Background

Classical lipid profiles, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) cholesterol (LDL-C) and high-density lipoprotein (HDL) cholesterol (HDL-C), were identified to play very important roles in cardiovascular diseases (CVD) over past decades. Of these lipid profiles, LDL-C is considered to be one of the strongest predictors of CVD, and lowering LDL-C is fundamental in current CVD prevention and treatment strategies [1,2,3,4]. The 2016 European Society of Cardiology guideline for the management of dyslipidemias stated that, LDL-C had to be used in primary lipid analysis and should be the primary target for treatment, while other lipid parameters could be considered in selected cases, for example, those at high risk [4]. However, this LDL-C-based cardiovascular risk assessment and lipid management did not pay much attention to the role of various lipid profiles apart from LDL-C. Numerous studies showed that other lipid profiles, for example HDL, independently associated with CVD [5]. Recent years, there were some attempts to investigate that if these individual lipid parameters could be combined to improve the risk assessment and prediction of cardiovascular events [6]. Non-HDL-C, which calculated as TC - (HDL-C), was found to be another strong independent risk factor of CVD [7]. Based on these findings, the International Atherosclerosis Society guideline recommended that non-HDL-C was as important as LDL-C and non-HDL-C should be the primary targets of therapy since it carried more information of lipids than LDL-C alone [2]. Besides, the recent American National Lipid Association guideline and British National Institute for Health and Care Excellence guideline recommended that non-HDL-C was a better risk indicator than LDL-C [1, 3]. Given the fact that different studies had various population and methodologies, the clinical significance of these combined lipid parameters was still in discussion.

Target organ damage (TOD) is the intermediate stage in the development of CVD, and is a determinant cardiovascular risk factor [8]. Because lipid profiles largely attributed to atherosclerosis, they may closely associate with vascular TOD. Thus, we investigated and compared the individual lipid parameters, which were represented by LDL-C, and the combined lipid parameters, which were represented by non-HDL-C, in association of vascular TOD, aiming to examine the clinical significance of these indices.

Methods

Study design and population

The present analysis was based on the “Northern Shanghai Study” (Registry Number: NCT02368938), whose study design and selection criteria has been published before [21]. Several studies tried to compare the effects of non-HDL-C and TC/HDL, but the difference was too little to distinguish these two lipid parameters [22, 23]. Given the fact that non-HDL-C and TC/HDL showed different aspects of the relationship of atherogenic and anti-atherogenic lipid profiles, namely the absolute difference and the ratio, the role of TC/HDL might be of great importance in risk stratification and treatment in the future.

There were some limitations in this study. As a cross-sectional study, we could not provide more information other than associations. However, the Northern Shanghai Study is an on-going study and we are doing the follow-up. Hopefully, we could have more interesting findings in the future. Second, we did not measure other lipid parameters such as apo B, which also showed its superiority over LDL-C in some studies [7]. Third, the present analysis did not include the analysis on intima-media thickness and carotid plaque, which had been regarded as an important marker of vascular TOD for several decades. However, emerging data showed that intima-media thickness might not be a good marker of TOD. Fourth, it should be pointed out that though the associations between TOD and lipid parameters were significant in our study, the correlation coefficients were not high, suggesting that TOD was a multi-factor-driven process.

Conclusion

The present analysis showed that, in this community-dwelling elderly cohort, non-HDLC and TC/HDLC were better associated with vascular TOD including arterial stiffening, PAD and CKD. This finding should be considered in future clinical practice and dyslipidemia management. Large clinical trials, especially RCTs directly comparing LDL-C and non-HDL-C as treatment target, are warranted in the future.