Lipids, Screening, and Stroke: What Matters?

As the mean BMI in the U.S. edges higher, I thought that a discussion of two recent analyses regarding lipids was pertinent to the season.

The first question of the day is which lipid components are associated with important vascular endpoints. The Emerging Risk Factors Collaboration sought to address this question. Their objective was to determine the associations between major lipid fractions and apolipoproteins with stroke and CHD. This is a sub-analysis of a database of 1.2 million people, comprising some 112 prospective studies. The master group was taken from 68 studies with 302,430 participants. The study population was rather geographically heterogeneous: 60% from Western Europe and 32% from North America. Mean age at enrollment was 59 years old. The final data set included a total of 2.79 million person-years, and the first outcome occurred a median of 6.1 years after entry. First outcome totals were: 8,857 non-fatal MI, 3,928 deaths due to CHD, 2,534 ischemic str okes, 513 hemorrhagic strokes, and 2,536 unclassified strokes. This was a very large, relatively young group, with a large number of target outcomes included in the analysis.

The findings are rather complex, but the final message is not. Triglycerides were not associated with target outcomes, even adjusting for fasting status of the samples. HDL status was significant from a cardiac risk standpoint, and did not vary when adjusted for ethanol ingestion. Of note, however, HDL status was not associated with stroke risk. LDL status was strongly associated with target CHD outcomes (HR of 1.50 even after multiple adjustments). The associations between apolipoproteins and outcomes was similar to those found with lipids. Hemorrhagic stroke was not associated with any of the variables measured.

Based on the findings, the authors conclude that effective lipid screening can be done fasting or non-fasting, using either cholesterol fractions or apolipoproteins. They posit that it is not important to assay triglycerides. The absence of association with stroke is interesting; the authors wonder about heterogeneity of stroke subtype as a factor in producing different outcomes in other studies. Notable strengths of this study are its very large size and prospective analysis. The findings are likely to be of particular importance and significance as a result.

And the other issue for today's contemplation is a more specific analysis of stroke with regard to lipid status. This is considered in a sub-analysis of the NOMAS study, a large population study in New York. The primary outcome was ischemic stroke; 2,940 people with no previous history of stroke were included in the final analysis. The mean age was somewhat older than the other study: 68.8 years. And, over half of the participants were Hispanic. 168 strokes, made up of a variety of stroke subtypes, were detected.

And the outcomes, again, were not consistent with previous findings about lipids. As with the first study, HDL status and triglyceride were not associated with risk for stroke. On the surface, LDL was inversely associated with stroke risk. However, there was a strong effect of treatment with statin agents: A subset of persons not taking statin drugs did not show the LDL/stroke inverse association, negating the rather counter-intuitive finding. In considering the outcomes, the authors explain the absence of findings as likely related to effects of statin treatment. They also consider whether their older population is a factor, since some other studies have included younger patients who may have had stroke directly related to primary dyslipidemia. They note that the small number of strokes detected likely comprised an inadequate sample size to assess the effects of lipids on stroke subtypes.

So, the lipid-disease association is not yet completely clarified. However, triglycerides appears to be less significant than previously considered. HDL may not affect stroke risk. LDL is still important. Multiple stroke subtypes cloud the association of stroke with lipids. And, the effects of ubiquitous statin treatment is altering the vascular risk characteristics of the entire population in complex ways. Given the propensity for excess food consumption during the holiday season, perhaps such ubiquitous statin therapy is not such a bad thing.