C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in a general Japanese population: the Hisayama Study

Stroke. 2006 Jan;37(1):27-32. doi: 10.1161/01.STR.0000194958.88216.87. Epub 2005 Nov 23.


Background and purpose: The role of high-sensitivity C-reactive protein (hsCRP) in the development of stroke is not clearly understood. We investigated the relationship between serum hsCRP levels and stroke occurrence in a general Japanese population.

Methods: We followed 2692 subjects > or =40 years of age for 12 years. The relative risks and 95% CIs for ischemic and hemorrhagic stroke occurrence were calculated according to the hsCRP quintiles.

Results: During the follow-up, 129 first-ever ischemic and 59 hemorrhagic strokes occurred. In men, the age-adjusted incidence of ischemic stroke significantly increased with elevated serum hsCRP levels; the difference between the first and fifth quintiles was statistically significant (1.4 versus 6.6 per 1000 person-years; P=0.02). This association remained significant even after adjustment for other confounding factors, such as age, systolic blood pressure, ECG abnormalities, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol, smoking habits, alcohol intake, and regular exercise (adjusted relative risks, 3.11; 95% CI, 1.04 to 9.32; P=0.04). However, such associations were not observed for ischemic stroke in women or in hemorrhagic stroke in either sex. Among male subjects who were both in the fifth hsCRP level and had hypertension, diabetes, obesity, hypercholesterolemia, or a smoking habit, the risk of ischemic stroke was extremely increased, even after adjustment for other risk factors.

Conclusions: Our findings suggest that elevated serum hsCRP levels are an independent risk factor for future ischemic stroke in Japanese men and that the coexistence of a high hsCRP level with another risk factor extremely increases the risk of ischemic stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Blood Pressure
  • C-Reactive Protein / biosynthesis*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Hemorrhage / blood
  • Hemorrhage / etiology*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Risk
  • Risk Factors
  • Sex Factors
  • Stroke / blood
  • Stroke / diagnosis*
  • Stroke / etiology*
  • Time Factors


  • C-Reactive Protein