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Lifelong reductions in LDL linked to consistent reduction in CHD risk
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CHICAGO — Individuals with lower LDL levels beginning early in life were much less likely to develop CHD, according to data presented here.
Brian A. Ference, MD, MPhil, MSc, FACC, director of the CV genomic research center at Wayne State University School of Medicine, said, “We attempted to answer the question of whether lowering cholesterol earlier in life before the development of atherosclerosis would be more effective than lowering it later, after a lifetime of exposure to LDL and after atherosclerotic plaques have already developed.”
The current study involved a series of Mendelian randomization studies designed to estimate the effective of nine single nucleotide polymorphisms (SNPs) known to be associated with differences in lifelong exposure to LDL on the risk for developing CHD.
Ference said the nine SNPs were chosen to assess for consistency of effect.
“If we had only evaluated one, we could not be confident as to whether the result was due to lower LDL or a combination of lower LDL plus some other pleiotropic effect, and the results might not have been as conclusive,” he said.
The aim was to translate genomic information into something clinically useful, according to Ference.
“We couldn’t do a randomized trial so, as an alternative, we used genotypes linked to a lower LDL level as a proxy for treatment,” he said.
The researchers conducted a “natural” randomized trial for each SNP. They used the allele associated with a lower LDL level for each SNP as a proxy for a treatment that lowers LDL beginning at birth in order to estimate the effect of lowering LDL beginning early in life.
“These alleles are inherited randomly. Therefore, comparing the risk for CHD among persons with and without such an allele is analogous to a randomized trial comparing a treatment that lowers LDL with usual care,” he said.
Results indicated that each SNP was associated with a very consistent reduction in the risk for CHD for each unit of lower LDL. There was no evidence for heterogeneity.
The researchers also conducted a meta-analysis of the “natural” randomized trials by combining nonoverlapping data from multiple SNPs involving 326,443 participants. Results of this study indicated that lifetime exposure to lower LDL was associated with a 54% (95% CI, 48-59) relative reduction of CVD for each 38.7 mg/dL (1 mmol/L) lower LDL.
Ference added that the effect is an approximately threefold greater per unit decrease in LDL than that observed during treatment with a statin started later in life.
“Prolonged exposure to lower LDL beginning early in life appears to be associated with a much greater clinical benefit than previously recognized,” Ference said. He added that “the lack of heterogeneity of effect among the included SNPs suggests that the benefit of long-term exposure to lower LDL appears to be independent of the mechanism by which LDL is lowered. This suggests that diet and exercise are probably as effective as are statins or other treatments when started early in life.” – by Rob Volansky
For more information:
- Ference BA. Late-breaking clinical trials IV. Presented at: the American College of Cardiology 61st Scientific Session & Expo; March 24-27, 2012; Chicago.
Disclosure: Dr. Ference reports no relevant financial disclosures.
PERSPECTIVE
There is really nothing new here in terms of what we know, but the data have been put together in a compelling fashion. It is a sophisticated genetic analysis that brings it into the area under the curve. It demonstrates that a lifetime of exposure to a lower cholesterol level has an effect. This study adds to the body of information which tells us that anything we can do as a society from a nutrition standpoint to reduce our cholesterol levels is going to have serious public health implications.
They tested the hypothesis that we debate in public, which is whether it is better to start early and treat everybody, even though there are some people who will not benefit from the treatment — which, in this case is a low fat diet — or wait until those who require treatment need it, and then treat. Should we get everybody eating right and exercising, or should we target? These data show that the public health approach is better because you get three times the bang for your buck. This is a good public health lesson and I am glad it is getting this much attention.