The Relation Between HbA1c and Cardiovascular Events in Patients With Type 2 Diabetes With and Without Vascular Disease

Kranenburg, Guido; Graaf, Yolanda van der; Leeuw, Joep van der; Nathoe, Hendrik M.; Borst, Gert J. de; Kappelle, L. Jaap; Visseren, Frank L.J.; Westerink, Jan

doi:10.2337/dc15-0493

Cited by 42 publications

(32 citation statements)

References 29 publications

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“…In a recent meta-analysis including prospective cohort studies with data on HbA1c and CVD, 9 (Table 3). 27 The asscociation between HbA1c and mortality in all patients with T2D is consistent with previous literature. 11,[28][29][30][31] These comparisons support the external validity of the present study.…”

Section: Discussionsupporting

confidence: 91%

“…A possible explanation for the absent association in the present study is the large number of patients with vascular disease at baseline when compared with other cohorts. This assumption is strengthened by the significant association between HbA1c and CVD in patients without vascular disease at baseline in the cohort, and the absence of this association in patients with pre‐existing vascular disease (Table ) . The asscociation between HbA1c and mortality in all patients with T2D is consistent with previous literature .…”

Section: Discussionsupporting

confidence: 87%

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Effect modification in the association between glycated haemoglobin and cardiovascular disease and mortality in patients with type 2 diabetes

Munster

Graaf

Valk

et al. 2016

Diabetes Obesity Metabolism

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 87%

Effect modification in the association between glycated haemoglobin and cardiovascular disease and mortality in patients with type 2 diabetes

Munster

Graaf

Valk

et al. 2016

Diabetes Obesity Metabolism

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“…Our aim was to investigate the incidence of a first stroke; therefore, all individuals with earlier stroke were excluded. In the prospective Second Manifestations of Arterial Disease (SMART) study, there was only a modest association between increased HbA1c levels and CV events, with no interaction for people with or without former vascular disease . In the present study, people with T2D with HbA1c >53 mmol/mol (7%) were prone to having a greater number of CV complications; however, adjustments for this and other potential CV risk factors did not change our results, lending support to the observation that glucose exposure is a strong predictor for stroke.…”

Section: Discussionsupporting

confidence: 78%

Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: A nationwide observational study

Zabala

Darsalia

Holzmann

et al. 2019

Diabetes Obesity Metabolism

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Aims To compare stroke incidence in people with type 2 diabetes (T2D) with that in a matched control group, and to investigate whether glucose exposure in people with T2D can predict a first‐time stroke event and mortality. Material and methods In a nationwide observational cohort study, individuals with T2D were linked in the Swedish National Diabetes Register and matched with five individual population‐based control subjects. We calculated crude incidence rates and 95% confidence intervals (CIs), and used Cox regression and multivariable hazard ratios (HRs), to estimate the risk of stroke and mortality in relation to glycated haemoglobin (HbA1c) levels. Results A total of 406 271 people with T2D (age 64.1 ± 12.4 years, 45.7% women) and 2086 440 control subjects (age 64.0 ± 12.4 years, 45.7% women) were included. During a median follow‐up of 7.3 years, 26 380 people with T2D (6.5%) versus 92 375 control subjects (4.4%) were diagnosed with a stroke. The incidence rate was 10.12 events per 1000 person‐years versus 7.26 events per 1000 person‐years (HR 1.54, 95% CI 1.52‐1.56). In the T2D group after multivariable adjustments, the HRs for stroke stratified by HbA1c level were: 54‐64 mmol/mol: 1.27 (95% CI 1.22‐1.32); 65‐75 mmol/mol: 1.68 (95% CI 1.60‐1.76); 76‐86 mmol/mol: 1.89 (95% CI, 1.75‐2.05); and > 87 mmol/mol: 2.14 (95% CI 1.90‐2.42), respectively, compared with the reference category of HbA1c ≤53 mmol/mol. There was a stepwise increased risk of death after stroke, for every 10‐mmol/mol categorical increment of HbA1c (HR 1.71; 95% CI 1.47‐2.00) for the highest HbA1c category. Conclusions An increased risk of stroke and death was associated with poor glycaemic control in people with T2D.

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“…Figure summarizes the meta‐analyses assessing the association between study‐quoted rising 1% HbA 1c increments and first‐ever stroke risk, stratified by diabetes mellitus status and ischemic stroke subtype. For every 1% HbA 1c increment (or equivalent), the average HR (95% CI) for first‐ever stroke risk was 1.12 (0.91, 1.39) in non–diabetes mellitus cohorts and 1.17 (1.09, 1.25) in diabetes mellitus cohorts.…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta‐Analysis

Mitsios

Ekinci

Mitsios

et al. 2018

JAHA

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BackgroundDiabetes mellitus is a major risk factor for ischemic stroke. Rising hemoglobin A1c (HbA1c) levels are associated with microvascular diabetes mellitus complication development; however, this relationship has not been established for stroke risk, a macrovascular complication.Methods and ResultsWe conducted a systematic review and meta‐analysis of observational cohort and nested case‐control cohort studies assessing the association between rising HbA1c levels and stroke risk in adults (≥18 years old) with and without type 1 or type 2 diabetes mellitus. Random‐effects model meta‐analyses were used to calculate pooled adjusted hazard ratios (HRs) and their precision. The systematic review yielded 36 articles, of which 29 articles (comprising n=532 779 participants) were included in our meta‐analysis. Compared to non–diabetes mellitus range HbA1c (<5.7%), diabetes mellitus range HbA1c (≥6.5%) was associated with an increased risk of first‐ever stroke with average HR (95% confidence interval) of 2.15 (1.76, 2.63), whereas pre–diabetes mellitus range HbA1c (5.7–6.5%) was not (average HR [95% confidence interval], 1.19 [0.87, 1.62]). For every 1% HbA1c increment (or equivalent), the average HR (95% confidence interval) for first‐ever stroke was 1.12 (0.91, 1.39) in non–diabetes mellitus cohorts and 1.17 (1.09, 1.25) in diabetes mellitus cohorts. For every 1% HbA1c increment, both non–diabetes mellitus and diabetes mellitus cohorts had a higher associated risk of first‐ever ischemic stroke with average HR (95% confidence interval) of 1.49 (1.32, 1.69) and 1.24 (1.11, 1.39), respectively.ConclusionsA rising HbA1c level is associated with increased first‐ever stroke risk in cohorts with a diabetes mellitus diagnosis and increased risk of first‐ever ischemic stroke in non–diabetes mellitus cohorts. These findings suggest that more intensive HbA1c glycemic control targets may be required for optimal ischemic stroke prevention.

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The Relation Between HbA1c and Cardiovascular Events in Patients With Type 2 Diabetes With and Without Vascular Disease

Cited by 42 publications

References 29 publications

Effect modification in the association between glycated haemoglobin and cardiovascular disease and mortality in patients with type 2 diabetes

Effect modification in the association between glycated haemoglobin and cardiovascular disease and mortality in patients with type 2 diabetes

Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: A nationwide observational study

Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta‐Analysis

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