Table 3: Traditional and non-traditional risk factors associated with cardiovascular disease and rheumatoid arthritis in Latin America.

Risk factor associated with CVD CommentsReference(s)

Traditional

HypertensionIncreases the risk to suffer IHD or stroke with an important impact on mortality in patients with RA[16]

T2DMPatients with RA have a similar risk of developing CVD when compared to the same risk in patients with T2DM. Unfortunately, when there is a coexistence of both diseases, this risk is increased by three times[69]

DyslipidemiaAltered lipid profiles in RA patients are related with higher probability of IHD by accelerating atherosclerosis[25, 70]

Is characterized for an alteration in production/secretion of proinflammatory adipokines and leads to increased activity of RA and accelerating atherosclerosis[68, 71]
MetSStudies about the prevalence of MetS in LA patients have not achieved definitive conclusions, although its presence has been directly associated with a worse prognosis[53]
In RA patients, was related with pain and functional status, suggesting disease activity. Therefore, a better control of disease activity may reduce CVD risk[50]

HyperhomocysteinemiaHomocysteine is considered as biomarker for atherosclerosis and a risk factor related with CAD and stroke[22, 72]
There is still controversy about whether hyperhomocysteinemia is a causative agent of cardiovascular damage or only an epiphenomenon of inflammation[48]
A high prevalence of this biomarker in Mexican patients with RA had a statistical association with male gender and higher radiological damage[48]
High homocysteine concentration can be an important risk marker for CVD in Chilean patients with RA, as it was significantly associated[30]

Nontraditional

Related with chronic inflammation, endothelial dysfunction, and premature death for CVD[7375]
Genetic HLA-DRB1 SE allelesAssociated with severe RA and with more EAM, high activity, and systemic inflammation[7477, 79]
Being a carrier of a single copy of HLA-DRB1 SE were significantly associated with an increased risk of atherosclerotic plaque in RA Colombian patients[25]

PolyautoimmunitySome articles included patients with poliautoimmunity, but no correlation with CVD subphenotypes was described [25, 46, 55, 58]
Familial autoimmunityWas associated with presence of atherosclerotic plaque in RA Colombian patients. [25]
High titers have been established to be a predictor of CVD due to immune complex formation and tissue injury. It has been shown that such immune complexes from RF can be deposited in the endothelium and through inflammatory reactions generate endotelial disfunction and atherosclerotic process [86]
RF positivityRF seropositivity was significantly associated with an increased risk of endothelial dysfunction in RA Colombian patients[25]
A statistical association between increased IMT, atherosclerosis plaque, and presence of RF was described in Mexican population with RA[49]
anti-oxLDLPromote instability and rupture of the atheromatous plaque within the coronary arteries[24, 88]
Only one LA study evaluated this antibodies, but no correlation with CVD was found[30]
Other autoantibodies
The presence of plaques was higher in Brazilian patients with RA, but no correlation between IMT or plaques and autoantibodies were found[51]
AD associated Other autoantibodies were assessed in LA population, such as aCL, anti-β2GPI, anti-HSP 60/6, and anti-CCP antibodies with no association regarding CVD outcomes[25, 30, 51, 55]
Inflammatory markersThe association of inflammatory pathways with CVD is complex and is composed of several intermediate factors, including dyslipidemia, homocysteinemia, insulin resistance, and endothelial dysfunction[89]
May accelerate atherogenic processes, either by the accentuation of known pathways of plaque formation or by the onset of additional immune pathways[90]
Disease activity The lipid profile in RA depends on disease activity. Higher disease activity leads to depressed levels of total cholesterol. However, HDL cholesterol levels are even more depressed, resulting in a more unfavourable atherogenic index[90]
Long duration of RA (>10 years)Implies more time for chronic inflammatory process to generate sequelae such as atherosclerosis and endothelial dysfunction[39]
Were significantly associated with an increased risk of atherosclerotic plaque in RA Colombian patients[25]
EAMIs an indirect indicator of disease severity and systemic compromise.
Patients are considered to have three times higher risk to develop CVD
[55, 76]
GCCould enhance cardiovascular risk owing to their potentially deleterious effects on lipids, glucose tolerance, insulin production and resistance, blood pressure, and obesity. On the other hand, it may actually decrease the risk of atherosclerosis and CVD by suppressing inflammation, which paradoxically may improve glucose intolerance and dyslipidaemia[93]

Others Thrombogenic factorsvWF has been recognized to induce a procoagulant state
Represent a biomarker of endothelial dysfunction
[96, 97]
The measurements of the IMT together with the vWF serum levels could give valuable information about the artery status and the atherosclerosis process in early stages in Mexican patients with RA without cardiovascular risk factors[49]

CVD: cardiovascular disease; IHD: ischemic heart disease; RA: rheumatoid arthritis; T2DM: type 2 diabetes mellitus; LA: Latin America; MetS: metabolic syndrome; SE: shared epitope; RF: rheumatoid factor; IMT: intima-medial thickness; anti-oxLDL: anti-oxidized low-density lipoprotein antibodies; aCL: anticardiolipins antibodies; anti-B2GPI: anti-β2glycoprotein I antibodies; anti-HSP 60/65: antiheat shock proteins 60/65 antibodies; anti CCP: anti-cyclic citrullinated peptide antibodies; HDL: high-density lipoprotein cholesterol; EAM: extra-articular manifestations; GC: glucocorticoids; vWF: von Willebrand factor.