In RA patients without prevalent CVD, incident CVD is mainly associated with traditional risk factors: A 20-year follow-up in the CARRÉ cohort study

Raadsen, R.; Agca, Rabia; Boers, Maarten; Halm, Vokko P. van; Peters, Mike J L; Smulders, Yvo M.; Beulens, Joline; Blom, Marieke T.; Stehouwer, C.D.A.; Voskuyl, Alexandre E.; Lems, Willem F.; Nurmohamed, Michael T.

doi:10.1016/j.semarthrit.2022.152132

Cited by 11 publications

(9 citation statements)

References 33 publications

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“…These results suggest that the current CVD risk in IA patients is nowadays highly influenced by the increased prevalence of these risk factors. This is in agreement with another recent study in patients with longstanding RA, where the contribution of these risk factors on the CVD risk increased over the years [40]. The risk of CVD in RA patients has similarly decreased, with the over two-fold risk compared to the general population found more than 10 years ago lowering to a current increased risk of about 50-60% [22,40].…”

Section: Discussionsupporting

confidence: 91%

“…This was substantially better than in a previous study from our center (inclusion period 2011 -2016), in which more than half of patients with an indication for medication did not receive it a year after their screening consultation [14]. RA patients are often undertreated for CV risk factors, partly due to unawareness among patients and healthcare professionals [40,41]. In a comparison between RA patients with and without diabetes mellitus (DM), RA patients without DM were less likely to be prescribed preventive medication [42].…”

Section: Discussionmentioning

confidence: 76%

“…As the increased CVD risk in RA patients is already present at the moment of diagnosis it is important to realize that these changes in CV risk factors also occur before diagnosis [39][40][41][42]. Timely assessment of lipid profile with cardiovascular risk management (CVRM) and quick, efficient reduction of inflammation is necessary to reduce the CVD risk.…”

Section: Discussionmentioning

confidence: 99%

“…General introduction and thesis outline Several pro-inflammatory cytokines prominent in RA pathology can further influence coagulation activation, such as TNF [36,37]. While TNF-inhibition seems to have some favorable effects on pro-thrombotic markers, patients treated with TNF-inhibitors paradoxically are initially at a higher risk for developing VTE than patients treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or no DMARDs at all [38][39][40]. While the exact cause of this phenomenon is unknown, it is suggested that an increased formation of autoantibodies or anti-drug antibodies might be involved [41].…”

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confidence: 99%

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Epidemiology and predictors of cardiovascular diseases in rheumatoid arthritis

Raadsen

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In chapter 2 we explored changes in lipid-profile and NT-proBNP throughout the development of RA. Thirty-eight patients were followed from the preclinical phase until up to 6 months treatment with bDMARDs. Most changes in lipid-profile and NT-proBNP seemed to be related to changes in CRP. These changes were already present at the moment of diagnosis, indicating the need for timely intervention to prevent atherosclerosis development and thus future CVD. However, these results should be interpreted with caution, as larger studies are needed to confirm our findings. In chapter 3 we investigated the longitudinal effects of four years of anti-rheumatic therapy on several markers for subclinical atherosclerosis in RA patients and compared baseline values with OA patients. Although IMT remained stable throughout the entire follow up, AIx and PWV decreased in the first six months of anti-inflammatory therapy. Additionally, we found a positive correlation between disease activity and IMT, AIx, and PWV. These results suggest modest beneficial changes in surrogate markers for subclinical CVD. This should be investigated further in larger, prospective studies with a comparative, matched control group during the entire follow up period. In chapter 4 we described CV risk management procedures of 125 consecutive, newly diagnosed RA patients. We found that the majority of patients already had either dyslipidemia, hypertension, or both, with a higher prevalence in male patients. Of the female patients, only 4% had a high CV mortality risk, while 50% of male patients had a high or very high risk. Of these high-risk patients, only 26% were started on preventive medication by their general practitioner within a year of screening. We concluded that CV risk screening needs to be part of standard care, to reduce the CV burden of RA patients. In chapter 5 we investigated the presence of CVD in patients with IA compared to healthy controls in a large cross-sectional study. We found that the prevalence of CV risk factors was increased for all IA patient groups. Additionally, the prevalence of CVD was increased in IA patients. Adjusting results for CV risk factors highly attenuated the odds ratios, suggesting that the current CVD risk in IA patients is heavily influenced by these risk factors. More attention needs to be paid to screening for and treatment of traditional CV risk factors, not only in RA patients, but in individuals with PsA and SpA as well. In chapter 6 we extended the CARRÉ cohort study to a follow up of 20 years. We found increased HRs for both RA patients and DM patients without prevalent CVD compared to healthy controls. When the analyses were adjusted for ‘traditional’ CV factors, no significant ‘RA-specific’ risk remained, while a ‘DM-specific’ risk was retained. This suggests that the increased CVD risk in RA patient without previous CVD is mainly attributable to increased prevalences of CV risk factors as hypertension and dyslipidemia. With better control of inflammation in RA due to modern, early treatment, structural CV risk screening and management needs to be implemented to further decrease the CVD risk. Finally, in chapter 7 we studied the activation of the coagulation system of RA patients during treatment with either TNF-blockers or JAK-inhibitors. The coagulation markers were measured at baseline, and after one, three and six months of follow up. In TNF-blocker users, both D-dimer and fibrinogen levels significantly declined, while TAT levels significantly increased after 6 months follow up. In JAK-inhibitor users, only vWF levels significantly declined. Our data suggests that an increased VTE risk due to treatment with either medication type is unlikely, however, this needs to be verified in larger studies with a longer follow up duration.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Epidemiology and predictors of cardiovascular diseases in rheumatoid arthritis

Raadsen

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“…This is in agreement with another recent study in patients with longstanding RA, where the contribution of these risk factors on the CVD risk increased over the years. 40 The risk of CVD in patients with RA has similarly decreased, with the over twofold risk compared with the general population found more than 10 years ago lowering to a current increased risk of about 50–60%. 22 40 A possible explanation could be that current treatment of systemic inflammation has improved, while screening and treatment of ‘traditional’ risk factors remains insufficient.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular disease risk in patients with inflammatory arthritis nowadays still substantially elevated

Raadsen,

Hansildaar,

Pouw

et al. 2023

RMD Open

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ObjectivesThis study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (SpA).Methods2050 consecutive patients with inflammatory arthritis (IA) and 939 controls were included, with 1308 patients with RA, 356 patients with PsA and 386 patients with SpA. In a prospective cohort setting, questionnaires regarding previous cardiovascular events and risk factors were used to assess cardiovascular risk and prevalence in patients with IA by calculating ORs using logistic regression models.Results‘Traditional’ cardiovascular (CV) risk factors were significantly elevated in patients with IA compared with controls. Cardiovascular disease (CVD) ORs were increased in patients with RA and PsA compared with controls, 1.61 (95% CI: 1.04 to 2.48) and 2.12 (95% CI: 1.23 to 3.66), respectively, and a trend towards increased odds was observed in patients with SpA (OR 1.43; 95% CI: 0.79 to 2.59). After adjusting for traditional risk factors, CV risk was not increased in patients with RA (OR; 0.95, 95% CI: 0.58 to 1.55), PsA (OR 1.19; 95% CI: 0.64 to 2.22) and SpA (OR; 0.91, 95% CI: 0.47 to 1.77).ConclusionCVD is currently still more prevalent in patients with IA compared with healthy controls and, more importantly, this elevated risk is highly influenced by an increased prevalence of ‘traditional’ CV risk factors. More attention to, as well as improvements in, identification and treatment of ‘traditional’ risk factors, need to be made for not only RA, but other IA conditions as well.

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