contrary."

In this study of 15, 823 adults from the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988 to 1994 in the US and with follow-up 2006, the research team sought to examine in detail the risks associated with transferrin saturation ratio and determine the optimal levels that were associated with best survival.

"In this very large population-based study, we found that individuals at both ends of the spectrum-people with very high and very low levels were at increased risk of death" said Professor Stack. This pattern of association was what we call a j-shaped relationship. We found that adults with the lowest levels of transferrin saturation ratio (< 17.5 %) had higher percentage of anaemia and several other chronic conditions like heart disease, diabetes, and poor socioeconomic status, indicators that might have accounted for the higher rates of death. Yet, when we accounted for these factors in our analysis, low levels continued to predict higher death risk."

"What was even more surprising, was that adults who had high transferrin saturation ratio > 31% also experienced higher rates of death, a relationship that was not accounted for by levels of inflammation or other medical conditions."

"When we looked at the relationship between transferrin saturation and deaths from cardiovascular disease, the results were even more striking. A low transferrin saturation ratio less than 17.5 % increased the risk of cardiovascular death by over 200% while a higher TSAT level above 31% increased the risk by almost 60%" said Dr John Ferguson PhD, biostatistician and senior author of the study.

"We believe that these results have important practical implications for the wider medical community" said Professor Stack. Our analysis suggests that the optimal transferrin saturation range for patient survival should be between 23% to 40% and that careful clinical assessment is warranted for patients with low and high levels in order to identify states of iron deficiency or iron excess. Our study demonstrates that transferrin saturation ratio is a useful prognostic tool in assessing a patient's health and while we support the correction of low transferrin saturation levels in the general population, we would also advise caution against excessive iron loading to levels beyond 40%.

The study ' Transferrin Saturation Ratio and Risk of Total and Cardiovascular Mortality in the General Population' is published by Quarterly Journal of Medicine (QJM): An International Journal of Medicine and authored by ¹²³Austin G. Stack MD MSc, ²Arif I. Mutwali MBBS, ¹³Hoang T. Nguyen PhD, ¹³Cornelius J. Cronin MBBCh, ¹³Liam F. Casserly MBBCh MSc, John Ferguson PhD

The Graduate Entry Medical School is leading a number of national and international projects to evaluate the health status and clinical outcomes for patients with chronic disease in order to improve patient outcomes. The study was performed at the Graduate Entry Medical School in collaboration with the Departments of Nephrology and Internal Medicine, University Hospital Limerick.

Gems UHL Group

Image caption: Members of the Kidney Health Research Consortium at the Graduate Entry Medical School and University Hospital Limerick. (left to right) Dr Ells Gillis, Darya Yermak, Dr Mohamed Elsayed, Dr Liam Casserly, Professor Austin Stack, Professor Ailish Hannigan, Dr John Ferguson, Dr Hatim Yagoub, Dr Waleed Mohamed.

Research Cover

Transferrin Saturation Ratio and Risk of Total and Cardiovascular Mortality in the General Population

Stack AG, Mutwali AI, Nguyen HT, Cronin CJ, Casserly LF, Ferguson J, Transferrin Saturation Ratio and Risk of Total and Cardiovascular Mortality in the General Population QJM(2014)doi: 10.1093/qjmed/hcu045.

Background: The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear. Purpose: To better understand this relationship, we explored the association of TSAT ratio (serum iron/total iron binding capacity) with mortality in the general population.