June 23rd, 2010
• Lowering Homocysteine Fails Again to Reduce Events
• European Atherosclerosis Society Will Recommend Lp(a) Screening and Niacin
Larry Husten, PHD
Lowering Homocysteine Fails Again to Reduce Events: U.K. investigators randomized 12,064 MI survivors to folic acid and vitamin B12 or placebo. No difference was observed between the two groups in either major vascular events or in the incidence of cancer. In their report in JAMA, the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) investigators concluded that “taken together with the previous homocysteine-lowering trials, the results of SEARCH indicate that folic acid supplementation has no significant adverse effects on cancer or other major health outcomes, even if it also produces no beneficial effects on cardiovascular disease.”
European Atherosclerosis Society Will Recommend Lp(a) Screening and Niacin: In a consensus statement not yet published, the EAS will recommend that patients at high to moderate risk of cardiovascular disease should be screened for elevated Lp(a) levels. Details of the statement were presented at the EAS Congress in Hamburg, Germany, and reported on TheHeart.Org by Reed Miller. The statement will also recommend the use of niacin to bring Lp(a) levels below 50 mg/dL. Although the consensus panel “acknowledges that there have not been randomized, controlled trials selectively targeting plasma levels of Lp(a),” consensus panel cochair Dr. John Chapman said: “We consider the level of evidence to be sufficient to warrant the identification of Lp(a) as a causal, independent cardiovascular risk.”
6 Responses to “• Lowering Homocysteine Fails Again to Reduce Events
• European Atherosclerosis Society Will Recommend Lp(a) Screening and Niacin”
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Thanks, Larry, for these news briefs. Seems like another nail in the coffin for homocysteine lowering. Given the lack of any proven therapies for lowering Lp(a), it’ll be interesting to see the extent to which these EAS recommendations are adopted…
I’d love to hear what people here think about the EAS consensus statement. What’s the evidence to support it?
Homocysteine was thought to be a “causal, independent cardiovascular risk” and look what the randomized controls trials have taught us — lowering its concentration with vitamins (safe and nontoxic) isn’t beneficial. I’m surprised the EAS thinks that the Lp(a) story is any different. Those silly Europeans……
Atherosclerosis. 2009 Apr;203(2):371-6. Epub 2008 Jul 26.
Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy.
Chasman DI, Shiffman D, Zee RY, Louie JZ, Luke MM, Rowland CM, Catanese JJ, Buring JE, Devlin JJ, Ridker PM.
Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215, United States. dchasman@rics.bwh.harvard.edu
Abstract
OBJECTIVE: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women’s Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers. METHODS AND RESULTS: Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants. Median Lp(a) levels at baseline were 10.0, 79.5, and 153.9mg/dL for major allele homozygotes, heterozygotes, and minor allele homozygotes, respectively (P<0.0001). During the 9.9 years of follow-up, minor allele carriers (3.7%) in the placebo group had twofold higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR)=2.21, 95% CI: 1.39-3.52). Among carriers, risk was reduced more than twofold by aspirin: for aspirin compared with placebo the age-adjusted HR was 0.44 (95% CI: 0.20-0.94); risk was not significantly reduced among non-carriers (age-adjusted HR=0.91, 95% CI: 0.77-1.08). This interaction between carrier status and aspirin allocation was significant (P=0.048). CONCLUSIONS: In the Women’s Health Study, carriers of an apolipoprotein(a) variant had elevated Lp(a), doubled cardiovascular risk, and appeared to benefit more from aspirin than non-carriers.
PMID: 18775538 [PubMed – indexed for MEDLINE]PMCID: PMC2678922Free PMC Article
Publication Types, MeSH Terms, Substances, Grant SupportPublication Types:
Dan, how does that paper relate to the EAS recommendation? Do you think it is enough to support the recommendation? Just what is the standard for making this sort of recommendation?
There are therapies that lower Lp(a) such as nicotinic acid and bezafibrate. The data from the WHS RCT and HERS RCT on Lp(a) are pretty compelling. I imagine the EAS statement is based on the recent systematic collaborative overview in the Lancet suggesting genetic causality for Lp(a) and c.v. risk. We often find it to be the only treatable abnormality in young patients with atherothrombosis and no other risk factors. It is potently prothrombotic and antifibrinolytic (due to its homology with clotting factors) and some study data suggest an important role in VTE as well (DVT/PE). The settings where I order it: 1) progressive plaque on subclinical atheroma imaging despite strong risk factor modification; 2) premature atherosclerosis, atherothrombosis, or venous thromobis; 3) strong family history of the same. It is also often elevated in patients with intraplaque hemorrhage which is a very potent marker of unstable plaque. We’ve published on this issue (Klein et al, 2008, ATVB) in terms of its risk for carotid stenosis, plaque area, and progression.