An estimated 50 percent of patients with cardiovascular disease do not have elevated low-density lipoprotein cholesterol levels in their blood, the traditional marker for cardiovascular disease risk. But in recent years, new biochemical markers have been discovered to help physicians identify and treat patients at risk for CVD.
In an Assembly Dialogue session on Sept. 30, John Holman, M.D., M.P.H., director of the family medicine residency program at the Naval Hospital at Camp Pendleton, Calif., and Gordon Zubrod, M.D., a family physician at the Robert E. Bush Naval Hospital in Twenty Nine Palms, Calif., described new biomarkers for CVD and their possible uses in identifying patients at risk.
"C-reactive protein is a nonspecific biochemical marker of systemic inflammation," Zubrod said. "Inflammation plays a key role in plaque formation." Elevated human serum C-reactive protein, or hs-CRP, levels indicate low-grade inflammation and serve as an independent predictor of future cardiovascular events.
Hs-CRP levels between 1 mg per dL and 3 mg per dL indicate an intermediate risk of CVD, and levels above 3 mg per dL indicate high risk. Statins have been shown to lower hs-CRP levels by 13 percent to 50 percent, said Zubrod.
"Homocysteine is a chemical that modulates endothelial function," Holman said. Elevated serum levels of homocysteine are associated with an increased risk of coronary artery disease, stroke and peripheral artery disease.
The American Heart Association recommends that patients with a personal or family history of cardiovascular disease but without other risk factors should be screened for homocysteine levels. Levels above 15 µmol per L indicate high risk for CVD. Folate and vitamin B12 lower homocysteine levels, said Holman.
Apolipoprotein B, or apo B, is a surface component of LDL found on all serum lipid components, Zubrod said. Elevated serum apo B levels reflect elevated levels of all atherogenic particles in blood and identify individuals with small, dense LDL particles, which are associated with a high risk of CVD. Statins lower apo B levels.
Fibrinogen is a substrate for thrombin that also modifies endothelial function, Holman said. Elevated fibrinogen levels are associated with smoking, a sedentary lifestyle, hypertriglyceridemia, and insulin resistance and have been shown to be an independent risk factor for CVD and stroke.
However, the assay for fibrinogen is "terrible," he said, and can't be relied on. In addition, there is no good evidence on how to lower elevated serum levels, so screening is not recommended, Holman concluded.
