Traditional and nontraditional risk factors associated with CVD and RA.
Risk factor
Comments
References
Traditional risk factors
Obesity
(i) Insulin resistance due to release of inflammatory cytokines such as TNF-. (ii) Increased coronary calcification due to insulin resistance. (iii) Abdominal fat.
(i) Old age prompts structural and functional deterioration in the heart and vessels structure. (ii) Senescent immune system is normally associated with phenotypical and functional changes.
(i) Coexistence of T2DM and RA increases three times the risk of developing CVD. (ii) Abdominal obesity, antihypertensive medication, disease activity, and use of GCs affect glucose metabolism in RA patients.
(i) It is considered as biomarker for AT and a risk factor related to CAD and CVA. (ii) There is still controversy about whether hyperhomocysteinemia is a causative agent of cardiovascular damage or only an epiphenomenon of inflammation. (iii) A high prevalence of this biomarker had a statistical association with male gender and higher radiological damage.
(i) Alteration in the production of cytokines and proinflammatory adipokines leads to an increasing activity of RA and an accelerating AT. (ii) It was related to pain and functional status, suggesting disease activity (iii) Increased prevalence of waist circumference, blood pressure, and fasting glucose (i.e., worse prognosis). (iv) Increased epicardial adipose tissue volume.
(i) Patients are less physically active than controls due to pain, stiffness, deformity, and impaired mobility. (ii) Impairment of altered lipid pattern.
(i) Smokers with RA have worse prognosis than nonsmokers RA patients in terms of RF titers, disability, radiological damage, CVD, and treatment response. (ii) Premature CVD mortality.
(i) Its alleles are related to chronic inflammation, high disease activity, EAMs, endothelial dysfunction, increasing CV events, AT plaque, and premature mortality. Some of them are independent of autoantibody status. (ii) Being a carrier of a single copy of HLA-DRB1 SE was significantly associated with an increased risk of atherosclerotic plaque in RA Colombian patients.
(i) Polymorphisms in endothelin-1, MTH-FR, TRAF1/C5, STAT4, factor XIIIA, PAI-1, TNFR-II, LT-A, LGALS2, TGF-, GSTT1, ACP1, and NF-1 genes may be contributed to CVD risk and adverse outcome. (ii) Interaction between smoking and polymorphism in the VEGFA gene is associated with IHD and MI in RA patients. (iii) The IL6-174 gene polymorphism may play a role in the development of subclinical atherosclerosis in patients with RA. (iv) TNFA rs1800629 (GA) gene polymorphism is associated with predisposition to CV complications in RA patients. This predisposition seems to be restricted to individuals carrying the SE. (v) Genetically determined high serum levels of MBL and high serum levels of agalactosyl IgG are associated with increased risk of IHD, MI, and premature death.
(i) Independent factor for developing MI and accelerated AT. (ii) It represents a broad spectrum of conditions related with the autoimmune nature of the disease.
(i) It confers additional susceptibility to CVD in RA patients, as well as presence of atherosclerotic plaque, radiographic progression, high disease activity, and persistent inflammation. (ii) Increased frequency of HLA-DR4.
(i) It targets inflammation but its adverse effects include carotid plaques, arterial stiffness, decreased insulin sensitivity, elevated lipid levels, hypertension, and CVD. (ii) Patients that are treated with a daily dose 7.5 mg/day appeared to have twice as the risk of heart disease as patients that are in nonsteroidal treatment. (iii) The increased mortality in patients under low-dose oral GC for more than 10 years has been related mainly to CVD.
(i) Disease duration over 10 years was significantly associated with increased risk of atherosclerotic plaque in Colombian population. (ii) Patients with prolonged RA have more atherosclerosis than patients of the same age with more recent disease onset. They have more extensive subclinical atherosclerosis or CAC, independent of other CHD risk factors. (iii) RA duration is independently associated with LVDD suggesting the impact of chronic autoimmune inflammation on myocardial function.
(i) Immune complexes from RF can be deposited in the endothelium generating endothelial dysfunction and AT through inflammatory reactions. (ii) RF-positive patients were at increased risk of CV events following exposure to GC. (iii) RF titers were independently predictive of endothelial dysfunction and increased mortality in RA. (iv) Anti-CCP and RF-IgM were related to impaired endothelial function independent of other CV risk factors, and they are independently associated with impaired left ventricular relaxation and development of IHD. (v) Anti-ox-LDL, ACLA, APLA, and anti-ApoA-1 are associated with early atherosclerotic changes and future thrombotic events. (vi) The presence of ACLA and an altered lipid profile may represent an important risk factor for thrombotic events in patients affected by RA. Anti-PC, anti-HSP 60/65, and anti-MDA-LDL may have independent roles in subclinical AT. (vii) Anti-ox-LDL was strongly related with the degree of inflammation and carotid plaque and may predispose to a higher risk for CVD, as they were independently associated with subclinical atherosclerosis. (viii) High levels of anti-MCV and LDL-immune complexes are risk factors for increased AT and are associated with inflammation.
(i) It may accelerate atherogenic processes and microvascular dysfunction: accentuation of known pathways of plaque formation. (ii) Inflammatory stimuli may be involved in the initiation of CHF among patients with RA. (iii) Markers of chronic inflammation (i.e., current and cumulative inflammation) such as CRP, ESR, TNF-, IL-6, IL-17, and haptoglobin are present in endothelial activation and increased in carotid IMT, carotid plaque, CAD, CV complications, and mortality. (iv) Both established CV risk factors and manifestations of RA inflammation contribute significantly to carotid atherosclerosis in RA and may modify one another’s effects.
(i) Higher activity index is associated with CV events and mortality. (ii) DAS-28 was a significant predictor of major adverse CV events and mortality. (iii) The occurrence of new CV events in very early RA was explained by traditional CV risk factors and was potentiated by high disease activity.
(i) Increases three times the risk of having CVD and these patients, also present greater IMT. (ii) CVD is considered a severe EAM of the disease. (iii) Severe EAM manifestations are associated with an increased risk of CVD events. Systemic EAM disease is a major determinant of CVD morbidity.
(i) State of hypofibrinolysis is associated with CVD progression and levels of von Willebrand factor, PAI-1, and tissue type plasminogen (ii) Other biomarkers have been related to CVD: OPG, OPN, sPTX-3, periodontal disease, hepcidin, seric uric acid, para-articular bone loss, and MBL.
Associated with high levels of LDL, low levels of atheroprotective anti-PC, and high frequency of HTN in RA patients. Patients with RA experience a 4.3% increase in body fat mass for a given BMI compared to healthy individuals.
