Traditional Cardiovascular Risk Factors and Systemic Lupus Erythematosus: A Bad Combination

Systemic lupus erythematosus (SLE) affects multiple organs. The kidney is most commonly identified as a prominent target organ, but the standardized cardiovascular mortality for persons with SLE is actually 2.7 compared to controls.^1,2 There is also a 1.3 to 2.3-fold higher risk for cerebrovascular disease and a 9.4 times higher incidence of peripheral vascular disease in the setting of SLE.^1,2 There is room for aggressive cardiovascular risk factor intervention in this population prone to vascular disease.

The following question, answers, and short discussion offer a brief review of a dangerous combination.

1. Which of the following statements regarding cardiovascular risk factor modification in SLE are true? 

A. Studies have demonstrated that hydroxychloroquine and aspirin may provide synergistic vascular protection when used in combination, thereby decreasing cardiovascular events in SLE.

B. Statins cause a higher number of side effects in persons with SLE.

C. Selected therapeutic agents (eg, rituximab and mycophenolate mofetil) can lower cardiovascular risk by reducing corticosteroid use.

Answer and discussion on next page>

The correct answers: A and C are true

Hydroxychloroquine has been proven to be safe during long-term use in SLE patients. Treatment benefits include maintenance of remission, decreased thrombotic potential, and positive effects on lipid profiles. Hydroxychloroquine and aspirin used in combination may have a synergistic effect in primary prevention of cardiovascular events.¹

Statins should be used appropriately and frequently in patients with SLE. In 4,095 people with SLE and dyslipidemia, over 144 months, treatment with low- and high-dose statins in groups based on lipid panels and review of risk factors reduced all-cause mortality (hazard ratio = 0.44).² The high-dose statin group experienced reductions in coronary disease, cerebrovascular disease, and end-stage renal disease as well.² No increase in statin-related adverse effects have been observed in patients with SLE.

The primary agents to treat the inflammatory autoimmune manifestations of SLE are corticosteroids; this class of drugs, however, is known to accelerate atherosclerosis. In fact, corticosteroids at doses of 40 mg/day or more can be solely responsible for the progression of atherosclerosis.¹ Corticosteroids can also precipitate diabetes, yet one more traditional CVD risk factor that may affect this vulnerable population. Whenever possible, steroid-sparing strategies to suppress inflammation are an important adjunct to therapy. Both mycophenalate mofetil and rituximab have proven effective in this regard and may allow lower corticosteroid doses over time, thus reducing cardiovascular risk.

Remember, common cardiovascular risks are common in SLE. Driven by renal disease, corticosteroid use, and weight gain, hypertension also is a frequent SLE comorbidity. Blood pressure control is an essential intervention to reduce cardiovascular morbidity and mortality.

Too often, SLE is characterized as a disease that belongs only in the realm of rheumatology. Primary care clinicians and cardiologists have important roles as well. Every patient with SLE should be approached as a bundle of cardiovascular risks which in its sum is greater than the total of the individual contributions.

References

1. Fasano S, Pierro L, Pantano I, et al. Longterm hydroxychloroquine therapy and low-dose aspirin may have an additive effectiveness in the primary prevention of cardiovascular events in patients with systemic lupus erythematosis. J. Rheumatol. 2017; 44:1-7.

2. Yousef Yengej FA, Limper M, Leavis HL. Statins for prevention of cardiovascular disease in systemic lupus erythematosus. Netherlands J Med. 2017; 75:99-105.