Cardiovascular disease in systemic lupus erythematosus: an update

Burden of cardiovascular disease in lupus

Despite therapeutic advances, cardiovascular disease (CVD) remains a major cause of morbidity and mortality in systemic lupus erythematosus (SLE, lupus). Although a nationwide population-based study from 1968–2013 found improving mortality in SLE, with a consistent downtrend since 1999, SLE-related mortality continues to remain high compared to non-SLE-related mortality. Furthermore, significant disparities in mortality based on sex, race/ethnicity, age, and geographic region were noted. Patients with lupus have an increased risk of death from any cause compared to the general population, with a three-fold greater risk of death from CVD. A study conducted from 1996 to 2012 that examined national trends in hospitalization rates for CVD events found that the rate of myocardial infarction and ischemic stroke hospitalizations went up over time in patients with SLE but decreased in the general population.

In 2011 the American Heart Association (AHA) first acknowledged SLE as a unique risk factor for CVD. This increased cardiovascular risk cannot be fully explained by traditional risk factors alone or conventional risk scores like the Framingham 10-year risk score or the 2013 ACC/AHA risk score. Some authors in North America and Europe have proposed 10-year CVD risk stratification scores specific to lupus, by incorporating disease-specific variables. A modified Framingham risk score, where each item is multiplied by 2, was shown to more accurately predict CVD in SLE. Other investigators have proposed using the PREDICTS (Predictors of Risk for Elevated Flares, Damage Progression and Cardiovascular Disease in Patients with SLE) score, a panel of biomarkers and risk factors to better identify who will have progression of atherosclerosis using carotid imaging. Specifics of this panel are further detailed below.

In the United Kingdom QRISK2/3 scores (clinical and immunological/biochemical measures specific to SLE) more accurately identified lupus patients with an increased 10-year risk of CVD as compared to healthy controls. In fact, since 2008, the United Kingdom has used QRISK 2 scores as a standard practice to calculate the 10-year risk of a major cardiovascular event in patients with lupus. A score ≥10% is considered high risk necessitating clinical intervention. QRISK3 scores specifically incorporate markers for endothelial dysfunction and steroid use, making it more sensitive to capture lupus patients at an increased 10-year risk of CVD compared to QRISK2 scores; it is expected to replace QRISK2 scores in time.

It is likely that composite risk scores, like those discussed here, are needed to accurately predict 10-year CVD risk in lupus patients. In this review, we will discuss the evidence to support the role of traditional risk factors, SLE-specific risk factors, and novel biomarkers in predicting who is at risk for CVD. Furthermore, we will review recent updates in our understanding of atherogenesis, the use of imaging modalities for early detection, and management strategies.

Traditional risk factors for cardiovascular disease in SLE

CVD in lupus likely includes an interplay of traditional risk factors and disease-specific immune and inflammatory factors. Traditional risk factors, such as hypertension, diabetes, smoking, hyperlipidemia, obesity, and a sedentary lifestyle, are prevalent in SLE and clearly contribute to the increased risk of CVD. Hypertension in lupus patients is associated with a 2.6-fold increased risk of cardiovascular events and coronary artery disease as well as progression of carotid plaque. Diabetes has been shown to double the risk of cardiovascular events in this population. Furthermore, smoking is associated with a three-fold increase in cardiovascular events in lupus. A prospective European study found that smoking was the only traditional risk factor to predict mortality from CVD.

In the Toronto lupus cohort, there was a 2.07-fold increase in CVD with persistently elevated total cholesterol levels. Although sedentary lifestyle and obesity, influenced by limitations in physical activity and glucocorticoid use, are common in lupus and regarded as traditional risk factors, their effects on cardiovascular events in these patients are not well defined. A recent study by Rodríguez-Carrio et al. found that a low bone mineral density, defined as either osteopenia or osteoporosis, was independently associated with an increased risk of CVD. In the same study, a paradoxical effect of body mass index (BMI) on subclinical atherosclerosis was found. BMI <20 kg/m ² was associated with more carotid plaques with no effect on carotid intima media thickness (CIMT), whereas patients with BMI >30 kg/m ² had less carotid plaques, despite increased CIMT sometimes labeled as an “obesity paradox.” On the other hand, patients with high BMI can develop metabolic syndrome, which is well documented in lupus and may be related to the inflammation that drives the metabolic changes.