Combined effects of hemoglobin A1c and C-reactive protein on the progression of subclinical carotid atherosclerosis: the INVADE study.

BACKGROUND AND PURPOSE: Glycohemoglobin (hemoglobin A1c [HbA1c]) 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 HbA1c were performed at baseline and after 2 years of follow-up. RESULTS: For the entire population, IMT progression was significantly related to HbA1c (P=0.003) but not to hsCRP (P=0.06) after risk factor adjustment. The interaction hsCRPxHbA1c 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 HbA1c and hsCRP on IMT progression in the diabetic (n=882) as well as the nondiabetic subgroup (n=2652). Subjects with HbA1c 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.

High-sensitivity C-reactive protein at different stages of atherosclerosis: results of the INVADE study.

Evidence on the role of high-sensitivity C-reactive protein (hsCRP) at different stages of atherosclerosis is limited. We therefore analyzed the relationship between hsCRP and measures of subclinical and advanced atherosclerosis in a population-based sample of the INVADE study (n = 3,092, >55 years). The parameters of interest were IMT, ABI, and the stage of atherosclerosis. Differences between participants with normal and pathological hsCRP were analyzed by t test for independent samples or Fishers' exact test. Differences of hsCRP between IMT quartiles, ABI quartiles, and different stages of atherosclerosis were analyzed by one-way ANOVA. Adjusted stepwise multiple linear regression analysis (IMT and ABI) and adjusted analysis of variance (stage of atherosclerosis) were performed, including significant baseline parameters as covariates. ANOVA showed significant differences of hsCRP among IMT quartiles, ABI quartiles, and patients with and without atherosclerosis. The adjusted analyses confirmed that the effects of IMT, ABI, and atherosclerosis on hsCRP were independent from other significant baseline parameters, but did not yield a significant difference between subclinical and advanced stages of atherosclerosis. The present analysis indicates an independent relationship between hsCRP and both IMT and ABI as measures of subclinical atherosclerosis. The comparison of subclinical and advanced stages of atherosclerosis yielded no significant difference, indicating that hsCRP is sensitive to identify vascular risk patients, but not suited to monitor progression of the disease.