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Am Fam Physician. 2005;71(11):2200

Persons with diabetes are at higher risk for cardiovascular disease because classical risk factors including obesity, dyslipidemia, and hypertension are common in this group. However, the link between cardiovascular disease and hyperglycemia is not as clear. Studies have shown that improved glycemic control decreases the risk of microvascular conditions (e.g., retinopathy, neuropathy, nephropathy), but its effect on coronary heart disease, stroke, peripheral arterial disease, and other macrovascular diseases has been equivocal. Selvin and associates performed a systematic review of published reports to explore the relationship between long-term glycemic control and the risk of cardiovascular disease in persons with type 1 and type 2 diabetes.

Studies conducted between 1966 and 2003 that reported A1C measures; included persons with diabetes; and examined for cardiovascular outcomes such as peripheral arterial disease, coronary heart disease, and stroke were included.

In their final analysis, the authors pooled data from 17 reports to measure the relative risk (RR) estimate per percentage-point increase in A1C for each cardiovascular outcome. For persons with type 1 diabetes, the RR was 1.15 (95 percent confidence interval [CI], 0.92 to 1.43) for coronary heart disease and 1.32 (95 percent CI, 1.19 to 1.45) for peripheral arterial vascular disease. Stroke data by level of A1C were not available for this group.

For persons with type 2 diabetes, the RR was 1.18 (95 percent CI, 1.10 to 1.26) for total cardiovascular disease, 1.17 (95 percent CI, 1.09 to 1.25) for stroke, and 1.28 (95 percent CI, 1.18 to 1.39) for peripheral arterial vascular disease. These results support the concept that hyperglycemia increases cardiovascular risk in persons with type 1 and type 2 diabetes. The only study included in this analysis that specifically evaluated the ability of glucose-lowering regimens to decrease cardiovascular morbidity or death was the United Kingdom Prospective Diabetes Study. Although the study found that improved glycemic control can moderately decrease cardiovascular risk (with the exception of stroke), it did not demonstrate statistical significance.

The authors conclude that, according to the meta-analysis, hyperglycemia is associated with increased cardiovascular risk in persons with types 1 and 2 diabetes. If this is accurate, improved glycemic control may lower cardiovascular risk in patients with diabetes. Cardiovascular disease is common among persons with diabetes because of factors other than hyperglycemia; therefore, further studies are needed to confirm this finding. Also, the only study included in this analysis that specifically looked at the ability of glucose-lowering regimens to decrease cardiovascular morbidity did not demonstrate statistically significant results.

editor’s note: In an editorial1 in the same issue, Gerstein notes that the results of the meta-analysis above demonstrate the significant association between elevated A1C levels and the risk of coronary heart disease and peripheral vascular disease. A six-year cohort study2 that evaluated the relationship between A1C measurement and cardiovascular events in persons with and without diabetes found that A1C levels may be an independent predictor of cardiovascular complications. Gerstein concludes that, based on the results of these two reports, elevated A1C levels in persons with or without diabetes should be added to the list of commonly accepted cardiovascular risk factors, such as hypertension and elevated cholesterol levels. Further studies are needed to confirm whether lowering A1C levels has a positive impact on cardiovascular event risk. In the meantime, the author encourages lifestyle changes that can help reduce diabetes and A1C levels.—r.s.

REFERENCESGersteinHCGlycosylated hemoglobin: finally ready for prime time as a cardiovascular risk factor.Ann Intern Med2004;141:475–6.KhawKWarehamNBinghamSLubenRWelchADayNAssociation of hemoglobin A1c with cardiovascular disease and mortality in adults: the European Prospective Investigation into Cancer in Norfolk.Ann Intern Med2004;141:413–20.

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