Non-HDL-C a better predictor of mortality than LDL-C
Usefulness of Non-High Density Lipoprotein Cholesterol as a Predictor of Cardiovascular Disease Mortality in Men in 22 Year Follow UpHarari G, Green MS, Magid A, et al. - Am J Cardiol 2017; published online ahead of print
Conflicting data exist regarding the superiority of non-HDL-C for the prediction of cardiovascular disease (CVD) risk, compared with LDL-C [1-5]. Therefore, there is a need to assess the predictive value of non-HDL-C for CVD and total mortality, in comparison to the predictive value of LDL-C in various populations.
In the prospective Cardiovascular Occupational Risk Factor Determination in Israel Study (CORDIS), it was evaluated whether lipid levels, including non-HDL-C, in 4,832 young, apparently healthy, male workers from 21 industrial plants have a better predictive value for total mortality and CVD mortality, compared with other lipid measures, in a long-term follow-up of 22 years, ending in 2007. The current analysis was restricted to a working population of Jewish men aged 20 to 70 years at baseline. Arab men were excluded from the current analysis.
- Non-HDL-C levels were positively associated with several cardiovascular (CV)-related parameters: age at screening, BMI, total cholesterol (TC), LDL-C, triglycerides (TG), hypertension, diabetes mellitus (DM), family history of myocardial infarction (MI), alcohol and coffee consumption, and maintaining a special diet. Non-HDL-C levels were negatively associated to HDL-C and leisure-time physical activity.
- The Kaplan-Meier analysis demonstrated significantly lower CVD survival rate among men with increasing non-HDL-C levels (log rank P<0.0001). Risk increased with increasing non-HDL-C levels, in a dose-response manner (HR non-HDL-C 130-159, 160-189, ≥190 compared to <130 mg/dl were 1.98 [95% CI 1.15-3.41], 2.57 [95% CI 1.52-4.33], 4.71 [95% CI 2.90-7.64], respectively). However, after adjustment for CVD risk factors associations were attenuated and only remained significant for non-HDL-C levels ≥190 mg/dl (HR 1.80, 95% CI 1.10-2.96, P=0.020).
- Similarly, the univariate analysis indicated a positive association between baseline LDL-C levels and CVD mortality (HR LDL-C 100-129, 130-159, ≥160 compared to <100 mg/dl were 1.09 [95% CI 0.65-1.83], 1.82 [95% CI 1.15-2.89], 3.60 [95% CI 2.33-5.57], respectively) but this significance disappeared in an adjusted model, although the HR for CVD mortality indicated a trend for increased risk in men with LDL-C levels ≥160 mg/dl (HR: 1.53; 95% CI: 0.98-2.39, P=0.062 compared to <100 mg/dl).
- Also TC levels showed a positive linear association with CVD mortality in a univariate model. After adjustment for potential confounders, only the association between TC levels ≥240 mg/dl and CVD mortality remained statistically significant (HR: 1.54; 95% CI: 1.06-2.25; P=0.025 compared to <200 mg/dl).
- Both non-HDL-C, LDL-C and TC associated also with all-cause mortality in a univariate model but not after correction for confounders in a multivariate analysis.
- Only TG levels of ≥200 mg/dl predicted all-cause mortality and CVD mortality with a significant HR when comparing to TG levels of <150 mg/dl, but after adjustment for potential confounders, all the associations were attenuated (HR 1.12, 95% CI 0.79-1.59, P=0.532).
- When adjusted for LDL-C levels, increased levels of non-HDL-C tended to be associated with higher CVD mortality rates, but without statistical significance.
- The highest risk of CVD mortality was observed in the group with the highest levels of both LDL-C (≥160 mg/dl) and non-HDL-C (≥190 mg/dl), and in the group with the lowest level of LDL-C (<100 mg/dl) and the highest level of non-HDL-C (≥190 mg/dl).
In a large population of young males who were followed-up for 22 years, non-HDL-C was a more potent predictor of CVD mortality compared with LDL-C levels, after adjustment for many relevant confounding factors. These findings support existing data, according to which, non-HDL-C should be preferred over LDL-C for CV risk stratification. Interestingly, higher levels of non-HDL-C seemed to attenuate the “protective” effect of lower levels of LDL-C, although these results need to be confirmed in larger studies.