Elevated C-Reactive Protein Values and Atherosclerosis in Sudden Coronary Death

Abstract

Background — Elevations in serum C-reactive protein measured by high-sensitivity assay (hs-CRP) have been associated with unstable coronary syndromes. There have been no autopsy studies correlating hs-CRP to fatal coronary artery disease. Methods and Results — Postmortem sera from 302 autopsies of men and women without inflammatory conditions other than atherosclerosis were assayed for hs-CRP. There were 73 sudden deaths attributable to atherothrombi, 71 sudden coronary deaths with stable plaque, and 158 control cases (unnatural sudden deaths and noncardiac natural deaths without conditions known to elevate CRP). Atherothrombi were classified as plaque ruptures (n=55) and plaque erosion (n=18); plaque burden was estimated in each heart. Total cholesterol, high-density lipoprotein cholesterol, diabetes, smoking history, and body mass index were also determined. Immunohistochemical stains for CRP and numbers of thin cap atheromas per heart were quantitated in coronary deaths with hs-CRP in the highest and lowest quintiles. The median hs-CRP was 3.2 μg/mL in acute rupture, 2.9 μg/mL in plaque erosion, 2.5 μg/mL in stable plaque, and 1.4 μg/mL in controls. Mean log hs-CRP was higher in rupture ( P <0.0001), erosion ( P =0.005), and stable plaque ( P =0.0003) versus controls. By multivariate analysis, atherothrombi ( P =0.02), stable plaque ( P =0.003), and plaque burden ( P =0.03) were associated with log hs-CRP independent of age, sex, smoking, and body mass index. Mean staining intensity for CRP of macrophages and lipid core in plaques was significantly greater in cases with high hs-CRP than those with low CRP ( P =0.0001), as were mean numbers of thin cap atheromas ( P <0.0001). Conclusions — hs-CRP is significantly elevated in patients dying suddenly with severe coronary artery disease, both with and without acute coronary thrombosis, and correlates with immunohistochemical staining intensity and numbers of thin cap atheroma.