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• Is there adequate evidence for the adoption of multipliers for cardiovascular risk estimation in rheumatic autoimmune diseases?
  Maria G. Tektonidou, Michael M. Ward
  Published on: 5 January 2023

• Published on: 5 January 2023

  Is there adequate evidence for the adoption of multipliers for cardiovascular risk estimation in rheumatic autoimmune diseases?

  • Maria G. Tektonidou, Professor of Rheumatology Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Laiko Hospital, Medi
  • Other Contributors:
    • Michael M. Ward, Rheumatologist

  We read with interest the article by Conrad et al. [1] that advocated modification of cardiovascular risk (CVR) scores to incorporate risk multipliers for each rheumatic and musculoskeletal disease (RMD). The proposed multipliers were based on hazard ratios for incident cardiovascular diseases in a nationwide study of electronic medical records in the UK [2]. This proposal contradicts recent recommendations in the 2022 EULAR recommendations for CVR management in patients with RMDs [3]. Based on a review of the evidence, including data of elevated CVR in other nationwide studies, and appraisal by experts, these recommendations did not support use of CVR multipliers in RMDs [3]. It is therefore important to examine several issues raised by this proposal.
  First, the objective of study from which the multipliers were derived [1] was not to assess the added predictive validity of CVR score modifiers, but rather to examine the incidence of cardiovascular disease in patients with autoimmune diseases. Confidence in the validity of the multipliers is not high, considering that data on blood pressure were missing in one-third of patients, while data on cholesterol and smoking were missing in two-thirds and almost one-half, respectively [2]. Also, whether these risk estimates apply in countries with baseline CVRs different from the UK is unclear [3].
  Second, the suggested multipliers were based on risk estimates of a wide range of cardiac or vascular diseases, including p...

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  We read with interest the article by Conrad et al. [1] that advocated modification of cardiovascular risk (CVR) scores to incorporate risk multipliers for each rheumatic and musculoskeletal disease (RMD). The proposed multipliers were based on hazard ratios for incident cardiovascular diseases in a nationwide study of electronic medical records in the UK [2]. This proposal contradicts recent recommendations in the 2022 EULAR recommendations for CVR management in patients with RMDs [3]. Based on a review of the evidence, including data of elevated CVR in other nationwide studies, and appraisal by experts, these recommendations did not support use of CVR multipliers in RMDs [3]. It is therefore important to examine several issues raised by this proposal.
  First, the objective of study from which the multipliers were derived [1] was not to assess the added predictive validity of CVR score modifiers, but rather to examine the incidence of cardiovascular disease in patients with autoimmune diseases. Confidence in the validity of the multipliers is not high, considering that data on blood pressure were missing in one-third of patients, while data on cholesterol and smoking were missing in two-thirds and almost one-half, respectively [2]. Also, whether these risk estimates apply in countries with baseline CVRs different from the UK is unclear [3].
  Second, the suggested multipliers were based on risk estimates of a wide range of cardiac or vascular diseases, including pericarditis, atrial fibrillation, valve disorders, venous thromboembolism, and infective endocarditis, and not only incident atherosclerotic cardiovascular disease (ASCVD) events. In contrast, CVR scores (e.g. Framingham, SCORE, ASCVD, Globorisk) are used to predict ASCVD events specifically (heart attack and stroke). It would not be surprising that Systemic lupus erythematosus or Systemic sclerosis were associated with the highest risk since the outcome included pericarditis, valve disease, arrhythmias and heart failure, common disease features. The proposed risk multipliers were based on outcomes that were different from those predicted by generic CVR scores.
  Third, a likely consequence of multipliers’ adoption would be to increase the number of patients eligible for statin treatment. Although this is an effective intervention to lower rates of ASCVD events in the general population, evidence that statins provide comparable benefit in the prevention of ASCVD events in patients with RMDs, or additional benefit at lower treatment thresholds than those used in the general population, is lacking ([3]; Systematic Literature review Supplementary material]), possibly because of a different pathophysiology of cardiovascular events in RMDs related to inflammation, disease-related mediators, and glucocorticoid use. In the 2021 European Society of Cardiology guidelines on cardiovascular disease prevention [4], the best evidence for chronic inflammation increasing CVR is available for rheumatoid arthritis, however the strength of evidence is less strong for other chronic inflammatory conditions, as is the independence of such increased risks from classical CVR factors.
  Fourth, since clinical presentations are heterogeneous, universal use of the same risk multiplier for all patients with the same RMD diagnosis, without accounting for their specific disease features and treatments [5], may lead to over- or under-estimation of cardiovascular risk.
  We agree with the motivation of Conrad and colleagues to develop better methods to combat high CVR in RMDs. Generally, we are not doing enough to help patients stop smoking, control hypertension and weight, and exercise more [6]. These practical steps and better management of disease-related factors can improve cardiovascular health in these patients. However, use of these risk multipliers for each RMD represents a jump from theory to policy, without support from the intervening step of evidence. We encourage additional studies dedicated to optimize CVR estimation that recognize the potentially unique pathophysiology of cardiovascular events in patients with RMDs.
  References
  1. Conrad N, McInnes IB, McMurray JJV, et al. Ann Rheum Dis Epub ahead of print: doi:10.1136/ard-2022-223315
  2. Conrad N, Verbeke G, Molenberghs G, et al. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet 2022; 400:733–43.
  3. Drosos GC, Vedder D, Houben E, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis 2022;81:768–79.
  4. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies with the special contribution of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2021;42:3227-3337.
  5. Petri MA, Barr E, Magder LS. Development of a systemic lupus erythematosus cardiovascular risk equation. Lupus Sci Med 2019;6:e000346.
  6. Bartels CM, Roberts TJ, Hansen KE, et al. Rheumatologist and Primary Care Management of Cardiovascular Disease Risk in Rheumatoid Arthritis: Patient and Provider Perspectives. Arthritis Care Res 2016;68:415-23.

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  Conflict of Interest:
  None declared.

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