medwireNews: The association between hyperglycemia and cardiovascular disease (CVD) is increasingly mediated by traditional cardiovascular risk factors as patients with type 1 diabetes age, researchers report.
Using data from the DCCT and the EDIC observational follow-up study, Ionut Bebu (The George Washington University, Rockville, Maryland, USA) and fellow researchers found that 184 of 1441 participants experienced at least one CVD event over a median follow-up of 27 years.
As reported in Diabetologia, the total effect of glycated hemoglobin (HbA1c) levels on CVD risk was “largely constant over time” after adjustment for age and duration of diabetes, with each 1% (10.9 mmol/mol) rise in HbA1c levels associated with an increase of approximately 3.3 CVD events per 1000 individuals per year. However, the relative importance of the direct effects of HbA1c on CVD risk and its indirect effects via vascular risk factors changed over time.
Mediation analyses including systolic blood pressure (SBP), pulse rate, triglycerides, and low-density lipoprotein (LDL) cholesterol as covariates showed that only 14.2% of the association between HbA1c levels and CVD risk was mediated by these traditional CVD risk factors from year 10 to 20. However, this rose to 42.7% between years 15 and 25, and the traditional risk factors explained 66.5% of the association from year 20 to 30.
“Thus, while the total effect of HbA1c remained unchanged over time, the patterns of mediation changed substantially as the cohort aged,” explain the researchers.
In analyses of the individual mediators, Bebu and colleagues showed that 2.7% of the association between HbA1c levels and CVD risk was mediated by SBP over years 10–20, while SBP at year 20 mediated 25.6% of the risk from years 20 to 30. The corresponding proportions were 6.3% and 29.3% for pulse rate, 2.2% and 22.4% for triglycerides, and 9.2% and 30.7% for LDL cholesterol.
The study authors point out that these changes over time “might be explained in several ways,” noting that because participants with high blood pressure and hypercholesterolemia at baseline were excluded from the analysis, it is possible that hyperglycemia “naturally predominated” early in the study.
“It is also possible that hyperglycaemia has its major impact early in the course of CVD progression, e.g. in the early initiation of the atherosclerotic process,” whereas traditional vascular risk factors “may begin to affect CVD risk increasingly as individuals age,” they suggest.
And the researchers conclude that their findings “reinforce the value of aggressive glycaemic management early in the course of diabetes, followed by aggressive management of the other CVD risk factors as they become increasingly operant.”
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