The impact of C-reactive protein on risk of stroke, stroke subtypes, and ischemic heart disease in middle-aged Japanese: the Japan public health center-based study

J Atheroscler Thromb. 2012;19(8):756-66. Epub 2012 Jul 11.


Aim: To examine the impact of C-reactive protein on the risks of stroke and its subtypes, particularly among Asian populations in which median C-reactive protein levels are typically lower than in Western populations.

Methods: A prospective, nested case-control study was conducted to examine the associations between high sensitivity-CRP (hs-CRP) and risks of cardiovascular disease within a cohort of 29,876 men and women aged 40-69 years, with no history of stroke, ischemic heart disease or cancer, who submitted blood samples between 1990 and 1993. Systematic cardiovascular surveillance was performed throughout 2007. One control for each stroke and two controls for each ischemic heart disease were matched for sex, age, date of blood drawing, time since last meal and study location.

Results: We documented 1,132 incident strokes (638 ischemic and 494 hemorrhagic strokes) and 209 ischemic heart diseases (168 myocardial infarctions and 41 sudden cardiac deaths), and observed a linear association between hs-CRP levels and risks of ischemic stroke and ischemic heart disease, more specifically myocardial infarction. The multivariable odds ratios associated with 1-SD increment of logarithmically transformed hs-CRP were 1.13 (0.99-1.29),p= 0.07 for ischemic stroke, 1.16 (0.96-1.41),p= 0.13 for lacunar infarction, 1.41 (0.98-2.01),p= 0.06 for embolic infarction, and 1.28 (1.03-1.59),p= 0.03 for myocardial infarction. The predictive value of hs-CRP for ischemic stroke was reduced primarily after adjustment for hypertensive status and body mass index. No association was found between hs-CRP levels and the risk of hemorrhagic or total stroke.

Conclusions: High serum hs-CRP levels were associated with the risk of myocardial infarction and more weakly with the risk of ischemic stroke among middle-aged Japanese men and women.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Ischemia / blood
  • Ischemia / diagnosis*
  • Ischemia / etiology
  • Japan
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / etiology
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis*
  • Stroke / etiology


  • Biomarkers
  • C-Reactive Protein