Glycated hemoglobin (HbA1c) likely causes coronary artery disease (CAD), but the underlying mechanisms are not yet clear, according to study results published in Diabetes Care.
Previous studies have found that HbA1c is positively associated with cardiovascular disease (CVD), but the evidence has been primarily observational.
The study included 38 genetic variants strongly and independently related to HbA1c (n=123,665) applied to the UK Biobank data (n=392,038).
The researchers used inverse variance weighting (IVW) to determine the associations between HbA1c and CVD, CAD, stroke, and stroke subtypes. The performed sensitivity analyses included Mendelian randomization (MR)-Egger, a weighted median, and exclusion of potentially invalid single nucleotide polymorphisms (SNPs).
Using IVW, the researchers found that HbA1c was not associated with CVD (odds ratio [OR] 1.11 per %; 95% CI, 0.83-1.48). HbA1c was, however, associated with increased risk for CAD (OR 1.50 per %; 95% CI, 1.08-2.11) with directionally consistent results from MR-Egger and weighted median. After the researchers excluded potentially invalid SNPs, the association became more pronounced (OR 2.24 per %; 95% CI, 1.55-3.25).
Due to a lower number of cases, the researchers could not determine the association between HbA1c and stroke and its subtypes.
“Our study provides more evidence of a causal role of HbA1c in CAD. Interventions that target HbA1c reduction may be potential targets for reducing the global burden of CAD,” the researchers wrote.
Yeung SLA, Luo S, Schooling CM. The impact of glycated hemoglobin (HbA1c) on cardiovascular disease risk: a Mendelian randomization study using UK Biobank [published online June 27, 2018]. Diabetes Care. doi:10.2337/dc18-0289