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11-year follow-up data from 21,448 men and women aged ≥45 years without diabetes or coronary heart disease (CHD) at baseline, were included in this prospective population-based study. The relative contributions to coronary risk of non-fasting:
Across all LDL-C categories, individuals with an elevated non HDL C (as defined above), TG ≥150 mg/dL or TC/HDL C ≥5 were at increased risk of CHD.
This was especially notable in subjects with LDL-C levels at goal (<100 mg/dL). In this group, adjusted hazard ratios for coronary risk were:
Current guidelines recommend LDL-C as the primary lipid target for prevention of cardiovascular disease. However, even in individuals with LDL-C levels at goal, there remains a high residual cardiovascular risk.2,3
Non-HDL-C is a measure of the combined cholesterol from all atherogenic apolipoprotein B100-containing lipoproteins and, to a lesser degree, of apolipoprotein B48-containing lipoproteins, including LDL, very low-density lipoproteins, intermediate-density lipoproteins, lipoprotein(a), chylomicrons and their remnants. Non-HDL-C is already recognised by US guidelines as a secondary target for therapy.1,4 In fact, the recent ADA/ACC Consensus statement for lipoprotein management 20085 highlights the importance of measurement of apolipoprotein B100-containing lipoproteins as a component of residual cardiovascular risk. In an accompanying editorial,6 it is proposed that the current study supports the use of non-HDL-C as a routine target of therapy to reduce cardiovascular risk.
Non-LDL lipids are predictive of residual coronary risk
The EPIC-Norfolk study clearly demonstrates that non-LDL components of the lipid-lipoprotein profile, specifically elevated TG, and by inference, low HDL-C, (presence of both abnormalities being labeled atherogenic dyslipidemia), are important contributors to residual coronary risk in individuals at LDL-C goal.
With respect to TG, coronary risk associated with TG ≥150 mg/dL was consistent with that reported from a grand meta-analysis of 29 prospective studies including 262,525 subjects. This analysis reported an odds ratio of 1.72 (95% CI 1.56-1.90) when individuals in the third log-TG tertile were compared with those in the first log-TG tertile (corresponding to mean TG values >178 mg/dL vs. <115 mg/dL). The strength of this association was maintained even after adjustment for HDL-C levels.7 Additionally, the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22) study,8 post-hoc analysis showed that statin-treated patients at LDL-C goal with elevated fasting TG (≥150 mg/dL) had a high residual coronary risk, even after adjustment for confounders, including HDL-C. As discussed,6 non-fasting TG, as measured in the current study, may even better predict residual coronary risk than fasting TG values. The authors of the EPIC-Norfolk study do, however, recognize that the lack of adjustment for HDL-C, as well as for diabetes and/or insulin resistance, may limit the strength of the observed association between TG and coronary risk.
The importance of low HDL-C as another major contributor to residual cardiovascular risk is supported by data from observational studies such as the Prospective Cardiovascular Münster (PROCAM) study,9 as well as post-hoc analysis of statin-treated patients at LDL-C goal (<70 mg/dL) with low levels of HDL-C (<37 mg/dL).10 Findings from the EPIC-Norfolk study are consistent with evidence from PROCAM in showing that in individuals with a TC/HDL-C ratio ≥5.0, coronary risk was more than 2 fold higher than in those with a ratio <5. This provides further support for the use of this ratio for coronary risk assessment beyond LDL-C, as recognised in the recently updated Canadian guidelines for management of dyslipidemia.11
Together with findings from the EPIC-Norfolk study, there is mounting evidence to support measurement of non-LDL parameters associated with the hallmark abnormalities defining atherogenic dyslipidemia – elevated TG and the TC/HDL-C ratio - for assessing residual coronary risk beyond LDL-C.
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