Application of non-HDL cholesterol for cardiovascular risk prediction in apparently healthy men and women: Results from the ATTICA prospective epidemiological study
Authors: Kouvari M , Chrysohoou C , Georgousopoulou E , Skoumas J , Pitsavos C , Panagiotakos DB 
Published: May 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

Background/Introduction: Consistent evidence exists for a causal association between blood cholesterol and cardiovascular disease (CVD) yet alternative lipid markers are still discussed. To this issue, non-High Density Lipoprotein (non-HDL) cholesterol offers a simple way to analyze the total amount of pro-atherogenic lipoproteins containing apolipoprotein B100. Purpose: The aim of the present work was to evaluate the 10-year first fatal/non fatal CVD incidence related to non-HDL cholesterol on the basis of existing thresholds suggested by the European Society of Cardiology (ESC) in a sample with prevalent CVD. Methods: ATTICA study was conducted during 2001-2012 including n = 1,514 men and n = 1,528 women (aged &gt;18 years old) from the greater Athens area, Greece. Baseline serum blood lipids profile was measured. Non-HDL cholesterol was evaluated according to the formula "total cholesterol minus HDL cholesterol" and the following categories were used: &lt;100 mg/dL; 100 to &lt;145 mg/dL; 145 to &lt;185 mg/dL; 185 to &lt;220 mg/dL, and ≥220 mg/dL. Ten-year follow up was performed (2011-12) in 2,020 participants (n = 317 cases, man-to-woman CVD incidence ratio = 1.66). Results: About 42% of women had non-HDL values within the range of 100 to &lt;145 mg/dL while in case of men about one third of them had non-HDL values within the range of 100 to 185mg/dL. Ranking from low to high non-HDL cholesterol CVD incidence was 5.3%, 13.3%, 18.0%, 20.0% and 28.9%. The man-to-woman age-standardized CVD incidence ratio was 1.50, 1.93, 1.37, 1.24, 1.64, respectively; indicating a steep rise in CVD incidence rate in favor of men when non-HDL cholesterol levels reached the 2nd category levels (i.e. 100 to &lt;145 mg/dL) while women seemed to present CVD incidence rates closer to their men counterparts in case of higher non-HDL cholesterol values (i.e. 145 to &lt;220 mg/dL). Multi-adjusted Cox regression analysis revealed that 30mg/dL increase in non-HDL cholesterol values corresponded to 34% higher risk to develop CVD within the decade (Hazard ratio (HR)=1.34, 95% Confidence Interval (95%CI) (1.00, 1.81)). The association remained significant only in case of men (p for gender interaction = 0.01); HR = 1.45, 95%CI (1.09, 1.95). Additionally, when the categorical non-HDL variable was used, its independent aggravating effect on CVD outcome reached the level of significance only for non-HDL cholesterol values &gt;220mg/dL; HR5th vs. 1st category = 1.95, 95%CI (1.10, 4.30). Sex-based stratified analysis revealed significance only in men and particularly HR5th vs. 1st category = 3.14, 95%CI (1.26, 5.10). In case of women the aggravating effect was retained yet without reaching the level of significance. Conclusion: Even if non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic CVD, its use in daily clinical practice is challenged. These outcomes could be useful for physician–patient communication about primary prevention strategies.