New Cardiac Biomarkers Target Plaque, Protein & Platelets

EndoPAT2000 measures changes in the peripheral arterial tone (PAT) signal in response to a five-minute occlusion of the brachial artery. Source: Itamar Medical
While well-established cardiovascular biomarkers still play a major role in clinical practice, many more biomarkers are vying for clinical attention. Following are just a few in the works.

  • EndoPAT2000 (Itamar Medical). This FDA-approved test measures endothelial health by “listening” to minute vascular functions through sensors attached to the patient’s index finger. Endothelial cell dysfunction indicates early warning signs of long-term diseases, such as diabetes and heart disease, developing quietly under the radar of conventional risk factors. “Fifty percent of those who arrive at emergency rooms with heart attacks don’t have conventional risk factors. Endothelial function may be the missing link,” says Amir Lerman, MD, a cardiologist at the Mayo Clinic in Rochester, Minn., who expects the EndoPAT2000 to become a routine procedure at Mayo in the next two years.
  • VAP Test (Atherotech). This comprehensive cholesterol test directly measures (as opposed to indirectly calculating) LDL, HDL and all relevant lipid subclasses. It also routinely reports apolipoprotein AI (apoAI)—the primary protein constituent of HDL, apolipoprotein B100 (apoB)—a component of LDL, and the apoB/apoAI ratio. In April, the company received a patent on its method to derive and report apoB using the VAP technology.

    “ApoB is much more predictive of risk than LDL,” says Michael Cobble, MD, director of Canyons Medical Center in Sandy, Utah, and a board-certified lipidologist. “It aligns with non-HDL and VLDL [very low-density lipoprotein] more accurately and is an important treatment target recently confirmed by both the American College of Cardiology and the American Diabetes Association.”
  • PLAC Test (diaDexus). This blood test measures lipoprotein-associated phospholipase A2 (Lp-PLA2), a vascular-specific inflammatory enzyme implicated in the formation of rupture prone plaque. It is the only FDA-cleared blood test to aid in assessing risk for coronary heart disease and ischemic stroke associated with atherosclerosis. A consensus panel recently recommended Lp-PLA2 testing as an adjunct to traditional risk assessment in patients at moderate and high 10-year risk (Am J Cardiol 2008;101[suppl]:51F–57F).

    A study presented at the 2009 International Symposium on Atherosclerosis in Boston found that Lp-PLA2 was significantly reduced in patients receiving lifestyle intervention and multiple drug therapies including extended release niacin and statins. The reduction in Lp-PLA2 did not correspond to a concomitant reduction in LDL. “This finding may help lead to a better understanding of why statins reduce stroke risk, independent of changes in cholesterol levels,” says lead researcher Kota Reddy, MD, from Reddy Cardiac Wellness, Houston, Texas.
  • AspirinWorks (Corgenix Medical). AspirinWorks measures the urine levels of 11-dehydrothromboxane, or 11d, a metabolite of thromboxane, the target of aspirin therapy. It is intended to help the 20 percent of Americans who are unknowingly resistant to the antiplatelet effect of aspirin. It is the only FDA-cleared test of its kind and was used in the Polycap study—a five-in-one pill combining statin, aspirin and three hypertensive drugs—to determine the effect of aspirin.

    The U.S. Preventive Services Task Force guidelines for aspirin therapy are tailored to match age and gender, i.e., men 45 to 79 and women 55 to 79. Paul A. Gurbel, MD, director, Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, says that lumping all patients together based on arbitrary age-defined cutoffs is potentially dangerous. “Platelet physiology is a heterogeneous entity that is only partially related to age. We should move toward the physiologic assessment of platelet function in the individual patient in order to optimize treatment. Therapeutic recommendations based upon post hoc analyses of trials that don’t prospectively assess aspirin dose efficacy should no longer have a role in contemporary medicine,” Gurbel says.

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