Effect modification in the association between glycated haemoglobin and cardiovascular disease and mortality in patients with type 2 diabetes.
To identify patients with type 2 diabetes (T2D) who may benefit from lower or higher glycated haemoglobin (HbA1c) targets, based on readily available patient characteristics.



Patients with T2D were included in the present study from the Second Manifestations of ARTerial disease (SMART) cohort. Several patient characteristics were evaluated for effect modification in the relationship between HbA1c and cardiovascular disease and all-cause mortality, using multiplicative interaction analyses and stratified Cox proportional hazard analyses. Combinations of patient characteristics, as used in existing treatment algorithms, were similarly evaluated.



Of 1753 patients, 323 experienced a vascular event during a median of 6.6 years of follow-up and 375 patients died. For the association between HbA1c and cardiovascular events, no effect modifiers were found. Body mass index (BMI) and weight showed significant interaction for the association between HbA1c and mortality ( P = .04). Analyses, stratified for 25 kg/m2or 30 or 35 kg/m2, showed quite dissimilar hazard ratios without reaching statistical significance. Combinations of patient characteristics used in existing treatment algorithms, did not influence the relationship between HbA1c and cardiovascular disease or mortality ( P = .46 to P = .92).



Using easily obtainable patient characteristics, whether alone or in combinations used in existing treatment algorithms, it was not possible, except for BMI or weight, considered continuously, to identify patients with T2D who had a differential association between HbA1c and cardiovascular events or all-cause mortality in our cohort.
Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Sanne N
SN
van Munster
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
Yolanda
Y
van der Graaf
Department of Diabetology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Harold W
HW
de Valk
Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Frank L J
FL
Visseren
Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Jan
J
Westerink
D000368:Aged; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009765:Obesity / Q000453:epidemiology*; D050177:Overweight / Q000453:epidemiology; D016016:Proportional Hazards Models; D012307:Risk Factors
D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human

HbA1c
; all-cause mortality; glycaemic control; individualized HbA1c goals; macrovascular complications