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

Abstract

ObjectiveTo 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 methodsWe 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.ResultsSeventy-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.ConclusionHbA1c 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.

Longitudinal changes in glycated haemoglobin following treatment intensification after inadequate response to two oral antidiabetic agents in patients with type 2 diabetes

“…Of the necessary assessments for comprehensive diabetes management, glycated haemoglobin (HbA1c) has been a primary indicator for the performance of antidiabetic care and a key predictor of long‐term outcomes . Studies have shown that well‐controlled glycaemic level (HbA1c <53 mmol/mol or 7.0%) reduces the risk of complications . Conversely, inadequately controlled HbA1c is associated with a significantly higher risk of vascular complications and leads to blindness or premature death .…”

“…2 Studies have shown that wellcontrolled glycaemic level (HbA1c <53 mmol/mol or 7.0%) reduces the risk of complications. 3 Conversely, inadequately controlled HbA1c is associated with a significantly higher risk of vascular complications and leads to blindness or premature death. 4,5 Consequently, patients with poorly controlled diabetes are expected to have worse outcomes.…”

Infant cholesterol and glycated haemoglobin concentrations vary widely—Associations with breastfeeding, infant diet and maternal biomarkers

“…Little is known about HbA1c concentrations among infants. A dose‐response relationship has been found between HbA1c and CVD mortality . Furthermore, the pertinence of lifelong exposure of cholesterol has been emphasised as an important concept for defining risk of CVD .…”

“…Elevated total cholesterol (TC) and glycated haemoglobin (HbA1c) concentrations are established risk factors for cardiovascular disease (CVD). 1,2 Adult TC is determined by both lifestyle and genetics, 3,4 factors that can be similar in mother and offspring. Dietary fat quality has been shown to affect both TC and risk of developing CVD in adults.…”

“…A dose-response relationship has been found between HbA1c and CVD mortality. 2 Furthermore, the pertinence of lifelong exposure of cholesterol has been emphasised as an important concept for defining risk of CVD. 11 Thus, the recognition of factors that affect TC and HbA1c concentrations from early life is important.…”