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Threshold haemoglobin levels and the prognosis of stable coronary disease: two new cohorts and a systematic review and meta-analysis.

Shah AD, Nicholas O, Timmis AD, Feder G, Abrams KR, Chen R, Hingorani AD, Hemingway H - PLoS Med. (2011)

Bottom Line: For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2-13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76-2.29) compared to those with haemoglobin values in the lowest risk range.Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl; 95% CI 12.1-13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI.We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.

View Article: PubMed Central - PubMed

Affiliation: Clinical Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, UK. anoop@doctors.org.uk

ABSTRACT

Background: Low haemoglobin concentration has been associated with adverse prognosis in patients with angina and myocardial infarction (MI), but the strength and shape of the association and the presence of any threshold has not been precisely evaluated.

Methods and findings: A retrospective cohort study was carried out using the UK General Practice Research Database. 20,131 people with a new diagnosis of stable angina and no previous acute coronary syndrome, and 14,171 people with first MI who survived for at least 7 days were followed up for a mean of 3.2 years. Using semi-parametric Cox regression and multiple adjustment, there was evidence of threshold haemoglobin values below which mortality increased in a graded continuous fashion. For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2-13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76-2.29) compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl; 95% CI 12.1-13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI. We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.

Conclusions: There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here. Intervention trials would clarify whether increasing the haemoglobin concentration reduces mortality.

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Adjusted HRs for death for patients with stable angina or MI, by haemoglobin concentration.(A) Legend and diagram for haemoglobin threshold model; (B) HRs for death by gender and coronary diagnosis (new onset stable angina or first MI), adjusted for age, eGFR, systolic BP, total cholesterol, family history, diabetes, smoking, and comorbidity (Charlson index). The black squares denote HRs from the stratified haemoglobin model (with 95% CIs).
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pmed-1000439-g001: Adjusted HRs for death for patients with stable angina or MI, by haemoglobin concentration.(A) Legend and diagram for haemoglobin threshold model; (B) HRs for death by gender and coronary diagnosis (new onset stable angina or first MI), adjusted for age, eGFR, systolic BP, total cholesterol, family history, diabetes, smoking, and comorbidity (Charlson index). The black squares denote HRs from the stratified haemoglobin model (with 95% CIs).

Mentions: Our statistical model aimed to identify upper and lower thresholds of an optimal haemoglobin range beyond which mortality risk increased (Figure 1A, Haemoglobin threshold model). Similar types of models have been used in other studies exploring prognosis and biomarkers (e.g., glycated haemoglobin, Selvin et al. [18]). In Text S1 and Figure S3, our model is reported fully, following recent recommendations [19].


Threshold haemoglobin levels and the prognosis of stable coronary disease: two new cohorts and a systematic review and meta-analysis.

Shah AD, Nicholas O, Timmis AD, Feder G, Abrams KR, Chen R, Hingorani AD, Hemingway H - PLoS Med. (2011)

Adjusted HRs for death for patients with stable angina or MI, by haemoglobin concentration.(A) Legend and diagram for haemoglobin threshold model; (B) HRs for death by gender and coronary diagnosis (new onset stable angina or first MI), adjusted for age, eGFR, systolic BP, total cholesterol, family history, diabetes, smoking, and comorbidity (Charlson index). The black squares denote HRs from the stratified haemoglobin model (with 95% CIs).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104976&req=5

pmed-1000439-g001: Adjusted HRs for death for patients with stable angina or MI, by haemoglobin concentration.(A) Legend and diagram for haemoglobin threshold model; (B) HRs for death by gender and coronary diagnosis (new onset stable angina or first MI), adjusted for age, eGFR, systolic BP, total cholesterol, family history, diabetes, smoking, and comorbidity (Charlson index). The black squares denote HRs from the stratified haemoglobin model (with 95% CIs).
Mentions: Our statistical model aimed to identify upper and lower thresholds of an optimal haemoglobin range beyond which mortality risk increased (Figure 1A, Haemoglobin threshold model). Similar types of models have been used in other studies exploring prognosis and biomarkers (e.g., glycated haemoglobin, Selvin et al. [18]). In Text S1 and Figure S3, our model is reported fully, following recent recommendations [19].

Bottom Line: For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2-13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76-2.29) compared to those with haemoglobin values in the lowest risk range.Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl; 95% CI 12.1-13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI.We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.

View Article: PubMed Central - PubMed

Affiliation: Clinical Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, UK. anoop@doctors.org.uk

ABSTRACT

Background: Low haemoglobin concentration has been associated with adverse prognosis in patients with angina and myocardial infarction (MI), but the strength and shape of the association and the presence of any threshold has not been precisely evaluated.

Methods and findings: A retrospective cohort study was carried out using the UK General Practice Research Database. 20,131 people with a new diagnosis of stable angina and no previous acute coronary syndrome, and 14,171 people with first MI who survived for at least 7 days were followed up for a mean of 3.2 years. Using semi-parametric Cox regression and multiple adjustment, there was evidence of threshold haemoglobin values below which mortality increased in a graded continuous fashion. For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2-13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76-2.29) compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl; 95% CI 12.1-13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI. We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.

Conclusions: There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here. Intervention trials would clarify whether increasing the haemoglobin concentration reduces mortality.

Show MeSH
Related in: MedlinePlus