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Prediabetes Based on A1c Predicts Cardiovascular Risk

The study covered in this summary was published in Research Square as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Prediabetes, as defined by the International Expert Committee (IEC) (A1c 6.0% to < 6.5%), was associated with significantly increased risk for major adverse cardiovascular events (MACE) compared with normoglycemia.

  • Newly diagnosed diabetes was associated with MACE based on all current common definitions.

  • The findings suggest using the IEC definition of prediabetes to identify patients at high risk for MACE who could benefit from early lifestyle interventions.

Why This Matters

  • The prevalence of prediabetes varies substantially according to different definitions.

  • A large proportion of patients with coronary intermediate lesions without a previously known history of diabetes have abnormal glycemic metabolism, suggesting the importance of screening for prediabetes or diabetes in this population.

  • Most previous studies have enrolled individuals with acute coronary syndrome or those with prior revascularization, rather than those with intermediate coronary lesions.

  • There is no current consensus as to the optimal definition of prediabetes to identify those at high risk of MACE.

Study Design

  • The study included 1532 patients with intermediate coronary lesions on coronary angiography who were not undergoing revascularization.

  • The primary endpoint was MACE, defined as a composite of all-cause death, nonfatal myocardial infarction (MI), and repeated revascularization therapy.

  • Prediabetes was defined as impaired fasting plasma glucose (FPG), according to World Health Organization (WHO) criteria (6.1 to < 7 mmol/L) or the American Diabetes Association (ADA) FPG-based definition (5.6 to < 7 mmol/L), or by A1c according to the ADA (5.7% to < 6.5%) or IEC (6.0% to < 6.5%) criteria.

Key Results

  • The proportions of patients who had prediabetes according to the IEC A1c-, ADA A1c -, WHO FPG-, and ADA FPG-based definitions were 27.4% (n = 419), 47.1% (721), 3.9% (60), and 10.3% (158), respectively.

  • A total of 197 MACE occurred during a median follow-up of 6.1 years, including 62 deaths, 31 MI, and 125 revascularizations (21 patients had both MI and revascularization).

  • According to the IEC A1c-based definition, a total of 7.8% (41) events, 13.8% (58) events, and 16.7% (98) events occurred among those with normoglycemia, prediabetes, and diabetes, respectively.

  • Compared with normal glucose metabolism, each category of abnormal glucose metabolism was associated with higher risk of MACE.

  • In multivariable analysis compared to the group with normoglycemia, the adjusted hazard ratios for MACE were 1.5 for prediabetes and 1.9 for diabetes.

  • There was no increased MACE risk with the other prediabetes definitions, while diabetes was associated with increased MACE according to the ADA A1c -, WHO FPG-, and ADA FPG-based definitions.

  • The best A1c cut-off for predicting MACE in patients without known diabetes was 6.0%, with a sensitivity of 0.667 and a specificity of 0.493.


  • Oral glucose tolerance tests were not performed in most patients.

  • Only baseline A1c was collected.

  • Single center.

  • Retrospective design.

  • Potential unmeasured confounders.


  • Study funding: CAMS Innovation Found for Medical Sciences.

  • Author disclosures: None.

This is a summary of a preprint research study, “Comparative prognostic value of different definitions of prediabetes in patients with angiographic coronary intermediate lesions: A prospective cohort study,” by Chenxi Song of the Chinese Academy of Medical Sciences and Peking Union Medical College, and colleagues. This summary is brought to you by Medscape. The study has not yet been peer reviewed.

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