April 17, 2019 / Heart & Vascular
Nontraditional markers help doctors
pinpoint who needs aggressive treatment
Many of us know that cholesterol, blood sugar, blood pressure, body-mass index and smoking are modifiable risk factors
for heart disease. If you smoke or have high levels
of the other risk factors, you will need to make lifestyle changes and/or take
medications to prevent a heart attack. But these measures don’t always stop a
serious cardiac event from occurring.
“Treating these risk factors reduces heart
attacks by 50 percent. This means 50 percent still happen,” says Stanley Hazen, MD, PhD,
Co-section Head of Preventive Cardiology and Rehabilitation.
Researchers have looked long and hard for
additional ways to improve risk prediction. Over the years, many substances in
the blood have been identified as possibilities. However, only a small number of
these biomarkers have been proven effective enough to be widely adopted.
We want to be able to identify people who remain at risk, so we
can treat them more aggressively to attenuate that risk.
Useful new biomarkers
At Cleveland Clinic, nontraditional biomarkers
in routine use include high-sensitivity C-reactive protein (hsCRP),
lipoprotein(a), homocysteine, trimethylamine N-oxide (TMAO), myeloperoxidase
and N-terminal pro-brain natriuretic peptide (NT-proBNP).
“All have significant data supporting findings
that they provide independent prognostic value beyond traditional risk
factors,” says Dr. Hazen.
Here we explain what these biomarkers are, and
why your doctor might want to test for one of them:
hsCRP. HsCRP indicates inflammation is present
somewhere in the body. High CRP levels are associated with higher risk of coronary artery disease (CAD) and heart attack.
In clinical trials, hsCRP was shown to
be a reliable indicator of patients who would substantially benefit from more
intensive statin therapy.
“The test is useful for identifying people
whose elevated risk was not picked up by tests for traditional risk factors, as
well as those who remain at risk, despite being on treatment. I order a CRP
test at the first visit to see if a patient’s statin therapy is adequate or
needs to be more aggressive,” Dr. Hazen explains.
Myeloperoxidase. Myeloperoxidase is a marker of
inflammation in the blood vessels. A high level signifies an increased risk of
heart attack.
“We may measure myeloperoxidase at a patient’s
initial visit in order to determine our LDL goal. If myeloperoxidase levels are
high, we will be more aggressive with antiplatelet and LDL-lowering therapy,”
he says.
Lipoprotein(a). Lipoprotein(a) is a genetic marker of
increased risk of CAD and heart attack in men under age 55 and all women,
especially those over age 55.
In patients with a strong family history of
CAD, high lipoprotein(a) levels indicate higher risk. “We recommend all
first-degree relatives of these patients be screened,” says Dr. Hazen.
Because lipoprotein(a) is attached to LDL cholesterol, more aggressive lowering of
LDL is necessary to lower risk. Aspirin also may be prescribed to decrease an
elevated risk of thrombosis (blood clots).
Homocysteine. Every 10 percent rise in homocysteine levels is associated with a
10 percent increased risk of CAD. However, lowering homocysteine does not
decrease risk.
Currently, homocysteine is used primarily to
identify which patients with chronic kidney disease (CKD) are at
increased risk for a cardiac event. “We are more aggressive with blood pressure
and cholesterol reduction in these patients,” says Dr. Hazen.
TMAO. TMAO makes blood platelets prone to
clotting. High levels of TMAO have been found to be a strong predictor of
increased risk for a heart attack or stroke caused by a blood clot.
Dr. Hazen led Cleveland Clinic’s team that
discovered this biomarker. They subsequently, developed a blood test that is
now available nationwide to determine TMAO levels. More recently, they
developed a new type of drug that blocks the formation of TMAO in the gut.
NT-proBNP. BNP is a hormone that causes blood
pressure to rise and the body to retain sodium and water. High levels of
NT-proBNP can alert doctors to worsening left ventricular ejection fraction,
making the test valuable for diagnosing heart failure in asymptomatic patients.
“When we see NT-proBNP levels are high, we
take extra care to make sure blood pressure is well controlled with standard
heart failure medications,” says Dr. Hazen.
This article originally appeared in Cleveland Clinic Heart Advisor.
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