Q&A: ‘Normal’ blood glucose may still increase risk for heart disease
Key takeaways:
- Elevated but “normal” blood glucose may be a target for cardiovascular disease risk reduction.
- Researchers proposed newly reclassified stages for plasma glucose as it relates to heart disease risk.
Slightly elevated blood glucose within a range of what is generally considered “normal” may be associated with increased risk for heart disease, researchers reported.
Gregg C. Fonarow, MD, FACC, FAHA, FHFSA, director of the Ahmanson-UCLA Cardiomyopathy Center, co-director of the UCLA Preventive Cardiology Program, co-chief of the division of cardiology at UCLA and Eliot Corday Chair in Cardiovascular Medicine and Science, and Moein Ebrahimi, MD, of the School of Medicine at Shahid Beheshti University of Medical Sciences in Tehran, Iran, recently published an editorial in the American Heart Journal detailing the association between high but within normal-range fasting plasma glucose — 95 mg/dL to 99 mg/dL — and elevated risk for CVD.
In the editorial, the authors explained how blood glucose variability can also contribute to CV risk and proposed a new system of stages related to blood glucose to potentially guide care of those who may be at risk for heart disease.
Healio spoke with Fonarow about the reclassified stages of blood glucose as related to CV risk and more.
Healio: What prompted you and your Dr. Ebrahimi to take a closer look at CV risk in individuals with normal but higher fasting plasma glucose?
Fonarow: We were both interested in recent literature showing elevated risks, but there seemed to be, clinically, less awareness and gaps in clinical practice, with CVD remaining the leading but highly preventable cause of death. With the overall age-adjusted CV mortality rates actually rising rather than falling, we felt there was an opportunity to provide perspective beyond the already well-recognized increased risk with diabetes and prediabetes. To highlight the opportunity to recognize increased risk in those with higher but within normal-range glucose or HbA1c levels, but importantly take action to help lower excess risk associated with this as well as other risk factors in these individuals.
Healio: Can speak more about the studies and study populations you researched for this editorial?
Fonarow: There have been a number of studies. We highlighted a few. One study involved close to 11,000 individuals without clinically manifest CVD and data on fasting glucose ranges who were followed for 4.3 years. There were over 1,100 CV events during this time period. The researchers looked beyond just what category the glucose was, and the fasting blood levels, even in the normal range, which is traditionally viewed as 99 mg/dL or less, individuals with blood glucose levels between 95 mg/dL and 99 mg/dL had a 12.5% risk for CV events compared with 7% in those with fasting plasma glucose below 80 mg/dL, even after adjusted for other risk factors (Shaye K, et al. Am Heart J. 2012;doi:10.1016/j.ahj.2012.03.023).
There was a separate study that looked at about 7,000 individuals followed for 6 years and found those with HbA1c not quite to the prediabetes range, but still on the higher end of what was viewed as normal, had increased risk for CVD. They also identified that some variability in HbA1c was associated with increased risk (Ghouse J, et al. Diabetes Care. 2018;doi:10.2337/dc18-1396).
When patients or clinicians see in the lab report a value is normal, what is conveyed is that it is a normal range and probably isn’t associated with excess risk. But really there’s a continuum of risk, and that our current terminology around HbA1c levels may be contributing to a missed opportunity to recognize patients at increased risk. Not as high as those with overt diabetes, but higher than those with levels that are within the normal range, but on the lower end of that range.
Healio: You and Dr. Ebrahimi proposed a revised classification for glucose levels based on CV risk. Could you explain the revised classification?
Fonarow: We proposed four stages. Stage 1 being those with lower levels of fasting plasma glucose within a normal range, whereby this risk factor would be low CVD risk. Stage 2 were those with a higher level of glucose within a normal range, whose CVD risk would be increased. Stage 3, for individuals with criteria for prediabetes whose risk would be further increased. Stage 4 was overt diabetes. Those patients would be at the highest absolute risk.
At stage 2, the risk for CVD starts to increase even when the plasma glucose levels are within normal range, and preventive measures and screening can be applied.
Healio: Is prospective research needed before implementing these revised classifications, or do you think the evidence is strong enough for immediate action?
Fonarow: Conceptually, the evidence is strong. The issue of whether this is the best categorization in terminology is open to further study to learn the most useful conceptual framework clinicians will understand and appreciate and one patients and their family members understand, appreciate and act upon. We have tremendous risk-prevention therapies and lifestyle modifications that are well known and advocated, but are not implemented in routine clinical practice such that many patients are having preventable CV events. We know for a fact that increasing physical activity is associated with lower CV risk; statin therapy across these ranges and stages can lower the risk for having major CV events; and BP control and more intensive BP control in those with elevated BP or overt hypertension can lower the risk. We have data now for those individuals with obesity, elevated BMI and one additional CV risk factors or overt heart disease, that using a GLP-1 receptor agonist to lower weight and reduce inflammation translates to less CV events, CV death and all-cause mortality, in the SELECT trial.
Healio: Do you foresee any barriers to implementation of a revised classification for blood glucose as it relates to CV risk?
Fonarow: Inertia is such a powerful force that when patients are coming in for a visit, even when risk factors are identified, there is often this approach to just reassess it on the next visit, and the next, and not taking proactive steps to modify that risk, ensure adherence and reassess. Overcoming inertia and improving adherence to evidence-based prevention therapy is critically important.
This is a step toward recognizing an additional group of individuals that is at increased risk and trying to modify that. There is the opportunity to prevent individuals entering prediabetes or progressing to diabetes.
There is a lot of opportunity here, but a tremendous amount of work that needs to be done at the individual, health system and population health level to make this knowledge actionable and acted on to ultimately improving clinical outcomes.
For more information:
Gregg C. Fonarow, MD, FACC, FAHA, FHFSA, can be reached at gfonarow@mednet.ucla.edu; X (Twitter): @gcfmd.
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