Incidence Rate of Cardiovascular Events in Rheumatoid Arthritis: An Observational Cohort Study in Saudi Arabia

Figures & data

Figure 1 Participants Flowchart.

Table 1 Patients’ Baseline Characteristic (n=651)

Demographics
Age, mean (SD)	51.43 (13.29)
Female, n (%)	524 (80.5)
Saudi, n (%)	607 (93.2)
Past medical history, n (%)
Diabetes	123 (18.9)
Hypertension	122 (18.7)
Dyslipidemia	48 (7.4)
Obesity	279 (42.9)
History of established CVD	11 (1.7)
Family history of CVD	91 (14.0)
Arrhythmia	1 (0.2)
Osteoporosis	85 (13.1)
Respiratory disease	52 (8.0)
Hypothyroidism	57 (8.8)
Liver disease	6 (0.9)
Chronic kidney disease	15 (2.3)
Cancer	4 (0.6)
Smoking status n (%)
Current smokers	23 (3.5)
Past smokers	9 (1.4)
Home medications n (%)
Aspirin	34 (5.2)
Other anti-platelet therapy	6 (0.9)
Angiotensin-converting enzyme inhibitors or Angiotensin receptor blockers	61 (9.4)
Calcium channel blockers	47 (7.2)
Beta blockers	38 (5.8)
Diuretics	24 (3.7)
Proton pump inhibitors	99 (15.2)
Warfarin	3 (0.5)
Direct oral anticoagulants	7 (1.1)
Insulin	83 (12.7)
Non-insulin diabetes medications	36 (5.5)
Statin	83 (12.7)
Rheumatoid Arthritis history
Duration of disease (years), median (IQR)	9.2 (6 to 10)
Diagnosis in years categories, n (%)
< 5 years	103 (16.0)
5 to 9 years	242 (37.6)
10 to 14 years	206 (32.0)
15 to 20	44 (6.8)
> 20 years	49 (7.6)
Inflammatory markers at baseline
Erythrocyte sedimentation rate, median mm/h (IQR)	45.4 (22 to 64)
C reactive protein, median mg/dL(IQR)	4.8 (1.3 to 7.2)
Rheumatoid Arthritis Medications n (%)
Conventional synthetic DMARDs
Methotrexate	594 (91.2)
Hydroxychloroquine	569 (87.4)
Targeted synthetic DMARDs
Tofacitinib	47 (7.2)
Biologics - TNF alpha inhibitors
Adalimumab	160 (24.6)
Infliximab	21 (3.2)
Etanercept	104 (16.0)
Biologics – Non-TNF alpha inhibitors
Tocilizumab	28 (4.3)
Abatacept	84 (12.9)
Rituximab	27 (4.1)
Adjunctive medication use
Steroids use n (%)
Systemic glucocorticosteroids (prednisolone < 7.5 mg or equivalent)	431 (66.2)
Systemic glucocorticosteroids (prednisolone ≥ 7.5 mg or equivalent)	235 (36.1)
None	114 (17.5)
Frequency of steroid use, n (%)
Chronic ≥ 6 months	227 (47.5)
Intermittent > 5 months/year	68 (14.2)
Intermittent < 5 months/year	183 (38.3)
NSAIDsd use
Chronic NSAID users, n (%)	145 (22.3)

Notes: Missing %: years of diagnosis (1.1%), Erythrocyte sedimentation rate (2.3%), C reactive protein (91.2%), rheumatoid factor (59.2%).

Abbreviations: CVD, cardiovascular disease; DMARDs, disease-modifying antirheumatic drugs; SD, standard deviation; TNF, Tumor necrosis factor; NSAIDs, non-steroidal anti-inflammatory drugs; IQR, interquartile range.

Table 2 Six-Year Cumulative Incidence and Incidence Rates of Cardiovascular Disease in RA Patients

	Cumulative 6 Years Incidence N (%)	Incidence Rate (Events/1000 Person-Years)
Any cardiovascular event	54 (8.2%)	11.2
Ischemic heart disease	17 (2.6%)	3.4
Ischemic stroke or transient ischemic attack	10 (1.5%)	2.0
Venous Thromboembolism	5 (0.7%)	1.0
Arrhythmias	17 (2.6%)	3.5
Heart Failure	9 (1.3%)	1.8

Notes: Ischemic heart disease includes myocardial infarction, unstable angina, coronary revascularization (Coronary artery bypass graft, Percutaneous coronary intervention).

Table 3 Univariable and Multivariable Logistic Regression for Cardiovascular Disease in Rheumatoid Arthritis Patients

Predictor	Odds Ratio (95% CI, P value)	Adjusted Odds Ratio (95% CI, P value)
Demographics
Age (years)	1.07 (1.04 to 1.10, P <0.001)	1.03 (0.98 to 1.07, P= 0.247)
Male sex	1.88 (0.98 to 3.16, P = 0.058)	3.17 (1.10 to 9.14, P = 0.033)
Past medical history and risk factors
Diabetes	2.93 (1.57 to 5.46, P= 0.001)	2.34 (0.67 to 1.16, P= 0.137)
Hypertension	4.15 (2.29 to 7.51, P < 0.001)	3.40 (1.09 to 10.61, P= 0.035)
Dyslipidemia	3.67 (1.77 to 7.59, P< 0.001)	2.44 (0.56 to 10.63, P= 0.234)
Cardiovascular disease history	4.95 (1.35 to 18.14, P= 0.016)	2.29 (0.19 to 27.93, P= 0.548)
Obesity	1.17 (0.66 to 2.06, P= 0.596)	1.41 (0.57 to 3.47, P= 0.452)
Family history of CVD	1.32 (0.67 to 2.59, P= 0.419)	1.42 (0.50 to 4.03, P= 0.507)
Rheumatoid Arthritis history
Rheumatoid arthritis duration
< 5 years	Reference
5 to 9 years	2.65 (0.75 to 9.40, P= 0.132)	9.75 (0.87 to 126.2, P= 0.081)
10 to 14 years	3.33 (0.95 to 11.72, P= 0.061)	12.82 (0.75 to 190.18, P= 0.064)
15 to 20 years	7.33 (1.8 to 29.94, P= 0.005)	64.81 (3.68 to 1140.6, P= 0.004)
> 20 years	4.97 (1.20 to 20.51, P= 0.027)	24.23 (1.35 to 433.9, P= 0.030)
Erythrocyte sedimentation rate	0.99 (0.99 to 1.01, P= 0.912)	1.00 (0.98 to 1.01, P= 0.618)
C reactive protein	1.04 (0.94 to 1.15, P= 0.417)	*
Rheumatoid Arthritis Medications
Methotrexate	0.76 (0.28 to 2.05, P= 0.584)	0.99 (0.19 to 5.25, P= 0.995)
Hydroxychloroquine	0.58 (0.27 to 1.24, P= 0.159)	0.71 (0.20 to 2.45, P=0.826)
Tofacitinib	0.36 (0.09 to 1.56, P= 0.173)	0.54 (0.09 to 3.35, P=0.508)
Biologics - TNF alpha inhibitors	0.83 (0.46 to 1.48, P= 0.524)	1.76 (0.64 to 4.820, P=0.272)
Biologics - Non-TNF alpha inhibitors	0.56 (0.25 to 1.29, P=0.174)	0.32 (0.09 to 1.065, P=0.063)
Steroid and NSAIDs use
Systemic glucocorticosteroids (prednisolone < 7.5 mg or equivalent)	1.56 (0.81 to 3.03, P= 0.184)	9.50 (1.348 to 66.89, P=0.024)
Systemic glucocorticosteroids (prednisolone ≥ 7.5 mg or equivalent)	0.89 (0.49 to 1.62, P=0.694	1.842 (0.65 to 5.25, P=0.252)
Any NSAID use	0.58 (0.24 to 1.39, P= 0.224)	0.43 (0.081 to 2.33, P= 0.330)

Notes: P-value in Bold; statistically significant values. *C-reactive protein was not included in the multivariable logistic regression model due to large missing data.

Abbreviations: CVD; cardiovascular disease, NSAID; non-steroidal anti-inflammatory drug, TNF; tumor necrosis factor.