The Coronary Artery Inflammation Controversy

Summary

Why did a big clinical trial that tested an anti-inflammatory drug fail to reduce heart events? Why did another pivotal trial of lowering Lp(a) fail to reduce heart events? In this edition of Ground Truths I’ll offer some explanations and introduce some new and relevant information. In part, this is about relying on surrogate endpoints like increased blood levels of interleukin-6 or Lp(a), which have been generally regarded as an accurate reflection of heightened risk for coronary artery events. That may not be true. That these biomarkers are actually indicative of heightened arterial inflammation could be assessed using non-invasive AI quantitative assessment (FAI) of inflammation in the coronary arteries. That has now been done for high-sensitivity CRP (hs-CRP) and the results are informative. An example below is for a right coronary artery (RCA) that is not obstructed (red arrow) by atherosclerosis seen via a dye injection study (angiogram) but is actually highly inflamed (high FAI score right panel]. Subscribe now We’ll address each of the trials separately. First some general background on coronary atherosclerosis and inflammation. Some Background The coronary arteries have been center stage in recent weeks. Presented at the European Congress in Munich last weekend and published at NEJM, a prospective study of over 16,000 people age d 18-70 years found “silent atherosclerosis” (←no symptoms) in 57%, with many starting to show this at the young age of 18 to 29 years: 8.7% in men, 6.7% in women. Prior studies suggest the prevalence in young adults is considerably higher (~4-5 fold using intravascular ultrasound). In JAMA last week, an assessment of calcium scores of the coronary arteries by CT scans questioned their overall utility compared with clinical criteria, recommending selective use. Both new studies underscore the high incidence of coronary atherosclerosis, cholesterol-laden plaque, that is not accompanied by symptoms. An important differentiation: coronary atherosclerosis per se is extremely common, but plaque rupture leading to heart attacks (MI, myocardial infarction) or unstable angina is relatively infrequent (about a 50:1 ratio, US data, Figure below, citation ). Why? Estimated number of Americans with coronary atherosclerosis vs those who have a myocardial infarction (heart attack) with a corresponding schematic of artery cross-sections t…