Moderate Levels of N-Terminal Pro-B-Type Natriuretic Peptide is Associated with Increased Risks of Total and Ischemic Strokes among Japanese: The Circulatory Risk in Communities Study.

N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese. We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (＜55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes. During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14-28.0) for ischemic stroke and 6.81 (1.11-41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes. We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.