By Michael H. Crawford, MD
Dr. Crawford is a professor of medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: A large Danish registry study of patients with autoimmune disease referred for coronary computed tomography angiography compared to those without autoimmune disease has shown that autoimmune disease increases the incidence of atherosclerotic events and that the event rate is influenced by traditional atherosclerotic disease risk factors. These results support aggressive risk factor management in patients with autoimmune disease.
SOURCE: Mortensen MB, Jensen JM, Sand NPR, et al. Association of autoimmune diseases with coronary atherosclerosis severity and ischemic events. J Am Coll Cardiol 2024;83:2643-2654.
Atherosclerotic cardiovascular disease (ASCVD) is more common in patients with autoimmune disorders, but the pathophysiology of this relationship and the effect of traditional risk factors for ASCVD on this relationship are unclear. Thus, these investigators from the Western Danish Heart Registry (WDHR) evaluated all patients who had a coronary computed tomography angiogram (CTA) and coronary artery calcium score (CAC) between 2008 and 2021. After excluding those with known coronary artery disease (CAD), 85,512 patients remained (median age 58 years, 48% men) of whom 4,064 had one of 18 autoimmune diseases grouped as any autoimmune disease; a connective tissue disease, e.g., rheumatoid arthritis; or an organ-specific autoimmune disease, e.g., Hashimoto thyroiditis.
CTA results were divided into four groups: any plaque, a plaque with > 50% luminal narrowing, a CAC > 0, or a CAC > 90th percentile for age and sex. Traditional risk factors that are potentially modifiable were noted: type 2 diabetes; hypertension; smoking; low-density lipoprotein cholesterol; and high-density lipoprotein cholesterol. Finally, the patients without autoimmune disease were propensity score matched 2:1 with the autoimmune disease patients. The primary endpoint was the development of ASCVD, defined as myocardial infarction (MI), ischemic stroke, or CV death. Autoimmune disease was associated with the presence of any coronary plaque (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.20-1.40), CAC score > 0 (OR, 1.28; 95% CI, 1.19-1.37), and severe CAC (OR, 1.53; 95% CI, 1.39-1.68), but not obstructive coronary artery disease (OR, 1.04; 95% CI, 0.91-1.17).
During the median follow-up of five years, 3,832 ASCVD events occurred and patients with autoimmune disease had a higher risk for ASCVD (hazard ratio [HR], 1.46; 95% CI, 1.29-1.65). A stepwise increase in ASCVD events with increasing CV risk factors was observed: Compared to patients without autoimmune disease and no CV risk factors, patients with autoimmune disease and no, one, two, or three or more risk factors had an HR of 1.37, 1.90, 2.48, and 4.94 for developing ASCVD, respectively.
Comparing autoimmune disease patients with a favorable risk factor profile to those without a favorable risk factor profile, a 54% lower risk of ASCVD was observed (HR, 0.46; 95% CI, 0.27-0.81). The authors concluded that autoimmune disease increases the risk of ASCVD by accelerating atherogenesis, and the risk can be attenuated by traditional risk factor control.
Commentary
Prior observational studies of autoimmune disease patients have shown an association with ASCVD and arrhythmias but have been criticized because autoimmune disease patients may get more medical attention than the general population, thereby inflating their prevalence of ASCVD. This WDHR study somewhat circumvents this criticism because it includes all patients referred for CTA. Prior studies have lacked information on CTA and ASCVD risk factors. Also, no patient was lost to follow-up in the WDHR. In addition, the findings were consistent across all subgroups including sex, age, risk factors, and CTA findings.
A major finding of this study is that autoimmune disease is strongly associated with the presence of CAD, but not coronary artery obstruction by CTA. By contrast, studies of traditional risk factors do demonstrate an association with the severity of CAD. Also, the autoimmune disease association with CAD occurs across the CAC spectrum. In fact, the risk of an ASCVD event in autoimmune disease patients with a CAC score of 0 is twice that of a non-autoimmune disease patient with a score of 0. In non-autoimmune disease patients, a score of 0 would suggest that cholesterol-lowering drugs could be withheld, but this would not be the case with autoimmune disease patients. Thus, autoimmune disease alone should occasion aggressive risk factor treatment. Furthermore, WDHR supports this concept, in that their patients with a favorable risk factor profiles had about half as many ASCVD events as those without.
In addition to being an observational study, the WDHR had other limitations. The main reason for ordering a CTA was chest pain, which introduces a selection bias. However, few of their patients had obstructive CAD, so they still were low risk. The presence of traditional risk factors did increase the likelihood of ASCVD in the autoimmune disease patients as expected. Also, the data were weighted toward rheumatoid arthritis (37% of the population) with other common autoimmune diseases such as lupus and psoriasis being 3% each. Perhaps the latter patients were less likely to have CTA ordered. In addition, there was no characterization of autoimmune disease activity or therapy, which could affect ASCVD rates. Finally, no inflammatory markers, such as high sensitivity C-reactive protein, or advanced lipid parameters, such as lipoprotein (a), were reported.
In summary, the WDHR has confirmed that autoimmune disease is a strong risk factor for ASCVD and that this risk is associated with the presence of traditional ASCVD risk factors. Also, since ASCVD events can occur in autoimmune disease patients with low to 0 CAC scores, perhaps autoimmune disease can facilitate the formation of vulnerable plaques. Thus, the concept that all patients with an autoimmune disease of any type should receive aggressive ASCVD risk factor control is strongly supported by the WDHR study.
A large Danish registry study of patients with autoimmune disease referred for coronary computed tomography angiography compared to those without autoimmune disease has shown that autoimmune disease increases the incidence of atherosclerotic events and that the event rate is influenced by traditional atherosclerotic disease risk factors. These results support aggressive risk factor management in patients with autoimmune disease.
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