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Cardiovascular risk increases with higher levels of hemoglobin A1C, even when diabetes is not present. Khaw and colleagues prospectively followed a group of 10,000 subjects 45 to 79 years of age. Persons with hemoglobin A1C < 5% had the lowest rates of cardiovascular disease and all-cause mortality. For an increase in 1% in hemoglobin A1C, the relative risk for death was 1.24 in men and 1.28 in women.
Cardiovascular risk is also elevated when there are mild degrees of renal dysfunction even when serum creatinine is in the normal range. As part of the Valsartan in Acute Myocardial Infarction Trial, Anavekar and colleagues studied 14,527 patients with known serum creatinine. Glomerular filtration rate (GFR) at baseline was estimated. A GFR of 75 mL/min/1.73m2 corresponds to a serum creatinine between 0.8 and 1.0 mg/dL. Below 81 mL/min/1.73m2, each reduction in GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10. These studies illustrate the increase in risk that is associated with measures of hyperglycemia and renal impairment. On a population basis, lifestyle changes that will normalize glucose and kidney function are likely to have a significant impact on future cardiovascular disease incidence.