Cardiovascular Disease in Rheumatoid Arthritis: A Systematic Literature Review in Latin America

Table 1

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

Ref.	Country	Author		𝑁	Cardiovascular outcome measured
			Prevalence; of CVD; in RA (%)		Traditional risk factors of CVD 𝑛/𝑁 (%)	Nontraditional risk factors of CVD 𝑛/𝑁 (%)	Physiopathological changes in CVD; 𝑛/𝑁 (%)	Subphenotype of CVD described 𝑛/𝑁 (%)
[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.	14.3^b	37 (14 with RA)	Dyslipidemia^c: TGL 106.2 ± 55.1^†; male gender 2/14 (14.3)	RA duration 8.2 ± 7.1^c	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	7.3^g	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	14.1^g	71 RA patients/51 controls	Male gender^j 7/71 (9.9)	CRP^k (mg/L): 8.64 ± 8.27^†/19.75 ± 25.08, ESR^k: 24.1 ± 14.6^†/34.07 ± 23.54; DAS 28: 4.24 ± 1.02^†/4.64 ± 1.05; SDAI^k: 35.54 ± 12.34/48.5 ± 30.28^§; MTX^k (mg/w): 20 ± 5/19.09 ± 5.74, GC^k (mg/day): 7.25 ± 2.75/7.72 ± 3.59; fibrinogen^k 326.04 ± 113.56^†/371.94 ± 121.08^§	IMT^j: 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	14.1^g	71 RA patients/53 controls	Dyslipidemia^k: CT 243.3 ± 31.2/191.54 ± 36.21^§, male gender^j (9.9/13.9)	Same data from [48] and autoantibodies: RF^k: 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)	IMT^j: 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	Hypertension^m 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-𝛽2glycoprotein 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.
^§𝑃 values < 0.05 were considered significant.