Combined Effects of Hemoglobin A 1c and C-Reactive Protein on the Progression of Subclinical Carotid Atherosclerosis

Abstract

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 hsCRP×HbA _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.