Hyperglycemia: A Very Early Warning of Coronary Risk?
Numerous epidemiologic studies have long shown that elevated risk for CVD is associated with fasting glucose and A1camong persons with and those without diabetes. It stood to reason that reducing glycemia would therefore reduce CVD risk, but large clinical trials that tested the effect of intensive vs standard glycemic control failed to show a benefit from intensive control. However, for a variety of reasons, these trials still did not quite address the direct effect of glycemic level on CVD risk.
Researchers keep searching for the elusive link. For example, a post hoc analysis of the ACCORD trial showed that it was the patients in the treatment arm who did not achieve the treatment goal and who experienced increased mortality and drove the overall results. Meanwhile, large observational studies have suggested that the relationship among A1c, CVD, and mortality may be U-shaped.
A definitive answer to this perplexing question remains elusive. However, the studies recapped herein contain some intriguing clues.
Selvin and colleagues demonstrated that glycemia-associated myocardial damage appears to begin before a diabetes diagnosis and may require a highly sensitive assay to detect it. This is consistent with the notion that CVD risk accumulates with long-term exposure to hyperglycemia and clarifies why diabetes is not a coronary heart disease risk-equivalent state at diagnosis, or even in those with short diabetes duration. It is also consistent with a study showing that although impaired fasting glucose is a risk factor for heart failure, the risk is only elevated among persons who subsequently develop diabetes.
A second clue to the relationship between CVD and glycemia is uncovered in the current ADVANCE analysis, where greater VVV was associated with increased risk for both microvascular and macrovascular events. This association was independent of glycemic level, suggesting that minimizing long-term glycemic excursions may play an important role in risk-reduction regardless of level of control, as may short-term excursions.
It was interesting that VVV in A1c was predictive of future risk. Because A1c is already a measure of glycemic exposure over time, one might think that variability and associated risk would have been blunted in the A1c. That may be the case: ADVANCE reported that VVV of fasting glucose was a better predictor of risk than VVV of A1c.
Busy clinicians know that hyperglycemia, diabetes, and CVD are inextricably entwined. They also know that successfully treating patients with these conditions requires a multifaceted approach that controls risk factors while imposing the least possible burden. Intuitively, it makes sense that minimizing the ups and downs of glycemic control, even if that means that the point of stability for a given patient is a little higher than the "optimal" level of glycemia, is in the patient's best interest.
Analysis and Commentary
Numerous epidemiologic studies have long shown that elevated risk for CVD is associated with fasting glucose and A1camong persons with and those without diabetes. It stood to reason that reducing glycemia would therefore reduce CVD risk, but large clinical trials that tested the effect of intensive vs standard glycemic control failed to show a benefit from intensive control. However, for a variety of reasons, these trials still did not quite address the direct effect of glycemic level on CVD risk.
Researchers keep searching for the elusive link. For example, a post hoc analysis of the ACCORD trial showed that it was the patients in the treatment arm who did not achieve the treatment goal and who experienced increased mortality and drove the overall results. Meanwhile, large observational studies have suggested that the relationship among A1c, CVD, and mortality may be U-shaped.
A definitive answer to this perplexing question remains elusive. However, the studies recapped herein contain some intriguing clues.
Selvin and colleagues demonstrated that glycemia-associated myocardial damage appears to begin before a diabetes diagnosis and may require a highly sensitive assay to detect it. This is consistent with the notion that CVD risk accumulates with long-term exposure to hyperglycemia and clarifies why diabetes is not a coronary heart disease risk-equivalent state at diagnosis, or even in those with short diabetes duration. It is also consistent with a study showing that although impaired fasting glucose is a risk factor for heart failure, the risk is only elevated among persons who subsequently develop diabetes.
A second clue to the relationship between CVD and glycemia is uncovered in the current ADVANCE analysis, where greater VVV was associated with increased risk for both microvascular and macrovascular events. This association was independent of glycemic level, suggesting that minimizing long-term glycemic excursions may play an important role in risk-reduction regardless of level of control, as may short-term excursions.
It was interesting that VVV in A1c was predictive of future risk. Because A1c is already a measure of glycemic exposure over time, one might think that variability and associated risk would have been blunted in the A1c. That may be the case: ADVANCE reported that VVV of fasting glucose was a better predictor of risk than VVV of A1c.
Busy clinicians know that hyperglycemia, diabetes, and CVD are inextricably entwined. They also know that successfully treating patients with these conditions requires a multifaceted approach that controls risk factors while imposing the least possible burden. Intuitively, it makes sense that minimizing the ups and downs of glycemic control, even if that means that the point of stability for a given patient is a little higher than the "optimal" level of glycemia, is in the patient's best interest.
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