Elevated Hemoglobin A1c(HbA1c) Is Independently Associated with Large Lipid-Rich Necrotic Cores in Hypertensive Patients with Symptomatic Carotid Atherosclerosis: A 3.0T MRI Study
Huilin Zhao1, Beibei Sun1, Xiaosheng Liu1, Xihai Zhao2, Yongming Dai3, Chun Yuan4, and Jianrong Xu1

1Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, People's Republic of, 2Center for Biomedical Imaging Research, Tsinghua University School of Medicine, Beijing, China, People's Republic of, 3Philips Healthcare, Shanghai, China, People's Republic of, 4Radiology, University of Washington, Seattle, WA, United States


Further understanding of the association of hemoglobin A1c(HbA1c) levels with symptomatic carotid plaque characteristics will be helpful for stroke risk stratification and treatment strategy modification. This study sought to investigate the associations of HbA1c levels with MR-identified carotid plaque characteristics in hypertensive patients with acute stroke. Our key findings are that elevated HbA1c was associated with carotid plaque presence, higher HbA1c level tended to exhibit an increased plaque burden and larger lipid-rich necrotic core, independent of other cardiovascular risk factors. Our findings indicate that elevated HbA1c may contribute to the development of advanced carotid plaques in stroke patients with hypertension.


Diabetes and hypertension have important effects on the burden of stroke and increased risk of atherosclerosis. Previous studies have shown that high levels of hemoglobin A1c (HbA1c) is associated with an increased risk of atherosclerosis assessed as carotid intima-media thickness or plaque prevalence by ultrasound1,2. However, few studies have reported an association between HbA1c levels and MR-identified carotid plaque characteristics in hypertensive patients with acute stroke.


To determine the associations of HbA1c level with the carotid atherosclerotic lesions with emphasis on plaque morphological and compositional characteristics by MR vessel wall imaging in hypertensive patients with acute stroke.


Study population

Eighty-four hypertensive patients with acute ischemic stroke in the anterior circulation were recruited. All subjects underwent HbA1c measurements and carotid artery black-blood MR imaging within 1 week after onset of symptoms. Extensive clinical workup (lab, brain MRA, duplex sonography and 24-hour ECG ) was performed to exclude other causes of ischemic stroke.

Carotid MR imaging and image interpretation

A multi-contrast black-blood imaging protocol(T1WI,T2WI,MP-RAGE and time of flight) described before3 was performed on a whole body 3.0T MR scanner (Philips Achieva, Best, the Netherlands) with an 8 channel phased-array carotid coil to acquire the cross-sectional carotid MR images. Carotid MR images were analyzed using a custom program (CASCADE, Seattle, WA, USA)4. The values of luminal stenosis, maximum wall thickness (Max WT), the percent wall volume (PWV=100% × wall volume/total vessel volume) and the proportion of each component relative to the wall volume including calcification (CA), lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) (eg, % volume of LRNC = 100% ×LRNC volume/wall volume) along the symptomatic side were measured based on previously published criteria validated by histology5.

Data analysis

We divided the patients into two groups by the HbA1c status in Asian adults6 (group 1: ≤6.0%; group 2: >6.0 %). These two groups’ clinical profiles and symptomatic carotid plaque features were compared. Logistic regression was performed to assess the association between HbA1c and the presence of symptomatic carotid plaques as well as the LRNC size after adjustment for other cardiovascular risk factors and demographic factors. ROC curve was generated from multiple sensitivity/specificity pairs to evaluate the diagnostic efficiency and identify the optimal cutoff level of HbA1c for diagnosing carotid lesions.


Four patients were excluded because of inadequate MR image quality. Of the remaining 80 subjects, 62 (77.5%) were male, 37 (46.3%) had history of type 2 diabetes mellitus, and the mean age was 63.6 ± 10.8 years. Compared with HbA1c ≤6%, larger plaque burden and higher prevalence of a large LRNC were found in HbA1c >6 % (Table 1). Of note, the multivariate logistic regression analysis in Figure 1 showed that HbA1c > 6% (OR,4.75; 95% CI:1.44 to 15.60, P <0.05) and current smoking (OR,4.37; 95% CI:1.26 to 15.17, P <0.05) were independently risk factors for the presence of LRNC plaques. Moreover, an increasing trend was observed in HbA1c level in carotid arteries without plaque, with plaque and ≤40% LRNC, and with plaque and >40% LRNC (P <0.001, Figure 2,3). The ROC curve showed that the optimal threshold of HbA1c level to predict the presence of symptomatic plaque and %volume of LRNC>40% was 6.36% and 7.22%, respectively (Figure 4).

Discussion and Conclusions

Our findings demonstrate that elevated HbA1c was associated with plaque presence, higher HbA1c level tended to exhibit an increased plaque burden and larger LRNC size, independent of other cardiovascular risk factors in those symptomatic patients with hypertension. Our results are in accordance with the results from most of these ultrasonography studies1,2,7 and extend them with regard to the relationship with plaque compositional characteristics, suggesting that HbA1c are useful for assessing carotid atherosclerosis and plaque vulnerability. Because of the cross-sectional study design, we cannot formally conclude that a high HbA1c level is causally related to advanced atherosclerosis. Prospective follow-up studies should be conducted to determine the predictive value of HbA1c with regard to carotid atherosclerotic plaque progression and as well as stroke risk in participants.




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Table 1

Fig 1. Multivariable-adjusted ORs and 95% CIs for plaque presence (1) and LRNC presence (2) (n = 80)

Fig 2. HbA1c levels according to carotid plaque features

Fig 3. Transverse MR images of an advanced carotid plaque with a large LRNC(arrow) in the left internal carotid artery(star) of an 67y male patient. The patient experienced ipsilateral neurologic symptoms 3 days before MR imaging and HbA1c was measured as 7.36.

Fig 4. ROC curve to determine the optimal cutoff value of HbA1c for the plaque presence and large LRNC

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)