Physician’s Weekly: online CME courses, articles on hypertension, arthritis

Traditional risk factor identification remains an important approach to preventing cardiovascular disease (CVD), but catching the known risk factors alone fails to identify many people with hidden CVD risk. Approximately 50% of all coronary events strike people with low-to-moderate cholesterol levels, and about 20% occur in people with none of the four major risk factors (high cholesterol, high blood pressure, smoking, or diabetes). As such, there is a critical need to improve the ability to identify all at-risk patients.

Part of the disease process in CVD involves arterial inflammation, which may occur at any point—from its inception to the culmination in a vascular event (eg, a heart attack or stroke). Reliable tests for vascular inflammation are available and can benefit clinicians when predicting CVD risk. Inflammatory markers may further help identify a substantial number of patients with hidden cardiovascular risk. When these people are identified early, medical management can be initiated and sustained to help patients avoid CVD events.

Assessing Key Markers

Highly sensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A₂ (Lp-PLA₂) are two well-established markers of arterial inflammation. While hs-CRP is a good test to identify inflammation in the body, the measure frequently lacks the ability to identify inflammation that’s specific to just the arteries. Factors such as infection and arthritis will cause hs-CRP levels to be elevated, so this marker cannot be relied upon as a definite indicator of increased CVD risk. In fact, the Framingham Study measured hs-CRP and determined that it wasn’t an independent predictor of CVD risk. Other recent research suggests that hs-CRP may not be involved in the atherosclerotic process, but more research is needed before any definitive conclusions can be made.

Lp-PLA₂ is a cardiovascular-specific inflammatory enzyme that has been implicated in the formation of vulnerable, rupture-prone plaques. In more than 65 studies, Lp-PLA₂ was associated with CVD risk. Testing for it was approved by the FDA for coronary heart disease risk assessment in 2003 and for ischemic stroke risk assessment in 2005. In the June 2008 American Journal of Cardiology, experts recommended the Lp-PLA₂ test be used in patients with moderate or higher risk for heart attack or stroke. This includes:

• People at any age with two or more traditional CVD risk factors.

• Anyone 55 and older.

• Smokers.

• Patients with prediabetes or diabetes.

• Anyone with known vascular disease.

The Lp-PLA₂ test is now the only blood test approved to assess stroke risk. Periodontal inflammation is the only non-arterial inflammation shown to affect Lp-PLA₂ levels; arthritis and other forms of infection do not appear to increase levels.

Analyzing Lp-PLA₂ Involvement

A study published in the September 9, 2008 issue of Circulation demonstrated that using darapladib—an experimental drug designed to block the activity of Lp-PLA₂ in the walls of arteries in patients with known coronary artery disease—prevented the enlargement of the necrotic core of atherosclerotic lesions. Advancement of the necrotic core has been linked to an increased risk of a cardiovascular event. The study demonstrated that Lp-PLA₂ appears to be a therapeutic target in the atherosclerotic disease process.

Considering the growing body of data emerging on the role of arterial inflammation and its involvement in the atherosclerotic disease process, it appears Lp-PLA₂ may be superior to hs-CRP testing. This is clinically relevant because improving the ability to identify patients earlier in the disease process can enable clinicians to take immediate and aggressive actions to enhance outcomes.

Bradley F. Bale, MD, has indicated to Physician’s Weekly that he has worked as a consultant for de Code Genetics and as a paid speaker for Abbott, Takeda, and Berkeley Heart Lab. He has also received grants/research aid from KOS and Abbott.