Plasma Natriuretic Peptides and Incidence of Subtypes of Ischemic Stroke

Abstract

Background and Purpose: Natriuretic peptides predict poor outcomes in cardiovascular disease. However, the knowledge of their relationship to stroke is limited and prospective studies from the general population are few. The purpose of this study was to explore the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) plasma levels and the risk for ischemic stroke and its subtypes. Methods: 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.

Serum Soluble Corin Is Decreased in Stroke

“…7 Largescale prospective cohort studies found that increased natriuretic peptides were significantly associated with increased risks for incident stroke, 3,4 although the mechanism is not clear. Clinical studies reported that natriuretic peptides were increased in patients with stroke and associated with infarct size.…”

“…Recently, increased natriuretic peptides were suggested to be risk factors for stroke, although the mechanism is not clear. 3,4 Human corin, a type II transmembrane serine protease highly expressed in the heart, 5,6 played a physiological role in the activation of natriuretic peptides. 7 This indicated a potential role of human corin in stroke.…”

Atrial cardiopathy: a mechanism of cryptogenic stroke

“…73 NT-proBNP is an independent predictor of cardiovascular events including incident AF in epidemiological and clinical populations, 74–77 and NT-proBNP has been associated with subclinical cerebrovascular disease 78 and risk of cardioembolic stroke. 79, 80 NT-proBNP is also associated with increased likelihood of detection of paroxysmal AF in patients with ischemic stroke. 81, 82 …”

The Link between Early Biomarker Analysis and the Neurological Outcome in Stroke Patients

“…A prospective cohort study concluded that people with an elevated MRproANP are at a higher risk to experience a cardio-embolic stroke. The risk of other stroke subtypes is not elevated [51]. MRproANP is a precursor hormone of atrial natriuretic peptide (ANP) which regulates blood pressure [52].…”