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A1C levels are Indicators of Coronary Atherosclerotic Plaque Formation 

May 5, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Antonio Bess, Pharm D Candidate, Florida Agricultural & Mechanical University School of Pharmacy

Coronary atherosclerotic plaques can be identified early, but specific risk factors are not fully understood.  

Atherosclerosis is the main factor in the development of the cardiovascular disease. If the detection of atherosclerosis is made early, medications can be given to slow disease progression and prevent further complications. Diabetes mellitus increases the risk of cardiovascular events and is accompanied by macrovascular complications. The ACC/AHA guidelines recommend statin therapy for any person with diabetes and that both diseases are treated evenly. This study analyzed the patterns and severity of atherosclerotic plaques in patients without diabetes in hopes of finding a correlation between subclinical atherosclerosis and risk factors in study subjects.  

This crosssectional, observation designed study enrolled people who underwent coronary computed tomography angiography (CCTA) during a routine health evaluation at the Taipei Veterans General hospital between December 2013 and May 2017. Only patients age 30 – 79 with no history of CAD, HbA1c <6.5%, and fasting glucose <126 mg/dL were included. Subjects were considered hypertensive if blood pressure was >140/80 or if they were taking medications for blood pressure. The atherosclerotic plaque segment score (SIS score), which represents the degree of plaque involvement, was used to divide and group subjects on a score range of 1 to 16. A chi-square or fishers exact test was used to compare categorical data. Independent factors that were related to coronary plaque involvement were measured using multivariate logistic regression analysis. A plaque was considered significant if there was >50% stenosis. The p-value was 2-sided, and P< 0.05 was considered statistically significant. 

One thousand sixty-four people were enrolled in the study, with there being 752 males and 312 females. In 56.9% of subjects, coronary artery disease was observed. There were three groups divided by the SIS score. SIS scores equal to 0 included 458 subjects, SIS scores 1 to 2 had 300 subjects, and SIS scores >/=3 had 306 subjects. Higher SIS scores were associated with more risk factors such as higher BMI and HbA1c, older age, and history of smoking and statin use. Also, higher SIS scores were accompanied by additional comorbidities such as hypertension and hypercholesteremia. Plaque lesions were found in nearly half of the participants, including 33.2% with calcified plaques, 16.4% soft, and 26.5% mixed plaques. Patients in the multiple atherosclerotic plaque group reported up to 32.7% statin use and LDL-C levels that did not correlate with higher SIS scores. 

Some baseline characteristics were shown to be more of risk than others in the study. Males had more risk factors and more severe coronary atherosclerosis than females. Only age, the male gender, BMI, and HbA1c levels could be used as predictors of greater coronary atherosclerosis involvement in nondiabetic patients. For >50% stenotic calcified plaques, only age (OR: 1.082, 95% CI: 1.47 – 1.118), former smoking status (OR: 2.061, 95% CI: 1.013 – 4.193) and HbA1C (OR: 3.892, 95% CI: 1.949 – 7.77) can be used as predictors of plaque development. For partial calcified (mixed) type plaques, only age (OR: 1.085, 95% CI: 1.052 – 1.119), the male gender (OR: 7.082, 95% CI:2.638 – 19.018), HbA1C levels (OR: 2.074, 95% CI: 1.036 – 4.151), and current smoking status (OR: 1.848, 95% CI: 1.089 – 3.138) could be used as predictors. Non-calcified (soft) plaques had no factors of significance. 

The results of this study strengthen the theory that HbA1c is associated with coronary atherosclerosis development in subjects without diabetes. Mixed patterned plaques were found to be more associated with higher HbA1c levels. In most subjects, lipid levels were favorable, but the presence of plaques remained when A1c levels were slightly elevated, indicating the importance of controlling and maintaining a lower HbA1c. Thus, HbA1c levels can be used to identify high-risk subjects, even in low risk, non-diabetic populations. This study did not have a diverse population, and all the participants came from the same center, so these results cannot be accepted universally. Future studies need to include a diverse group of people, an adequate population, and a balance between male and female participants to identify more risk factors and monitoring parameters.  

Practice Pearls: 

  • HbA1c levels 5.7% > can be used to identify people at risk for early development of mixed atherosclerotic plaques. 
  • Age, smoking, BMI, and HbA1c are all risk factors for atherosclerotic plaques. 
  • Triglyceride and HDL levels cannot be used to identify subjects at risk for atherosclerotic plaques. 

Wang WT, Hsu PF, Lin CC, Wang YJ, Ding YZ, Liou TL, Wang YW, Huang SS, Lu TM,  Huang PH, Chen JW, Chan WL, Lin SJ, Leu HB. Hemoglobin A1C Levels are Independently Associated with the Risk of Coronary Atherosclerotic Plaques in Patients without Diabetes: A Cross-Sectional Study. J Atheroscler Thromb. 2019 Dec 27. doi: 10.5551/jat.51425. 

Antonio Bess, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy 


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