苅尾 七臣

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.

Diabetes and hypertension are potent risk factors for cerebrovascular disease. We studied the effects of an angiotensin II type 1 receptor blockade (ARB) on brain damage in hypertensives in relation to diabetes. We studied cerebral metabolism ( by proton magnetic resonance spectroscopy) and hemodynamics (by phase-contrast magnetic resonance angiography) before and 3 to 4 months after candesartan therapy in 20 diabetic hypertensives (DHTs) and 20 matched nondiabetic hypertensives (HTs). Silent multiple cerebral infarcts detected by brain MRI were more common in DHTs than in HTs (50% versus 25%). Cerebral N-acetyl aspartate (NAA; an indicator of functional neuronal mass) was lower in DHTs than in HTs (8.35 versus 9.58 mmol/kg; P=0.007). Baseline quantitative volume flow in the internal carotid arteries (ICAs) and the middle cerebral arteries (MCAs) was comparable between the 2 groups, whereas cerebrovascular reserve (CVR) assessed using acetazolamide ( a cerebral arteriolar dilator) in ICAs (25% versus 35%; P=0.03) and MCAs (20% versus 31%; P=0.01) was lower in DHTs than in HTs. These baseline CVR and NAA values of DHT group were lower than those of 12 matched normotensives (CVR: 44% for ICA; 41% for MCA; NAA: 10.5 mmol/kg; all P<0.005). After candesartan therapy, CVR in ICAs and MCAs was significantly increased (P=0.001) independently of the reduction of the 24-hour blood pressure level, whereas the cerebral NAA level did not change. In conclusion, brain damage is advanced in DHTs. ARB partly improved the impaired cerebral microvascular function in DHTs.

White-coat hypertension (WCH) has been associated with a low risk for stroke, but long-term data are scanty. We analyzed individual data from 4 prospective cohort studies from the United States, Italy, and Japan that used comparable methodology for 24-hour noninvasive ambulatory blood pressure monitoring (ABPM). Overall, 4406 subjects with essential hypertension and 1549 healthy normotensive controls who were untreated at the time of initial ABPM were followed for a median of 5.4 years up to censoring or occurrence of a first stroke. At entry, mean age of subjects was 56 years ( range 18 to 97). Prevalence of WCH was 9%. During follow-up, there were 213 new cases of stroke. Stroke rate ( x 100 person years) was 0.35 in the normotensive group, 0.59 in the WCH group, and 0.65 in the group with ambulatory hypertension. In a multivariate analysis, the adjusted hazard ratio for stroke was 1.15 (95% confidence interval [CI], 0.61 to 2.16) in the WCH group ( P = 0.66) and 2.01 ( 95% CI, 1.31 to 3.08) in the ambulatory hypertension group ( P = 0.001) compared with the normotensive group. After the sixth year of follow-up, the incidence of stroke tended to increase in the WCH group, and the corresponding hazard curve crossed that of the ambulatory hypertension group by the ninth year of follow-up. In conclusion, WCH was not associated with a definitely increased risk of stroke during the total follow-up period. However, WCH might not be a benign condition for stroke in the long term.