Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Cardiac chamber volumes and left ventricular mass in people living with HIV and matched uninfected controls.

OBJECTIVES: People living with HIV (PLWH) have increased risk of cardiovascular diseases compared with uninfected populations. We assessed structural cardiac abnormalities and their associated risk factors in well-treated PLWH and uninfected controls using multidetector computed tomography (MDCT). METHODS: People living with HIV and age- and sex-matched uninfected controls underwent MDCT to determine left atrial volume (LAV), left ventricular diastolic volume (LVDV), right ventricular diastolic volume (RVDV) and left ventricular mass (LVM). All outcomes were indexed to body surface area (BSA) (LAVi, LVDVi, RVDVi and LVMi). RESULTS: A total of 592 PLWH and 1184 uninfected controls were included in the study. PLWH had smaller mean (SD) LAVi [40 (8) vs. 41 (9) mL/m2 ; P = 0.002] and LVDVi [61 (13) vs. 65 (14) mL/m2 ; P < 0.001] but larger RVDVi [89 (18) vs. 86 (17) mL/m2 ; P < 0.001] than uninfected controls. HIV was independently associated with 7 mL (95% CI: -10 to -3) smaller LVDV, and with 12 mL (95% CI: 8-16) larger RVDV, and 4 g (95% CI: 1-6) larger LVM after adjustment for cardiovascular risk factors and BSA. Large RVDV in PLWH was not associated with obstructive lung function. CONCLUSIONS: HIV was independently associated with smaller LVDV and larger RVDV and LVM. Alterations in cardiac chamber volumes in PLWH were mainly minor. The clinical impact of these findings is uncertain, but it seems unlikely that alterations in cardiac chamber volumes explain the increased burden of cardiovascular disease previously observed in PLWH.

Biologic therapies targeting the interleukin (IL)-23/IL-17 immune axis for the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis.

There are a rapidly increasing number of novel biologic therapies for psoriasis targeting interleukin-23 (IL-23) and interleukin-17 (IL-17). This systematic review and meta-analysis evaluated the efficacy and safety of induction therapy (12-16 weeks) with biologic therapies targeting the IL-23/IL-17 immune axis for the treatment of moderate-to-severe plaque psoriasis. Twenty-seven randomized controlled trials met the specified inclusion criteria. The results showed that ixekizumab q2w had the greatest efficacy in terms of achieving 90% reduction in Psoriasis Area and Severity Index when compared to placebo [risk ratio (RR): 65.01, 95% confidence intervals (CI): 13.97-302.56, P < 0.00001], etanercept (RR: 3.14, 95% CI: 2.22-4.45) and ustekinumab (RR: 1.73, 95% CI: 1.41-2.12). The IL-17 inhibitors were overall shown to have a higher efficacy than the IL-23 inhibitors during induction therapy. However, the IL-17 inhibitors had an increased risk of adverse events when compared to placebo, while there was no increased risk with any of the IL-23 inhibitors. In conclusion, induction therapy with IL-17 inhibitors is highly efficacious but carries a higher risk of adverse events than induction therapy with IL-23 inhibitors.

Localization of treatment-resistant areas in patients with psoriasis on biologics.

BACKGROUND: Traditionally, psoriasis in certain body sites such as the scalp, nails, palms, soles and intertriginous areas has been acknowledged as difficult to treat. OBJECTIVES: To investigate the body location of treatment-resistant psoriasis in patients treated with biologic agents in real-world clinical practice, and to study the association between localization and quality of life. METHODS: This was an observational, noninterventional, study. We investigated the skin and/or nail location of treatment-resistant psoriasis in patients with moderate-to-severe psoriasis treated for > 6 months with biologic agents. A partial or good response to treatment was defined as having a Psoriasis Area and Severity Index (PASI) score ≥ 1 and ≤ 5. Experienced PASI assessors used a uniform data collection form in which the body area was divided into 26 regions and 20 nails. RESULTS: We included 146 patients with chronic plaque-type psoriasis (109 men, 74·7%, mean ± SD age 49·8 ± 13·7 years), with a median PASI score of 2·4 (interquartile range 1·2-3·2). The median PASI reduction from treatment initiation was 86·1% (interquartile range 78·1-91·3). The most common site of recalcitrant psoriasis was the anterior lower leg [49·3%; 95% confidence interval (CI) 41·2-57·4]. Further common sites of recalcitrant psoriasis were the posterior lower leg (24·7%; 95% CI 17·7-31·6), elbow (35·6%; 95% CI 27·8-43·4) and the scalp (19·2%; 95% CI 12·8-25·6%). No association between Dermatology Life Quality Index and specific areas of recalcitrant psoriasis were observed. CONCLUSIONS: In real-world clinical practice, the most common sites of recalcitrant psoriasis in patients treated with biologic agents are the anterior lower leg, posterior lower leg and elbows. Recalcitrant psoriasis in no specific area caused a greater impact on quality of life than any other area.

Increased risk of depression in patients with cutaneous lupus erythematosus and systemic lupus erythematosus: a Danish nationwide cohort study.

BACKGROUND: There is a wide range in the reported prevalences of depression in patients with systemic lupus erythematosus (SLE), while the prevalence of depression in patients with cutaneous lupus erythematosus (CLE) remains severely understudied. OBJECTIVES: To examine whether patients with SLE or CLE have an increased risk of depression. METHODS: In this nationwide observational cohort study, we included patients aged ≥ 18 years with a first-time diagnosis of SLE or CLE between 2000 and 2015 identified in the Danish National Patient Register, which were matched with the general population in a ratio of 1 : 10. After linkage to national Danish health registers of primary and secondary care, analyses of risk for depression and antidepressant use were performed using Cox regression models adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, prior depression and prior antidepressant use. RESULTS: A total of 3489 patients with lupus erythematosus were followed for 23 373 person-years. Compared with the general population, the adjusted hazard ratios (HRs) of depression were 2·07 [95% confidence interval (CI) 1·55-2·75] and 2·22 (95% CI 1·77-2·77) for patients with CLE and SLE, respectively; for hospitalization owing to depression at a department of psychiatry HRs were 2·63 (95% CI 0·80-8·67) and 3·52 (95% CI 1·53-8·11) for patients with CLE and SLE, respectively. The adjusted HRs for antidepressant use were 1·47 (95% CI 1·34-1·63) and 1·70 (95% CI 1·58-1·83) for patients with CLE and SLE, respectively. CONCLUSIONS: The risk of depression was significantly increased in patients with SLE and CLE. Awareness of an increased risk of depression in patients with SLE and CLE might be warranted.

Plasma levels of ß2-microglobulin are associated with atherosclerosis in patients with systemic lupus erythematosus: a cross-sectional cohort study.

Objective The objective of this paper is to examine the association between plasma levels of ß2-microglobulin (ß2MG), a protein previously associated with atherosclerosis, and the presence of carotid plaque (CP) or coronary artery calcium (CAC) in a cross-sectional cohort study of patients with systemic lupus erythematosus (SLE). Methods Patients with SLE were enrolled between June 2013 and May 2014. The presence of CP and CAC was assessed with ultrasonography and computed tomography scan, respectively. The presence of CP or CAC in the SLE patients was analyzed with respect to plasma levels of ß2MG and renal function expressed as the estimated glomerular filtration rate (eGFR). Results The study cohort consisted of 147 patients, 89% women and 95% Caucasians. The median age was 46 (range: 21-75) years with a median disease duration of 14 years. CP and CAC was observed in 29 (20%) and 57 (39%) of patients, respectively. CP or CAC was seen in 62 (42%) patients and was associated with the highest quartile of plasma ß2MG in patients with eGFR ≥ 90 ml/min/1.73 m2; OR = 18 (95% CI: 1.7-181). ß2MG adjusted for eGFR was also associated with presence of CP or CAC in the total cohort. The exclusion of 25 patients with a prior history of cardiovascular disease did not change the observed associations. Conclusion In this study, we found significant associations between imaging markers of atherosclerosis and high plasma levels of plasma ß2MG. These data suggest that ß2MG is a candidate for further study as a biomarker for atherosclerosis in SLE.

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

Cutaneous lupus erythematosus and the risk of deep venous thrombosis and pulmonary embolism: A Danish nationwide cohort study.

Background Venous thromboembolism (VTE) is a major public health concern. Lupus erythematosus (LE) is a chronic autoimmune disease ranging from localized cutaneous disease (CLE) to systemic involvement (SLE). Patients with SLE have an increased risk of venous thromboembolism (VTE), but little is known about the CLE-related risk of VTE. Methods To evaluate the risk of VTE in patients with SLE and CLE as compared to the general population, a retrospective cohort study was conducted. Incidence rates and hazard ratios (HRs) with 95% confidence intervals (CIs) from multivariable Cox regression models were used to evaluate and compare the risk of VTE. Registries of hospitalizations, outpatient visits, and prescription drug use were studied to determine the risk of VTE in patients with CLE and SLE and the general population between 1997 and 2011. Results A total of 3234 patients with CLE and 3627 patients with SLE were identified and compared to 5,590,070 individuals in the reference population. The incidence rates per 1000 year of VTE were higher in patients with LE, i.e. 1.20, 3.06, and 5.24 for the reference population, CLE, and SLE, respectively. In adjusted models, both CLE (HR 1.39; 95% CI 1.10-1.78) and SLE (HR 3.32; 95% CI 2.73-4.03) were associated with a statistically significant increased risk of VTE, compared to the reference population. Conclusion In this nationwide study, both CLE and SLE were significant risk factors for VTE. The results add to our understanding of comorbidities in patients with LE, and call for further studies and increased awareness of thromboembolic complications in patients with CLE.

Cutaneous lupus erythematosus and systemic lupus erythematosus are associated with clinically significant cardiovascular risk: a Danish nationwide cohort study.

Systemic lupus erythematosus (SLE) is a well-known cardiovascular risk factor. Less is known about cutaneous lupus erythematosus (CLE) and the risk of developing cardiovascular disease (CVD). Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients diagnosed with SLE and CLE. We conducted a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular endpoint and all-cause mortality, for patients with SLE and CLE. A total of 3282 patients with CLE and 3747 patients with SLE were identified and compared with 5,513,739 controls. The overall HR for the composite CVD endpoint was 1.31 (95% CI 1.16-1.49) for CLE and 2.05 (95% CI 1.15-3.44) for SLE. The corresponding HRs for all-cause mortality were 1.32 (95% CI 1.20-1.45) for CLE and 2.21 (95% CI 2.03-2.41) for SLE. CLE and SLE were associated with a significantly increased risk of CVD and all-cause mortality. Local and chronic inflammation may be the driver of low-grade systemic inflammation.

Optimisation of coronary vascular territorial 3D echocardiographic strain imaging using computed tomography: a feasibility study using image fusion.

Current echocardiographic assessments of coronary vascular territories use the 17-segment model and are based on general assumptions of coronary vascular distribution. Fusion of 3D echocardiography (3DE) with multidetector computed tomography (MDCT) derived coronary anatomy may provide a more accurate assessment of left ventricular (LV) territorial function. We aimed to test the feasibility of MDCT and 3DE fusion and to compare territorial longitudinal strain (LS) using the 17-segment model and a MDCT-guided vascular model. 28 patients underwent 320-slice MDCT and transthoracic 3DE on the same day followed by invasive coronary angiography. MDCT (Aquilion ONE, ViSION Edition, Toshiba Medical Systems) and 3DE apical full-volume images (Artida, Toshiba Medical Systems) were fused offline using a dedicated workstation (prototype fusion software, Toshiba Medical Systems). 3DE/MDCT image alignment was assessed by 3 readers using a 4-point scale. Territorial LS was assessed using the 17-segment model and the MDCT-guided vascular model in territories supplied by significantly stenotic and non-significantly stenotic vessels. Successful 3DE/MDCT image alignment was obtained in 86 and 93 % of cases for reader one, and reader two and three, respectively. Fair agreement on the quality of automatic image alignment (intra-class correlation = 0.40) and the success of manual image alignment (Fleiss' Kappa = 0.40) among the readers was found. In territories supplied by non-significantly stenotic left circumflex arteries, LS was significantly higher in the MDCT-guided vascular model compared to the 17-segment model: -15.00 ± 7.17 (mean ± standard deviation) versus -11.87 ± 4.09 (p < 0.05). Fusion of MDCT and 3DE is feasible and provides physiologically meaningful displays of myocardial function.

Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have a high prevalence of thrombosis, the most frequently described locations being the cerebral and pulmonary vessels. The reported prevalence of both cerebral infarction and pulmonary thrombosis has been highly variable. The aim of this study was to examine the prevalence of both cerebral and pulmonary thrombosis in CCHD according to medical history and imaging. In addition, the role of known erythrocytosis and haemostatic abnormalities as risk factors was evaluated. METHODS AND RESULTS: A cross-sectional descriptive study examining 98 stable adult patients with CCHD with a medical questionnaire, blood samples, MRI of the cerebrum (n=72), multidetector CT imaging (MDCT) of the thorax (n=76) and pulmonary scintigraphy (ventilation/perfusion/single-photon emission computerised tomography/CT) (n=66). The prevalence of cerebral infarction and pulmonary thrombosis according to imaging were 47% and 31%, respectively. Comparing the findings with previous medical history revealed a large under-reporting of thrombosis with only 22% of the patients having a clinical history of stroke and 25% of pulmonary thrombosis. There was no association between the degree of erythrocytosis or haemostatic abnormalities and the prevalence of thrombosis. CONCLUSIONS: Patients with CCHD have a prevalence of both cerebral and pulmonary thrombosis of around 30%-40%, which is much higher than that reported previously. Furthermore, there is a large discrepancy between clinical history and imaging findings, suggesting a high prevalence of silent thrombotic events. Neither erythrocytosis nor haemostatic abnormalities were associated with the prevalence of thrombosis in patients with CCHD. TRIAL REGISTRATION NUMBER: http://www.cvk.sum.dk/CVK/Home/English.aspx (H-KF-2006-4068).

Myocardial perfusion at rest in patients with Diabetes Mellitus Type 1 compared with healthy controls assessed with Multi Detector Computed Tomography.

AIM: Type 1 diabetes mellitus (T1DM) is associated with an increased risk of ischemic heart disease (IHD). The relative contribution of structural and functional abnormalities of the coronary circulation determining clinically manifested IHD remains unknown. The aim of this study was to assess potential differences in myocardial perfusion at rest and coronary atherosclerosis between asymptomatic T1DM patients and healthy controls. METHODS: Left ventricular (LV) myocardial perfusion at rest measured as LV myocardial Attenuation Density/LV blood pool Attenuation Density (MyoAD-ratio) and coronary artery atherosclerosis were evaluated with 320-multidetector computed tomography angiography in 57 asymptomatic T1DM patients and 114 sex and age matched controls. RESULTS: In both groups median age was 53 years (p5,p95: 42,67) and 59.6% were men. Median duration of diabetes in the T1DM group was 35 years (p5,p95: 17,49). Median coronary calcium score was higher in T1DM patients (51 vs. 2, p=0.037) compared with controls. However, a similar frequency of >50% stenosis in one or more coronary arteries was found in T1DM patients and controls (18% vs. 14%, p=0.49). LV myocardial perfusion at rest (MyoAD-ratio) was 18% higher in T1DM patients than controls (0.13 vs. 0.11, p<0.0001). This difference was noted throughout all the LV myocardial segments. In a multiple regression analysis including diabetes, sex, age, cardiovascular risk factors, heart rate, calcium score and coronary stenosis >50%, MyoAD-ratio remained significantly higher in T1DM patients (p=0.0001). CONCLUSIONS: LV myocardial perfusion at rest is higher in T1DM patients compared with controls independent of coronary atherosclerosis and cardiovascular risk factors.

Calcium score of small coronary calcifications on multidetector computed tomography: results from a static phantom study.

INTRODUCTION: Multi detector computed tomography (MDCT) underestimates the coronary calcium score as compared to electron beam tomography (EBT). Therefore clinical risk stratification based on MDCT calcium scoring may be inaccurate. The aim of this study was to assess the feasibility of a new phantom which enables establishment of a calcium scoring protocol for MDCT that yields a calcium score comparable to the EBT values and to the physical mass. MATERIALS AND METHODS: A phantom containing 100 small calcifications ranging from 0.5 to 2.0mm was scanned on EBT using a standard coronary calcium protocol. In addition, the phantom was scanned on a 320-row MDCT scanner using different scanning, reconstruction and scoring parameters (tube voltage 80-135 kV, slice thickness 0.5-3.0mm, reconstruction kernel FC11-FC15 and threshold 110-150 HU). The Agatston and mass score of both modalities was compared and the influence of the parameters was assessed. RESULTS: On EBT the Agatston and mass scores were between 0 and 20, and 0 and 3mg, respectively. On MDCT the Agatston and mass scores were between 0 and 20, and 0 and 4 mg, respectively. All parameters showed an influence on the calcium score. The Agatston score on MDCT differed 52% between the 80 and 135kV, 65% between 0.5 and 3.0mm and 48% between FC11 and FC15. More calcifications were detected with a lower tube voltage, a smaller slice thickness, a sharper kernel and a lower threshold. Based on these observations an acquisition protocol with a tube voltage of 100 kV and two reconstructions protocols were defined with a FC12 reconstruction kernel; one with a slice thickness of 3.0mm and a one with a slice thickness of 0.5mm. This protocol yielded an Agatston score as close to the EBT as possible, but also a mass score as close to the physical phantom value as possible, respectively. CONCLUSION: With the new phantom one acquisition protocol and two reconstruction protocols can be defined which produces Agatston scores comparable to EBT values and to the physical mass.

Assessment of coronary artery disease using coronary computed tomography angiography in patients with aortic valve stenosis referred for surgical aortic valve replacement.

BACKGROUND: In patients referred for aortic valve replacement (AVR) a pre-surgical assessment of coronary artery disease is mandatory to determine the possible need for additional coronary artery bypass grafting. The diagnostic accuracy of coronary computed tomography angiography (coronary CTA) was evaluated in patients with aortic valve stenosis referred for surgical AVR. METHODS: Between March 2008 and March 2010 a total of 181 consecutive patients were included. All patients underwent pre-surgical coronary CTA (64- or 320-detector CT scanner) and invasive coronary angiography (ICA). The analyses were performed blinded to each other. RESULTS: The mean ± SD age of the included patients was 71 ± 9 years and 59% were male. The prevalence of significant coronary artery stenosis >70% by ICA was 36%. Average heart rate during coronary CTA was 65 ± 16 b pm. In a patient based analysis 94% of the patients (171/181) were considered fully evaluable. Coronary CTA had a sensitivity of 68%, a specificity of 91%, a positive predictive value of 81%, and a negative predictive value of 83%. Advanced age, obstructive lung disease, NYHA function class III/IV, and high Agatston score were found to be significantly associated with disagreement between ICA and coronary CTA in univariate analysis. CONCLUSION: In patients with aortic valve stenosis referred for surgical AVR the diagnostic accuracy of coronary CTA to identify significant coronary artery disease is moderate. Coronary CTA may be used successfully in a subset of patients with low age, no chronic obstructive lung disease, NYHA function class

Anogenital warts in Danish men who have sex with men.

To determine the prevalence of anogenital warts (AGWs) and concurrent sexually transmitted infections (STIs) in men who have sex with men (MSM), and their knowledge of human papillomavirus (HPV). Attitudes towards the HPV vaccine among MSM are explored. A web-based cross-sectional survey on AGWs, sociodemographic factors and sexual behaviour conducted in August 2009 in Denmark. Overall 25.2% of the 1184 respondents reported a prior or current episode of AGWs. The prevalence of AGW was significantly higher in homosexuals compared with bisexuals, in men with high levels of education and in those with a high number of sexual partners within the last year. MSM with a history of another STI reported a significantly higher prevalence of warts. More than 70% did not know what causes AGWs. If a free HPV vaccine were to be offered, 94.4% would like to receive it. These data suggest a high prevalence of AGWs in Danish MSM. The awareness of HPV is low; however, the acceptance of a HPV vaccine seems high.

Left ventricular contractile function after distal protection in primary percutaneous coronary intervention: results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial.

BACKGROUND: Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function. METHODS: Patients with STEMI were randomly referred within 12 h for PCI with (N = 312) or without distal protection (N = 314). Left ventricular (LV) contractile function was assessed with echocardiography 8 months after PCI. Global LV myocardial wall motion index (WMI) was calculated as the average wall motion score of all myocardial segments. The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI were also recorded. RESULTS: The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI was 7.1% after distal protection and 5.7% after conventional treatment (p = 0.17). WMI improved by 4.1% at 8 months in patients treated with distal protection compared to patients receiving conventional PCI (p < 0.01). In myocardium supplied by a culprit artery treated by distal protection regional LV function was 9-11% higher than myocardial regions treated conventionally ( p < 0.02). CONCLUSIONS: Routine use of distal protection during primary PCI is associated with a significant improvement in LV contractile function, with no detectable impact on intermediate term clinical outcome.

Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy.

OBJECTIVES: To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)-containing regimen in HIV-1-infected individuals already receiving combination antiretroviral therapy (ART). METHODS: Thirty-five HIV-1-infected individuals who switched ART to an ABC-containing regimen were identified. Twenty-two HIV-1-infected individuals who switched ART from and to a non-ABC-containing regimen served as controls. Plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP9), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hs-CRP) were measured in blood samples before the switch in ART, and 3 months and 12 months afterwards. Log10-transformed data were compared with paired t-tests. RESULTS: Median MMP9 increased from 45.5 to 64.4 microg/mL after 3 months of ABC exposure (P = 0.011) and remained increased after 12 months (64.2 microg/mL; P = 0.013). MPO increased from median 8.8 to 10.4 microg/mL (P = 0.036) after 3 months of ABC exposure but was not increased after 12 months of exposure (9.1 microg/mL). hs-CRP increased from 3.3 to 4.2 microg/mL after 3 months (P = 0.031) but was not increased after 12 months of exposure (2.8 microg/mL). Neither sVCAM-1 nor sICAM-1 changed after the initiation of ABC. No changes were observed in the control group. CONCLUSIONS: MMP9, MPO and hs-CRP all increased after a switch in ART to an ABC-containing regimen. This indicates increased cardiovascular risk in viral load-suppressed HIV-1-infected individuals switching to ABC and proposes a proinflammatory potential as the underlying pathogenetic mechanism.

Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy.

OBJECTIVES: Antiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART. METHODS: In 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean+/-standard error of the mean. RESULTS: Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296+/-24 vs. 144+/-12 ng/mL), tPAI-1 (18 473+/-1399 vs. 5490+/-576 pg/mL) and hsCRP (28 060+/-5530 vs. 6665+/-2063 ng/mL) compared with controls (P<0.001). In contrast, sVCAM-1 and E-selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E-selectin (15.1+/-0.8; P<0.01), sICAM-1 (248+/-12 ng/mL; P<0.05), sVCAM-1 (766+/-33 ng/mL; P<0.001) and hsCRP (14 708+/-2358 ng/mL; P<0.001) after 2 months, which remained reduced at 14 months. tPAI-1 was not influenced by initiation of ART. CONCLUSIONS: Markers of endothelial dysfunction were elevated in treatment-naïve HIV-infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.