OGTT outperforms HbA1c for cardiovascular risk prediction in people with CAD

medwireNews: A 2-hour post-load glucose [2-hPG] measurement obtained from an oral glucose tolerance test (OGTT) is better at detecting dysglycemia and predicting cardiovascular events than glycated hemoglobin (HbA1c) in patients with coronary artery disease (CAD), research shows.

Lars Rydén (Karolinska Institutet, Stockholm, Sweden) and co-investigators report that adding either fasting plasma glucose (FPG) or HbA1c to 2-hPG does not improve its predictive value. They therefore suggest that 2-hPG should be used “as the primary screening tool for dysglycaemia in this patient population.”

The researchers explain in The Lancet Diabetes & Endocrinology that international guidelines recommend that all patients with CAD are screened for dysglycemia first with FPG or HbA1c, and then, if needed, with an OGTT.

However, they note that “European surveys of clinical practice conclude that screening, and particularly the use of OGTT, is ignored.”

In the current study, Rydén and team compared the diagnostic and predictive performance of different glycemic indicators using pooled data from the EUROASPIRE IV and V studies, which included 8364 people (mean age 63.3 years, 76% men) with CAD but no known diabetes.

At baseline, type 2 diabetes was detected in 22.5% of 8263 patients using OGTT alone at the recommended thresholds of at least 7.0 mmol/L (126 mg/dL) for FPG or at least 11.1 mmol/L (200 mg/dL) for 2-hPG.

By comparison, just 4.2% of patients were newly diagnosed with type 2 diabetes based on an HbA1c measurement of 6.5% (48 mmol/mol).

When the HbA1c cutoff for type 2 diabetes was reduced to 5.7% (39 mmol/mol), the diagnostic performance improved, with 44.8% of participants then meeting the criteria for a type 2 diabetes diagnosis.

However, “this comes at the price of low sensitivity and specificity,” said Rydén and co-authors. “Consequently, it cannot be recommended for screening purposes.” Indeed, using OGTT as a gold standard for detecting type 2 diabetes, the sensitivity of HbA1c at a cutoff of 5.7% was 68% and the specificity was 62%.

New dysglycemia, defined as newly detected type 2 diabetes or impaired glucose tolerance (IGT), was present in 47.1% of the patients according to 2-hPG (≥7.8 mmol/L, 140 mg/dL). Screening with HbA1c and applying the threshold of less than 5.7% had a sensitivity of 57% and a specificity of 67% for dysglycemia.

During a median follow-up of 1.6 years, 10.8% of 7892 patients with available data experienced cardiovascular death, nonfatal myocardial infarction, stroke, hospitalization for heart failure, emergency coronary artery bypass grafting, or percutaneous coronary intervention.

After adjustment for potential confounders, the researchers found that a 2-hPG level in the highest quartile (≥9 mmol/L, 162 mg/dL) was the strongest predictor of cardiovascular events, at a significant hazard (HR) of 1.58, relative to the lowest quartile (<6.1 mmol/mol, 110 mg/dL).

The corresponding HR was a significant 1.48 for an HbA1c in the top quartile (5.9%, 41 mmol/mol) relative to the bottom quartile (<5.4%, 36 mmol/mol), and the researchers found no significant association between FPG and cardiovascular risk.

Further analyses revealed that the effect of HbA1c on cardiovascular events was mainly explained by 2-hPG.

Rydén et al conclude: “This study demonstrates the superiority of screening patients with coronary artery disease for dysglycaemia by means of an OGTT. Both fasting glucose and HbA1c are inferior in diagnostic and prognostic capability.”

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Lancet Diabetes Endocrinol 2024; doi:10.1016/ S2213-8587(24)00201-8