J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 17, Number 2, February 2025, pages 89-96

Metabolomics for Distinguishing Cardiovascular Risk in Rheumatoid Arthritis Across Different Disease-Modifying Antirheumatic Drug Therapies

**Table 1.** Baseline Characteristics of all Included Patients
Variables	Result
SD: standard deviation; BMI: body mass index; VAS: visual analogue scale; HFQ: Hannover Functional Questionnaire; RF: rheumatoid factor; DAS28: 28-joint Disease Activity Score; NSAID: non-steroidal anti-inflammatory drug; CV: cardiovascular; CAD: coronary artery disease; HF: heart failure; CCP: cyclic citrullinated peptide; TNF: tumor necrosis factor; IL: interleukin; CRP: C-reactive protein; Hb: hemoglobin; HbA1c: hemoglobin A1c; LDL: low-density lipoproteins; HDL: high-density lipoproteins.
Gender females/males, n (%)	134 (67%)/66 (33%)
Age, years (mean ± SD)	62.5 ± 12.4
BMI, kg/m²	28.7 ± 5.6
VAS (mean ± SD)	4 ± 2.5
HFQ, % (mean ± SD)	75.2 ± 22.2
DAS28 (mean ± SD)	3.7 ± 1.4
Swollen small joints (mean n ± SD)	3.1 ± 7.8
Swollen large joints (mean n ± SD)	0.7 ± 1.3
Painful small joints (mean n ± SD)	5.8 ± 9.8
Painful large joints (mean n ± SD)	2.1 ± 2.4
RF, %	64.1
Anti-CCP, %	55.6
Medication
NSAID therapy, %	23.4
Daily prednisolone, mg (mean ± SD)	3.4 ± 2.9
Sulfasalazine, %	12.5
Leflunomide, %	7.5
Anti-TNF-alpha, %	11
Anti-IL6, %	3
Anti-CD80/86, %	0
Anti-CD20, %	1.5
CV risk factors/morbidities
Smoking, %	32.3
Physical exercise, %	42.3
Distress, %	38.9
Arterial hypertension, %	65
CAD, %	7
HF, %	4.1
Family history of CAD, %	23
Diabetes mellitus, %	14
Obesity, %	35.5
Laboratory findings
CRP, mg/L (mean ± SD)	4.2 ± 7.3
Hb, g/L (mean ± SD)	134.8 ± 22.2
Platelets, × 100,000/µL (mean ± SD)	273.6 ± 73.1
Serum creatinine, µmol/L (mean ± SD)	71.2 ± 15.9
HbA1c, % (mean ± SD)	5.6 ± 0.7
Triglycerides, mmol/L (mean ± SD)	1.5 ± 0.9
Total cholesterol, mmol/L (mean ± SD)	5.4 ± 1
LDL, mmol/L (mean ± SD)	3.1 ± 0.9
HDL, mmol/L (mean ± SD)	1.7 ± 0.5

Table 1. Baseline Characteristics of all Included Patients

Variables

Result

SD: standard deviation; BMI: body mass index; VAS: visual analogue scale; HFQ: Hannover Functional Questionnaire; RF: rheumatoid factor; DAS28: 28-joint Disease Activity Score; NSAID: non-steroidal anti-inflammatory drug; CV: cardiovascular; CAD: coronary artery disease; HF: heart failure; CCP: cyclic citrullinated peptide; TNF: tumor necrosis factor; IL: interleukin; CRP: C-reactive protein; Hb: hemoglobin; HbA1c: hemoglobin A1c; LDL: low-density lipoproteins; HDL: high-density lipoproteins.

Gender females/males, n (%)

134 (67%)/66 (33%)

Age, years (mean ± SD)

62.5 ± 12.4

BMI, kg/m²

28.7 ± 5.6

VAS (mean ± SD)

4 ± 2.5

HFQ, % (mean ± SD)

75.2 ± 22.2

DAS28 (mean ± SD)

3.7 ± 1.4

Swollen small joints (mean n ± SD)

3.1 ± 7.8

Swollen large joints (mean n ± SD)

0.7 ± 1.3

Painful small joints (mean n ± SD)

5.8 ± 9.8

Painful large joints (mean n ± SD)

2.1 ± 2.4

RF, %

64.1

Anti-CCP, %

55.6

Medication

NSAID therapy, %

23.4

Daily prednisolone, mg (mean ± SD)

3.4 ± 2.9

Sulfasalazine, %

12.5

Leflunomide, %

7.5

Anti-TNF-alpha, %

Anti-IL6, %

Anti-CD80/86, %

Anti-CD20, %

1.5

CV risk factors/morbidities

Smoking, %

32.3

Physical exercise, %

42.3

Distress, %

38.9

Arterial hypertension, %

CAD, %

HF, %

4.1

Family history of CAD, %

Diabetes mellitus, %

Obesity, %

35.5

Laboratory findings

CRP, mg/L (mean ± SD)

4.2 ± 7.3

Hb, g/L (mean ± SD)

134.8 ± 22.2

Platelets, × 100,000/µL (mean ± SD)

273.6 ± 73.1

Serum creatinine, µmol/L (mean ± SD)

71.2 ± 15.9

HbA1c, % (mean ± SD)

5.6 ± 0.7

Triglycerides, mmol/L (mean ± SD)

1.5 ± 0.9

Total cholesterol, mmol/L (mean ± SD)

5.4 ± 1

LDL, mmol/L (mean ± SD)

3.1 ± 0.9

HDL, mmol/L (mean ± SD)

1.7 ± 0.5

**Table 2.** Significantly Different Metabolites Between Individuals With Elevated Versus Non-Elevated Stress Levels (Distress)
Metabolite	Notation (correlation)	Fold change	Cohen’s d
**P ≤ 0.01. Glucose level was reduced, whereas histidine was increased.
Glucose	**	0.81	-0.49
Histidine	**	1.11	0.57

Table 2. Significantly Different Metabolites Between Individuals With Elevated Versus Non-Elevated Stress Levels (Distress)

Metabolite

Notation (correlation)

Fold change

Cohen’s d

**P ≤ 0.01. Glucose level was reduced, whereas histidine was increased.

Glucose

0.81

-0.49

Histidine

1.11

0.57

**Table 3.** Metabolic Differences Between RA Patients With a Framingham Score of Under 10 Compared to Those With a Score of 20+
Metabolite	Notation (correlation)	Fold change	Cohen’s d
P ≤ 0.05. *P ≤ 0.01. The majority of metabolites were significantly reduced (exception: HDL). HDL: high-density lipoproteins; RA: rheumatoid arthritis.
Triglycerides	**	0.69	-0.96
Sphingomyelin	**	0.68	-0.98
Creatinine	**	0.66	-1.11
Untargeted signal 33	**	0.85	-0.85
Untargeted signal 35	*	0.68	-0.81
HDL	*	1.18	0.65
Glucose	*	0.85	-0.46
Untargeted signal 21	*	0.46	-0.78
Untargeted signal 34	*	0.86	-0.70
Mannose	*	0.75	-0.67

Table 3. Metabolic Differences Between RA Patients With a Framingham Score of Under 10 Compared to Those With a Score of 20+

Metabolite

Notation (correlation)

Fold change

Cohen’s d

*P ≤ 0.05. **P ≤ 0.01. The majority of metabolites were significantly reduced (exception: HDL). HDL: high-density lipoproteins; RA: rheumatoid arthritis.

Triglycerides

0.69

-0.96

Sphingomyelin

0.68

-0.98

Creatinine

0.66

-1.11

Untargeted signal 33

0.85

-0.85

Untargeted signal 35

0.68

-0.81

HDL

1.18

0.65

Glucose

0.85

-0.46

Untargeted signal 21

0.46

-0.78

Untargeted signal 34

0.86

-0.70

Mannose

0.75

-0.67