Abstract
Purpose: Although carotid intima-media thickness (IMT) is widely used as a surrogate marker for atherosclerosis, the relationship between long-term IMT progression and plasma inflammatory cytokine levels is only partially clarified. We prospectively investigated the association of 10-year IMT progression and mean circulating levels of inflammatory cytokine during follow-up in atherosclerotic high-risk patients with intensive management of conventional risk factors. Methods: We prospectively evaluated 207 atherosclerotic high-risk patients who continued to attend our ambulatory care center and underwent carotid ultrasound in 2001-2003 and in 2010-2012. Participants had to have a previous diagnosis of cardiovascular disease, diabetes, hypertension, dyslipidemia, or current smoking. All participants consecutively received intensive medical treatment and the management of risk factors was evaluated by mean values of annual physical examination and blood tests, including high-sensitive C-reactive protein (hsCRP), interleukin (IL)-6, and IL-18. Results: The mean baseline age was 64±8 years, and the mean follow-up period was 9.0±1.0 years. Conventional risk factors were generally well-controlled during follow-up period; mean blood pressure was 134±9/76±7mmHg, mean total cholesterol level was 204±23 mg/dl, and mean HbA1c (JDS) was 5.6%±0.7%. IMT increased 0.28±0.24 mm throughout the observation period. IMT progressions was positively correlated with baseline IMT, age, male sex, mean plasma glucose, HbA1c, hsCRP, IL-6, and IL-18 levels during follow-up, and negatively correlated with mean diastolic blood pressure levels. In multiple regression analyses adjusted for age, sex, conventional risk factors and statin use, mean plasma IL-6 (β=0.39, p=0.047) together with baseline IMT (β=0.45, p=0.044) and mean HbA1c (β=0.21, p=0.0038) were independently associated with IMT progression. Conclusion: In atherosclerotic high-risk patients under intensive medical therapy, mean plasma IL-6 level during follow-up period was an independent predictor of IMT progression.
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