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Meta-Analysis
. 2017 Jul 31;7(7):e015949.
doi: 10.1136/bmjopen-2017-015949.

Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis

Iván Cavero-Redondo  1 , Barbara Peleteiro  2   3 , Celia Álvarez-Bueno  1 , Fernando Rodriguez-Artalejo  4 , Vicente Martínez-Vizcaíno  1   5
Affiliations
Meta-Analysis

Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis

Iván Cavero-Redondo et al. BMJ Open. .

Abstract

Objective: To examine the relationship between glycated haemoglobin A1c (HbA1c) levels and the risk of cardiovascular outcomes and all-cause mortality based on data from observational studies and to determine the optimal levels of HbA1c for preventing cardiovascular events and/or mortality in diabetic and non-diabetic populations.

Review methods: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews and Web of Science databases, from inception to July 2016, for observational studies addressing the association of HbA1c levels with mortality and cardiovascular outcomes. Random effects models were used to compute pooled estimates of HR and respective 95% CI for all-cause mortality, cardiovascular mortality and risk of cardiovascular events, separately for people with and without diabetes.

Results: Seventy-four published studies were included in the systematic review, but only 46 studies could be incorporated in the meta-analysis. In both diabetic and non-diabetic populations, there was an increase in the risk of all-cause mortality when HbA1c levels were over 8.0% and 6.0%, respectively. The highest all-cause mortality in people with diabetes was HbA1c above 9.0% (HR=1.69; 95% CI 1.09 to 2.66) and in those without diabetes was HbA1c above 6.0% (HR=1.74; 95% CI 1.38 to 2.20). However, both diabetic and non-diabetic populations with lower HbA1c levels (below 6.0% HR=1.57; 95% CI 1.14 to 2.17 and below 5.0% HR=1.19; 95% CI 1.04 to 1.36, respectively) had higher all-cause mortality. Similar pooled estimates were found when cardiovascular mortality was the outcome variable.

Conclusion: HbA1c is a reliable risk factor of all-cause and cardiovascular mortality in both diabetics and non-diabetics. Our findings establish optimal HbA1c levels, for the lowest all-cause and cardiovascular mortality, ranging from 6.0% to 8.0% in people with diabetes and from 5.0% to 6.0% in those without diabetes.

Keywords: All-cause mortality; Cardiovascular mortality; HbA1c; Meta-analysis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Literature search Preferred Reporting Items for Systematic Reviews and Meta-Analyses consort diagram. HbA1c, glycated haemoglobin A1c; WOS, Web of Science.
Figure 2
Figure 2
Pooled HRs for all-cause mortality in diabetic population, according to HbA1c levels. HbA1c, glycated haemoglobin A1c.
Figure 3
Figure 3
Pooled HRs for all-cause mortality in non-diabetic population, according to HbA1c levels. HbA1c, glycated haemoglobin A1c.
Figure 4
Figure 4
Pooled HRs for cardiovascular mortality and risk of cardiovascular events in diabetic population, according to HbA1c levels. HbA1c, glycated haemoglobin A1c.
Figure 5
Figure 5
Pooled HRs for cardiovascular mortality and risk of cardiovascular events in non-diabetic population, according to HbA1c levels. HbA1c, glycated haemoglobin A1c.
See this image and copyright information in PMC

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