Low-Grade Inflammation Is a Risk Factor for Clinical Stroke Events in Addition to Silent Cerebral Infarcts in Japanese Older Hypertensives

Background and Purpose—High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is associated with atherosclerosis, hypertensive target organ damage, and cardiovascular events. In the general Japanese population, the level of hsCRP is reported to be lower than that in Western countries, and the relationships among hsCRP, silent cerebral infarcts (SCIs), and clinical stroke events in older Japanese hypertensives remain unclear. Methods—We conducted brain MRI and measured hsCRP at baseline in 514 older Japanese hypertensives (clinic blood pressure 140/90 mm Hg, age 50 years old) who were enrolled in the Jichi Medical School ABPM Study, wave 1. They were followed up for an average of 41 months (range: 1 to 68 months, 1751 person-years) and the incidence of subsequent clinical stroke events was evaluated. Results—The subjects with SCIs at baseline (n 257) had a higher hsCRP level than those without SCIs (geometric mean hsCRP [SD range]; 0.19 [0.18 to 0.21] versus 0.14 [0.13 to 0.16] mg/L, P 0.007) after adjustment for confounding factors, and the OR for the presence of SCIs was increased with the quartile of hsCRP levels. In Cox regression analysis, the patients with above median hsCRP level ( 0.21 mg/L) (hazard ratio [HR]: 2.50, 95% CI: 1.24 to 5.00, P 0.01) and those with SCIs (HR: 4.60, 95% CI: 1.91 to 11.03, P 0.001) at baseline had independently higher risks for clinical stroke events after adjustment for age, smoking status, antihypertensive medication use, and 24-hour systolic blood pressure level. Compared with the patients with below median hsCRP level without SCIs, those with above median hsCRP level and SCIs at baseline had a higher risk for clinical stroke events (HR: 7.32, 95% CI: 2.17 to 24.76, P 0.001), although those with below median hsCRP level and SCIs (HR: 2.46, 95% CI: 0.64 to 9.47, P 0.19) and those with above median hsCRP level without SCIs (HR: 1.11, 95% CI: 0.22 to 5.55, P 0.90) did not have significant risks. Conclusion—High-sensitivity C-reactive protein is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives, indicating that the risk for clinical stroke events increases with preexisting hypertensive target organ damage in the brain and additionally with ongoing low-grade inflammation. (Stroke. 2007; 38:911-917.)