Cardiovascular risk factors predate the onset of symptoms of rheumatoid arthritis: a nested case–control study

Heidi Kokkonen, Hans Stenlund, Solbritt Rantapää-Dahlqvist

Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD). Our aim was to evaluate the impact of factors related to CVD, such as smoking, lipid levels, hypertension, body mass index (BMI) and diabetes, in individuals prior to the onset of symptoms of RA. A nested case-control study was performed including data from 547 pre-symptomatic individuals (i.e. individuals who had participated in population surveys in northern Sweden prior to onset of symptoms of RA, median time to symptom onset 5.0 (interquartile range 2.0-9.0) years) and 1641 matched controls. Within the survey, health examinations prior to symptom onset were performed, blood samples were analysed for plasma glucose and lipids, and data on lifestyle factors had been collected with a questionnaire. CVD risk factors were extracted and further analysed with conditional logistic regression models for association with subsequent RA development, including hypertension, apolipoprotein (Apo)B/ApoA1 ratio, BMI, diabetes and smoking habits. Smoking and BMI ≥ 25 (odds ratio (OR) (95% confidence interval (CI)) =1.86 (1.48-2.35) and OR = 1.28 (1.01-1.62), respectively) were associated with increased risk for future RA development. In women, elevated ApoB/ApoA1 ratio (OR = 1.36 (1.03-1.80)) and smoking (OR = 1.82 (1.37-2.41)) were significantly associated with being pre-symptomatic for RA, whilst in men smoking (OR = 1.92 (1.26-2.92)) and diabetes (OR = 3.62 (95% CI 1.13-11.64)) were significant. In older (>50.19 years) individuals, only smoking (OR = 1.74 (1.24-2.45)) was significantly associated with increased risk of future RA, whereas in younger individuals the significant factors were elevated ApoB/ApoA1 ratio (OR = 1.39 (1.00-1.93)), BMI ≥ 25.0 (OR = 1.45 (1.04-2.02)) and smoking (OR = 2.11 (1.51-2.95)). Pre-symptomatic individuals had a higher frequency of risk factors: 41.5% had ≥3 compared with 30.4% among matched controls (OR = 2.81 (1.78-4.44)). Several risk factors for CVD were present in pre-symptomatic individuals and significantly associated with increased risk for future RA. These factors differed in women and men. The CVD risk factors had a greater impact in younger individuals. These results urge an early analysis of cardiovascular risk factors for proposed prevention in patients with early RA.