Orosomucoid, Carotid Plaque, and Incidence of Stroke.
Orosomucoid (α-1-acid glycoprotein) is an acute-phase protein that has been implicated in anti-inflammatory, immunomodulating, and angiogenic pathways. Orosomucoid has also been associated with coronary disease and stroke. The relationship between orosomucoid, carotid plaque, and stroke incidence were explored in this study.



Plasma levels of orosomucoid were assessed in 4285 subjects (39.8% men; mean age 57.5±5.9 years) without cardiovascular disease, who participated in the Malmö Diet and Cancer Study, between 1991 and 1994. The right carotid artery was examined for plaque using B-mode ultrasound examination. Incidence of stroke was followed up during a median follow-up time of 17.7 years.



Carotid plaque was present in 43.5% at baseline. Orosomucoid was significantly higher in subjects with carotid plaque (mean±SD: 0.72±0.22 versus 0.69±0.20 g/L; P<0.001). A total of 234 subjects were diagnosed with ischemic stroke during follow-up. Orosomucoid was associated with ischemic stroke after adjustment for risk factors, with hazard ratio 1.48 (95% confidence interval, 1.02-2.16) comparing the third versus first tertile. In subjects with plaque and belonging to the top tertile of orosomucoid, the hazard ratio was 2.07 (95% confidence interval, 1.38-3.11) compared with those without plaque and with orosomucoid in the first and second tertiles, after adjustment for C-reactive protein and other risk factors.



Elevated levels of orosomucoid are associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke. The combination of high orosomucoid and carotid plaque substantially increase the risk of stroke.
From the Department of Clinical Sciences Malmö (J.B., G.Ö., M.P., J.G.S., B.H., G.E.) and Department of Cardiology (J.G.S.), Lund University, Lund, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden (J.G.S.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (J.G.S.); and Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston (J.G.S.). john.berntsson@med.lu.se.
John
J
Berntsson
From the Department of Clinical Sciences Malmö (J.B., G.Ö., M.P., J.G.S., B.H., G.E.) and Department of Cardiology (J.G.S.), Lund University, Lund, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden (J.G.S.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (J.G.S.); and Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston (J.G.S.).
Gerd
G
Östling
From the Department of Clinical Sciences Malmö (J.B., G.Ö., M.P., J.G.S., B.H., G.E.) and Department of Cardiology (J.G.S.), Lund University, Lund, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden (J.G.S.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (J.G.S.); and Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston (J.G.S.).
Margaretha
M
Persson
From the Department of Clinical Sciences Malmö (J.B., G.Ö., M.P., J.G.S., B.H., G.E.) and Department of Cardiology (J.G.S.), Lund University, Lund, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden (J.G.S.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (J.G.S.); and Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston (J.G.S.).
J Gustav
JG
Smith
From the Department of Clinical Sciences Malmö (J.B., G.Ö., M.P., J.G.S., B.H., G.E.) and Department of Cardiology (J.G.S.), Lund University, Lund, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden (J.G.S.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (J.G.S.); and Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston (J.G.S.).
Bo
B
Hedblad
From the Department of Clinical Sciences Malmö (J.B., G.Ö., M.P., J.G.S., B.H., G.E.) and Department of Cardiology (J.G.S.), Lund University, Lund, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden (J.G.S.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (J.G.S.); and Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston (J.G.S.).
Gunnar
G
Engström
D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D016893:Carotid Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D015897:Comorbidity; D055316:Cystatin C / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology; D004198:Disease Susceptibility; D050171:Dyslipidemias / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D015994:Incidence; D007249:Inflammation / Q000097:blood / Q000453:epidemiology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000032:analysis*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000097:blood / Q000453:epidemiology*; D011795:Surveys and Questionnaires
D000959:Antihypertensive Agents; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D009961:Orosomucoid; D002097:C-Reactive Protein
acute-phase reaction; carotid artery disease; cytokines; risk factor; stroke