Abstract
Introduction: Increased small dense low-density lipoprotein cholesterol (sdLDL-C) has been reported to be a significant atherosclerotic cardiovascular disease (ASCVD) risk factor Hypothesis: SdLDL-C is an independent ASCVD risk factor in men, women, African Americans, and non-African Americans. Methods: A total of 15,933 participants (median age 62 years, 56.7% female, 19.7% African-American, free of inclusive ASCVD at baseline) pooled from three studies (Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis) were followed for 10 years for incident hard ASCVD and inclusive ASCVD (includes angioplasty and/or coronary artery bypass). These endpoints occurred in 6.1% and 9.7% of subjects, respectively. Information on all standard risk factors was obtained, and serum sdLDL-C levels were measured at baseline using automated analysis. The utility of traditional cardiovascular risk factors and sdLDL-C in 10-year hard and inclusive ASCVD risk was assessed-using univariate and multivariable regression analyses. Results: All standard risk factors were significant for hard and inclusive ASCVD in men, women, African-Americans and non-African-Americans on univariate statistical analysis. SdLDL-C was a significant risk factor when added to the pooled cohort equation for hard and inclusive ASCVD in all subjects, and for inclusive ASCVD in all subgroups, and significantly improved the C-Statistic and affected the net reclassification index for all subjects (p<0.0001). When subjects with elevated sdLDL-C levels of > 50 mg/dL were compared to those with optimal levels of <25 mg/dL after adjustment for all standard risk factors, the hazard ratios (HR) and confidence intervals (CI) for incident inclusive ASCVD were all significant at p<0.01: all subjects (HR 1.54, CI 1.30-1.83), men (HR 1.59, CI 1.27-1.99), women (HR 1.51, CI 1.05-1.27), non-African-Americans (HR 1.49, CI 1.24-1.80[CLA3] ), and African-Americans (HR 1.88, CI 1.23-2.89). Conclusions: An elevated sdLDL-C value > 50 mg/dL was independently associated with a 50% increased 10-year inclusive ASCVD risk in all subjects regardless of sex or race[MD1] , and therefore is an important ASCVD risk enhancer.
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