FROM Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases by Yehuda Shoenfeld and Colleague
SSc affects the microcirculation and injures the endothelium, leading eventually to vessel occlusion and tissue anoxia. In addition, SSc significantly accelerates the sufferance of the vessel wall of the macrocirculation, increasing the risk of vascular occlusive diseases. The link between SSc and atherosclerosis was identified in some cases of patients with SSc who underwent amputation of the lower limbs because of peripheral macrovascular disease.
Four SSc patients were reported with severe macrovascular involvement of the lower or upper limbs, characterized by the presence of very low vascular risk factors. In the biopsy of the ulnar artery of these patients, only a marked vessel narrowing without plaques was detected. In limited cutaneous SSc, macrovascular disease was detected in 18 of 31 patients (58%), and amputation was performed in 5 patients: Biopsies showed marked intimal thickening, proliferation with destruction of the internal elastic lamina, and transmural lymphocytic and plasmacellular infiltrate.
In 10 of 53 SSc patients, intermittent claudication (21.7%) and coexistent ischemic heart disease (15.2%) and cerebrovascular disease (6.5%) were detected.66 Doppler study of the main arteries of the limbs, neck, and abdomen demonstrated that primarily the ulnar artery was affected, with stenosis also confirmed by subtraction angiography in 9 of 26 patients and by angiography in 15 SSc patients. Angiography demonstrated an increased rigidity of the radial artery and lower-limb involvement.
The carotid artery was involved in approximately 64% of SSc patients, compared with 35% of control subjects. The involvement of the carotid artery was also recently confirmed in 53 SSc patients, because the IMT of the common carotid artery, evaluated by ultrasound, was significantly increased and correlated with the presence of the D allele of the ACE gene, which is associated with accelerated atherosclerosis (M.M.C., unpublished data, 2004). An increased frequency of the D allele has been demonstrated as correlating with the presence of SSc. These findings suggest that significantly higher IMT and DD/ID ACE polymorphism are correlated with and predispose to macrovascular involvement in SSc.
The diffuse involvement of the vascular tree in SSc, ranging from the microcirculation to the macrocirculation, may be linked primarily to 2 factors: The disease pathogenesis and the predisposition of the single subject to atherosclerosis. These 2 elements can thus overlap, jeopardizing the integrity of the vessel wall. In genetically predisposed SSc patients, characterized by ischemia and oxidative stress, with raised levels of LDL undergoing oxidation, triggering vessel wall inflammation, the overlap with SSc-dependent endothelial injury creates a noxious loop involving the microcirculation and macrocirculation.
In this scenario, pathogenetic factors participating in endothelial sufferance, such as anti–endothelial cell antibodies, dysfunction of the fibrinolytic and coagulation system, and an increase of circulating levels of homocysteine, soluble intercellular adhesion molecule-1, and CRP may contribute significantly to increased risk of developing accelerated macrovascular disease. In the future, drugs protecting the vessel wall, such as statins and antioxidants, might become potential tools for the management of microvascular and macrovascular involvement in SSc. The extent of enhanced atherosclerosis in SSc, if any at all, is not yet clear, because fewer studies (compared with those of RA, SLE, and APS) addressed this specific question.
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FROM Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases by Yehuda Shoenfeld and Colleague
SSc affects the microcirculation and injures the endothelium, leading eventually to vessel occlusion and tissue anoxia. In addition, SSc significantly accelerates the sufferance of the vessel wall of the macrocirculation, increasing the risk of vascular occlusive diseases. The link between SSc and atherosclerosis was identified in some cases of patients with SSc who underwent amputation of the lower limbs because of peripheral macrovascular disease.
Four SSc patients were reported with severe macrovascular involvement of the lower or upper limbs, characterized by the presence of very low vascular risk factors. In the biopsy of the ulnar artery of these patients, only a marked vessel narrowing without plaques was detected. In limited cutaneous SSc, macrovascular disease was detected in 18 of 31 patients (58%), and amputation was performed in 5 patients: Biopsies showed marked intimal thickening, proliferation with destruction of the internal elastic lamina, and transmural lymphocytic and plasmacellular infiltrate.
In 10 of 53 SSc patients, intermittent claudication (21.7%) and coexistent ischemic heart disease (15.2%) and cerebrovascular disease (6.5%) were detected.66 Doppler study of the main arteries of the limbs, neck, and abdomen demonstrated that primarily the ulnar artery was affected, with stenosis also confirmed by subtraction angiography in 9 of 26 patients and by angiography in 15 SSc patients. Angiography demonstrated an increased rigidity of the radial artery and lower-limb involvement.
The carotid artery was involved in approximately 64% of SSc patients, compared with 35% of control subjects. The involvement of the carotid artery was also recently confirmed in 53 SSc patients, because the IMT of the common carotid artery, evaluated by ultrasound, was significantly increased and correlated with the presence of the D allele of the ACE gene, which is associated with accelerated atherosclerosis (M.M.C., unpublished data, 2004). An increased frequency of the D allele has been demonstrated as correlating with the presence of SSc. These findings suggest that significantly higher IMT and DD/ID ACE polymorphism are correlated with and predispose to macrovascular involvement in SSc.
The diffuse involvement of the vascular tree in SSc, ranging from the microcirculation to the macrocirculation, may be linked primarily to 2 factors: The disease pathogenesis and the predisposition of the single subject to atherosclerosis. These 2 elements can thus overlap, jeopardizing the integrity of the vessel wall. In genetically predisposed SSc patients, characterized by ischemia and oxidative stress, with raised levels of LDL undergoing oxidation, triggering vessel wall inflammation, the overlap with SSc-dependent endothelial injury creates a noxious loop involving the microcirculation and macrocirculation.
In this scenario, pathogenetic factors participating in endothelial sufferance, such as anti–endothelial cell antibodies, dysfunction of the fibrinolytic and coagulation system, and an increase of circulating levels of homocysteine, soluble intercellular adhesion molecule-1, and CRP may contribute significantly to increased risk of developing accelerated macrovascular disease. In the future, drugs protecting the vessel wall, such as statins and antioxidants, might become potential tools for the management of microvascular and macrovascular involvement in SSc. The extent of enhanced atherosclerosis in SSc, if any at all, is not yet clear, because fewer studies (compared with those of RA, SLE, and APS) addressed this specific question.
Read More.......