Accelerated cardiovascular disease 
in patients with lupus: A review

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■ Both patient and clinician should be aware that systemic lupus erythematosus (SLE) increases the risk for cardiovascular disease, including a 10-fold increased risk of nonfatal MI and a 17-fold increased risk for coronary heart disease death.

■ In addition to monitoring the traditional risk factors for atherosclerosis (hyperlipidemia, hypertension, obesity, diabetes mellitus, tobacco use, and family history), identify and monitor those factors specific to patients with SLE (disease activity, pharmacotherapy, renal parameters, and antiphospholipid antibodies).

■ Minimize corticosteroid dose and frequency when managing SLE. Consider prescribing hydroxychloroquine, which has been found to lower overall occurrence of vascular events in patients with SLE.  

The autoimmune disorder systemic lupus erythematosus (SLE) is characterized by chronic inflammation and affects many organ systems. Over time, the number of deaths directly related to SLE activity has decreased; however, the incidence of cardiovascular disease (CVD) in SLE patients has not diminished, and CVD is the most common cause of death not directly related to SLE itself in this population.1

Accelerated development of atherosclerosis leading to premature CVD is well-documented in patients with SLE. Women 35 to 44 years old with SLE may be as much as 52 times more likely to have an MI compared with women in the same age-group without the disease.2 Esdaile and colleagues found that initially asymptomatic SLE patients have a greater than 7-fold increased risk of coronary heart disease (CHD) or stroke, including a 10-fold increased risk for nonfatal MI and a 17-fold increased risk for CHD death.3 Increased prevalence of coronary artery calcification (CAC) has been observed in SLE patients (31% vs 9% in controls).4 This increase in CAC correlated with the extent of atherosclerosis in those patients and occurred at an earlier age than in those without SLE.4 Another study compiled data from the Health Care Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database that included 31,927,484 hospitalizations for non-SLE patients and 124,688 hospitalizations for SLE patients. The goal was to determine risk discrepancies for age and race. The researchers found that the average age for a CVD event in women with SLE was 10.5 years younger than for a CVD event in women without SLE.5 The youngest group to be affected with a CVD event that led to death was black women with SLE, who were 19.8 years younger than controls.5 Other studies have reported even higher risk of CVD and thrombotic events in males with SLE, although the prevalence of SLE is much lower in men.6,7 The risks posed by CHD in patients with SLE put great importance on the monitoring of risk factors—both the traditional Framingham risk factors and SLE-specific risk factors for CHD.


While progression of atherosclerosis in SLE patients is not completely understood, it is thought to be a multifactorial process. The increased risk of premature CHD in SLE cannot be fully accounted for by the traditional Framingham risk factors (hyperlipidemia, hypertension, obesity, diabetes mellitus, tobacco use, and family history).3 To determine an SLE patient’s risk for atherosclerosis, one must consider not only traditional risk factors for CHD but also risk factors that are unique to SLE, including the adverse effects of chronic systemic inflammation (Table 1).8,9 Like SLE, atherosclerosis is a systemic inflammatory process.8 This shared component of inflammation may be the cause of the accelerated atherosclerosis in SLE patients. Several inflammatory mediators, toxins, and proteins are being studied to determine their roles in atherosclerosis progression in SLE. These include C-reactive protein (CRP), homocysteine, tumor necrosis factor-alpha (TNF-), interferon alpha (INF-), and several lupus antibodies, all of which have been found at elevated levels in SLE patients.8,9

Risk factors unique to lupus patients include SLE disease duration, level of disease activity, and corticosteroid doses used in treatment. In a study by Karp and colleagues, the level of SLE disease activity and its correlations with CHD risk factors were assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The researchers found that a 6-pt increase in SLEDAI was associated with a 5% increased risk of CHD in the next 2 years.10 One way to reduce average disease activity is pharmacologic therapy, specifically corticosteroids. However, Karp and associates also found that a 10-mg increase in corticosteroid dose from the previous year increased the 2-year CHD risk by 16%. This 10-mg increase in average dose had major effects on many of the CHD risk factors. The following increases were seen with the higher corticosteroid dose: total serum cholesterol, 0.41 mmol/L; low-density lipoprotein cholesterol (LDL), 0.22 mmol/L; apolipoprotein (apo) B, 0.06 mmol/L; triglycerides (TGs), 0.15 mmol/L; systolic BP, 1.6 mm Hg; body mass index (BMI), 0.4 kg/m2; and blood glucose, 0.02 mmol/L.10 In addition to the increased CHD risk observed with corticosteroid use, two major cohorts of patients showed increased risk with longer duration of SLE,11 indicating that the longer a person has SLE, the more atherosclerosis he or she is likely to develop.

Traditional risk factors for CHD have a major role in the atherosclerosis process in SLE patients. In their review, Nikpour and colleagues compared findings in major SLE cohorts from Toronto, Baltimore, and Pittsburgh. All three studies found that hypercholesterolemia was a risk factor for increased atherosclerosis in SLE patients.11 Another recent study used noninvasive techniques to examine the development of subclinical atherosclerosis in SLE patients. Carotid and coronary arteries were studied to determine the extent of CAC, carotid intima-media thickness (IMT), and carotid plaque, all of which are associated with atherothrombotic events. After 2 years, the researchers found that carotid plaque developed in 24% of SLE patients and was associated with increases in systolic BP, urinary protein, and duration of SLE. Carotid IMT was associated with increased systolic BP. CAC was associated with smoking and increased total serum cholesterol.12

This article originally appeared on JAAPA