Haemoglobin A1C for coronary heart disease risk stratification in non-diabetic patients

Human-Hemoglobin Diabetes is one of the top chronic diseases in India and it is well known to have a correlation to coronary heart disease through the Haemoglobin A1C (HbA1C) marker. HbA1C, a clinical marker of glycated haemoglobin, is increasingly being used to diagnose diabetes. As it is a time-integrated marker, it is widely used in evaluating the glycemic control in patients with diabetes. It is well known that HbA1C levels in diabetes predict risk of coronary heart disease (CHD), however, it is unclear whether the same can be used to predict CHD risks in non-diabetic patients. Researchers from the Department of epidemiology, Harvard Medical School, Boston studied two cohorts to address this issue.

Key Point: HbA1C may be an important early clinical marker of CHD risk, even in Indian patients who have not been diagnosed with diabetes. It is established that there is a positive relationship between the level of HbA1C, the severity of diabetes mellitus and the risk of coronary heart disease (CHD). It was unclear if HbA1C was associated with risk of CHD in non-diabetic patients, but this study concluded that HbA1C may be used as an early marker to assess CHD risk in healthy individuals.

The researchers studied the cohort from The Nurses’ Health Study (NHS)-all women, and Health Professionals Follow-up Study (NPFS)-all men, which began in 1976 and 1986 respectively. Over a follow-up period of 14 and 10 years, 468 women and 454 men developed non-fatal myocardial infarction and fatal CHD. They were matched with controls free of CHD on a 1:2 ratio. The controls were randomly selected based on age, smoking and date of blood drawn for the test. Those who had history of diabetes or HbA1C levels ≥ 6.5% were not included in the study for further analysis. The researchers chose ≥ 6.5% as cut off, as that is the recommended level defining diabetes by American Diabetes Association and World Health Organization.

alexanderThis is a very interesting paper and could have very important implications especially for countries like India with a very high burden of cardiovascular disease. It would be very interesting to see if there is a correlation with metabolic syndrome. Using HbA1c as a screening test raises interesting possibilities, apart from its obvious utility to diagnose Diabetes Mellitus, that of using it as a marker to target aggressive life style modifications to prevent CHD.
– Dr. Thomas Alexander, MD, DM, FACC, FICC, FCSI, Coimbatore, Tamilnadu, India. Dr. Alexander is an interventional cardiologist who is the Head of the Division of Cardiology at Kovai Medical Center and Hospital in Coimbatore, India and is a member of the mdCurrent-India Editorial Advisory Board.

They found that in cases, cardiovascular risk factors were[s2If !is_user_logged_in()]…

[/s2If][s2If is_user_logged_in()] higher compared to controls in both men and women. The cases were also more likely to have higher CRP levels. There was positive correlation of HbA1C levels with triglycerides: HDL ratio, triglycerides, CRP levels and BMI. There was inverse correlation between HbA1C levels and HDL and alcohol intake. The researchers found that higher HbA1C levels were significantly associated with increased risk for CHD in both men and women. A significantly elevated risk of CHD was observed with levels of ≥ 5.5%. HbA1C of 6.0% to <6.5% had a multivariable-adjusted relative risk (RR) of CHD of 1.90 (95% CI 1.11 to 3.25) in women and 1.81 (95% CI 1.09 to 3.03) in men (Figure). For every 0.5% increment increase in HbA1C levels the RR was 1.32 in women, 1.27 in men and 1.29 when both were pooled. Furthermore, the participants who had HbA1C levels between 6% to 6.5% and CRP >3mg/dl had 2.5 fold higher risk of developing CHD compared with those who had lower levels.

The researchers bring out some interesting and useful information on HbA1C:

  • HbA1C is associated with CHD risk even among non-diabetic individuals.
  • It may be an important early clinical marker of CHD risk.
  • The combined use of HbA1C and CRP levels can be used for risk stratification for CHD on non-diabetes individuals.

With greater pre-analytical stability, greater convenience (fasting state not required) and no acute fluctuations (e.g., like infection, stress) compared to plasma glucose, HbA1C could be a very useful tool in risk assessments in not only diabetic patients but also healthy, non-diabetic population.

Multivariable-adjusted relative risk (RR) of incident CHD among women and men according to categories of HbA1c levels.

CHD-HbA1c chart-2


Click to enlarge chart.






Source: Pai JK, Cahill LE, Hu FB, Rexrode KM, Manson JE, Rimm EB. Hemoglobin A1c is associated with increased risk of incident coronary heart disease among apparently healthy, nondiabetic men and women. J Am Heart Assoc. 2013;2: e000077. doi: 10.1161/ JAHA.112.000077. Available at: http://www.ncbi.nlm.nih.gov/pubmed/?term=J+Am+Heart+Assoc.+2013%3B2%3Ae000077+doi%3A+10.1161%2F+JAHA.112.000077

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This entry was posted in Cardiovascular, Diabetes and tagged , , . Volume: .


  1. Atul Kansara
    Posted Jun 2013 at 4:39 pm | Permalink

    Very interesting and useful information regarding relationship of HbA1c and CHD on non diabetic person.

  2. Manju Wadhwan
    Posted Jun 2013 at 4:06 am | Permalink

    Very interesting article and good markers for detection of CHD. The simple test like hbA1c and CRP levels for early
    Detection of CHD.

  3. Rajesh Parikh
    Posted Jun 2013 at 2:31 am | Permalink

    Interesting. If so, all routine screening must go with HbA1c

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