Cardiovascular disease in systemic sclerosis
Author: Nordin, Annica
Date: 2014-04-11
Location: Föreläsningssalen Centrum för Molekulär Medicin (CMM), plan 0, Karolinska Universitetssjukhuset, Solna
Time: 09.00
Department: Inst för medicin, Solna / Dept of Medicine, Solna
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Thesis (2.607Mb)
Abstract
Systemic Sclerosis (SSc) is an autoimmune rheumatic disease, characterized by fibrosis of the skin and internal organs, vasculopathy and the production of autoantibodies. Cardiac and pulmonary disease manifestations are major causes of morbidity and mortality. Microvascular manifestations such as digital ulcers and Raynaud´s phenomenon are common, but whether macrovascular disease is also enhanced in SSc has not been clear. In a cross-sectional design we examined the heart, the macro- and microvasculature and how vascular disease manifestations correlated to each other, to SSc subsets and to biomarkers. Population based age- and gender-matched controls were used as comparators.
Carotid atherosclerosis, measured by ultrasound, and history of ischemic arterial events (IAE) were investigated in 111 SSc patients and 105 controls. Previous IAE were three times more common in the patients, especially ischemic heart disease (IHD) and ischemic peripheral vascular disease (IPVD). Measures of atherosclerosis, i.e. intima media thickness, plaque occurrence and anklebrachial index, did not differ on a group level, but patients with anticentromere antibodies (ACA+) had more IAE and more plaques than ACA- patients and controls. Echocardiographic (echo) findings and their association with cardiac troponin I (cTnI), N-terminal pro brain natriuretic hormone (NT-proBNP) and Uric Acid (UA) were investigated. The patients had higher levels than controls of cTnI and NT-proBNP but not of UA. All three biomarkers were associated with echo abnormalities among the SSc patients. A low left ventricular ejection fraction (LVEF) and hypokinesia were more common in patients but associated with previous IHD. Patients had more valve regurgitations than controls and 15 patients, but no controls, had an elevated echo-estimated systolic pulmonary arterial pressure (ePAP). A standard 12-lead electrocardiogram (ECG) was performed on all, and Holter-ECG on a subgroup of participants. Conduction defects, especially left bundle branch block (LBBB) and ventricular extrasystoles were more common in the patient group. Finally, the nailfolds of 163 SSc patients were examined by widefield microscopy for signs of dilated capillaries, avascular areas and capillary density. SSc patients with a higher ePAP, ACA+, digital ulcers and IAE, especially IPVD, had a lower nailfold capillary density.
These studies demonstrate that patients with SSc had more IAE than controls, and SSc patients with previous IAE also have a disturbed microcirculation in the nailfolds. It is a new observation that both macrovascular IAEs and accelerated atherosclerosis prevails in the ACA+ SSc subgroup. SSc patients had more valve regurgitations, higher ePAP and more left and right ventricular impairment on echo. These echo abnormalities were associated with higher levels of the cardiac biomarkers, NT-proBNP and cTnI. The latter is a new clinically useful finding.
Carotid atherosclerosis, measured by ultrasound, and history of ischemic arterial events (IAE) were investigated in 111 SSc patients and 105 controls. Previous IAE were three times more common in the patients, especially ischemic heart disease (IHD) and ischemic peripheral vascular disease (IPVD). Measures of atherosclerosis, i.e. intima media thickness, plaque occurrence and anklebrachial index, did not differ on a group level, but patients with anticentromere antibodies (ACA+) had more IAE and more plaques than ACA- patients and controls. Echocardiographic (echo) findings and their association with cardiac troponin I (cTnI), N-terminal pro brain natriuretic hormone (NT-proBNP) and Uric Acid (UA) were investigated. The patients had higher levels than controls of cTnI and NT-proBNP but not of UA. All three biomarkers were associated with echo abnormalities among the SSc patients. A low left ventricular ejection fraction (LVEF) and hypokinesia were more common in patients but associated with previous IHD. Patients had more valve regurgitations than controls and 15 patients, but no controls, had an elevated echo-estimated systolic pulmonary arterial pressure (ePAP). A standard 12-lead electrocardiogram (ECG) was performed on all, and Holter-ECG on a subgroup of participants. Conduction defects, especially left bundle branch block (LBBB) and ventricular extrasystoles were more common in the patient group. Finally, the nailfolds of 163 SSc patients were examined by widefield microscopy for signs of dilated capillaries, avascular areas and capillary density. SSc patients with a higher ePAP, ACA+, digital ulcers and IAE, especially IPVD, had a lower nailfold capillary density.
These studies demonstrate that patients with SSc had more IAE than controls, and SSc patients with previous IAE also have a disturbed microcirculation in the nailfolds. It is a new observation that both macrovascular IAEs and accelerated atherosclerosis prevails in the ACA+ SSc subgroup. SSc patients had more valve regurgitations, higher ePAP and more left and right ventricular impairment on echo. These echo abnormalities were associated with higher levels of the cardiac biomarkers, NT-proBNP and cTnI. The latter is a new clinically useful finding.
List of papers:
I. Nordin A, Jensen-Urstad K, Björnådal L, Pettersson S, Larsson A, Svenungsson E. Ischemic arterial events and atherosclerosis in patients with systemic sclerosis: a population-based case-control study. Arthritis Research & Therapy. 2013, 15:R87.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Nordin A, Björnådal L, Larsson A, Svenungsson E Jensen-Urstad K. Electrocardiogram in 110 patients with systemic sclerosis:a cross-sectional study with population-based controls. Scand J Rheumatol. 2013 [Epub ahead of print].
Fulltext (DOI)
Pubmed
III. Nordin A, Svenungsson E, Björnådal L, Larsson A, Jensen-Urstad K. Echocardiography and Troponin I in patients with systemic sclerosis (SSc) and matched population controls. [Manuscript]
IV. Nordin A, Björnådal L, Roubi L, Jensen-Urstad K, Svenungsson E. Microcirculation and macrovascular disease in systemic sclerosis – a nailfold capillary study. [Manuscript]
I. Nordin A, Jensen-Urstad K, Björnådal L, Pettersson S, Larsson A, Svenungsson E. Ischemic arterial events and atherosclerosis in patients with systemic sclerosis: a population-based case-control study. Arthritis Research & Therapy. 2013, 15:R87.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Nordin A, Björnådal L, Larsson A, Svenungsson E Jensen-Urstad K. Electrocardiogram in 110 patients with systemic sclerosis:a cross-sectional study with population-based controls. Scand J Rheumatol. 2013 [Epub ahead of print].
Fulltext (DOI)
Pubmed
III. Nordin A, Svenungsson E, Björnådal L, Larsson A, Jensen-Urstad K. Echocardiography and Troponin I in patients with systemic sclerosis (SSc) and matched population controls. [Manuscript]
IV. Nordin A, Björnådal L, Roubi L, Jensen-Urstad K, Svenungsson E. Microcirculation and macrovascular disease in systemic sclerosis – a nailfold capillary study. [Manuscript]
Institution: Karolinska Institutet
Supervisor: Svenungsson, Elisabet
Issue date: 2014-03-21
Rights:
Publication year: 2014
ISBN: 978-91-7549-528-6
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