Elevation of Hemoglobin A1c Increases the Atherosclerotic Plaque Vulnerability and the Visit-to-Visit Variability of Lipid Profiles in Patients Who Underwent Elective Percutaneous Coronary Intervention

Abstract

Background: Increased plaque vulnerability and higher lipid variability are causes of adverse cardiovascular events. Despite a close association between glucose and lipid metabolisms, the influence of elevated glycated hemoglobin A1c (HbA1c) on plaque vulnerability and lipid variability remains unclear.

Methods: Among subjects undergoing percutaneous coronary intervention (PCI) from 2009 through 2019, 366 patients received intravascular optical coherence tomography (OCT) assessment and 4,445 patients underwent the scheduled follow-ups within 1 year after PCI. Vulnerability features of culprit vessels were analyzed by OCT examination, including the assessment of lipid, macrophage, calcium, and minimal fibrous cap thickness (FCT). Visit-to-visit lipid variability was determined by different definitions including standard deviation (SD), coefficient of variation (CV), and variability independent of the mean (VIM). Multivariable linear regression analysis was used to verify the influence of HbA1c on plaque vulnerability features and lipid variability. Exploratory analyses were also performed in non-diabetic patients.

Results: Among enrolled subjects, the pre-procedure HbA1c was 5.90 ± 1.31%, and the average follow-up HbA1c was 5.98 ± 1.16%. By OCT assessment, multivariable linear regression analyses demonstrated that patients with elevated HbA1c had a thinner minimal FCT (β = -6.985, P = 0.048), greater lipid index (LI) (β = 226.299, P = 0.005), and higher macrophage index (β = 54.526, P = 0.045). Even in non-diabetic patients, elevated HbA1c also linearly decreased minimal FCT (β = -14.011, P = 0.036), increased LI (β = 290.048, P = 0.041) and macrophage index (β = 120.029, P = 0.048). Subsequently, scheduled follow-ups were performed during 1-year following PCI. Multivariable linear regression analyses proved that elevated average follow-up HbA1c levels increased the VIM of lipid profiles, including low-density lipoprotein cholesterol (β = 2.594, P < 0.001), high-density lipoprotein cholesterol (β = 0.461, P = 0.044), non-high-density lipoprotein cholesterol (β = 1.473, P < 0.001), total cholesterol (β = 0.947, P < 0.001), and triglyceride (β = 4.217, P < 0.001). The result was consistent in non-diabetic patients and was verified when SD and CV were used to estimate variability.

Conclusion: In patients undergoing elective PCI, elevated HbA1c increases the atherosclerotic plaque vulnerability and the visit-to-visit variability of lipid profiles, which is consistent in non-diabetic patients.

Keywords: hemoglobin A1c; lipid variability; optical coherence tomography; percutaneous coronary intervention; plaque vulnerability.

Figure 1

Flow chart of the current study.

Figure 2

Representative cross-sectional OCT images. (A) Lipid core (*) and minimal FCT were detected. (B–D) The arcs of lipid accumulation, macrophage infiltration, and calcium deposition were measured in representative cross-sectional OCT images, respectively. FCT indicates fibrous cap thickness.

Figure 3

LOWESS curves of the association between pre-procedural HbA1c levels and vulnerability features. Locally weighted scatterplot smoothing (LOWESS) curves were used to visualize the rough association between pre-procedural HbA1c levels and vulnerability features, including (A) minimal fibrous cap thickness, (B) lipid index, (C) macrophage index, and (D) calcium index. The semi-transparent ribbon around the solid line indicates the 95% confidence interval. Rug plots show the distribution of pre-procedural HbA1c levels.

Figure 4

Forest plots of the vulnerability feature analyses. By using OCT assessment, forest plots depicted the effect of pre-procedure HbA1c levels on the vulnerability feature of culprit vessels, including minimal fibrous cap thickness, lipid index, macrophage index, and calcium index. Subgroups were determined according to Type 2 DM (yes or no), HbA1c categories (<5.7%, 5.7–6.4%, ≥6.5%), clinical symptom (SAP or ACS). OCT, optical coherence tomography; SAP, stable angina pectoris; ACS, acute coronary syndrome; FCT, fibrous cap thickness; DM, diabetes mellitus. *P < 0.05.

Figure 5

Forest plots of the lipid variability analyses. Forest plots depicted the effect of average follow-up HbA1c levels on visit-to-visit variability of lipid profiles, including LDL-C, HDL-C, Non-HDL-C, TC, and TG. Lipid variability was represented by the variability independent of the mean (VIM). Subgroups were determined according to Type 2 DM (yes or no), types of statins (atorvastatin or rosuvastatin), and lipid-lowering therapy strategy (regular statins/intensive statins/statins plus ezetimibe). LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; Non-HDL-C, non-high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride; DM, diabetes mellitus. *P < 0.05.