NT-proBNP and MR-proANP were measured in fasting blood samples from 4,862 subjects (40.2% men, mean age 57.5 ± 6.0 years) without
cardiovascular disease from the Malmö Diet and
Cancer Study, a prospective, population-based study in Sweden. Incidence of
ischemic stroke was monitored over a mean follow-up of 14.9 ± 3.0 years.
Stroke cases were etiologically classified according to the TOAST classification. Cox proportional-hazards regression was used to study the incidence of
stroke in relationship to
NT-proBNP and MR-proANP.
RESULTS: During follow-up, 227 had a first-ever
ischemic stroke (large-artery
atherosclerosis, n = 35;
cardioembolic stroke, n = 44; small-artery occlusion, n = 80; undetermined cause, n = 68). In the age- and sex-adjusted model, only
NT-proBNP was associated with total
ischemic stroke. This association was completely explained by an increased incidence of
cardioembolic stroke. Adjusted for cardiovascular risk factors (age, sex,
hypertension, diabetes, smoking, body mass index and
low-density lipoprotein cholesterol), the hazard ratios (HRs, 95% confidence interval, 95% CI) for
cardioembolic stroke were 1.00 (reference), 1.42 (0.34-6.00), 2.79 (0.77-10.12) and 5.64 (1.66-19.20), respectively, for the 1st, 2nd, 3rd and 4th quartiles of
NT-proBNP. The corresponding HRs (95% CIs) for quartiles of MR-proANP were 1.00 (reference), 1.83 (0.55-6.14), 1.20 (0.33-4.34) and 3.96 (1.31-11.99), respectively. In total, 335 (6.9%) subjects were diagnosed with
atrial fibrillation during follow-up. Among the
cardioembolic stroke cases, 30% were diagnosed with
atrial fibrillation before the
stroke event and another 36% within 6 months after the
stroke. Of the
cardioembolic stroke cases with
atrial fibrillation, 59% were in the top quartile of
NT-proBNP, 69% in the top quartile of MR-proANP and 79% were either in the top quartile of
NT-proBNP or in the top quartile of MR-proANP.
CONCLUSION: High plasma levels of
NT-proBNP and MR-proANP are associated with a substantially increased risk of
cardioembolic stroke, but not with other subtypes of
ischemic stroke. The results suggest that assessment of
stroke risk, including electrocardiography, is warranted in subjects with high
NT-proBNP or MR-proANP.