Familial mediterranean fever and long-term cardiovascular disease burden

Familial Mediterranean fever is a lifelong autoinflammatory disorder characterized by recurrent systemic inflammation. Although chronic inflammation is a recognized driver of cardiovascular disease, the long-term cardiovascular and renal consequences of Familial Mediterranean fever remain incompletely defined at the population level.

We conducted a matched cohort study within a nationwide Israeli health maintenance organization. Patients with Familial Mediterranean fever were matched to controls by age, sex, and follow-up duration (3,403 FMF patients and 13,296 matched controls). FMF was defined by ≥ 2 physician-documented diagnoses and ≥ 2 colchicine dispensings; adherence, dose intensity, and treatment duration were not assessed. Cardiovascular and renal outcomes were evaluated over up to 20 years of follow-up. Inflammatory indices-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)-were longitudinally assessed. Conditional logistic regression was used to estimate end-of-follow-up prevalence odds.

Compared with matched controls, patients with Familial Mediterranean fever demonstrated persistently elevated inflammatory indices throughout follow-up. Familial Mediterranean fever was associated with a higher long-term prevalence of ischemic heart disease, atrial fibrillation, stroke, heart failure, and major adverse cardiovascular events. Renal manifestations, including albuminuria and chronic kidney disease, were also more prevalent among Familial Mediterranean fever patients. These associations persisted despite lower levels of traditional cardiometabolic risk factors.

Familial Mediterranean fever is associated with a persistent, inflammation-driven burden of cardiovascular and renal disease over decades, emphasizing the importance of proactive vascular surveillance and targeted anti-inflammatory strategies.