Published Online
on December 22, 2005

A more recent version of this article appeared on February 1, 2006

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Submitted on August 20, 2005
Revised on September 29, 2005
Accepted on November 2, 2005

Combined Effects of Hemoglobin A_1c and C-Reactive Protein on the Progression of Subclinical Carotid Atherosclerosis. The INVADE Study

Dirk Sander MD^*; Carla Schulze-Horn MD; Horst Bickel PhD; Hans Gnahn MD; Eva Bartels MD; and Bastian Conrad MD

From the INVADE Study Group (H.G., E.B.) and Departments of Neurology (D.S., C.S.-H., B.C.) and Psychiatry (H.B.), Technical University of Munich, Munich, Germany.

^* To whom correspondence should be addressed. E-mail: Dirk.Sander{at}neuro.med.tu-muenchen.de.

Background and Purpose--Glycohemoglobin (hemoglobin A_1c [HbA_1c]) and high-sensitivity C-reactive protein (hsCRP) are risk indicators for atherosclerosis. Limited information exists regarding the combined effects of inflammation and hyperglycemia. We investigated the joint effects of both parameters on early carotid atherosclerosis progression and major vascular events in diabetic and nondiabetic subjects.

Methods--We analyzed the data of INVADE (Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria), a prospective, population-based study conducted in 3534 subjects (mean age, 69 years). In addition to common risk factors, measurements of carotid intima-media thickness (IMT), hsCRP, and HbA_1c were performed at baseline and after 2 years of follow-up.

Results--For the entire population, IMT progression was significantly related to HbA_1c (P=0.003) but not to hsCRP (P=0.06) after risk factor adjustment. The interaction hsCRPxHbA_1c was highly significant (P=0.001), and the most pronounced IMT progression was seen in subjects with both parameters in the fourth quartiles compared with subjects with both parameters in the first quartiles (0.028 [0.025, 0.031] versus 0.012 mm/year [0.007, 0.019]; P=0.0013). We observed a significant joint effect of HbA_1c and hsCRP on IMT progression in the diabetic (n=882) as well as the nondiabetic subgroup (n=2652). Subjects with HbA_1c and hsCRP in the upper 2 quartiles had an increased risk for new vascular events (adjusted hazard ratio in diabetics: 4.3 [1.8, 7.3]; P=0.001; nondiabetics: 2.9 [1.6, 4.7]; P=0.001).

Conclusions--The combination of hyperglycemia and inflammation is associated with an advanced early carotid atherosclerosis progression and an increased risk of new vascular events in diabetic as well as nondiabetic subjects.

Key words: atherosclerosis • carotid arteries • diabetes mellitus • epidemiology • inflammation

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