Mira Merashli1, Tommaso Bucci2, Daniele Pastori3, Pasquale Pignatelli3, Paul R J Ames4,5. 1. Department of Rheumatology, American University of Beirut, Beirut, Lebanon. 2. Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini", Sapienza University of Rome, Rome, Italy. 3. Department of Clinical, Internal, Anesthesiological & Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy. 4. Immune Response & Vascular Disease Unit, Nova University Lisbon, Rua Camara Pestana, Lisbon, Portugal. paxmes@aol.com. 5. Department of Haematology, Dumfries Royal Infirmary, Cargenbridge, Dumfries, DG2 7AH, Scotland, UK. paxmes@aol.com.
Abstract
AIM: To perform a systematic review and meta-analysis of studies reporting data on atherosclerosis and inflammatory markers in familial Mediterranean fever (FMF). METHODS: EMBASE and PubMed databases were screened according to PRISMA guidelines from inception to January 2022 for articles reporting measurements of the intima media thickness (IMT) of carotid arteries and eventually carotid plaques; random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events were employed. RESULTS: The screening and selection search strategy yielded 18 case controls studies (16 full papers and 2 abstracts); the IMT was greater in FMF (n = 1112) than in controls (n = 901) (p < 0.0001) with wide heterogeneity (I2 = 86.4%); a sensitivity analysis according to mean age of participants, male to female ratio, disease duration, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen (FNG), atherogenic index of plasma (AIP), colchicine use and NOQAS revealed that the heterogeneity variance was partly explained by CRP (p = 0.01) and to a much lesser extent by the AIP (p = 0.10). The pooled prevalence of carotid plaques was greater in FMF (n = 137) than in controls (n = 156) (19% vs 8.3%, p = 0.02) with low heterogeneity. CONCLUSION: FMF is characterised by premature atherosclerosis expressed as a thicker intima media and a greater prevalence of carotid plaques, partially related to the C-reactive protein, as expected by the autoinflammatory nature of FMF. Key Points • Familial Mediterranean fever is characterised by premature atherosclerosis. • C-reactive protein relates to intima media thickness in keeping with the autoinflammatory nature Familial Mediterranean fever. • Targeting the inter-critical low-grade inflammation may be relevant to minimise the additional cardiovascular risk posed by premature atherosclerosis.
AIM: To perform a systematic review and meta-analysis of studies reporting data on atherosclerosis and inflammatory markers in familial Mediterranean fever (FMF). METHODS: EMBASE and PubMed databases were screened according to PRISMA guidelines from inception to January 2022 for articles reporting measurements of the intima media thickness (IMT) of carotid arteries and eventually carotid plaques; random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events were employed. RESULTS: The screening and selection search strategy yielded 18 case controls studies (16 full papers and 2 abstracts); the IMT was greater in FMF (n = 1112) than in controls (n = 901) (p < 0.0001) with wide heterogeneity (I2 = 86.4%); a sensitivity analysis according to mean age of participants, male to female ratio, disease duration, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen (FNG), atherogenic index of plasma (AIP), colchicine use and NOQAS revealed that the heterogeneity variance was partly explained by CRP (p = 0.01) and to a much lesser extent by the AIP (p = 0.10). The pooled prevalence of carotid plaques was greater in FMF (n = 137) than in controls (n = 156) (19% vs 8.3%, p = 0.02) with low heterogeneity. CONCLUSION: FMF is characterised by premature atherosclerosis expressed as a thicker intima media and a greater prevalence of carotid plaques, partially related to the C-reactive protein, as expected by the autoinflammatory nature of FMF. Key Points • Familial Mediterranean fever is characterised by premature atherosclerosis. • C-reactive protein relates to intima media thickness in keeping with the autoinflammatory nature Familial Mediterranean fever. • Targeting the inter-critical low-grade inflammation may be relevant to minimise the additional cardiovascular risk posed by premature atherosclerosis.
Authors: Melissa L Rethlefsen; Shona Kirtley; Siw Waffenschmidt; Ana Patricia Ayala; David Moher; Matthew J Page; Jonathan B Koffel Journal: Syst Rev Date: 2021-01-26