Table 1: Traditional, nontraditional risk factors, physiopathological changes, and subphenotypes of cardiovascular disease and rheumatoid arthritis in Latin America.

Ref. Country Author   Cardiovascular outcome measured Prevalence of CVD in RA (%) Traditional risk factors of CVD (%) Nontraditional risk factors of CVD (%) Physiopathological changes in CVD  (%) Subphenotype of CVD described (%) [46] Mexico Orozco-Alcalá et al.a 44.7 38 Male gender 12/38 (31.6) Polyautoimmunity 6/38 (15.8); RF 32/38 (84.2); EAM 16/38 (42.1); GC 9/38 (23.7); RA duration over 10 years 17/38 (44.7) N/A Stroke 10/38 (26.3), MI 3/38 (7.9), CHF 3/38 (7.9), acute pulmonary embolism 1/38 (2.6) [47] Zavaleta et al. 14.3b 37 (14 with RA) Dyslipidemiac: TGL 106.2 ± 55.1†; male gender 2/14 (14.3) RA duration 8.2 7.1c N/A Alterations in myocardial perfusion: Subclinical CAD 2/14 (14.3)b [48] Lopez-Olivo et al. 13.8 152 RA patients/153 controls Obesity: BMI 25 (16–36)‡, dyslipidemia: hypercholesterolemia 5/152 (3.3), T2DM 8/152 (5.3), male gender 26/152 (17.1)§, hyperhomocysteinemia 31/152 (20.4)§ and smoking 56/152 (36.8)§ RF 149 (0–3,050)‡; CRP (mg/dL) 17 (3–126)‡§; RADAR 1.0 (0.1–2.7)‡, HAQ-Di 0.7 (0–2.7)‡; MTX 14/31 (45.2)d N/A Hypertension 17/152 (11.2), stroke 4/152 (2.6) [49] Daza, et al.e,f 7.3g 55 RA patients/22 controls Obesity: BMI 27.51 ± 4.05/24.48 ± 3.73§ RF 506.5 (347.1–665.8)‡/13.3 (5.8–20.8)§; CRP (mg/dL) 1.48 (1.05–1.9)‡/0.6 (0.02–1.2)§, ESR 28.47 ± 14.48†/9.65 ± 3.56§; DAS 28 4.77 (4.5–5.1)‡; MTX 45/55 (81.8), SSZ 6/55 (10.9), GC 8/55 (14.5); vWF 145.6 ± 30.1†/121.8 ± 37.2§ IMT 0.67 ± 0.18†/0.58 ± 0.10 (mm)§, atherosclerosis plaque 4/55 (7.3) N/A [50] Zonana-Nacach et al. 24.5# 192 (107 RA and 85 SLE patients) Obesity 49/192 (25.5), dyslipidemia 49/192 (25.5), T2DM 14/192 (7.3), MetS (18.7), physical inactivity 75/192 (87), and smoking 28/192 (14.6) RA duration 135 ± 112† (months); Housewife 102/192 (53) N/A Hypertension 47/192 (24.5) [51] Brazil Pereira et al.i 14.1g 71 RA patients/51 controls Male genderj 7/71 (9.9) CRPk (mg/L): 8.64 ± 8.27†/19.75 ± 25.08, ESRk: 24.1 ± 14.6†/34.07 ± 23.54; DAS 28: 4.24 ± 1.02†/4.64 ± 1.05; SDAIk: 35.54 ± 12.34/48.5 ± 30.28§; MTXk (mg/w): 20 ± 5/19.09 ± 5.74, GCk (mg/day): 7.25 ± 2.75/7.72 ± 3.59; fibrinogenk 326.04 ± 113.56†/371.94 ± 121.08§ IMTj: 0.72 ± 0.17/0.67 ± 0.15 (mm). Carotid plaquesj (IMT > 1.5 mm) 10/71 (14.1)/1 (1.9)§ N/A [52] Pereira et al.l 14.1g 71 RA patients/53 controls Dyslipidemiak: CT 243.3 ± 31.2/191.54 ± 36.21§, male genderj (9.9/13.9) Same data from [48] and autoantibodies: RFk: 195.10 ± 281.71†/308.13 ± 584.46, anti-CCP (79/1.9), aCL (IgG 5.6/3.8, IgM 7/3.8), anti-B2GPI (IgG 1.4/1.9, IgM 4.2/1.9), anti-HSP 60 (14.1/7.5), anti-HSP 65 (36.6/17), anti-LPL antibodies (2.8/1.9) IMTj: 0.72 ± 0.17/0.67 ± 0.15 (mm). Carotid plaquesj (IMT > 1.5 mm) 10/71 (14.1)/1 (1.9)§ N/A [53] de Cunha et al. 80.6# 283 RA patients/226 controls Obesity: BMI 26.6 ± 5.1†/26.8 ± 4.3, dyslipidemia: HDL 58.9 ± 16.4†/52.7 ± 12.1§, LDL 109.9 ± 33.2/122.8 ± 37.7§, T2DM 32/283 (11.3)-6/226 (2.7)§, MetS 111/283 (39.2)-44/226 (19.5)§, male gender 50 (17.7)/34 (15) N/A N/A Hypertensionm 228 (80.6)/95 (42) [54] Colombia Pineda et al.n 32.4 41 Male gender 12/41 (29) N/A N/A Hypertension (24.2), CAD 9/41 (8.2) [25] Rojas-Villarraga et al.o 41# 140 Obesity 23/140 (16), dyslipidemia 49/140 (35), T2DM 6/140 (4), MetS 61/140 (44), physical inactivity 119/140 (85), male gender 16/(23), family history of CHD 22/140 (16), ever smoking 61/140 (44)§, and history of hormone replacement therapy 10/140 (7) Poly-autoimmunity 31/140 (22); family history of autoimmunity 29/140 (21)§; HLA-DRB1 SE 60/136 (46)§; RF 85/134 (63)§, anti-CCP antibodies 73/94 (78); CRP 5.9 ± 15†, ESR 38.9 ± 25.1†; DAS 28 4.4 ± 1.4†, HAQ 1.7 ± 0.7†; EAM 60/140 (43); MTX 131/140 (94), GC 131/140 (94); RA duration 13.8 ± 8.5§ Early endothelial dysfunction 44/140 (31)§, increased IMT 75/140 (54)§, atherosclerosis plaque 10/140 (7)§ Hypertension 57/140 (41) [55] Ortega-Hernandez et al.o 32 538 Dyslipidemia 64/534 (10), male gender 80/538 (15) Polyautoimmunity 48/538 (9); RF 246/385 (64)§, anti-CCP antibodies 146/183 (80); CRP 8.65 ± 20.21†, ESR† 38.86 ± 25.93§; EAM 113/538 (21); GC 39/486 (8); RA duration 12.53 ± 8.08§ N/A Hypertension 128/534 (24), thrombosis 43/534 (8) [56] Argentina Larroudé et al. 13.9# 137 Dyslipidemia 89/137 (65), T2DM 2/137 (1.45), and male gender N/A 11/137 (8) GC 71/137 (51.8) N/A Hypertension 19/137 (13.9) [57] Lascano et al.p 47 32 RA patients/32 controls N/A RF 27/32 (84); ESR 28 ± 15†; DAS 28 4.3 ± 1.4†; EAM 8/32 (25); GC 21/32 (66); RA duration 10.2 ± 8.4† N/A Ventricular diastolic dysfunction 15/32 (47) [30] Chile Cisternas et al.q 46.4 54 RA patients/32 controls Obesity: BMI 26 (18–39)‡, dyslipidemia 18/54 (33), male gender 7/54 (13), family history of CVD 9/54 (17), hyperhomocysteinemia 38/54 (70)§, and smoking 21/54 (39) RF 50/54 (92), aCL‡ IgM 3 (0.53–23)/1.6 (0.21–10.6) IgG 4.3 (0.3–85)/2.5 (0–12.3); CRP 0.73 (0.04–5.96)‡/0.31 (0.05–2.88)§, ESR 27 (3–99)‡; MTX 41/54 (75), GC 42/54 (77); RA duration 9.5 (0.2–32)‡ N/A Hypertension 21/54 (39), stroke 2/54 (3.7), stable angina 2/54 (3.7) [58] Cuba Acosta et al.r 55.9 172 Dyslipidemia 10/172 (5.8), T2DM 16/172 (9.3), and male gender 29/172 (16.9) Polyautoimmunity 2/172 (1.1); RF 52/85 (61.1) N/A Hypertension 46/172 (26.7), stroke 1/172 (0.5), CAD 8/172 (4.6), and peripheral vascular disease 4/172 (2.3) [59] Puerto Rico Santiago-Casas et al.s 56.1 214 Dyslipidemia§ (9.1)-(52.7)-(58.4) T2DM§ (9.1)-(52.7)-(58.4) MetS (18.2)-(39.6)-(43.4) Smoking (4.5)-(11.0)-(7.9) RF (52.4)-(52.9)-(57.1); ESR (81.0)-(92.2)-(91); Steroids§ (54.5)-(78.0)-(82.2); RA duration‡ (3.4 ± 2.9)-(9.5 ± 8.2)-(13.6 ± 10.7) N/A Hypertension (13.6)-(40.7)-(76.2), MI (0)-(2.2)-(9.1), angina pectoris (0)-(1.1)-(4.0), stroke (0)-(1.1)-(8.0), peripheral artery disease (0)-(1.1)-(5.0), and CHF (0)-(1.1)-(5.0)

CVD: cardiovascular disease; RA: rheumatoid arthritis; RF: rheumatoid factor; EAM: extraarticular manifestations; GC: glucocorticoids; N/A: not available; MI: myocardial infarction; CHF: congestive heart failure; TGL: triglycerides; CAD: coronary artery disease; BMI: body mass index; T2DM: type 2 diabetes mellitus; CRP: C-reactive protein; RADAR: rapid assessment of disease activity in rheumatology; HAQ-Di: health assessment questionnaire disability index; MTX: methotrexate; ESR: Erythrocyte Sedimentation Rate; DAS-28: Disease Activity Score-28; SSZ: sulfasalazine; vWF: von Willebrand Factor; IMT: intima-medial thickness; MetS: metabolic syndrome; SDAI: simplified disease activity index; TC: total cholesterol; anti-CCP: anti-cyclic citrullinated peptide antibodies; aCL: anticardiolipins antibodies; anti-B2GPI: anti-2glycoprotein I antibodies; anti-HSP 60/65: anti-heat shock proteins 60/65 antibodies; anti-LPL: antiLipoprotein lipase antibodies; HDL: high-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol. aOnly descriptive study, which evaluated causes of mortality in adult patients with RA. bBy echocardiogram and gammagraphy. cData from patients with RA 14/37 (37.8). dData from patients with hyperhomocysteinemia (>15 μmol/L). eExclusion criteria: patient with traditional cardiovascular risk factors. fOnly female were included, each with at least 5 years of duration of the disease and between 35 and 54 years of age. gNot CVD subphenotype measured. Prevalence regarding presence of atherosclerosis plaque. hOnly female were included. iExclusion criteria: smoking, diabetes and hypertension pregnancy, renal failure, chronic hepatopathy, nephrotic syndrome, hypothyroidism and use of statins/fibrates. jRA patients versus controls. lExclusion criteria: smoking, diabetes, and hypertension. mHigh blood pressure was defined above 130/85 mmHg. nThe objective was to analyze causes and direct costs of hospitalization of Colombian patients with RA. oSample population was originally from Northwestern Colombia. They are considered ethnically different. pExclusion criteria: any symptoms of heart disease or risk factors for CVD. qSubjects over 60 years were excluded. rOnly cohort, 6 years followup. Low mortality rate 9/32 (5.2%). sThree age group (<40 y)-(40–59 y)-(>60 y). Elder people (>60 y) have more probability to develop CVD independent of RA. †Mean ± standard deviation. ‡Median (interquartile range). #Prevalence of CVD regarding the only subphenotype described. § values < 0.05 were considered significant.