Novel risk factors for atrial fibrillation in an urban population

Sammanfattning: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population, and a major cause of morbidity and mortality. Low-grade inflammation, erythrocyte volume variation, and subclinical atherosclerosis have repeatedly been associated with cardiovascular disease, but it remains unclear whether these risk factors are also associated with incident AF. This thesis is based on four epidemiological papers. Paper I-II included subjects from the Malmö Preventive Project (n=22 444, aged 26-61 years), followed during a mean follow-up time of 25 years. Paper III-IV included subjects from the Malmö Diet and Cancer Study (n=30 477, aged 44-74 years), followed during mean follow-up of 13.6 and 15.3 years respectively. Cases of incident AF were retrieved by linkage with the Swedish Hospital Discharge Register and the Swedish Cause of Death Register. Participants in Paper I-II underwent measurements of inflammation-sensitive proteins (ISPs) and genotyping of polymorphisms in the ceruloplasmin gene (CP). Red blood cells distribution width (RDW) was measured in participants of Paper III. Carotid intima-media thickness (IMT) was measured in participants of Paper IV. All subjects were without history of AF, myocardial infarction and heart failure at study entry. A score of five ISPs (ceruloplasmin, fibrinogen, haptoglobin, orosomucoid and α1-antitrypsin) were significantly associated with incidence of AF. Plasma levels of ceruloplasmin were associated with incidence of AF. Genetic polymorphisms in the promoter of the ceruloplasmin gene were associated with elevated plasma levels of ceruloplasmin. One of these polymorphisms was also associated with incidence of AF, suggesting a causal relationship between ceruloplasmin and AF. RDW and carotid IMT were both independently associated with incidence of AF. In conclusion, this thesis shows that ceruloplasmin, RDW and carotid IMT are all factors that may predict future events of AF in the general population. Further studies are needed to elucidate the causal pathway between ceruloplasmin and AF.