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Correspondence on 'Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease' Globally, coronary artery disease (CAD) is one of the leading causes of mortality in patients with rheumatoid arthritis (RA). 1 2 The major pathological changes in RA-associated CAD are high rate of unstable coronary plaque and increased local inflammation, as inferred from autopsy reports. 3 Recently, Løgstrup et al 4 reported that RA was significantly associated with a 10-year risk of myocardial infarction, major adverse cardiovascular events and all-cause mortality regardless of the presence of CAD in patients undergoing coronary angiography (CAG). While the patients with RA associated CAD carry the largest risk, the additive risk of RA in patients without CAD is minor. These findings were published in the September 2020 issue of the Annals of the Rheumatic Diseases. Certainly, the findings of Løgstrup et al hold significance for clinicians; however, four points remain unaddressed, and we wish to communicate these to the authors. First, low-density lipoprotein cholesterol (LDL-C) plays a vital role in the perpetuation and pathogenesis of CAD. 5 The elevated level of LDL-C is a strong independent predictor of cardiovascular events, and lowering the LDL-C to <70 mg/ dL has proved to be effective in the primary and secondary prevention of CAD. 5-7 In recent reports, it has been stated that emphasising the importance of optimal LDL-C control early in life at a younger age. 8 However, the LDL level was not described in the baseline characteristics of these four groups. Therefore, the conclusions may not be rigorous without considering these vital factors. Second, several previous clinical trials in patients with CAD have demonstrated that high-intensity statin therapy significantly reduces cardiovascular events when compared with moderate-intensity statin therapy. 9-12 Furthermore, it has been established that higher-dose statin therapy was associated with a lower risk for cardiovascular events than moderate-dose statin therapy in patients with CAD. 13 However, the percentages of patients using statin were not comparable and the type and dosage of statin were not described in the baseline characteristics of these four groups. These issues might have nullified some of the results related to this study. Third, despite the higher risk for cardiovascular events, treatment compliance was poor in patients with RA because these patients are given many oral drugs. 14 In this situation, the comparison between those with and without CAD among the patients with RA may be influenced by treatment compliance. In particular, there was a low rate of compliance in long-term (over 10 years) follow-up. Thus, treatment compliance rates for patients with RA were probably suboptimal in this study and hence may act as a confounding variable. Finally, during the baseline participation in this study, only patients undergoing CAG were recruited, and the decision was made by the physician to either perform CA...
Correspondence on 'Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease' Globally, coronary artery disease (CAD) is one of the leading causes of mortality in patients with rheumatoid arthritis (RA). 1 2 The major pathological changes in RA-associated CAD are high rate of unstable coronary plaque and increased local inflammation, as inferred from autopsy reports. 3 Recently, Løgstrup et al 4 reported that RA was significantly associated with a 10-year risk of myocardial infarction, major adverse cardiovascular events and all-cause mortality regardless of the presence of CAD in patients undergoing coronary angiography (CAG). While the patients with RA associated CAD carry the largest risk, the additive risk of RA in patients without CAD is minor. These findings were published in the September 2020 issue of the Annals of the Rheumatic Diseases. Certainly, the findings of Løgstrup et al hold significance for clinicians; however, four points remain unaddressed, and we wish to communicate these to the authors. First, low-density lipoprotein cholesterol (LDL-C) plays a vital role in the perpetuation and pathogenesis of CAD. 5 The elevated level of LDL-C is a strong independent predictor of cardiovascular events, and lowering the LDL-C to <70 mg/ dL has proved to be effective in the primary and secondary prevention of CAD. 5-7 In recent reports, it has been stated that emphasising the importance of optimal LDL-C control early in life at a younger age. 8 However, the LDL level was not described in the baseline characteristics of these four groups. Therefore, the conclusions may not be rigorous without considering these vital factors. Second, several previous clinical trials in patients with CAD have demonstrated that high-intensity statin therapy significantly reduces cardiovascular events when compared with moderate-intensity statin therapy. 9-12 Furthermore, it has been established that higher-dose statin therapy was associated with a lower risk for cardiovascular events than moderate-dose statin therapy in patients with CAD. 13 However, the percentages of patients using statin were not comparable and the type and dosage of statin were not described in the baseline characteristics of these four groups. These issues might have nullified some of the results related to this study. Third, despite the higher risk for cardiovascular events, treatment compliance was poor in patients with RA because these patients are given many oral drugs. 14 In this situation, the comparison between those with and without CAD among the patients with RA may be influenced by treatment compliance. In particular, there was a low rate of compliance in long-term (over 10 years) follow-up. Thus, treatment compliance rates for patients with RA were probably suboptimal in this study and hence may act as a confounding variable. Finally, during the baseline participation in this study, only patients undergoing CAG were recruited, and the decision was made by the physician to either perform CA...
Response to 'Correspondence on 'Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease" by Jong et alWe appreciate the interest and comments by Jong et al 1 concerning our study: 'Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease'. 2 We would like to clarify and discuss the issues raised by Jong et al. 1 The comments by our colleagues highlight many inherent limitations of an epidemiological study that may provide considerations for a future prospective randomised trial.First, Jong et al 1 note that that low-density lipoprotein cholesterol (LDL-C) level was not part of the baseline characteristics.The reason is that biochemical data are currently not available from the national Danish Registries. While we do agree with our colleagues that LDL-C is a player in the pathogenesis of coronary artery disease (CAD) and that LDL-C is an independent predictor of cardiovascular events, there are several more important factors that were included. These are age, gender, heart failure, hypertension, diabetes, smoking and most importantly, the presence or absence of CAD. [3][4][5] Further, most of those with CAD were subsequently treated with statins, which reduces the baseline LDL-C levels and modifies the influence of this baseline characteristic. 6 We used statin treatment as a proxy for hypercholesterolaemia in the adjusted multivariate regression analysis.Second, Jong et al 1 raise an interesting question regarding the impact of high-intensity versus low-intensity statins. Simvastatin was the primary statin used among all patients with rheumatoid arthritis (RA) in this study (44%, median dose 40 mg/daily), followed by high-intensity statins, atorvastatin (19%, median dose 40 mg/daily) and rosuvastatin (3%, median dose 10 mg/ daily). It remains an open question whether early initiation of statin treatment will affect long-term outcomes in patients with RA and no CAD, and whether high-intensity versus low-intensity statin treatment will make a difference. 7 In the presence of CAD, however, statin treatment will aim to reach the levels dictated by the guidelines issued by scientific societies.Third, Jong et al 1 speculate that treatment compliance rates for patients with RA may have been suboptimal. However, the baseline medical treatment, based on prescription dispensations, did not show any significant differences in filling of prescriptions of aspirin, ADP-inhibitor and statins. 2 The fourth and final comment address that our study was based on a coronary angiography cohort. We agree, as also stated in our original publications, 2 8-10 that this is a potential limitation. Since we aimed to assess the impact of CAD on long-term future events, we needed to look at patients who had undergone coronary angiography. This may have introduced selection bias, since patients with RA are more likely to be referred to coronary angiography. However, compared with the general population, patients with no CAD by c...
ObjectiveTo investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA).DesignPopulation-based longitudinal cohort study.SettingUK Biobank.ParticipantsUK Biobank participants (n=502 533) aged between 37 and 73 years old.Primary outcome measuresPrimary outcome measures were risk of all-cause mortality and MACE.MethodsWe examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox’s proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor.Results75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports.ConclusionThose with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.
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