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Observational cohort studies in SLE have led to the description of accelerated atherosclerosis as an important cause of mortality and morbidity in this disease. The clinical observation of coronary artery disease occurring in premenopausal females with SLE gave rise to the concept of the bimodal mortality pattern. This pattern was confirmed in autopsy and epidemiological studies. These studies identified hypercholesterolemia and particularly its persistence in the first three years of disease, hypertension, and lupus itself as important risk factors for the development of accelerated atherosclerosis in these patients. It also became evident that corticosteroid therapy plays an important role in the elevation of plasma lipids while antimalarials resulted in a reduction of plasma cholesterol, LDL, and VLDL, especially in steroid-induced hyperlipidemia. Studies of clinical outcomes for atherosclerotic disease (angina, myocardial infarction) have shown a prevalence of 6-12% in a number of SLE cohorts. However, more sensitive investigations including myocardial perfusion imaging and carotid ultrasound have demonstrated a prevalence of atherosclerotic disease in 40% of patients studied. Further studies of SLE disease process, including immunological factors, may more clearly define the pathogenesis of accelerated atherosclerosis in patients with SLE, and may help elucidate mechanisms of atherosclerosis in the general population.
Lupus 2000
PMID:Accelerated atheroma in lupus--background. 1080 81

Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
Lupus 2000
PMID:Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. 1080 83

Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE. SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy-related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event. One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (p = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4-24.8, P < 0.001). We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia.
Lupus 2000
PMID:Vascular events in hypertensive patients with systemic lupus erythematosus. 1143 83

The clinical significance of lupus non-inflammatory necrotizing vasculopathy (NINV) is not well established. For example, since lupus renal NINV is usually reported to coexist with proliferative and active glomerulonephritis, it is difficult to demonstrate the role of NINV on renal pathophysiology. Here we report a 16-year-old SLE boy with renal NINV presenting as ischemic glomerulopathy and small vessels-related ischemic heart failure. The renal biopsy demonstrated mild proliferative glomerulonephritis and NINV initially, and one month later repeated renal biopsy showed NINV with ischemic glomerulopathy. These findings established that NINV, but not proliferative glomerulonephritis, was responsive for his acute renal failure (ARF). Another interesting question is about the pathophysiology of his myocardial dysfunction. This patient presented typical angina and congestive heart failure (CHF). Echocardiograms and ventriculography revealed dilatation of four chambers and low ejection fraction. Serial electrocardiograms demonstrated evolutionary ischemic changes. Coronary angiography revealed no abnormality of large vessels. These findings suggested small vascular lesions-induced myocardial ischemia was the underlying mechanism of dilated cardiomyopathy. As myocardial biopsy was not done in our case, we could only speculate, but not prove, that the NINV observed in renal biopsy may also involve in cardiac microvascular beds. Nevertheless, this interesting case emphasized the role of obliterative small vascular lesions in the pathophysiology of ARF and myocardial dysfunction. The patient was treated with high-dose corticosteroid, plasma infusion and hemodialysis. His cardiac function improved gradually, however the renal function did not recover.
Lupus 2002
PMID:Systemic lupus erythematosus presented as non-inflammatory necrotizing vasculopathy-induced ischemic glomerulopathy and small vessels-related ischemic cardiomyopathy. 1219 89

The objective of this study was to study cardiac valve morphology and function and ventricular function in systemic lupus erythematosus (SLE) patients with and without co-existing cardiovascular disease (CVD) and in population controls. Twenty-six women (52 +/- 8.2 years) with SLE (SLE cases) and a history of CVD (angina pectoris, myocardial infarction, cerebral infarction or intermittent claudication) were compared with 26age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched control women (population controls). Echocardiographywas performed to assess valvular abnormalities and manifestations of ischaemic heart disease. Thirteen of the 26 SLE cases but only one of the SLE controls and one of the population controls had cardiac valvular abnormalities. Three of the SLE cases had already undergone valve replacement and another had significant aortic insufficiency; the other nine had thickening of mainly mitral leaflets without hemodynamic significance. Among SLE cases, patients with valvular abnormalities had higher homocysteine (P < 0.001) and triglyceride (P = 0.02) concentrations than patients without valvular disease. In contrast atherosclerosis as determined by IMT, oxidized LDL as measured by the monoclonal antibody E06, autoantibodies against epitopes of OxLDL (aOxLDL) or phospholipids (aPL), disease duration or activity, or acute phase reactants did not differ between SLE cases with or without valvular abnormalities. Valvular abnormalities were not more common in SLE cases with stroke as compared to those with myocardial infarction, angina or claudication. In conclusion, valvular abnormalities are strongly associated with CVD in SLE. Raised levels of homocysteine and triglycerides characterize patients with cardiac valve abnormalities.
Lupus 2002
PMID:Cardiac valvular abnormalities are frequent in systemic lupus erythematosus patients with manifest arterial disease. 1247 5

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.
Lupus 2003
PMID:Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. 1289 91

Most patients suffering from systemic lupus erythematosus develop secondary heart disease at some time during the course of the primary illness. The most common forms of this type of heart disease are acute fibrinous pericarditis and hypertension. By means of echocardiography, an increased incidence of pericardial effusion has been demonstrated. Although commonly noted at autopsy, myocarditis is often clinically silent. However, endomyocardial biopsy may confirm its presence during life. Libman-Sacks endocarditis, although encountered in 40 to 50% of hearts at autopsy, is rarely diagnosed during life. When significant valve dysfunction such as aortic insufficiency or mitral regurgitation develops during the course of systemic lupus erythematosus, then Libman-Sacks endocarditis should be strongly suspected. Cardiac arrhythmias, first degree AV block, and acquired complete heart block may develop either de novo or in association with lupus pericarditis, myocarditis, vasculitis, etc. Complete congenital heart block has been reported in newborns of mothers with systemic lupus erythematosus, particularly those who have an antibody to a soluble tissue ribonucleoprotein antigen called RO(SS-A). Coronary arteritis and premature coronary atherosclerosis manifesting in either angina pectoris or myocardial infarction in young adults, particularly women suffering from systemic lupus erythematosus, have received attention recently. The development of hypertension and hyperlipidemia while such patients are receiving prolonged corticosteroid therapy has been incriminated as the significant risk factor in premature coronary atherosclerosis. Longstanding hypertension and congestive heart failure have unfavorable prognoses. This report is based on a cumulative review of 50 patients with acute and chronic systemic lupus erythematosus seen at our institution and in private practice during the last 10 years.
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PMID:Heart disease in systemic lupus erythematosus: diagnosis and management. 1522 37

Deficiency of mannan-binding lectin (MBL) has been reported to impact susceptibility to severe infections and atherosclerosis in systemic lupus erythematosus (SLE). In this study, MBL gene polymorphisms were analysed in 143 SLE patients and the frequency of severe infections and organ damage according to SLICC/ACR Damage Index regarding cerebrovascular accidents, angina pectoris, coronary by-pass surgery, myocardial infarction and peripheral arterial disease leading to significant tissue loss, were recorded during a mean follow-up time of 15 years from diagnosis. In a multiple logistic regression model, smoking (P = 0.001), hypertension (P = 0.030), alcohol intake (P = 0.027) and higher triglyceride concentration (P = 0.026) were associated with cerebrovascular, cardiovascular and peripheral arterial organ damage (CPAD), while the association with MBL deficiency did not reach significance (P = 0.098). Alcohol intake (>15 g/month) was inversely correlated with CPAD (OR = 0.29, 95%CI 0.096-0.87). MBL deficiency was not significantly more common in SLE patients with severe infections in a multivariate analysis (P > 0.3). In conclusion, classical risk factors such as smoking, hypertension, low alcohol intake and elevated triglyceride concentration were relatively more important for development of CPAD than MBL deficiency in SLE. Furthermore, MBL deficiency did not contribute to development of major infections in SLE.
Lupus 2007
PMID:Genetically determined mannan-binding lectin deficiency is of minor importance in determining susceptibility to severe infections and vascular organ damage in systemic lupus erythematosus. 1743 30

Thrombophilia-hypofibrinolysis may play an important role in rare premature (< or = age 45 years) arterial occlusive events in atherothrombotic cardiovascular (ATCVD) disease, particularly in normolipidemic patients. Whether thrombophilia-hypofibrinolysis contributed to ATCVD < or = age 45 years was assessed in 78 men and 40 women with 230 ATCVD events (myocardial infarction (MI) [n = 60], coronary artery bypass graft [CABG, n = 33], angioplasty [n = 52], chronic angina [n = 41], ischemic stroke [n = 11], transient ischemic attack [TIA, n = 24], claudication [n = 9]). Cases were compared with healthy normal adult controls (44 men and 76 women). In men, the Factor V Leiden mutation was present in 6/63 (10%) cases versus 0/44 (0%) controls (P = 0.042), Factor VIII was high (>150%) in 16/60 (27%) cases versus 1/42 (2%) controls (P = 0.001), Factor XI was high (>150%) in 9/57 (16%) cases versus 0/42 (0%) controls (P = 0.009), and plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 15/63 (24%) cases versus 3/43 (7%) controls (P = 0.023). In women, protein C was low (<73%) in 4/26 (15%) cases versus 0/74 (0%) controls (P = 0.004), and free protein S was low (<66%) in 5/27 (19%) cases versus 2/74 (3%) controls (P = 0.014). In women, Factor XI was high (>150%) in 3/27 (11%) cases versus 1/74 (1%) controls (P = 0.057), and the lupus anticoagulant was present in 9/32 (28%) cases versus 2/51 (4%) controls (P = 0.002). In patients with ATCVD < or = age 45 years, thrombophilias (Factor V Leiden, Factor VIII, Factor XI, protein C and S deficiency, lupus anticoagulant) and hypofibrinolysis (PAI-Fx, Lp[a]) may promote arterial thrombosis, which is synergistic with atherosclerotic endothelial injury.
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PMID:Thrombophilia-hypofibrinolysis and atherothrombotic cardiovascular disease < or = age 45 years. 1765 28

Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with overlap SLE-DM can present with clinical features common to both disorders. In this review, we describe the patients with overlap SLE-DM, focussing on the clinical features common to both diseases that these patients can present, and on the challenges of managing such complications. A detailed review of the patients' notes (n = 485) was performed. At every outpatient appointment the patients' urine was tested for glucose, protein and blood. Patients with persistent glycosuria were investigated with fasting blood glucose and a glucose tolerance test to help make the diagnosis of DM. Particular note was made of those patients whose symptoms could be due to SLE, DM or both. Nine patients with DM were identified. Three had type 1 DM, four had type 2 DM and two were considered to have steroid-induced DM. Among these patients, three had renal involvement (two with WHO class IV lupus nephritis); two had peripheral neuropathy (one had a mixed sensory and motor neuropathy, one had a sensory peripheral neuropathy); two patients had retinopathy and cataracts and one had angina. The combination of SLE and DM is uncommon but the predisposition to renal, peripheral neuropathy and retinal disease means that great care must be taken when deciding which clinical feature is due to which disease, because active SLE requires additional immunosuppression whereas DM requires optimization of the metabolic control. Interestingly, although in theory patients with SLE and DM are in double-jeopardy of developing atherosclerosis, to date, only one of our overlap patients has developed angina.
Lupus 2008 Nov
PMID:Diabetes mellitus complicating systemic lupus erythematosus - analysis of the UCL lupus cohort and review of the literature. 1885 20


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