Hypertension In Systemic Lupus Erythematosus Research Articles

Risk factors for coronary heart disease in connective tissue diseases

Atherosclerosis and cardiovascular disease risk is enhanced in certain connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis and antiphospholipid syndrome. The reason for this accelerated process is likely to be multifactorial. Traditional risk factors are more prevalent in some of these patient groups compared with the general population (e.g. smoking in RA and hypertension in SLE). However, these factors do not fully explain that enhanced risk. Chronic inflammation associated with these disorders as well as some specific autoantibodies have been shown to contribute to this increased risk although their role remains controversial. The role of therapies is unclear and while steroids may exacerbate metabolic risk factors, the anti-inflammatory effects of traditional and more novel biological therapies may reduce overall cardiovascular risk in these populations. We recommend proactive screening for modifiable cardiovascular risk factors in patients with these conditions.

Pulmonary hypertension in systemic lupus erythematosus: relationship with antiphospholipid antibodies and severe disease outcome

Pulmonary hypertension (PH) in systemic lupus erythematosus (SLE) is associated with an unfavorable prognosis. We investigated the characteristics of SLE patients with PH. The patients with a pulmonary artery systolic pressure more than 30mmHg at rest on echocardiogram were diagnosed with PH. Echocardiography was done only in patients with clinical or radiological evidence suggesting PH. Right heart catheterization was not performed. We identified 10 SLE patients with PH between 1980 and 2000. We compared their clinical and laboratory parameters with those of 97 consecutive SLE patients without PH. Nine of the ten patients with PH were females. The mean age at the time of SLE onset was 25.2±6.9years; the mean duration of follow-up was 93.4±52.8months, and the interval between the onset of SLE and PH diagnosis was 9.0±4.6 (5-21) years. Antiphospholipid antibody positivity was significantly higher in the PH group (80 vs. 36%; p<0.05), but there was no significant difference between two groups in regard to secondary antiphospholipid syndrome. The frequency of Raynaud's phenomenon was higher in PH group (60 vs. 27%; p<0.05). Renal involvement (80 vs. 43%; p<0.05), neuropsychiatric involvement (40 vs. 7.2%; p<0.005) and serositis (70 vs. 14.4%; p<0.001) were significantly more frequent in the PH group. The mean damage score in patients with and without PH were 4.0±2.4 and 0.4±1.0, respectively (p<0.001). Four patients with PH died during the follow-up. This study reveals that the presence of PH defines a subgroup of patients with a severe disease and increased mortality. Antiphospholipid antibodies and Raynaud's phenomenon may contribute to the pathogenesis of PH. We recommend that all patients with SLE, especially those positive for antiphospholipid antibodies and/or with signs of Raynaud's phenomenon should be regularly evaluated for the development of PH.

Pulmonary arterial hypertension in systemic lupus erythematosus: should we bother?

Pulmonary arterial hypertension in systemic lupus erythematosus: should we bother?

Young Investigator Award Lecture of the APS Water and Electrolyte Homeostasis Section, 2008: The pathophysiology of hypertension in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that predominantly affects women during their reproductive years. Although SLE can affect any organ system, the kidneys are prominently involved in the form of immune complex glomerulonephritis. In addition, in women with SLE, risk for the development of cardiovascular disease is dramatically increased. Hypertension is a major risk factor for cardiovascular disease and is highly prevalent in women with SLE. Nevertheless, there has been little exploration of the pathophysiological mechanisms that promote SLE hypertension. This review discusses the role of several mechanisms, with an emphasis on the kidney, in SLE hypertension. These mechanisms include the renin-angiotensin system, endothelin, oxidative stress, sex steroids, metabolic changes, peroxisome proliferator-activated receptor-γ, and, perhaps most importantly, chronic inflammation and cytokines. Growing evidence suggests a link between chronic inflammation and hypertension. Therefore, elucidation of mechanisms that promote SLE hypertension may be of significant value not only for patients with SLE, but also for a better understanding of the basis for essential hypertension.

A Role For TNF‐α in Hypertension During Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is an independent risk factor for developing hypertension. The inflammatory cytokine TNF‐α has been implicated in the pathology of hypertension and SLE, perhaps through increased oxidative stress. We tested whether the TNF‐α antagonist etanercept (ETAN) reduces mean arterial pressure (MAP) and protects the kidney in a female mouse model of SLE (NZBWF1). Thirty week old SLE and control mice (NZW/LacJ) received ETAN (0.8mg/kg SC weekly x 4 weeks) or vehicle. Mice with SLE were hypertensive compared to controls. Treatment with ETAN reduced MAP in SLE but not control mice. Treatment with ETAN also reduced the albuminuria associated with SLE. Renal cortex NADPH oxidase activity was higher in SLE mice compared to controls and lowered in SLE mice treated with ETAN. Interestingly, the pathognomonic Anti‐dsDNA antibodies were increased in ETAN treated SLE mice. These data suggest that TNF‐α, through increasing renal oxidative stress, is an important factor in the development of SLE hypertension. (Supported by HL 08597 MJR)*p&lt; 0.05 vs. Ctrl †p&lt;0.05 vs. SLE+Veh

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARgamma) agonist, has renal protective and antihypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty-week-old SLE and control (NZW/LacJ) mice (n > or = 6/group) were fed Rosi (5 mg.kg(-1).day(-1) in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 +/- 4 vs. 111 +/- 4, P < 0.05). Rosi treatment lowered BP in SLE mice (127 +/- 4, P < 0.05) but not in controls (111 +/- 4). Urinary albumin (mug/mg creatinine) was increased in SLE mice compared with controls (12,396 +/- 6,525 vs. 50 +/- 6) and reduced with Rosi treatment (148 +/- 117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 +/- 1.6 vs. 0.4 +/- 0.3, P < 0.05). Renal monocyte/macrophage numbers (cell number/1,320 points counted) were reduced in SLE mice treated with Rosi (32.6 +/- 11.0 vs. 10.6 +/- 3.6, P < 0.05) but unchanged in controls (3.7 +/- 1.6 vs. 3.7 +/- 2.0). Renal osteopontin expression, a cytokine-regulating macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 +/- 0.59 vs. 0.6 +/- 0.04, P < 0.05) and reduced in SLE mice treated with Rosi (0.8 +/- 0.11, P < 0.05). PPARgamma protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury.

Pulmonary Hypertension in Systemic Lupus Erythematosus complicated by exposure to Dexfenfluramine

Pulmonary arterial hypertension (PAH) is a well recognized, albeit uncommon, complication of systemic lupus erythematosus (SLE) and is characterized histologically by the presence of onionskin thickening of small arterioles. We described a 24 year-old female with SLE, complicated by pulmonary hypertension after a six-week exposure to dexfenfluramine, who died of acute myocardial infarction complicated with pneumococcal sepsis. Autopsy demonstrated pulmonary arteriolar thickening with severe sclerosis as well as the more advanced plexiform and angiomatoid lesions. Based on these findings, we hypothesize that in this case the use of dexfenfluramine, albeit for a relatively short period, exerted a synergistic effect on the predisposition to PAH already inherent in this patient with SLE.

An update in pulmonary hypertension in systemic lupus erythematosus – do we need to know about it?

An update in pulmonary hypertension in systemic lupus erythematosus – do we need to know about it?

An update in pulmonary hypertension in systemic lupus erythematosus – do we need to know about it?

Pulmonary hypertension (PH) is a serious form of pulmonary complication that occurs less frequently in lupus than in other connective tissue diseases like scleroderma; however, it is likely that it is under-recognized in lupus. The symptoms of PH in lupus are non-specific (dyspnea, fatigue, impaired exercise tolerance) and can also be caused by other factors such as pleural or pericardial effusions, interstitial lung disease and many more, making it possible to miss the diagnosis. There are several potential causes of PH in lupus including thromboembolic disease, pulmonary vasculitis, and hypoxia and fibrosis from interstitial lung disease. Endothelin-1 is elevated in lupus and may be associated with PAH. In some studies, pulmonary arterial hypertension (PAH) has been found to be a major cause of mortality in lupus patients. Echocardiograms are a screening tool, but may yield false positives, and a right heart catheterization must be performed to confirm PAH. Early identification is important and can alter the natural history of this dangerous complication of lupus. Treatment of PAH associated with lupus includes standard PAH treatment as well as immunosuppression.

Association of nodular regenerative hyperplasia of the liver with porto-pulmonary hypertension in a patient with systemic lupus erythematosus

A 37-year old woman with systemic lupus erythematosus (SLE) complicated by pulmonary hypertension (PHT) was admitted to evaluate abnormal liver function. Radiological imaging study, including ultrasonography, computed tomography and magnetic resonance imaging and upper gastrointestinal endoscopy, revealed multiple hepatic nodules, hepatosplenomegaly and esophageal varices. Percutaneous needle liver biopsy showed non-cirrhotic hepatic nodules with hyperplastic hepatocytes surrounded by atrophic hepatocytes, confirming the diagnosis of nodular regenerative hyperplasia (NRH) associated with non-cirrhotic portal hypertension (PT). NRH of the liver is known to be a very rare hepatic manifestation in rheumatic diseases. This case shows the association of NRH with porto-pulmonary hypertension in SLE.

Sildenafil no tratamento da hipertensão pulmonar associada a lúpus eritematoso sistêmico e síndrome antifosfolipídio

Hipertensão pulmonar grave é uma doença debilitante, com expectativa de vida reduzida, que acomete adultos jovens. Complicações pleuropulmonares no lúpus eritematoso sistêmico ocorrem em 50% a 70% dos pacientes. A hipertensão pulmonar grave no lúpus eritematoso sistêmico é rara e tem prognóstico reservado. Descreve-se, pela primeira vez, um paciente com hipertensão pulmonar grave associada a lúpus eritematoso sistêmico e síndrome antifosfolipídio secundário que apresentou boa resposta ao uso do sildenafil oral, após falha do tratamento convencional com corticosteróides, ciclofosfamida, warfarin e diltiazem.

Primary and secondary pulmonary hypertension in systemic lupus erythematosus.

To describe the aetiology and clinical profile of primary and secondary pulmonary hypertension (PHT) in SLE patients. A retrospective study of SLE patients with PHT identified from a cohort of 786 SLE patients seen at Tan Tock Seng Hospital, Singapore. 22 patients had primary and 24 patients had secondary PHT, with similar clinical features at presentation and a similar degree of pulmonary pressure elevation. Secondary PHT was due to valvular heart disease (50%), pulmonary embolism (13%), interstitial lung disease (8%) or a combination of these factors (29%). Primary PHT tended to present after a shorter duration of lupus than secondary PHT (8.8 vs 43.2 months, P=0.118). At presentation, Raynaud's phenomenon was present in 34.8% of subjects with primary or secondary PHT. Among those with secondary PHT, the presence of Raynaud's phenomenon was associated with a trend towards higher pulmonary artery systolic pressures (51.0 vs 40.5 mmHg, P=0. 101). 17% of patients with PHT died, but from causes unrelated to PHT. Primary and secondary PHT are equally common in SLE patients. Secondary PHT is often multi-factorial, and Raynaud's phenomenon may be a marker for the severity of PHT in this group of patients.

Five-year follow-up study of the prevalence and progression of pulmonary hypertension in systemic lupus erythematosus

The purpose of this study was to determine the prevalence and progression of pulmonary hypertension over a 5-year follow-up period in 28 patients with systemic lupus erythematosus (SLE) who were originally enrolled in an echocardiographic study of pulmonary hypertension in 1985 and 1986. Twenty healthy volunteers without cardiac or pulmonary disease participated as normal controls. Each patient and control underwent a complete Doppler echocardiographic study. Doppler echocardiographic recordings of tricuspid insufficiency, with saline contrast enhancement when necessary, were used to calculate pulmonary artery systolic pressure according to the modified Bemoulli equation. Doppler echocardiographic measurement of cardiac output was performed at rest for each subject, and pulmonary resistance was calculated by dividing the pulmonary artery systolic pressure by the cardiac output. These results were compared to results of the original studies to detect serial changes in pulmonary pressure and pulmonary resistance; results were also compared to the group of normal controls. The prevalence of pulmonary hypertension increased from 14% of the first study to 43% at follow-up. A significant increase in mean systolic pulmonary artery pressure wa detected in the SLE patients during the follow-up period: 23.4 vs 27.5 mm Hg ( p < 0.005). In addition, a significantly higher pulmonary artery pressure was detected in the SLE patients compared with the normal controls ( p < 0.005). An increase in pulmonary resistance during the follow-up period was detected for the SLE group as a whole ( p < 0.001) and for the subgroup of patients with pulmonary hypertension at the second study (p < 0.001), implying that the mechanism for pulmonary hypertension is common in SLE, is gradually progressive over time, and is related to an increase in pulmonary resistance.

Plexogenic pulmonary hypertension in systemic lupus erythematosus: Report of two cases and review of the literature

From the autopsy records of the Mayo Clinic, two patients with systemic lupus erythematosus were identified in whom plexogenic pulmonary hypertension also developed. Both were women (23 and 30 years old). Their pulmonary artery pressures were 96/30 and 115/45 mm Hg, respectively, and their survival after the diagnosis of pulmonary hypertension was only 21 and 19 months, respectively. To our knowledge, only two other cases have been reported. Thus, plexogenic pulmonary hypertension among patients with lupus is rare but is associated with a poor prognosis.

Pulmonary hypertension associated with non-cirrhotic portal hypertension in systemic lupus erythematosus

A case of non-cirrhotic portal hypertension in a patient with systemic lupus erythematosus, the first of our knowledge, is described. Severe pulmonary hypertension was associated with the portal hypertension and with markers of active auto-immunity. Pulmonary hypertension has not previously been associated with non-cirrhotic portal hypertension. The coexistence of vasculopathy of the portal and pulmonary vascular beds in this patient with active autoimmunity supports the postulate that portal-pulmonary hypertension may be immunologically mediated.

Prevalence and significance of hypertension in systemic lupus erythematosus.

SYSTEMIC lupus erythematosus (SLE) is a multisystem disease of putative autoimmune nature, which often heavily involves the cardiovascular system. Cardiac abnormalities, including systemic hypertension, are among the most severe complications of SLE, and have been reported in from 52% to 89% of cases. 1·3 Pericarditis, myocarditis, and Libman-Sachs endocarditis are the most common form of cardiac involvement. These lesions are characterized by inflammatory infiltrates in the pericardium and in the interstium of the myocardium. Coronary artery disease is recognized in a variable proportion of SLE patients (from 2% to 8% of cases).4,5 In a multicentric study involving 1,103 SLE patients,6 222 deaths were recorded and myocardial infarction was the cause of death in seven (3%). This proportion exceeded the expected value for a matched general population. These seven patients were older than the average when compared with the study population and had lupus for a longer time. Another study has shown that deaths in SLE patients were attributable to the activity of the disease in the early course and primarily to cardiovascular problems later on during the follow-up. Systemic hypertension was reported in 7% to 14% of patients in the early reports. I,4 More recently the prevalence of hypertension has ranged from 25% to 49% ofSLE patients.The reason for this apparent increase in the incidence of hypertension in unclear: the survival to an older age and the intensive use of corticosteroids may be involved.

Fatal pulmonary hypertension in identical twins with systemic lupus erythematosus

Identical twins were simultaneously diagnosed with systemic lupus erythematosus (SLE) at the age of 12. Later, both developed pulmonary involvement of SLE including pleural effusions, pleuritis, and recurrent bronchopneumonia. In their last year of life, their pulmonary condition deteriorated and they died of severe pulmonary hypertension at the age of 20. At autopsy, small to large pulmonary arterial walls were markedly thickened. There was no SLE renal involvement. Pulmonary hypertension in SLE without pulmonary parenchyma involvement is extremely rare, with only 18 such cases reported. This is the first report of pulmonary hypertension observed in identical twins with a similar clinical course. This case may suggest the possible genetic fate of pulmonary involvement of SLE.

Pulmonary hypertension, systemic lupus erythematosus, and the contraceptive pill.

Pulmonary hypertension in systemic lupus erythematosus (SLE) in the absence of chronic parenchymal lung disease or pulmonary emboli is rare. We report such a case with an acute and rapidly progressive onset of symptoms in a patient who had started taking the contraceptive pill eight months previously.

Pulmonary hypertension in systemic lupus erythematosus: hemodynamics and effects of vasodilator therapy

A case is reported of a 29-year-old woman with systemic lupus erythematosus (SLE) who developed clinical manifestations of pulmonary hypertension at a time when other manifestations of SLE were quiescent. She had a restrictive ventilatory defect but clear lung fields on chest x ray. Cardiac catheterization revealed severe pulmonary hypertension. Calculated pulmonary vascular resistance fell slightly after administration of oxygen and during infusion of vasodilators. Symptomatic improvement and a modest increase in right ventricular ejection fraction, as measured by radionuclide ventriculography, were noted following 1 week of oral hydralazine therapy. Clinically significant pulmonary hypertension is a rare complication of SLE and the increased pulmonary vascular resistance may not be entirely fixed. Cardiac catheterization and radionuclide ventriculography may be useful in assessing response to medical therapy.

Papilledema and asymptomatic intracranial hypertension in systemic lupus erythematosus. A fluorescein angiographic study of resolving papilledema.

The unique occurrence of benign intracranial hypertension (pseudotumor cerebri) in confirmed lupus erythematosus was seen in a 21-year-old woman. There was a moderate papilledema of both optic discs with dilated, tortuous, retinal veins. Lumbar puncture demonstrated a rise in intracranial pressure though there were no related neurologic findings. Fluorescein angiography was done at the time of admission and also two and seven weeks later, showing gradual resolution of the papilledema.