KUOPIO, FINLAND. In one of our very first Conference Room Sessions (Proceeding #2, January 2003) we discussed the possible role of natriuretic peptides in lone atrial fibrillation (LAF). There are two natriuretic peptides of interest – ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide). ANP is a hormone formed by stretching of the walls of the atria. It helps regulate blood pressure and salt (Na) and water balance in body fluids. Its main action is to cause the excretion of sodium and water via the kidneys and urine. Here is what we know about ANP:

• ANP levels are lower in people with LAF than in "normal" people.
• ANP levels decline with age and increased duration (years) of afib. This is probably due to the increase of fibrosis of the arterial wall over time.
• ANP is released during exercise. A stronger release predicts a better chance of staying in normal sinus rhythm (NSR).
• ANP levels are higher during an afib episode than during normal sinus rhythm.
• ANP levels are higher when laying on the right side (right lateral decubitus position).
• A higher ANP level predicts a quicker return to sinus rhythm.
• ANP blocks the calcium channels in cardiac myocytes.
• ANP suppresses the RAAS (renin-angiotensin-aldosterone system).

BNP is a hormone formed by stretching of the walls of the ventricles. Here is what we know about BNP:

• BNP causes the excretion of sodium and water via the kidneys and urine.
• BNP suppresses the renin-angiotensin-aldosterone system, lowers aldosterone level and inhibits the release of norepinephrine and other catecholamines.

One of the key observations in the above is that ANP levels are lower in people with LAF than in those without atrial fibrillation[1]. A group of Finnish researchers now report that high blood levels of ANP and BNP are potent markers of an increased risk of stroke and AF.

Their study involved 905 Finnish men between the ages of 46 and 65 years at baseline who had no history of heart failure, previous stroke, or AF. The average BMI of the men was 27.4 (slightly overweight), 28% were smokers, 21% had coronary heart disease, 33% hypertension, and 6% diabetes. The Finnish researchers measured blood plasma concentration of ANP and BNP (as N-terminal fragments) in all study participants and then followed them for an average of 9.6 years. During this time there were 46 cases of stroke (31 ischemic, 15 hemorrhagic) and 74 cases of new-onset AF giving a total stroke incidence of 0.5%/year, an ischemic stroke incidence of 0.36%/year, and a new-onset AF incidence of 0.85%/year. It is of interest that, at the end of the 10-year follow-up, the prevalence of AF among the men was 8%.

Analysis of the data collected revealed that men in the top 10% of ANP concentration (proA-type natriuretic peptide 455 pmol/L [mean]) had a 2.80-fold increased risk of ischemic stroke and a 3.2-fold increased risk of AF after adjusting for all confounding variables. Corresponding risk factors for men in the highest 90th percentile of BNP concentrations (mean of 133 pmol/L) were 2.12 and 3.71 respectively. The Finnish researchers conclude that elevated plasma levels of ANP and BNP (as measured by their N-terminal fragments of proANP and proBNP) could be used to predict the risk of stroke and AF.

Kurl, S, et al. Plasma N-terminal fragments of natriuretic peptides predict the risk of stroke and atrial fibrillation in men. Heart, March 2009 [Epub ahead of print]

Editor's comment: The finding that high ANP/BNP levels are associated with a 3-fold increase in the risk of ischemic stroke, combined with the observation that lone afibbers tend to have lower than normal ANP levels, may help explain why the risk of ischemic stroke is so low for lone afibbers.

[1] Mattioli, AV, et al. Clinical, echocardiographic, and hormonal factors influencing spontaneous conversion of recent-onset atrial fibrillation to sinus rhythm. American Journal of Cardiology, Vol. 86, August 1, 2000, pp. 351-52