Glycohemoglobin and high-sensitivity C-reactive protein are two risk factors for atherosclerosis. Usually studies of both we are limited to hyperglycemia and inflammation. For this reason, we investigated the combined effect of these two parameters at the onset of early carotid atherosclerosis and macrovascular events in diabetic and nondiabetic subjects. Methods; We analyzed data from INVADE (Community Intervention Program for Cerebrovascular Disease and Dementia in Ebersberg, Bavaria), a prospective cohort study of 3534 subjects (mean age 69 years). In addition to common risk factors, carotid intima-media thickness (IMT), high-sensitivity C-reactive protein, and glycated hemoglobin were measured at baseline levels during a two-year follow-up. RESULTS: For the entire population, after adjustment for risk factor parameters, progression of intima-media thickness was significantly associated with glycated hemoglobin (P=0.003) but not with high-sensitivity C-reactive protein. High-sensitivity C-reactive protein was highly correlated with glycated hemoglobin interaction (P=0.001), and the most significant IMT progression was seen in patients with both parameters in the fourth quartile compared with the first quartile spacing (0.028 [0.025, 0.031] versus 0.012 mm/year [0.007, 0.019]; P=0.0013). We found a significant combined effect of HbA1c and hsCRP in the progression of IMT both in diabetic (n=882) and non-diabetic patients (n=2652). patients with HbA1c and sCRP in the upper two quartiles had a higher risk of new vascular events (adjusted hazard ratio 4.3 [1.8, 7.3] in diabetic patients; P= 0.001; non-diabetic patients: 2.9 [1.6, 4.7]; P=0.001). CONCLUSION: Hyperglycemia and inflammation are associated with early carotid atherosclerosis progression and increase the risk of new vascular events in both diabetic and nondiabetic patients. Because the true risk factors for stroke and myocardial infarction cannot be explained by traditional risk factors, there is a great need for our research to find a truly significant risk factor. Recent studies have shown that high-sensitivity C-reactive protein (hsCRP) is a strong early warning for cardiovascular events and definitely increases the risk of atherosclerosis. Glycated hemoglobin, in addition to being associated with the diagnosis of diabetes mellitus and being an established risk factor for the development of atherosclerosis, is also an independent risk factor for cardiovascular disease and death in non-diabetic patients. Observation of the association between inflammation and hyperglycemia can be used to predict the likelihood and prognosis of future stroke. Measurement of carotid intima-media thickness is a simple and commonly used method.