BARCELONA — C-reactive protein was among 17 novel biomarkers of inflammation and atherosclerosis that failed to predict future cardiovascular events in statin-treated patients with established coronary heart disease, in a post hoc subanalysis of the landmark Treating to New Targets (TNT) study.
Only 1 of the 18 biomarkers assessed in the study was predictive of major cardiovascular events: osteopontin. At baseline, when TNT participants had already been on atorvastatin (Lipitor) at 10 mg/day for 8 weeks, a low osteopontin level was associated with a significant 16% increase in cardiovascular event risk during the median 4.9 years of follow-up, Dr. John J.P. Kastelein reported at the annual congress of the European Society of Cardiology.
In contrast, on-treatment levels of the traditional lipid risk factors—LDL cholesterol, HDL cholesterol, and triglycerides—were powerful predictors. The implication is that the appropriate treatment strategy in patients with established CHD is to put them on a statin, titrate to a dose that achieves guideline-recommended lipid levels, and don't bother with the novel biomarkers, said Dr. Kastelein, professor of medicine and chairman of the department of vascular medicine at the Academic Medical Center of the University of Amsterdam.
The TNT study, which randomized 10,001 patients with stable CHD to 10 or 80 mg/day of atorvastatin for a median of 4.9 years, was the first study to show that lowering LDL to a target of 75 mg/dL led to significantly fewer major cardiovascular events than did treatment to the previously accepted target of 100 mg/dL (N. Engl. J. Med. 2005;352:1425–35).
The new TNT subanalysis was a post hoc nested case-control study that utilized stored plasma samples from 507 TNT participants who experienced a major cardiovascular event—CHD death, nonfatal MI, fatal or nonfatal stroke, or resuscitated cardiac arrest—and 1,020 controls who did not. The biomarkers were measured in samples obtained after 8 weeks on low-dose atorvastatin during the study run-in period and again in samples gathered after 1 year of randomized treatment.
An on-treatment elevated LDL cholesterol level was associated with a 2.1-fold increased risk of major cardiovascular events, a high HDL cholesterol level was linked to a 65% reduction in risk, and elevated triglycerides were associated with a 27% increase in risk.
Among the 17 novel biomarkers that proved to have no predictive value were markers of general inflammation, including CRP, lipoprotein-associated phospholipase A2, adiponectin, and soluble intercellular adhesion molecule-1, receptor for advanced glycation end products (RAGE), and soluble vascular adhesion molecule-1.
Others, in addition to osteopontin, included cystatin C, lipoprotein (a), N-terminal pro-brain natriuretic peptide, myeloperoxidase, soluble CD-40 ligand, insulin, neopterin, monocyte chemotactic protein-1, and matrix metalloproteinase-9.
The main TNT trial as well as this analysis were sponsored by Pfizer.
The novel biomarkers do not offer increased predictive power over the standard lipids.
Source DR. KASTELEIN