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 study.
Indeed, only 1 of the 18 biomarkers that were assessed in the study proved predictive of major cardiovascular events: osteopontin.
At baseline, when Treating to New Targets (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 the risk of cardiovascular events 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 marked contrast to the underperformance of the novel biomarkers, on-treatment levels of the traditional lipid risk factors—LDL cholesterol, HDL cholesterol, and triglycerides—were powerful predictors of major cardiovascular events.
The implication is that the appropriate treatment strategy in patients with established coronary heart disease (CHD) is to put them on statins, titrate to a dose that achieves guideline-recommended lipid levels, and dispense with focusing on novel biomarkers, which do not offer increased predictive power over the standard lipids.
“Until further evidence is available and/or guidelines recommend otherwise, clinical decisions around statin therapy might continue to focus on traditional contributors to cardiovascular risk, such as lipid levels, prior medical history, and lifestyle factors,” 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 clinical trial to demonstrate that lowering LDL to a target of 75 mg/dL resulted in 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 undertaken to shed light on the potential utility of the much-discussed novel biomarkers in managing cardiovascular disease.
The post hoc nested case-control study 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 increase in the 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, 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.
Of 18 novel biomarkers assessed, 17 proved to have no predictive value. Osteopontin was the exception.
Source Dr. Kastelein