Cardiovascular Disease Risk in Patients With Systemic Lupus Erythematosus

The improved treatment of systemic lupus erythematosus (SLE) with increased life expectancy has been accompanied by a 9- to 50-fold elevated risk for developing cardiovascular disease (CVD) compared with the general population. Symptoms range from subclinical to life-threatening, reflecting the etiological heterogeneity of cardiovascular (CV) events in the SLE population.¹ Pericardial disease, myocardial dysfunction, valvular heart disease, conduction system abnormalities, and atheromatous disease are well recognized as cardiovascular complications of SLE, and are important criteria for the initial diagnostic evaluation.¹ Heart failure and acute myocarditis, however, have been traditionally considered rare events in the initial manifestation of SLE, and  heart failure is still not included in the SLE diagnostic criteria developed by the American College of Rheumatology (ACR).²

Although studies are limited, available data show that patients with SLE have a worse CV risk profile than the general population, and have a significantly higher risk for developing heart failure.³ A systematic review of 28 studies found strong evidence for an increased risk for CVD in patients with SLE vs the general population.⁴ Traditional CV risk factors, including older age, hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking, are well documented in patients with SLE. These risk factors, however, do not fully account for the higher rates of CV events reported in this patient population, suggesting that disease-specific factors may be involved.⁵ A study investigating risks for heart failure in patients with SLE indicated that 50% of the cases of heart failure were attributed to active SLE, 21% to coronary artery disease, and 29%, to other causes.⁶  

While the risk factors for CVD in the general population are known and have been extensively studied, SLE-specific risk factors leading to elevated CV events are less well defined. In the absence of robust clinical evidence to explain the increased risk for CV events in patients with SLE, the prevailing theory favors an interplay of traditional risk factors, dysfunctional immune system, inflammatory mechanisms, and adverse effects of specific SLE medications. These pathological changes are thought to lead to increased risk for CV events due to accelerated atherosclerosis, myocardial inflammation, elevation of inflammatory cytokines, and ventricular hypertrophy.^5,7

A set of inflammatory proteins are known to have elevated levels in SLE.⁸ These include anti-apolipoprotein A-I immunoglobulin G (IgG) antibodies, anti-high-densiy lipoprotein (HDL) antibody, C-reactive protein and several autoantibodies. Increased levels of inflammatory molecules may result in the development of atherosclerosis, and contribute to increased risk for cardiovascular disease, organ damage, and heart failure in this population.

The most consistent SLE-related factors explaining the elevated risk for CV events in this population include disease activity and duration, cumulative damage, antiphospholipid antibodies, high sensitivity C-reactive protein, and renal disease.⁹

It is critical that physicians treating patients with SLE be informed of the risk for CVD, and have a strategy for the management of the known modifiable risk factors in addition to controlling disease activity and inflammation.⁵ Expert panels in the United States and Europe recommend annual screening and management of modifiable risk factors.^10,11 Patient monitoring may include clinical, laboratory and imaging studies, including electrocardiography and conventional echocardiography. In addition, cardiac magnetic resonance imaging is considered reliable to detect subclinical myocardial involvement and pathophysiological changes associated with heart failure in patients with SLE. Strain echocardiography, nuclear imaging, and cardiac catheterization may also be considered in a select group of patients.⁶ Carotid ultrasonography (intima-media thickness and plaque) has been shown to independently predict CV events in SLE, and may be useful for predicting CV events in selected high-risk patients.⁹

As few studies have focused on risk factors for CVD in SLE, but understanding the link between pathology and clinical manifestations is limited, and specific recommendations for disease monitoring and management are lacking. No study has indicated that controlling CVD risk factors reduces the incidence of CV events in SLE. The Lupus Atherosclerosis Prevention Study, conducted to determine whether treatment with atorvastatin slowed the progression of subclinical atherosclerosis in SLE, found no benefit over a 2-year period.¹² The ACR recommends tight blood pressure control (target <130/80 mm Hg), statin therapy for low-density lipoprotein (>100 mg/dL), and treatment to control SLE.¹³

Well-designed trials are needed to help guide management recommendations. Until such studies are available, physicians need to be aware of the elevated CVD risks associated with SLE, and be cognizant of the need to monitor risk factors. 

References

1. Dhakal BP, Kim CH, Al-kindi SG, Oliveira GH. Heart failure in systemic lupus erythematosus [published online e September 6,m 2017]. Trends Cardiovasc Med.doi:10.1016/j.tcm.2017.08.015
2. Tiao J, Feng R, Carr K, Okawa J, Werth VP. Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE). J Am Acad Dermatol. 2016;74(5):862-869.
3. Kim CH, Al-Kindi SG, Jandali B, Askari AD, Zacharias M, Oliveira GH. Incidence and risk of heart failure in systemic lupus erythematosus. Heart. 2017;103(3):227-233.
4. Schoenfeld SR, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum. 2013;43(1):77-95.
5. Agarwal S, Elliott JR, Manzi S. Atherosclerosis risk factors in systemic lupus erythematosus. Curr Rheumatol Rep. 2009;11(4):241-247.
6. Dhakal BP, Kim CH, Al-Kindi SG, Oliveira GH. Heart failure in systemic lupus erythematosus [published online September 6, 2017]. Trends Cardiovasc Med.  doi:http://dx.doi.org/10.1016/j.tcm.2017.08.015
7. Sherer Y, Zinger H, Shoenfeld Y. Atherosclerosis in systemic lupus erythematosus. Autoimmunity. 2010;43(1):98-102.
8. O’Neill SG, Giles I, Lambrianides A, et al. Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 2010;62(3):845-854.
9. Tselios K, Sheane BJ, Gladman DD, Urowitz MB. Optimal monitoring for coronary heart disease risk in patients with systemic lupus erythematosus: a systematic review. J Rheumatol. 2016;43(1):54-65.
10. Yazdany J, Tonner C, Trupin L, et al. Provision of preventive health care in systemic lupus erythematosus: data from a large observational cohort study. Arthritis Res Ther. 2010;12(3):R84.
11. Mosca M, Tani C, Aringer M, et al. Development of quality indicators to evaluate the monitoring of SLE patients in routine clinical practice. Autoimmun Rev. 2011;10(7):383-388.
12. Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS. Lupus Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis. 2011;70(5):760-765.
13. Pons-Estel GJ, González LA, Zhang J, et al. Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort. Rheumatology (Oxford). 2009;48(7):817-822.