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CLINICAL RESEARCH: CORONARY HEART DISEASE

Impact of Impaired Fasting Glucose on Cardiovascular Disease

The Framingham Heart Study

Yamini S. Levitzky, MD^_*, Michael J. Pencina, PhD^_*,, Ralph B. D’Agostino, PhD^_*,, James B. Meigs, MD, MPH^,1, Joanne M. Murabito, MD, ScM^_*,_**, Ramachandran S. Vasan, MD^_*,||,#,2 and Caroline S. Fox, MD, MPH^_*,,,_*

^_* National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts
National Heart, Lung, and Blood Institute, Bethesda, Maryland
Statistics and Consulting Unit, Department of Mathematics, Boston University, Boston, Massachusetts
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
^|| Cardiology Section, Boston University School of Medicine, Boston, Massachusetts
^# Department of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts
^_** Section of General Internal Medicine, Department of Medicine, Boston Medical Center, Boston, Massachusetts
Department of Endocrinology, Metabolism, and Diabetes, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Manuscript received May 24, 2007; revised manuscript received September 12, 2007, accepted September 17, 2007.

^_* Reprint requests and correspondence: Dr. Caroline S. Fox, Framingham Heart Study, 73 Mount Wayte Avenue, Suite No. 2, Framingham, Massachusetts 01702-5827. (Email: foxca{at}nhlbi.nih.gov).

Objectives: We sought to determine whether impaired fasting glucose (IFG) predicts cardiovascular disease (CVD) events.

Background: It is unclear which glucose threshold should define prediabetes. We compared the 1997 and 2003 American Diabetes Association (ADA) definitions of IFG to predict CVD.

Methods: Framingham offspring participants free of CVD, categorized by the 1997 ADA IFG definition (fasting plasma glucose 110 to 125 mg/dl; 6.1 to 6.9 mmol/l) or the 2003 definition (100 to 125 mg/dl; 5.6 to 6.9 mmol/l), were followed from 1983 to 2004. Pooled logistic regression was used to calculate multivariable-adjusted odds ratios (ORs) for incident coronary heart disease (CHD; 291 events) or CVD (423 events).

Results: Four-year CHD event rates among women were 1.3% (100 to 109 mg/dl), 2.3% (110 to 125 mg/dl), and 2.9% (diabetes); whereas corresponding rates in men were 2.9%, 3.0%, and 8.7%. For the 2003 IFG definition, the OR for CHD among women was 1.7 (95% confidence interval [CI] 1.0 to 3.0, p = 0.048), whereas for the 1997 IFG definition, the OR for CHD in women was 2.2 (95% CI 1.1 to 4.4, p = 0.02), which was almost as high as for women with diabetes (OR 2.5, 95% CI 1.2 to 5.2, p = 0.01). For CVD, only the 1997 IFG definition yielded significantly greater odds of CVD in women (OR 2.1, 95% CI 1.2 to 3.6, p = 0.01). Men were not at increased odds of developing CVD or CHD by either definition.

Conclusions: In women, both IFG definitions were associated with increased CHD risk, whereas neither IFG definition identified men at increased short-term risk for CHD or CVD. The finding that women with FPG 110 to 125 mg/dl had similar CHD risk compared with women with diabetes suggests that CHD risk in women may be elevated at a lower glucose level than for men.

Abbreviations and Acronyms   ADA = American Diabetes Association   BMI = body mass index   CHD = coronary heart disease   CI = confidence interval   CVD = cardiovascular disease   FPG = fasting plasma glucose   IFG = impaired fasting glucose   IGT = impaired glucose tolerance   OR = odds ratio   TIA = transient ischemic attack

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