Cardiovascular and Metabolic Risk Factors in Inherited Autoinflammation

Context: The natural progression of metabolic abnormalities among patients with inherited autoinflammation is unclear. Objective: The objective of the study was to assess the cardiometabolic risk of participants with familial Mediterranean fever (FMF). Design and Setting: This study included nationwide cross-sectional and longitudinal cohorts. Participants: The prevalence of components of the metabolic syndrome at age 17 years was assessed from the medical database of the Israeli Defense Force from 1973 through 1997. Included were 745 males with FMF, 902 healthy male siblings, and a control group of 787 714 participants. A prospective follow-up study traced the incidence of components of the metabolic syndrome to age 45 years among 57 FMF and 1568 control army personnel participants. Interventions: Body mass index (BMI) and blood pressure (BP) were measured at age 17 years (cross-sectional); lifestyle, anthropometric, and biochemical data were periodically recorded from age 25 years. Main Outcome Measures: Abnormal BMI or BP (age 17 y) and Adult Treatment Panel III criteria of the metabolic syndrome were measured. Results: In multivariable regression analysis adjusted for known confounders of obesity, FMF participants had an odds ratio of 0.65 for the occurrence of over weight [95% confidence interval (CI) 0.44-0.96, P = .03] and 0.66 (95% CI 0.48-0.92, P = .012) for hypertension-range BP; their siblings tended to obesity (odds ratio 1.48; 95% CI1.04-2.11, P = .008). In the follow-uparm, a multivariable analysis adjusted for age, birthyear, BMI, education, socioeconomic status, ethnicity, and physical activity yielded hazard ratios of 0.32 (95% CI 0.10-0.82, P = .002) for incident obesity, 0.49(95% CI 0.25-0.95, P = .037) for incident triglycerides 150 mg/dL or greater, 0.56 (95% CI 0.31-0.98, P = .048) for low-density lipoprotein cholesterol 130 mg/dL or greater, and 2.14 (1.368-3.359, P = .001) for high-density lipoprotein cholesterol less than 40 mg/dL for FMF participants compared with controls. Incident elevated BP was lower among FMF participants (hazard ratio 0.49; 95% CI 0.23-1.00, P = .05), whereas dysglycemia incidence was comparable. Conclusions: FMF is associated with lower rates of most components of the metabolicsyndrome compared with normal subjects, unlike other inflammatory conditions.