Abstract

Introduction: Carotid intimal medical thickness (cIMT) is associated with cardiovascular disease (CVD). The association between atherogenic lipoproteins including small dense low-density lipoprotein cholesterol (sdLDL-C) and carotid intimal medial thickness (cIMT) progression has not been fully evaluated in a prospective cohort study. Hypothesis: We assessed the hypothesis that sdLDL-C is the most atherogenic lipoproteins with regard to cIMT progression. Methods: Kyushu and Okinawa Population Study (KOPS) is a community-based, prospective, and observational study in Japan which has been underway since 2004 and a total of 18,762 participants have been enrolled. For this study, we included 2,030 male and female participants (median age 59 years at baseline) who were free of CVD and off cholesterol lowering medication, and had cIMT measured at both baseline and after 5 years follow-up survey. Using plasma samples obtained from those subjects after overnight fast, we measured total cholesterol, direct low-density lipoprotein cholesterol (LDL-C), sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), adiponectin and high sensitivity C reactive protein (hs CRP). Their cIMT levels were measured by B-mode ultrasonography with a 10 MHz probe at far walls of their both right and left common carotid arteries. Results: Median cIMT at baseline was 0.63 mm and median 5 year progression was 0.18 mm. After adjustment for standard CVD risk factor including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C < 100 mg/dL, considered to be at low CVD risk, elevated sdLDL-C were associated with cIMT progression ( P for trend = 0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Conclusions: In conclusion, both sdLDL-C and direct LDL-C are significantly associated with cIMT progression. Moreover sdLDL-C has stronger relationship with cIMT progression than does LDL-C; therefore, measurement of sdLDL-C may allow for the formulation of optimal therapy to cIMT progression.

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