Limits...
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.

Show MeSH

Related in: MedlinePlus

Systematic review and meta-analysis.Systematic review and meta-analysis of studies investigating the relationship between haemoglobin concentration and prognosis in patients with stable coronary disease. Legend: aCI not reported in paper; standard error estimated from p-value. bReported by quintiles with fourth quintile as reference group; linear conversion by linear interpolation of relative risks across quintiles. cCardiovascular deaths and ACSs (all-cause mortality not reported in this study). dDerived from anaemia cutoff; HR 5.73 (95% CI 1.49–22.1) for anaemia (n = 14, mean haemoglobin  = 11.0) versus nonanaemia (n = 129, mean haemoglobin  = 14.4). eDerived from anaemia cutoff; HR 6.46 (95% CI 1.73–24.2) for anaemia (n = 71, mean haemoglobin  = 11.2) versus nonanaemia (n = 239, mean haemoglobin  = 14.0). fWe did not calculate risks from a linear model because it over-simplifies the shape of the relationship. gTotal number of patients is less than the sum of the individual cohort sizes because 861 patients were included in both angina and MI cohorts.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3104976&req=5

pmed-1000439-g003: Systematic review and meta-analysis.Systematic review and meta-analysis of studies investigating the relationship between haemoglobin concentration and prognosis in patients with stable coronary disease. Legend: aCI not reported in paper; standard error estimated from p-value. bReported by quintiles with fourth quintile as reference group; linear conversion by linear interpolation of relative risks across quintiles. cCardiovascular deaths and ACSs (all-cause mortality not reported in this study). dDerived from anaemia cutoff; HR 5.73 (95% CI 1.49–22.1) for anaemia (n = 14, mean haemoglobin  = 11.0) versus nonanaemia (n = 129, mean haemoglobin  = 14.4). eDerived from anaemia cutoff; HR 6.46 (95% CI 1.73–24.2) for anaemia (n = 71, mean haemoglobin  = 11.2) versus nonanaemia (n = 239, mean haemoglobin  = 14.0). fWe did not calculate risks from a linear model because it over-simplifies the shape of the relationship. gTotal number of patients is less than the sum of the individual cohort sizes because 861 patients were included in both angina and MI cohorts.

Mentions: We identified ten eligible studies [7],[9],[26]–[33] that reported the relationship between haemoglobin and outcomes (1,127 events) in patients with stable coronary disease (Figure 3). None of these studies investigated evidence for the existence, or position, of any threshold haemoglobin value. According to a linear haemoglobin risk profile (a misleading model of the data), the summary relative risk from the meta-analysis was 1.29 (95% CI 1.20–1.38) for 1 g/dl lower haemoglobin. For comparison, the HR of death for 1 g/dl lower haemoglobin in our study was 1.18 (95% CI 1.14–1.21) for angina patients and 1.15 (95% CI 1.13–1.18) for MI patients.


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)

Systematic review and meta-analysis.Systematic review and meta-analysis of studies investigating the relationship between haemoglobin concentration and prognosis in patients with stable coronary disease. Legend: aCI not reported in paper; standard error estimated from p-value. bReported by quintiles with fourth quintile as reference group; linear conversion by linear interpolation of relative risks across quintiles. cCardiovascular deaths and ACSs (all-cause mortality not reported in this study). dDerived from anaemia cutoff; HR 5.73 (95% CI 1.49–22.1) for anaemia (n = 14, mean haemoglobin  = 11.0) versus nonanaemia (n = 129, mean haemoglobin  = 14.4). eDerived from anaemia cutoff; HR 6.46 (95% CI 1.73–24.2) for anaemia (n = 71, mean haemoglobin  = 11.2) versus nonanaemia (n = 239, mean haemoglobin  = 14.0). fWe did not calculate risks from a linear model because it over-simplifies the shape of the relationship. gTotal number of patients is less than the sum of the individual cohort sizes because 861 patients were included in both angina and MI cohorts.
© Copyright Policy
Related In: Results  -  Collection

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

pmed-1000439-g003: Systematic review and meta-analysis.Systematic review and meta-analysis of studies investigating the relationship between haemoglobin concentration and prognosis in patients with stable coronary disease. Legend: aCI not reported in paper; standard error estimated from p-value. bReported by quintiles with fourth quintile as reference group; linear conversion by linear interpolation of relative risks across quintiles. cCardiovascular deaths and ACSs (all-cause mortality not reported in this study). dDerived from anaemia cutoff; HR 5.73 (95% CI 1.49–22.1) for anaemia (n = 14, mean haemoglobin  = 11.0) versus nonanaemia (n = 129, mean haemoglobin  = 14.4). eDerived from anaemia cutoff; HR 6.46 (95% CI 1.73–24.2) for anaemia (n = 71, mean haemoglobin  = 11.2) versus nonanaemia (n = 239, mean haemoglobin  = 14.0). fWe did not calculate risks from a linear model because it over-simplifies the shape of the relationship. gTotal number of patients is less than the sum of the individual cohort sizes because 861 patients were included in both angina and MI cohorts.
Mentions: We identified ten eligible studies [7],[9],[26]–[33] that reported the relationship between haemoglobin and outcomes (1,127 events) in patients with stable coronary disease (Figure 3). None of these studies investigated evidence for the existence, or position, of any threshold haemoglobin value. According to a linear haemoglobin risk profile (a misleading model of the data), the summary relative risk from the meta-analysis was 1.29 (95% CI 1.20–1.38) for 1 g/dl lower haemoglobin. For comparison, the HR of death for 1 g/dl lower haemoglobin in our study was 1.18 (95% CI 1.14–1.21) for angina patients and 1.15 (95% CI 1.13–1.18) for MI patients.

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