Background/Purpose: Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular (CV) comorbidity compared with the general population. Contradictory results concerning CV disease prior to onset of RA have been reported. Of the known CVD risk factors, a more atherogenic lipid profile and smoking have been presented prior to RA onset. In this study, lifestyle factors, lipid levels, presence of hypertension and diabetes were evaluated in individuals prior to onset of symptoms of RA and matched population controls from northern Sweden.

Methods: A nested case-control study was based on population surveys from The Västerbotten Intervention Programme (VIP) and the WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA). Data were collected by a questionnaire (socioeconomic and lifestyle factors), assessments by a nurse (body mass index; BMI, waist and blood pressure), and blood sampling. The registers of patients with RA (ARA criteria) attending the Department of Rheumatology, Umeå was co-analysed with the registers from VIP and MONICA. This study included 547 pre-symptomatic individuals (median age 50.2 years; 372f/175m, median (IQR) predating time 5.0 (7.0) years), and 1641 controls (median age 50.3 years; 1116f/525m). CVD risk factors were defined as: hypertension (systolic ≥140 mmHg and/or diastolic ≥90 mmHg including hypertensive treatment), elevated ApoB/ApoA1 ratio (females ≥0.7, males ≥0.8, including lipid lowering treatment), BMI ≥25, diabetes, and ever smoker.

Results: In conditional logistic regression models elevated ApoB/ApoA1 ratio (OR 1.3 (95% CI 1.0,1.6)), smoking (OR 2.0 (95% CI 1.6,2.5)), BMI≥ 25 (OR 1.3 (95% CI 1.1,1.6)) and diabetes (OR 2.0 (95% CI 1.1,3.7)) were associated with individuals who subsequently developed RA. In women elevated ApoB/ApoA1 (OR 1.4 (95% CI 1.1-1.8)), smoking (OR 1.9 (95% CI 1.1-1.8)), and BMI ≥25 (OR 1.3 (95% CI 1.1-1.7)) were significant for being pre-symptomatic for RA, in men the risk factors were smoking (OR 2.2 (95% CI 1.5-2.5), and diabetes (OR 4.7 (95% CI 1.71-13.1)). Stratifying on the median age, the factor remaining significant for the future RA group in older individuals was smoking (OR 1.7 (95% CI 1.2,2.5)), whereas in the individuals ≤50.2 years the factors were: elevated ApoB/ApoA1 ratio (OR 1.4 (95% CI 1.0,1.9)), BMI ≥25.0 (OR 1.5 (95% CI 1.0-2.0)), and smoking (OR 2.1 (95% CI 1.5,3.0). The pre-symptomatic individuals had significantly higher frequency of risk factors, 42% had ≥3 of these compared with 30% of the matched controls (OR 2.8 (95% CI 1.8, 4.5)). Especially, ACPA positive pre-symptomatic individuals had a high OR for future RA when having ≥3 of the CV risk factors (OR 5.7 (95% CI 2.1-15.3)).

Conclusion: Several of the CV risk factors were present in individuals already years before onset of symptoms of RA. One third of the pre-symptomatic individuals had at least 3 of these factors present. The risk factors for CVD associated with future RA differ between women and men. In younger individuals as well as ACPA positive individuals the CVD risk factors have a greater impact. These results urge an early CV prevention in patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-cardiovascular-disease-predate-the-onset-of-symptoms-of-rheumatoid-arthritis/