Coronary heart disease in systemic lupus erythematosus

INTRODUCTION — Systemic lupus erythematosus (SLE) is associated with several cardiovascular manifestations, of which accelerated atherosclerosis with coronary heart disease (CHD) is a significant cause of morbidity and premature death. The greatest increase in relative risk (RR) is among young women, who otherwise have a low risk of CHD, although the absolute risk of CHD increases with age, as it does in the general population [1-7].

Issues related to CHD in patients with SLE will be reviewed here. Other cardiac manifestations of SLE, including pericardial, myocardial, and valvular heart disease, are discussed separately. (See "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults".)

EPIDEMIOLOGY — The burden of cardiovascular disease, including coronary heart disease, is high in patients with systemic lupus erythematosus (SLE) and greater than that in the general population.

Cardiovascular disease is the leading cause of death among patients with SLE. In a cohort of 816 patients with SLE followed over a decade, cardiovascular disease was the cause of death for one-third of patients [8]. In this study, patients with SLE were over three times more likely to die of cardiovascular disease than patients in the general population (standardized mortality ratio [SMR] 3.83, 95% CI 2.09-6.42), while Hispanic patients with SLE were over six times more likely to die of cardiovascular disease than Hispanic patients without SLE (SMR 6.45, 95% CI 2.59-13.29).

A meta-analysis that included 46 studies found that the risk of myocardial infarction, cardiovascular disease, stroke, and hypertension among patients with SLE is approximately doubled when compared with people without SLE [9]. Younger patients with SLE had the greatest relative risk (RR) of cardiovascular disease compared with their healthy counterparts, but the absolute risk was higher in older SLE patients as well. In autopsy studies of young patients with SLE, substantial atherosclerosis was present in up to half [10,11].

Among patients with SLE, traditional cardiovascular disease risk factors and current glucocorticoid use, along with disease duration and disease activity, are associated with increased risk. Additionally, Black patients with SLE have a higher risk of incident cardiovascular disease than non-Black patients with SLE; in one study, the risk was sevenfold higher [12].

While angina and myocardial infarction are most commonly due to atherosclerosis in patients with SLE, these may rarely be due to thrombosis in an angiographically normal coronary artery or result from coronary vasculitis or arterial emboli [13]. (See "Coronary artery disease and myocardial infarction in young people" and "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults".)

PATHOGENESIS — The pathogenesis of accelerated atherosclerosis in systemic lupus erythematosus (SLE) is incompletely understood and likely multifactorial. Traditional risk factors for atherosclerosis (diabetes, hyperlipidemia, hypertension, family history of coronary heart disease [CHD], obesity, sedentary lifestyle, and cigarette smoking) are common among patients with SLE [4,14-21]. Moreover, diabetes, hyperlipidemia, hypertension, obesity, and sedentary lifestyle may all be exacerbated by SLE itself or its treatment with glucocorticoids. Metabolic syndrome (the presence of two or more traditional CHD risk factors, including central obesity, dyslipidemia, hypertension, and disturbed glucose metabolism) is common among patients with SLE [22,23]. However, after accounting for the increased CHD risk associated with traditional risk factors, SLE itself and/or its treatment confer the greatest risk for premature CHD [15,24-26].

Inflammation — Atherosclerosis is an inflammatory process with immune cell activation, inflammation-driven plaque formation and subsequent rupture [27]. In mouse models of SLE, the degree of systemic inflammation correlates with the rapidity of development of atherosclerosis. Systemic inflammation is thought to accelerate atherosclerosis in human SLE as well [14,15,18,20,27-30].

Autoimmune vascular injury in SLE may predispose to atherosclerotic plaque formation via a number of possible mechanisms and is an area of active research:

●Excessive oxidative stress in SLE enhances inflammation, inducing apoptotic cell death. Reactive species and free radical production in SLE and antiphospholipid syndrome are thought to contribute to chronic inflammation of tissues and lead to dyslipidemia and accelerated atherogenesis. Anti-beta 2-glycoprotein I autoantibodies complex with oxidized low-density lipoprotein and accelerate macrophage uptake of oxidized low-density lipoprotein cholesterol [31-33]. Antiphospholipid antibodies were associated with an over fourfold elevated risk of myocardial infarction, stroke, or peripheral vascular disease in a study of 182 patients with SLE who were followed for a mean of 8.3 years [21,34]. (See "Clinical manifestations of antiphospholipid syndrome".)

●Dysfunctional proinflammatory high-density lipoprotein cholesterol, which is commonly present among SLE patients, may accelerate low-density lipoprotein oxidation and atherosclerosis [35,36]. Deposition of immune complexes also stimulates the accumulation of cholesterol in atherosclerotic plaques [37].

●Type I interferon (IFN) has been shown to promote atherosclerosis by stimulating macrophage recruitment to atherosclerotic lesions in vitro, and type I IFN may have other effects on the endothelium and atherogenesis as well [38,39]. Exposure to high levels of serum type I IFN activity (induction of IFN-inducible genes or the "interferon signature") was associated with atherosclerosis development among 95 SLE patients without history of overt cardiovascular disease and after controlling for Framingham risk factors, when compared with 38 healthy controls [40].

●Neutrophil extracellular trap (NET) formation is increased in SLE and appears to contribute to endothelial damage and premature cardiovascular disease [41-43].

●Antiphospholipid antibodies may lead to in situ thrombosis, embolization, and may drive the atherosclerotic process as well [21].

Traditional risk factors — Traditional risk factors for atherosclerosis are prevalent among patients with SLE. When compared with controls, 250 women in the Toronto Lupus Cohort had increased prevalence of hypertension, diabetes, premature menopause, sedentary lifestyle, and at-risk body habitus [44]. Among postmenopausal women in the aforementioned SLE cohort, use of hormone replacement therapy (HRT) was not a risk factor for the development of CHD [45].

Although men represent a small minority of patients with SLE, male sex is a strong risk factor for incident CHD in SLE, as it is in the general population. In the LUMINA study of 637 patients with a mean disease duration of 6.6 years, men represented about 10 percent of the group but had an odds ratio of 3.6 compared with women of having a CHD diagnosis or related event [20].

A high proportion of patients with SLE have metabolic syndrome (ie, central obesity, dyslipidemia, hypertension, disturbed glucose metabolism). Not surprisingly, presence of metabolic syndrome among SLE patients has been associated with endothelial damage, arterial stiffness, and atherosclerosis [46,47]. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)".)

Despite an increasing appreciation of the importance of CHD in SLE, recognition of traditional risk factors has been suboptimal. As an example, in one academic rheumatology practice, deficits in knowledge and management of cardiac risk factors were observed among both SLE patients and their clinicians [48].

Over time, the risk profile may change, and continued vigilance is necessary to identify the emergence of modifiable risk factors for CHD. This was illustrated in a study of an inception cohort of 935 patients with SLE; over three years of follow-up, the prevalence of all Framingham CHD risk factors increased, as did the proportion of patients treated for hypertension and, to a lesser extent, hyperlipidemia [49].

Glucocorticoids — The role of glucocorticoids in promoting atherosclerosis and their contribution to the risk of CHD is discussed in more detail elsewhere. (See "Major side effects of systemic glucocorticoids", section on 'Cardiovascular effects'.)

Glucocorticoids (which can cause or exacerbate hyperlipidemia, diabetes, and obesity) are associated with worsening of traditional risk factors for CHD, and current glucocorticoid use is strongly associated with increased risk of CHD among patients with SLE [26,50]. As an example, in a cross-sectional study of 264 SLE patients, after adjusting for age, weight and antihypertensive drug use, a 10 mg/day increase in prednisone dose led to:

●A 7.5 mg/dL (0.19 mmol/L) increase in serum cholesterol

●A 1.1 mmHg increase in mean arterial blood pressure

●A 2.5 kg increase in body weight

In a study that included 1874 SLE patients followed for a mean of 5.1 years, patients who were currently using glucocorticoids were found to be at increased risk of cardiovascular events, even after controlling for disease activity [26].

For these reasons, we suggest that the minimum dose of glucocorticoids be used for the shortest possible time to control life or organ-threatening manifestations of SLE. (See "Overview of the management and prognosis of systemic lupus erythematosus in adults".)

Inflammation-related risk factors — Clinical factors associated with CHD in patients with SLE include: higher disease activity [20,26], chronic nephritis, low serum levels of C3 and C4 [51,52], elevated levels of antibodies to double-stranded deoxyribonucleic acid (dsDNA) [51], antiphospholipid antibodies [53-56] (which promote thrombosis), increased oxidative stress [57], and CRP [20]. The presence of such risk factors may also enhance the risk of cerebrovascular disease [58].

A panel of clinical risk factors and investigative biomarkers of inflammation, including proinflammatory HDL function, leptin, homocysteine, and plasma soluble tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK), has been shown to be highly predictive of atherosclerosis and its progression among women with SLE [36].

It should be recognized that SLE patients with nephritis and renal disease are among those with the highest risks of CHD. This is likely due to excess traditional risk factors (hypertension, hyperlipidemia), higher doses of glucocorticoids, and higher levels of systemic inflammation [59]. Increasing overall severity of SLE, in terms of inflammation with multiorgan system involvement necessitating glucocorticoid and immunosuppressant use, is strongly associated with increasing CHD risks in large cohort studies, and the risk of CHD is elevated from the onset of SLE and even prior to diagnosis [49,60].

CLINICAL MANIFESTATIONS — Coronary heart disease (CHD) in systemic lupus erythematosus (SLE) patients may present with symptoms typical of ischemic heart disease (eg, exertional chest pain/angina pectoris) or with atypical or nonspecific symptoms (eg, dyspnea, diaphoresis, etc). Noninvasive approaches to determining the presence or absence of significant stenotic coronary lesions in asymptomatic individuals and those with nonspecific symptoms are being assessed.

Symptoms — As noted above, CHD may be present in SLE patients without symptoms or in those with nonspecific symptoms. In one report, 33 women (22 to 45 years of age) with lupus and nonspecific complaints such as chest discomfort and/or dyspnea underwent noninvasive testing with exercise or pharmacologic stress and nuclear imaging studies [61]. Perfusion abnormalities were present in 12 of 28 patients (43 percent).

Imaging — Various noninvasive imaging studies have been assessed as aids to predicting the risk of CHD in asymptomatic patients with SLE. Examples include electron-beam computed tomography (EBCT) to detect coronary artery calcification and ultrasonography to detect plaque or narrowing of the carotid arteries [62]. We do NOT use these tests to screen asymptomatic patients with SLE for CHD in the absence of other traditional risk factors for coronary disease

Electron-beam CT — EBCT may detect calcification of the epicardial arteries, a finding suggestive of atherosclerosis. (See "Coronary artery calcium scoring (CAC): Overview and clinical utilization".)

Coronary artery calcification is more prevalent in patients with SLE than in age- and sex-matched controls. The following studies utilizing EBCT are illustrative:

●A study of 65 patients with SLE and 69 controls, each of whom had EBCT evaluation [14]. The prevalence of coronary calcification was significantly higher in those with SLE (31 versus 9 percent).

●The prevalence of coronary artery calcification was similar (28 percent) in another study of 75 women with SLE, all of age <50 years, and none with symptomatic CHD [63].

●A separate study compared 105 patients with SLE with 105 patients with rheumatoid arthritis (RA) and with 105 controls [64]. Coronary artery calcification was observed in 47.6 percent of SLE patients, 47.6 percent of RA patients, and in 35.2 percent of the controls. Even after controlling for traditional cardiac risk factors including hypertension and insulin resistance, this increased frequency was strongly associated with inflammation as demonstrated by elevated C-reactive protein (CRP) and endothelial activation soluble intercellular adhesion marker (sICAM) levels. It is not surprising, however, that the patients with systemic autoimmune disease had more evidence of systemic inflammation.

●In a cross-sectional study of 200 SLE patients, coronary artery calcification was detected in 43 percent [65]. Inflammation, as reflected in erythrocyte sedimentation rate (ESR) and CRP, was associated with coronary artery calcification only in univariable models, but not after adjustment for multiple other clinical variables. In multivariable models, age, body mass index (BMI), and diabetes mellitus were significant predictors of the extent of coronary calcification.

Taken together, these studies indicate that the higher levels of ongoing and sustained inflammation in individuals with systemic autoimmune disease (compared with healthy individuals), are associated with coronary artery calcification. Single time-point and exact measures of systemic inflammation, such as ESR and CRP, however, do not distinguish who is likely to have coronary calcification in a group of SLE patients as well as longer-term factors that may reflect both ongoing inflammation and exposure to glucocorticoids.

Carotid ultrasound — Atherosclerotic plaques in the carotid arteries, which correlate with the presence of similar lesions in the coronary arteries, are found in a higher proportion of patients with SLE than age- and sex-matched controls [15,58,62]. As examples:

●Among 197 patients with SLE, ultrasonographically demonstrated carotid artery plaques were present in 37 percent but were present in only 15 percent of controls [15].

●A longitudinal study of 217 SLE patients, followed for an average of four years, noted that the carotid plaque prevalence increased from 31 percent at baseline to 40 percent at follow-up [62].

●In a study including 392 women with SLE followed for a mean of eight years, baseline carotid intima-medial thickness on ultrasound and presence of carotid plaque were predictive of any incident cardiovascular events including myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, and cerebrovascular accident, independent of traditional cardiovascular risk factors and medication use [66].

The high prevalence of carotid plaque may be associated with traditional cardiovascular risk factors as well as SLE per se [62].

Other noninvasive tests — Evidence of subclinical atherosclerosis, as determined by an abnormal ankle-brachial index, or endothelial dysfunction (eg, decreased flow-induced dilation of the brachial artery) has been noted in 17 to 55 percent of patients with SLE [67].

Although noninvasive studies have the potential to identify patients with SLE who have asymptomatic CHD, the utility of using one or more of these tests in the absence of symptoms is uncertain. Recommendations regarding screening asymptomatic people in the general population with multiple cardiac risk factors are summarized elsewhere. (See "Screening for coronary heart disease".)

We suggest not screening asymptomatic patients with SLE for CHD using EBCT or carotid ultrasonography. If, after a discussion of the risks and potential benefits of pursuing an evaluation for CHD, the patient and clinician decide to proceed we suggest exercise electrocardiographic testing. Patients unable to exercise (eg, because of severe arthritis or lung disease) may be assessed with a pharmacologic cardiac stress test and radionuclide imaging. (See "Overview of stress radionuclide myocardial perfusion imaging".)

There is increasing interest in using cardiac magnetic resonance imaging (MRI) with late gadolinium contrast enhancement (LGE) to identify areas of myocardial scarring for the detection of atherosclerosis in subjects with SLE, although the technique is not yet ready for widespread clinical use [68-70]. Positron emission tomography (PET) scans to assess coronary flow reserve and atherosclerotic lesions are being employed in research studies involving SLE patients and may have promise for early detection of endothelial dysfunction in the arteries of the heart [71].

EVALUATION — A high index of suspicion for coronary heart disease (CHD) is warranted in patients with systemic lupus erythematosus (SLE) presenting with chest pain/pressure, dyspnea, decreased exercise tolerance or other atypical symptoms. The differential diagnosis of such symptoms in the patient with SLE is broad, and also includes pleuritis, pericarditis, pulmonary embolus, pneumonia, interstitial lung disease, reflux esophagitis, and pulmonary hypertension, as well as other cardiac manifestations of SLE. (See "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults" and "Pulmonary manifestations of systemic lupus erythematosus in adults".)

The evaluation of the individual suspected of having CHD is performed similarly in patients with and without SLE, including electrocardiogram, chest x-ray, cardiac enzymes and stress testing when appropriate. (See "Outpatient evaluation of the adult with chest pain" and "Coronary artery disease and myocardial infarction in young people" and "Stress testing for the diagnosis of obstructive coronary heart disease".)

PREVENTION AND TREATMENT — Patients with systemic lupus erythematosus (SLE) and clinicians who treat them should be aware of the importance of risk factor reduction in the prevention and treatment of coronary heart disease (CHD). Awareness of patients with SLE of the presence of traditional risk factors for CHD is limited. In one study, for example, only 17 percent of the patients with SLE believed that they were at high risk for developing coronary disease within five years, when in fact three or more traditional risk factors were present in 53 percent of patients who had a mean age of 38 years [4]. (See "Overview of atherosclerotic cardiovascular risk factors in females".)

In our practice, we now refer most patients with moderate to severe SLE to at least a baseline visit with a preventive cardiologist for the assessment of cardiac risk factors and recommendations for screening and treatment.

Lifestyle modifications — Modifiable risk factors for CHD may be addressed with advice to not smoke cigarettes, to exercise regularly, to achieve a body mass index of <25 kg/m(2), and to follow dietary measures designed to improve lipid profiles [72-78].

Statins — Statins have been proposed as ideal lipid-lowering agents for patients with SLE, given their pleiotropic effects including antiinflammatory, antithrombotic, and plaque-stabilizing activities [79]. Statins are well-tolerated and effective in reducing lipid levels in patients with lupus [80]. Observational studies suggest effectiveness of statins in reducing cardiovascular disease risk among patients with SLE, although evidence from clinical trials has not been conclusive [81,82].

We suggest using a statin when a pharmacologic approach to lipid-lowering as a primary or secondary prevention strategy is otherwise indicated based on guidelines for the general population and generally after a trial of lifestyle and dietary modification has been ineffective in achieving desirable lipid levels. However, CHD prediction models for the general population perform poorly in SLE, and the development of improved models will help in the tailoring of statin therapy in those at highest risk [52,83] . (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Statins: Actions, side effects, and administration" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

For patients with SLE and significant renal disease who require lipid-lowering therapy, atorvastatin and fluvastatin may be preferred to other statins, as they do not require dose adjustment in those with severe reduction in glomerular filtration. (See "Statins: Actions, side effects, and administration", section on 'Chronic kidney disease'.)

Hydroxychloroquine — Several lines of evidence suggest that hydroxychloroquine may have beneficial effects on CHD risk, as it has been associated with decreased accumulation of organ damage and increased survival in SLE patients, reduced risk of thrombosis, and may act by reducing lipid profiles, and possibly risk of diabetes mellitus [67,84-90]. (See "Overview of the management and prognosis of systemic lupus erythematosus in adults".)

Control of hypertension — Hypertension is an important risk factor for CHD in SLE [4,44]. We favor aggressive therapy with a goal blood pressure similar to that recommended for patients without SLE who have diabetes or chronic kidney disease. (See "Goal blood pressure in adults with hypertension".)

The choice of an antihypertensive regimen depends in part upon coexisting disorders. As examples, we use nifedipine for patients with the Raynaud phenomenon and angiotensin-converting enzyme inhibitors for those with renal disease. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)

An observational study of 220,168 patients with SLE found that antihypertensive drugs that act on the renin-angiotensin system (RAS) were associated with a lower risk of incident cardiovascular disease compared with other antihypertensive treatments (relative risk [RR] 0.80, 95% CI 0.74-0.87) [91]. Use of RAS-modifying therapies increased the probability of remaining free of cardiovascular disease over a five-year period (86.0 versus 78.3 percent).

Prophylactic use of aspirin — Low-dose aspirin has been shown to decrease risk of myocardial infarction and ischemic stroke among older adults but is associated with a non-trivial risk of gastrointestinal and other bleeding. As in patients without SLE, the decision to use low-dose aspirin for primary prevention of cardiovascular disease in patients with SLE must be individualized and based on the estimated risk of a first cardiovascular event [92]. Retrospective studies have found that aspirin use was associated with decreased CHD event risks in SLE patients, but these were not controlled trials [89]. Importantly, other medications commonly used in patients with SLE (eg, nonsteroidal antiinflammatory drugs [NSAIDs] and glucocorticoids) may further increase the risk of bleeding. (See "Overview of primary prevention of cardiovascular disease", section on 'Aspirin' and "Aspirin in the primary prevention of cardiovascular disease and cancer".)

Minimizing glucocorticoid dose — As glucocorticoids contribute to CHD risk factors by worsening hypertension, hyperlipidemia, and diabetes, the glucocorticoid dosage should be reduced as soon as possible. (See "Major side effects of systemic glucocorticoids", section on 'Cardiovascular effects'.)

Reducing systemic lupus erythematosus disease activity — There is increasing consensus that keeping SLE disease activity low, without the use of glucocorticoids, should be the goal of therapy and is associated with improved overall prognosis and reduced risk of organ damage including CHD events. The target of Lupus Low Disease Activity State (LLDAS), incorporating low disease activity and low physician global assessment, as well as no use of glucocorticoids over 7.5 mg/day, has been associated with reduced CHD risk [93].

Noninvasive testing — In patients with SLE, but no other risk factors for CHD, we suggest not routinely performing noninvasive screening tests (eg, exercise or pharmacologic stress testing, electron-beam CT (EBCT) scanning, or ultrasonography of femoral or carotid arteries as surrogate markers of coronary atherosclerosis).

In selected patients with SLE, however, intermittent screening for CHD with exercise or pharmacologic stress testing may be advisable. Such patients may include those with longer duration of active SLE (>5 to 10 years), and those with high disease activity (eg, patients requiring glucocorticoids in addition to immunosuppressive therapy) [52,60,94]. As an example, myocardial perfusion imaging was performed in a group of 122 patients with a median disease duration of 8.7 years and no history of coronary artery disease [94]. The prevalence of abnormal perfusion scans was 38 percent; the incidence of cardiac events was greater in those with abnormal scans than those with no focal defects (15 versus 2 events, respectively). Of the cardiac events observed, 14 were new-onset angina and 1 was a myocardial infarction. Abnormal perfusion imaging was a better predictor of cardiac events than an elevated Framingham risk score (hazard ratios of 13 versus 1.8, respectively). Despite these results, it remains to be determined whether routine screening using noninvasive testing even in those with a long duration of disease will reduce the mortality from cardiovascular disease in this patient population.

If noninvasive testing suggests the presence of asymptomatic coronary atherosclerosis, one or more of the following may be appropriate, depending upon the severity of the abnormalities: angiographic assessment and/or percutaneous or surgical coronary revascularization procedures (as for the patient with symptomatic coronary disease). (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)

Symptomatic CHD should be treated aggressively, as in patients with diabetes, given the elevated risks in both disease states. (See "Chronic coronary syndrome: Overview of care" and "Acute myocardial infarction: Patients with diabetes mellitus" and "Coronary artery revascularization in stable patients with diabetes mellitus".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Systemic lupus erythematosus".)

SUMMARY AND RECOMMENDATIONS

●The risk of coronary heart disease (CHD) is greatly increased in systemic lupus erythematosus (SLE) patients compared with an age- and sex-matched segment of the general population. Patients with SLE have an increased prevalence of traditional risk factors, and active disease and treatment with glucocorticoids are powerful risk factors for CHD. Patients with high disease activity, lupus nephritis, and those with antiphospholipid antibodies are among those at highest risk. (See 'Traditional risk factors' above.)

●A high index of suspicion for CHD is warranted in patients with SLE. Symptoms may be atypical, nonspecific, or absent despite the presence of significant coronary artery stenoses. (See 'Symptoms' above.)

●Other causes of chest pain in patients with SLE include: pleuritis, pericarditis, pulmonary embolus, pneumonia, interstitial lung disease, reflux esophagitis, and pulmonary hypertension. The evaluation of patients with SLE suspected of having CHD is similar to that of other patients without lupus. (See 'Evaluation' above.)

●Prevention and treatment of CHD are similar in many respects in patients with and without SLE. Beneficial interventions include: not smoking, exercising regularly, optimizing lipid levels (based upon guidelines and risk categories using traditional risk factors to assess cardiovascular risk), achieving goal blood pressure in those with hypertension, use of prophylactic low-dose aspirin if not contraindicated and after consideration of bleeding risk, and minimizing or avoiding use of glucocorticoids. Hydroxychloroquine, widely used in SLE and disease-stabilizing, likely has additional anti-thrombotic and anti-atherogenic benefits. (See 'Prevention and treatment' above.)

●Studies using noninvasive screening tests such as exercise or pharmacologic cardiac stress testing, electron-beam CT (EBCT) scanning, and/or ultrasonography of the carotid or femoral arteries support an increased prevalence of asymptomatic cardiovascular disease in patients with SLE. However, we suggest not using these tests to screen asymptomatic patients with SLE for CHD in the absence of other traditional risk factors for coronary disease (Grade 2C). (See 'Imaging' above and 'Other noninvasive tests' above.)

●Patients with SLE and other traditional risk factors for coronary atherosclerosis are a group for whom further evaluation for CHD may be pursued in the absence of cardiac symptoms, and consultation with a preventive cardiologist may be beneficial. If, after a discussion of the risks and potential benefits of testing, a patient and clinician decide to proceed, we suggest exercise electrocardiography for the patient who is able to exercise, or pharmacologic cardiac stress testing with radionuclide imaging for those who cannot exercise. (See 'Prevention and treatment' above.)

●We suggest that statins not be used routinely in asymptomatic patients with SLE for primary prevention of CHD, unless otherwise indicated (eg, in those with known CHD, multiple risk factors for CHD, or hypercholesterolemia that is inadequately controlled by lifestyle and dietary modification) (Grade 2C). (See 'Statins' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Peter Schur, MD, who contributed to an earlier version of this topic review.