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 Up

Literature - Harari G, Green MS, Magid A, et al. - Am J Cardiol 2017; published online ahead of print

Background

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.

Main results

  • 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).

Conclusion

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.

References

1. Barter PJ, Kastelein JJ. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol 2006;47:492-499.

2. Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 – executive summary. Journal of clinical lipidology 2014;8:473-488.

3. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-3421.

4. Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993-2000.

5. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circulation Cardiovascular quality and outcomes 2011;4:337-345.

Find this article online at Am J Cardiol

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