Patients with rheumatoid arthritis (RA) have substantial risk for cardiovascular (CV) mortality, morbidity, and metabolic syndrome (MetS). Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are also associated with increased risk for cardiovascular disease (CVD). The increased risks are associated with accentuated effects of chronic inflammation on CVD risk factors. In addition to intervention to mitigate inflammation, annual CVD risk assessment and management has been recommended for all patients with RA and should also be considered for all patients with AS and PsA.
Rheumatoid arthritis (RA) shortens life span by 10-15 years. The standardized mortality rate for RA patients is at least 1.5 times greater than the general population. The primary cause of death is CVD, however traditional CVD risk factors do not fully account for the excessive risk. Additional risk is clearly associated with chronic systemic inflammation. CVD is a chronic inflammatory disease process and meta-analyses suggest that methotrexate reduces RA-associated CVD risk. Observational evidence suggests that the commonly used TNF blockers may also decrease CVD risk. However a large 15-year follow up study of RA patients indicates that the pharmaceuticals do not substantially decrease CV mortality. Moreover, methotrexate depletes folate and may induce hyperhomocysteinemia. Elevated homocysteine has toxic effects on the arterial endothelium and is a procoagulant.
Traditional CVD risk factors contribute to, but do not fully account for the excess CV risk associated with RA. Advanced CVD risk factors have been identified that align mechanistically with the inflammatory CV disease process and pro-thrombotic events. Serum total and LDL cholesterol levels do not predict CV events in patients with RA. Oxidized LDL and small dense LDL are proven atherogenic culprits, and their circulating levels are independent of LDL cholesterol levels. The levels of Apolipoproteins A-1 and B provide a better indication of protective and atherogenic lipoprotein balance, respectively. Lipoprotein(a) is an independent CVD risk factor that has high affinity for the arterial wall and has thrombogenic properties. High activity of lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with vascular inflammation and arterial plaque instability. Advanced CVD risk factors have only been sparsely assessed in RA patients, but may help explain the increased risk for CV mortality.
Patients with inflammatory arthritis have a high prevalence of MetS, which itself is a risk factor for CVD. Further, the magnitude of CV risk in RA appears comparable to that in patients with type-2 diabetes mellitus. Associated endocrine abnormalities of MetS include insulin and leptin resistance, and low adiponectin. A high leptin to adiponectin ratio (LAR) is an independent predictor of first cardiovascular events, and it appears especially prognostic when coupled with direct biomarkers of inflammation.
Awareness has been raised to excessive CV mortality associated with autoimmune arthritis in which systemic inflammation accentuates the atherogenic effects of modern CVD risk factors. Pharmacological amelioration of inflammation and pain may improve mobility and decrease MetS, but assessment and effective management of advanced CVD risk factors should also be considered for all autoimmune arthritic patients.