Heart valve calcification in young patients with systemic lupus erythematosus: A window to premature atherosclerotic vascular morbidity and a risk factor for all-cause mortality
Introduction
Premature atherosclerotic cardiovascular and cerebrovascular diseases are leading causes of morbidity and mortality in patients with SLE compared to age- and sex-matched individuals in the general population. Reported rate of coronary artery disease (CAD) in lupus ranges from 6 to 54% [1], and epidemiological as well as autopsy studies have provided evidence of an increased incidence of CAD in this patient population. The Toronto Lupus Clinic group reported a 30% death rate due to CAD and showed that mortality and morbidity follow a bimodal pattern in which late death is due to myocardial infarction (MI) and strongly correlates with corticosteroid therapy [2], [3].
Risk factors for CAD in SLE include older age at diagnosis, longer disease duration, longer duration of use and higher cumulative dose of corticosteroids, hypercholesterolemia, postmenopausal status, obesity, and diabetes mellitus [4]. SLE poses a higher risk for CAD than the traditional Framingham risk factors. The incidence of MI in women with SLE aged 35–44 years is over 50 times greater than in sex- and age-matched non-lupus populations [3], and the risk of CAD or stroke is over seven-fold higher in lupus than in non-lupus individuals [5], [6]. Accordingly, in a SLE cohort studied by our group, the incidence rates of CAD and stroke were 5.4 and 6.7%, respectively [7].
Mitral annulus calcification (MAC) and aortic valve calcification (AVC) are chronic degenerative processes associated with vascular atherosclerosis [8], [9]. The incidence of MAC and AVC in the general population increases with advanced age, especially after age 65 years, and is strongly associated with coronary as well as peripheral arterial atherosclerosis in the general population [8], [9], [10].
In this study, using transthoracic echocardiography (TTE), we analyzed the prevalence and risk factors of MAC and AVC in a cohort of patients with SLE.
Section snippets
Study subjects
The study group comprised 107 patients with SLE who were routinely followed between January 1995 and December 2002 in a Lupus Clinic of a university-affiliated primary community hospital and referral center. All patients met the revised criteria for the classification of SLE [11]. Patients were routinely evaluated for disease-related manifestations and co-morbidity every 3–4 months. Clinical and laboratory information was obtained at each routine clinic visit, and immediately converted into 25
Results
One hundred and seven patients with SLE (mean age 45.9 ± 14.7 years) were studied in our echocardiography laboratory. Ninety-six patients (89.7%) were female. Distribution by ethnic origin was as follows: 60.4% non-Ashkenazi Jews, 32.3% Ashkenazi Jews, 7.3% Arabs. Mean number of ACR criteria for SLE classification was 5.7 ± 1.4 (range 4–9). Mean disease duration was 9.8 ± 8.9 years (range 0–36). The clinical and laboratory features of the patients as well as the medications taken at the time of
Discussion
Our cross-sectional study of an unselected group of SLE patients who underwent TTE demonstrates a high prevalence of aortic (22.6%) and mitral (20.1%) valve calcification (overall prevalence of LV valve calcification 29.9%) compared to the rates reported in non-SLE patients [8], [9]. This finding is particularly impressive in light of the relatively young age of our patients (45.9 ± 14.7 years) compared to non-SLE patients with either MAC or AVR in other studies (mean age >70 years) [8], [9], [13]
References (30)
- et al.
The bimodal mortality pattern of systemic lupus erythematosus
Am J Med
(1976) - et al.
Risk factors for coronary heart disease in patients with systemic lupus erythematosus
Am J Med
(1992) - et al.
Mitral annulus calcification—a window to diffuse atherosclerosis of the vascular system
Atherosclerosis
(2001) - et al.
Nonobstructive aortic valve calcification: a window to significant coronary artery disease
Atherosclerosis
(2002) - et al.
Mitral annular calcification detected by transthoracic echocardiography is a marker for high prevalence and severity of coronary artery disease in patients undergoing coronary angiography
Am J Cardiol
(1998) - et al.
Prevalence of submitral (annular) calcium and its correlates in a general population-based sample (the Framingham Study)
Am J Cardiol
(1983) - et al.
Clinical factors associated with calcific aortic valve disease
J Am Coll Cardiol
(1997) - et al.
Cardiac valve involvement in systemic lupus erythematosus and primary antiphospholipid syndrome: lack of correlation with antiphospholipid antibodies
Int J Cardiol
(1995) - et al.
Correlation between lipoprotein(a) and aortic sclerosis assessed by echocardiography (The JMS Cardiac Echo and Cohort Study)
Am J Cardiol
(1995) Long-term complications of systemic lupus erythematosus
Rheumatology
(2002)
Corticosteroid induced morbidity in SLE
Arthritis Rheum
Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study
Am J Epidemiol
Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus
Arthritis Rheum
Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort
Lupus
The 1982 revised criteria for the classification of systemic lupus erythematosus
Arthritis Rheum
Cited by (18)
Genetic Disorders Involving Valve Function
2017, Encyclopedia of Cardiovascular Research and MedicineExtra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study
2016, Journal of Cardiovascular Computed TomographyCitation Excerpt :All four ECC types included in these analyses are areas of altered shear stress and turbulent blood flow, both of which predispose to endothelial dysfunction, lipid accumulation, and calcium deposition33–36. Furthermore, inflammation and inflammatory cells, including monocyte activation, play a large role in vascular calcifications37–39. We also know that inflammation plays a significant role in HIV disease and related complications9,40, and that HIV leads to advanced vascular aging41.
Clinical and echocardiographic features of mitral annular calcium in patients aged ≤50 years
2015, American Journal of CardiologyMitral annular calcium, inducible myocardial ischemia, and cardiovascular events in outpatients with coronary heart disease (from the Heart and Soul Study)
2012, American Journal of CardiologyCitation Excerpt :We previously found that fetuin-A (an inhibitor of calcification) concentrations are inversely associated with MAC, suggesting that other dystrophic valvular calcification mechanisms may play a role.26 Genetic factors may influence the development of MAC because its early presence has been reported in patients with Marfan syndrome and systemic lupus erythematosus.27,28 To our knowledge this is the first study to examine the association of MAC with CVD events in a large prospective cohort of patients with known CAD.
High prevalence of subclinical cardiovascular abnormalities in patients with systemic lupus erythematosus in spite of a very low clinical damage index
2009, Nutrition, Metabolism and Cardiovascular DiseasesCitation Excerpt :It was reported that valvular heart disease is significantly associated with overt CVD cerebrovascular events in SLE [40–44]. Molad et al. [45] found that aortic calcification correlated with premature diffuse atherosclerosis and subsequent all-cause mortality in SLE patients. Thus, LV wall motion abnormalities and focal aortic valve thickness are markers of increased CV disease in asymptomatic SLE.
Comorbidity of systemic lupus erythematosus
2008, Reumatologia Clinica