Focus on the Clinical Evidence on CHD and Lp-PLA2

Several large studies have demonstrated that inflammatory mediators play an important role in the development of atherosclerosis and potentially indicate an individual's risk for coronary heart disease. Recently, Lp-PLA2 (lipoprotein-associated phospholipase A2) has also been shown to have an association with atherogenesis and has demonstrated independent predictive power to determine coronary heart disease.

The WOSCOPS Study

The West of Scotland Coronary Prevention Study (WOSCOPS)

  • Five-year trial of 6,595 men with elevated cholesterol and no history of heart attack
  • Total of 580 men who went on to have a myocardial infarction or revascularization (cases) were compared to 1,160 age and smoking matched men who did not have an event (controls)
  • Four inflammatory biomarkers were evaluated as predictors of coronary events

Conclusions
Lp-PLA2 was shown to be the most powerful predictor of the biomarkers that were evaluated.1 The results showed that those with the highest levels of Lp-PLA2 had twice the risk of an event compared to those individuals with the lowest levels, even after adjustment for traditional risk factors and markers of systemic inflammation.

The ARIC CHD Study

A case-cohort evaluation based on the Atherosclerosis Risk in Communities (ARIC) Study

  • NIH-sponsored study in four U.S. communities on 12,819 African-American and Caucasian men and women, ages 45-65
  • Lp-PLA2 was evaluated to determine its ability to predict coronary heart disease
  • Approximate six-year follow-up period
  • A total of 608 CHD cases and 740 non-cases were evaluated

Conclusions
The results showed that elevated levels of Lp-PLA2 were higher in incident coronary heart disease cases. In individuals with non-elevated LDL levels (<130 mg/dL), Lp-PLA2 levels were independently associated with coronary heart disease, even after adjustment for traditional risk factors and C-Reactive Protein.2

The MONICA Study

A German sub study of the Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA)

  • MONICA was an international collaborative study with the objective of measuring over 10 years, and in many different populations, the trends in, and determinants of, cardiovascular disease
  • The study evaluated the relationship between Lp-PLA2 levels and risk of coronary events
  • A total of 934 apparently healthy men were followed for 14 years, with 97 men experiencing a coronary event

Conclusions
The study revealed that elevated levels of Lp-PLA2 were predictive of future coronary events in apparently healthy middle-aged men with only moderately elevated total cholesterol. Elevated Lp-PLA2 levels did not correlate with CRP, and were shown to be additive in their ability to predict risk of coronary heart disease.3

The Mayo Heart Study

A study of patients undergoing clinically indicated coronary angiography by researchers at the Mayo Clinic were followed up for major adverse events

  • 504 consecutive patients (mean age 60±11 years; 38% were women)
  • During four-year follow-up, 72 major adverse events occurred in 61 of 466 (13%) contacted patients (20 deaths, 14 myocardial infarctions, 28 coronary revascularizations, and 10 strokes)
  • The study evaluated the association of Lp-PLA2 with coronary artery disease (CAD) risk factors, with the severity of angiographic CAD, and with the incidence of major adverse events

Conclusions
The study found that higher Lp-PLA2 levels were associated with a significantly greater risk of events (death, MI, revascularization, stroke). The risk of an event increased by 28% (95% CI 1.06-1.54) with each standard deviation increase in Lp-PLA2 . The association remained significant after adjusting for clinical variables (age, gender, smoking, hypertension) and lipids (total and HDL cholesterol, Lp(a), and triglycerides) as well as CRP and fibrinogen.4

  

  1. Packard CJ, O'Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000;343:1148-1155.
  2. Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-Associated Phospholipase A2 , High-Sensitivity C-Reactive Protein, and Risk for Incident Coronary Heart Disease in Middle-Aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2004;109:837-842.
  3. Koenig W, Khuseyinova N, Löwel H, Trischler G, Meisinger C. Lipoprotein-Associated Phospholipase A2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population: Results From the 14-Year Follow-Up of a Large Cohort From Southern Germany. Circulation. 2004;110:1903-1908.
  4. Brilakis ES, McConnell JP, Lennon RJ, Elesber AA, Meyer JG, Perger PB. Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up. European Heart Journal. 2005;26:137-144.

CRP, Lp-PLA2: Association with CHD Risk in WOSCOPS

Lp-PLA2 and CRP in LDL<130 Population in ARIC Study