The impact of traditional cardiovascular risk factor control on 7-year follow-up atherosclerosis progression in systemic lupus erythematosus.

OBJECTIVES: The 2022 EULAR recommendations for cardiovascular risk management in patients with rheumatic disorders, including SLE, call for rigorous management of cardiovascular risk factors (CVRF). The impact of CVRF target attainment on atherosclerotic plaque progression hasn't been previously evaluated in prospective ultrasound studies. METHODS: A total of 115 patients with SLE and 1:1 age and sex-matched healthy controls who had a baseline carotid and femoral ultrasound examination in our cardiovascular research unit were invited for a 7-year follow-up assessment of new plaque development. We aimed to compare the incidence of plaque progression between SLE patients and controls and reveal the extent to which it is affected by the attainment of European Society of Cardiology (ESC) targets for modifiable CVRFs (blood pressure, smoking status, body weight, lipids and physical activity), and disease-related features (disease duration, disease activity, autoantibodies, treatments). RESULTS: Eighty-six SLE patients and 42 controls had a 7-year follow-up carotid and femoral plaque examination. New plaque development was observed in 32/86 patients vs 8/42 controls (P = 0.037). Patients with SLE had a 4-fold higher risk for plaque progression than controls (OR: 4.16, CI: 1.22, 14.19, P = 0.023), adjusting for potential confounders. Multivariate regression analyses showed a 50% decrease in plaque progression for every modifiable CVRF fulfilling ESC targets (OR: 0.56, CI: 0.34, 0.93, P = 0.026). CONCLUSION: Patients with SLE develop a rapid progression of atherosclerotic plaques which may be drastically reduced by CVRF target attainment according to ESC guidelines.

Arterial stiffness tested by pulse wave velocity and augmentation index for cardiovascular risk stratification in antiphospholipid syndrome.

OBJECTIVES: Cardiovascular disease is a major cause of morbidity and mortality in Antiphospholipid syndrome (APS). Arterial stiffness (ArS) has emerged as a predictor of future cardiovascular events in the general population. We aimed to assess ArS in patients with thrombotic APS versus diabetes mellitus (DM) and healthy controls (HC) and identify predictors of increased ArS in APS. METHODS: ArS was evaluated by carotid-femoral pulse wave velocity (cfPWV) and augmentation index normalized to 75 beats/min (AIx@75) using the SphygmoCor device. Participants also underwent carotid/femoral ultrasound for atherosclerotic plaque detection. We used linear regression to compare ArS measures among groups and assess ArS determinants in the APS group. RESULTS: We included 110 patients with APS (70.9% female, mean age 45.4 years), 110 DM patients and 110 HC, all age/sex matched. After adjustment for age, sex, cardiovascular risk factors and plaque presence, APS patients exhibited similar cfPWV [ß = -0.142 (95% CI -0.514, 0.230), p = 0.454] but increased AIx@75 [ß = 4.525 (95% CI 1.372, 7.677), p = 0.005] compared with HC and lower cfPWV (p < 0.001) but similar AIx@75 (p = 0.193) versus DM patients. In the APS group, cfPWV was independently associated with age [ß = 0.056 (95% CI 0.034, 0.078), p < 0.001], mean arterial pressure (MAP) [ß = 0.070 (95% CI 0.043, 0.097), p < 0.001], atherosclerotic femoral plaques [ß = 0.732 (95% CI 0.053, 1.411), p = 0.035] and anti-ß2-glycoprotein I IgM positivity [ß = 0.696 (95% CI 0.201, 1.191), p = 0.006]. AIx@75 was associated with age [ß = 0.334 (95% CI 0.117, 0.551), p = 0.003], female sex [ß = 7.447 (95% CI 2.312, 12.581), p = 0.005] and MAP [ß = 0.425 (95% CI 0.187, 0.663), p = 0.001]. CONCLUSION: APS patients exhibit elevated AIx@75 vs HC and similar to DM patients, indicating enhanced arterial stiffening in APS. Given its prognostic value, ArS evaluation may help to improve cardiovascular risk stratification in APS.

Outcomes of COVID-19 Omicron variant in patients with rheumatoid arthritis: a nationwide Greek cohort study.

OBJECTIVES: Patients with RA were at increased risk for COVID-19-associated hospitalization and death during the first year of the pandemic in Greece. We aimed to examine their outcomes after the SARS-Cov-2 Omicron, a more contagious but with milder clinical impacts variant, prevailed. METHODS: A retrospective, nationwide study was conducted between 1 January 2022 and 30 June 2022 in all RA patients under treatment and matched (1:5) on age, sex and region of domicile random general population comparators. Confirmed SARS-CoV-2 infections, hospitalizations and deaths, anti-rheumatic medications, prior COVID-19, vaccinations and anti-viral medications were recorded. RESULTS: Among 34 182 RA patients, infections (n = 5569, 16.29%), hospitalizations (n = 489, 1.43%) and deaths (n = 106, 0.31%) were more frequent than among comparators. Incidence rates per 1000 person/years of infection [IRR (95% CI):1.19 (1.16, 1.23)], hospitalization [IRR (95% CI):2.0 (1.82, 2.24)], and death [IRR (95% CI):1.81 (1.44, 2.27)] were increased in RA despite better vaccination coverage (89% vs 84%) and more frequent use of anti-viral medications (2.37% vs 1.08). Logistic regression analysis after correcting for age, sex, vaccinations, prior COVID-19, and anti-viral medications in SARS-CoV-2 infected RA patients and comparators revealed increased risk of hospitalization (OR: 2.02, 95% CI: 1.79, 2.27) and death [OR: 1.73, (95% CI: 1.36, 2.20)] in RA. Among infected RA patients, rituximab treatment conferred increased risks for hospitalization [OR: 6.12, (95% CI: 2.89, 12.92)] and death [OR: 12.06 (95% CI: 3.90, 37.31)], while JAK inhibitors increased only hospitalization risk [OR: 2.18 (95% CI: 1.56, 3.06)]. CONCLUSION: RA remains a risk factor for hospitalization and death in an era of a relatively low COVID-19 fatality rate, pointing to the need of perseverance in vaccination programs and wider use of anti-viral medications.

Progression of subclinical atherosclerosis in ankylosing spondylitis: a 10-year prospective study.

Chronic systemic inflammation contributes to increased CVD burden in Ankylosing Spondylitis (AS). Since long-term follow-up data on subclinical atherosclerosis acceleration are lacking, we examined its progression in contemporary AS patients during 10 years. Fifty-three (89% male, aged 50.4 (36.3-55.9) years,) non-diabetic, CVD-free AS patients and 53 age-sex-matched non-diabetic, control individuals were re-evaluated after 9.2-10.2 years by ultrasonography for carotid/femoral atheromatosis, pulse wave velocity (PWV) and intima-media thickness (IMT), performed by the same operator/protocol. New atheromatic plaque formation, PWV deterioration, and IMT increase were associated only with classical CVD risk factors, as reflected by the heartSCORE (age, gender, smoking status, blood pressure and cholesterol levels) by multivariate analysis, rather than disease presence. However, among AS patients, despite remission/low disease activity at follow-up end in 79%, atheromatosis progression was associated by multivariate analysis with higher BASDAI scores (p = 0.028), independently of biologic therapies administered in 2/3 of them. Moreover, in AS patients, but not in controls, PWV values at baseline were associated with plaque progression during the 10-year follow-up after taking into account baseline heartSCORE and plaque burden status (p = 0.033). Despite comparable prevalence of both hypertension and hypercholesterolemia at baseline between patients and controls, a lower percentage of AS patients had achieved "adequate" CVD risk factor control at follow-up end (11% vs 25% respectively, p = 0.076). Classical CVD risk factors and residual disease activity account for the progression of subclinical atherosclerosis in AS, pointing to the unmet needs in the contemporary management of these patients.

Different COVID-19 outcomes among systemic rheumatic diseases: a nation-wide cohort study.

OBJECTIVES: To investigate coronavirus disease 2019 (COVID-19)-associated risk of hospitalization and death in RA, AS, PsA, SLE and SSc in comparison with the general population during the first year of the pandemic, and compare their overall mortality with 2019. METHODS: Interlinking nationwide electronic registries, we recorded confirmed COVID-19-associated infections, hospitalizations and deaths, and all-cause deaths between 1 March 2020 and 28 February 2021 in all adults with RA, AS, PsA, SLE and SSc under treatment (n = 74 970, median age 67.5, 51.2, 58.1, 56.2 and 62.2 years, respectively) and in random comparators from the general population matched (1:5) on age, sex and region of domicile. Deaths from all causes during 2019 were also recorded. RESULTS: Compared with the general population, incidence rates (IR) for COVID-19-associated hospitalization were higher in RA [IR ratio (IRR) 1.71(1.50-1.95)], SLE [2.0 (1.4-2.7)] and SSc [2.28 (1.29-3.90)], while COVID-19-associated death rates were higher in RA [1.91 (1.46-2.49)]. When focusing only on severe acute respiratory syndrome coronavirus 2-infected subjects, after adjusting for age and gender, the odds ratio for COVID-19 associated death was higher in RA [1.47 (1.11-1.94)] and SSc [2.92 (1.07-7.99)] compared with the general population. The all-cause mortality rate compared with the general population increased in RA during the first year of the pandemic (IRR 0.71) with reference to 2019 (0.59), and decreased in SSc (IRR 1.94 vs 4.36). CONCLUSION: COVID-19 may have a more severe impact in patients with systemic rheumatic disease than in the general population. COVID-19-related mortality is increased in subgroups of patients with specific rheumatic diseases, underscoring the need for priority vaccination and access to targeted treatments.

Atherosclerosis progression in antiphospholipid syndrome is comparable to diabetes mellitus: a 3 year prospective study.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune thrombophilia leading to life-threatening cardiovascular events. Cross-sectional data support that APS is associated with accelerated atherosclerosis, but this has not been confirmed in prospective studies. We aimed to compare the rate of atherosclerosis progression over a 3 year period between patients with APS, diabetes mellitus (DM) and healthy controls (HCs). METHODS: Eighty-six patients with APS [43 with primary APS (PAPS), 43 with SLE-related APS (SLE-APS)] and an equal number of age- and sex-matched patients with DM and HCs who underwent a baseline US of the carotid and femoral arteries were invited for a 3 year follow-up evaluation for atherosclerotic plaque progression. Multivariate analysis was performed for the assessment of determinants of plaque progression after adjustment for disease-related and traditional cardiovascular risk factors. RESULTS: Seventy-four APS patients (74.3% female, 38 with PAPS), 58 DM patients and 73 HCs were included. APS patients exhibited a 3.3-fold higher risk of new atherosclerotic plaque formation compared with HCs (P = 0.031), similar to that in DM [odds ratio (OR) 3.45, P = 0.028]. In APS patients, plaque development risk was higher in SLE-APS vs PAPS (OR 7.75, P = 0.038) and was independently associated with the presence of traditional cardiovascular risk factors as expressed by the Systematic Coronary Risk Evaluation risk (OR 2.31, P = 0.008). CONCLUSION: APS is characterized by accelerated rates of subclinical atherosclerosis to a degree comparable to DM, which is more pronounced in SLE-APS patients. Traditional cardiovascular risk factors are major determinants of this risk, warranting aggressive management as in other disorders with high cardiovascular risk.

SLICC-Frailty Index is independently associated with impaired physical function, activities of daily living and quality of life measures.

OBJECTIVE: The SLICC Frailty Index (SLICC-FI) was developed to assess health deficits including disease activity, organ damage, comorbidities and functional status. We examined any relationship between SLICC-FI and objective physical function measures, activities of daily living performance and quality of life in SLE. METHODS: SLICC-FI was estimated using data from patient files and patient-reported questionnaires. Jamar Dynamometer, pinch gauge and Purdue pegboard test measured grip strength, pinch strength and dexterity, respectively. Activities of daily living performance was assessed by the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire and HAQ. Quality of life was evaluated by LupusQol questionnaire. RESULTS: This cross-sectional study included 240 SLE patients (90% female, mean (s.d.) age: 47.63 (13.01), median (IQR) disease duration: 9 (4-16)). Mean (s.d.) SLICC-FI was 0.09 (0.06). Forty-three (17.9%) patients were classified as robust, 105 (43.8%) as relatively less fit, 77 (32.1%) as least fit and 15 (6.2%) as frail. In univariate analysis, SLICC-FI was significantly associated with DASH and HAQ with an inverse association with grip strength, pinch strength and all purdue scores (all P < 0.001). A negative correlation was found between SLICC-FI score and all LupusQoL domain scores (all P < 0.001). All associations remained statistically significant in multivariate regression analysis, after adjustment for age, disease duration, SLEDAI-2K, SLICC, immunosuppressives, corticosteroids and Charlson score. CONCLUSION: SLICC-FI is independently associated with poor physical function and activities of daily living performance and impaired quality of life and may help to identify patients in need of additional interventions beyond routine care.

Cardiovascular disease detection using machine learning and carotid/femoral arterial imaging frameworks in rheumatoid arthritis patients.

The study proposes a novel machine learning (ML) paradigm for cardiovascular disease (CVD) detection in individuals at medium to high cardiovascular risk using data from a Greek cohort of 542 individuals with rheumatoid arthritis, or diabetes mellitus, and/or arterial hypertension, using conventional or office-based, laboratory-based blood biomarkers and carotid/femoral ultrasound image-based phenotypes. Two kinds of data (CVD risk factors and presence of CVD-defined as stroke, or myocardial infarction, or coronary artery syndrome, or peripheral artery disease, or coronary heart disease) as ground truth, were collected at two-time points: (i) at visit 1 and (ii) at visit 2 after 3 years. The CVD risk factors were divided into three clusters (conventional or office-based, laboratory-based blood biomarkers, carotid ultrasound image-based phenotypes) to study their effect on the ML classifiers. Three kinds of ML classifiers (Random Forest, Support Vector Machine, and Linear Discriminant Analysis) were applied in a two-fold cross-validation framework using the data augmented by synthetic minority over-sampling technique (SMOTE) strategy. The performance of the ML classifiers was recorded. In this cohort with overall 46 CVD risk factors (covariates) implemented in an online cardiovascular framework, that requires calculation time less than 1 s per patient, a mean accuracy and area-under-the-curve (AUC) of 98.40% and 0.98 (p < 0.0001) for CVD presence detection at visit 1, and 98.39% and 0.98 (p < 0.0001) at visit 2, respectively. The performance of the cardiovascular framework was significantly better than the classical CVD risk score. The ML paradigm proved to be powerful for CVD prediction in individuals at medium to high cardiovascular risk.

Joint microwave radiometry for inflammatory arthritis assessment.

OBJECTIVES: Increased in-depth joint temperature measured by the rapid, easy-to-perform microwave radiometry (MWR) method may reflect inflammation, even in the absence of clinical signs. We hypothesized that MWR is useful for RA and spondyloarthritis patients' assessment. METHODS: Clinical examination, joint ultrasound and/or MRI and MWR were performed in two independent patient-control cohorts (n = 243). RESULTS: Among single RA joints MWR performed best in the knee using ultrasound as reference, with 75% sensitivity-73% specificity for grey-scale synovitis score ⩾2, and 80% sensitivity-82% specificity for power Doppler positivity. A stronger agreement was evident between increased knee relative temperature (Δt) and power Doppler positivity (82%) than with clinical examination (76%). In a different patient cohort with painful knees, a knee Δt ⩽0.2 predicted power Doppler positivity with 100% positive and negative predictive values. A thermo-score summing 10 Δt values of three large and seven small RA joints (elbow, knee, ankle, wrist, four hand and two foot joints of the clinically dominant arm or hand and leg or foot) correlated with ultrasound scores of synovitis/tenosynovitis (all P < 0.001) and the 28-joint Disease Activity Score (DAS28) (P = 0.004). The agreement of the thermo-score with ultrasound-defined joint inflammation (82%) was stronger than with DAS28 (64%). The thermo-score improved significantly after 90 days of treatment in patients with active RA at baseline (P = 0.004). Using MRI as reference, Δt of sacroiliac joints could discriminate between spondyloarthritis patients with or without sacroiliitis with 78% sensitivity-74% specificity. CONCLUSION: In-depth increased MWR-derived joint temperature reflects both subclinical and clinically overt inflammation and may serve as a biomarker in arthritis.

Differential performance of nailfold video capillaroscopic parameters in the diagnosis and prognosis of systemic sclerosis.

OBJECTIVES: The contribution of nailfold video capillaroscopy (NVC) in identifying patients with Raynaud's phenomenon (RP) at risk for systemic sclerosis (SSc) is well established. Herein we comparatively assess the performance of different capillaroscopic parameters in diagnosing SSc among patients with RP and evaluate the prognostic capacity of NVC in SSc. METHODS: At baseline we clinically and capillaroscopically evaluated 242 consecutive patients referred to our department for NVC (138 with SSc); 175 were reevaluated after 3.38±1.47 years. Sixty-two healthy volunteers served as controls. Capillaroscopy pattern (normal/early/active/late) was qualitatively defined. Capillary loss, dilated, giant or ramified capillaries and micro-haemorrhages were scored semi-quantitatively. RESULTS: Capillary loss score had the highest diagnostic accuracy at discriminating patients with an SSc-spectrum disorder from patients with RP of different etiology and controls, as defined by ROC curve analysis [AUC (95% CI)=0.905 (0.869-0.942)], followed by dilatation score [0.863 (0.818-0.907)] and giant score [0.835 (0.787-0.884)]. By contrast, micro-haemorrhages [0.720 (0.662-0.779)] and ramifications scores [0.604 (0.539-0.670)] performed worse. Multivariate analysis in 94 SSc patients indicated that active (OR=3.305, p=0.043) and late (OR=6.900, p=0.023) baseline capillaroscopy pattern predicted occurrence of a combined adverse disease outcome [forced vital capacity (FVC) deterioration>10% and/or DLCO deterioration>15% and/or mRSS deterioration>3.5 and/or first occurrence of digital ulcers and/or death)] at 3 year follow-up. CONCLUSIONS: Dilatation score performs best of all semi-quantitative NVC parameters in diagnosing SSc. In addition, our study confirms earlier reports that worse capillaroscopy pattern at baseline correlates with higher likelihood for adverse prognosis.

Mechanics of early ventricular impairment in systemic sclerosis and the effects of peripheral arterial haemodynamics.

OBJECTIVES: Multiple mechanisms commonly lead to severe cardiac involvement in systemic sclerosis (SSc), an autoimmune disease characterised by microvascular lesions, systemic inflammation and fibrosis. Herein, we examined the mechanics of right and left ventricles (RV, LV) at the early stage of impairment and tested the hypothesis that peripheral vasculopathy influences the possible early compromise of LV. METHODS: Ninety-five SSc patients free of any cardiovascular disease or related symptoms (88% women, 53±14 years) and 54 subjects matched for age, gender, arterial hypertension, dyslipidaemia, and diabetes mellitus underwent echocardiography, including multilayer speckle-tracking, and tonometry-based pulse wave analysis of the peripheral arteries; 66 SSc patients were prospectively assessed after 32±7 months. Indices of ventricular and arterial structure and function, as well as LV-arterial coupling, were calculated. RESULTS: At baseline, patients presented RV diastolic/systolic impairment, as well as LV remodelling and diastolic/systolic impairment in terms of reduced deformation parameters versus controls. No association was found between RV and LV strain within individual patients, whereas both RV and LV abnormalities progressed independently during follow-up. Moreover, in the absence of differences in aortic stiffening and LV-arterial coupling between patients and controls, arterial pressure wave reflections assessing small vessel function and/or microcirculation were abnormal in SSc patients and strongly correlated with impaired indices of LV diastolic function and remodelling. CONCLUSIONS: Speckle-tracking echocardiography demonstrates the mechanics of RV early impairment in SSc that develops and progresses independently from the concomitant LV impairment, which, in turn, may be influenced by peripheral microvascular abnormalities in the absence of macrovascular damage.

Progression of subclinical atherosclerosis in systemic lupus erythematosus versus rheumatoid arthritis: the impact of low disease activity.

Objectives: The progression of subclinical atherosclerosis in SLE and RA has not been comparatively assessed. We sought to investigate the impact of low disease activity and other disease-related factors on atherosclerosis progression in SLE vs RA. Methods: We performed a 3-year follow-up carotid and femoral artery ultrasound in 101 patients with SLE, 85 with RA and 85 controls after a baseline examination in 115 SLE and 1:1 age- and gender-matched RA patients and controls. We used logistic regression to compare atherosclerosis progression (new plaque development) between SLE and RA vs controls, and assess determinants of progression in SLE patients with different lupus low disease activity state (LLDAS) durations, adjusting for disease-related factors, antihypertensives, antiplatelets, statins and the Systemic Coronary Risk Evaluation 10-year cardiovascular risk. Results: The odds ratio (OR) of plaque progression vs controls was significantly higher in SLE (OR = 2.81, P = 0.043), but not in RA (OR = 2.22, P = 0.109). Results were similar in patients with low disease activity (88% of SLE, 74% of RA). Multivariate determinants of progression in SLE included antiphospholipid antibodies (OR = 2.00, P = 0.043) and Systemic Coronary Risk Evaluation (OR = 2.87, P = 0.019) for all patients, and additionally cumulative corticosteroid dose during follow-up (OR = 1.38, P = 0.013) and disease duration (OR = 1.20, P = 0.022) for patients in LLDAS over entire follow-up. Results were similar for patients with shorter LLDAS durations (>75% or >50% of follow-up). Conclusion: Plaque progression is accelerated in SLE regardless of disease activity, and is associated with antiphospholipid antibodies and the Systemic Coronary Risk Evaluation. In LLDAS, cumulative corticosteroid dose and disease duration are additional determinants of progression.

Atherosclerosis is not accelerated in rheumatoid arthritis of low activity or remission, regardless of antirheumatic treatment modalities.

Objectives: RA associates with increased cardiovascular disease (CVD) morbidity and mortality due to accelerated atherosclerosis, attributed to both classical risk factors and chronic inflammation. The aim of this study was to test the hypothesis that effective disease control over 3 years modifies acceleration of atherosclerosis in RA. Methods: Consecutive, non-diabetic RA patients previously examined by ultrasonography for subclinical atherosclerosis were re-evaluated after 3.2 (0.2) years, provided that they were in remission/low disease activity (DAS28 <3.2) for at least 75% of this period. Patients (n = 139) were demographically matched with 139 non-diabetic, non-RA control individuals studied in parallel. Results: Patients and controls (mean age of 56 years at baseline) had a comparable burden of classical CVD risk factors. Patients' pulse wave velocity (reflecting arterial stiffness) changed by 0.07 m/s/year and left carotid intima-media thickness (reflecting wall hypertrophy) increased by 0.009 mm/year; formation of new atheromatic plaques in carotid and/or femoral arterial beds occurred in 22%. Multivariate analysis after correcting for all classical CVD risk factors and anti-hypertensive/lipid-lowering therapies demonstrated no significant differences between patients and controls in any of the subclinical atherosclerosis indices. Changes in all atherosclerosis indices from baseline to end of follow-up were comparable between those 56 patients treated with biologic DMARDs and their demographically matched patients treated with synthetic DMARDs. Conclusion: Effective disease control may abrogate any RA-specific effect on the progression of atherosclerosis regardless of treatment. Whether early and sustained RA control translates to the CVD outcomes expected in the general population should be examined in prospective studies.

Biologic treatment for rheumatic disease: real-world big data analysis from the Greek country-wide prescription database.

OBJECTIVES: To directly assess the prevalence of inflammatory rheumatic disease under treatment with biologic disease modifying anti-rheumatic drugs (b-DMARDs) and compare treatment patterns between rheumatoid arthritis (RA) and spondyloarthropathy (SpA), including psoriatic arthritis. METHODS: The obligatory country-wide prescription electronic database covering 10.223.000 Greek citizens (95.1% of the population, 99.5% Caucasian), all of whom with fully reinbursed access to b-DMARDs, was used to retrospectively capture all patients under b-DMARDs for RA/SpA between June 2014-May 2015. Age, gender and medications for RA/SpA and co-morbid classical cardiovascular risk factors (hypertension, dyslipidaemia, diabetes) were retrieved and analysed. RESULTS: A total of 9.824 RA (61.2±14.0 years, 79% women) and 9.279 SpA patients (51.4±13.1 years, 41% women) using pharmacy-dispensed prescriptions for b-DMARDs were identified (overall prevalence 0.19%). Tumour necrosis factor inhibitors were used in 73% and 99% of RA and SpA patients, respectively. B-DMARD monotherapy (RA: 18.71%, SpA: 52.11%), b-DMARD switching during 12 months (RA: 7.73%, SpA: 6.26%), and use of methotrexate (RA: 50.25%, SpA: 27.35%) and corticosteroids (RA: 55.8%, SpA: 23.63%) differed between the two patient subgroups. In both subgroups, women received more often than men methotrexate, leflunomide, hydroxychloroquine and corticosteroids, and less often b-DMARD monotherapy. After adjustments for age, gender and concomitant drugs, the probability for anti-hypertensive and lipid-lowering drug prescription was higher in SpA than RA [OR=1.41 (95%CI: 1.29-1.54) and 1.24 (1.14-1.36), respectively, p<0.001], whereas for anti-diabetics it was similar. CONCLUSIONS: In the first country-wide study that examines the characteristics of rheumatic disease patients under b-DMARD we show that their exact prevalence is 0.19%, with RA patients being older by 10 years, only slightly more numerous, and less likely to receive treatment for hypertension and dyslipidaemia than their demographically matched SpA counterparts. Longitudinal studies should assess the implications of these novel findings on the differential financial burden of rheumatic diseases, as well as on cardiovascular morbidity and mortality of these patients.

Cardiovascular risk assessment in patients with antiphospholipid syndrome: a cross-sectional performance analysis of nine clinical risk prediction tools.

OBJECTIVES: This study aimed to assess the performance of cardiovascular risk (CVR) prediction models reported by European Alliance of Associations for Rheumatology and European Society of Cardiology recommendations to identify high-atherosclerotic CVR (ASCVR) patients with antiphospholipid syndrome (APS). METHODS: Six models predicting the risk of a first cardiovascular disease event (first-CVD) (Systematic Coronary Risk Evaluation (SCORE); modified-SCORE; Framingham risk score; Pooled Cohorts Risk Equation; Prospective Cardiovascular Münster calculator; Globorisk), three risk prediction models for patients with a history of prior arterial events (recurrent-CVD) (adjusted Global APS Score (aGAPSS); aGAPSSCVD; Secondary Manifestations of Arterial Disease (SMART)) and carotid/femoral artery vascular ultrasound (VUS) were used to assess ASCVR in 121 APS patients (mean age: 45.8±11.8 years; women: 68.6%). We cross-sectionally examined the calibration, discrimination and classification accuracy of all prediction models to identify high ASCVR due to VUS-detected atherosclerotic plaques, and risk reclassification of patients classified as non high-risk according to first-CVD/recurrent-CVD tools to actual high risk based on VUS. RESULTS: Spiegelhalter's z-test p values 0.47-0.57, area under the receiver-operating characteristics curve (AUROC) 0.56-0.75 and Matthews correlation coefficient (MCC) 0.01-0.35 indicated moderate calibration, poor-to-acceptable discrimination and negligible-to-moderate classification accuracy, respectively, for all risk models. Among recurrent-CVD tools, SMART and aGAPSSCVD (for non-triple antiphospholipid antibody-positive patients) performed better (z/AUROC/MCC: 0.47/0.64/0.29 and 0.52/0.69/0.29, respectively) than aGAPSS. VUS reclassified 34.2%-47.9% and 40.5%-52.6% of patients classified as non-high-ASCVR by first-CVD and recurrent-CVD prediction models, respectively. In patients aged 40-54 years, >40% VUS-guided reclassification was observed for first-CVD risk tools and >50% for recurrent-CVD prediction models. CONCLUSION: Clinical CVR prediction tools underestimate actual high ASCVR in APS. VUS may help to improve CVR assessment and optimal risk factor management.

Lipid management in systemic lupus erythematosus according to risk classifiers suggested by the European Society of Cardiology and disease-related risk factors reported by the EULAR recommendations.

BACKGROUND: The European Alliance of Associations for Rheumatology recommended that lipid-lowering therapy (LLT) in systemic lupus erythematosus (SLE) should follow general population guidelines. We examined the eligibility for LLT in SLE according to Systematic Coronary Risk Evaluation (SCORE), with and without the addition of vascular ultrasound (VUS) and disease-related features. METHODS: 210 patients with SLE without prior cardiovascular events, diabetes or antiphospholipid syndrome underwent cardiovascular risk assessment with SCORE. LLT eligibility was evaluated in low-risk and moderate-risk patients following European Society of Cardiology (ESC) guidelines. Atherosclerotic plaques on carotid ultrasound (cUS)) and carotid and femoral ultrasound (cfUS), prolonged disease duration (PDD, ≥10 years), failure to achieve lupus low disease activity state (LLDASno), cumulative glucocorticoid 'cardiovascular harm' dose (GCCVH, optimal cut-off to predict ultrasound-detected plaques) and antiphospholipid antibody positivity (aPLpos) were tested as SCORE risk enhancers for classification ability (phi coefficient) and agreement (Cohen's kappa) using SCORE plus cfUS as a reference modality for LLT eligibility. RESULTS: Plaques were detected in 9.9% of low-risk cases and 54.6% of moderate-risk cases. SCORE alone would indicate 0% of low-risk patients and 3% of moderate-risk patients for LLT eligibility. According to SCORE+cfUS, 9.9% of low-risk patients and 57.6% of moderate-risk patients, respectively, would be eligible for LLT based on ESC guidelines. Ιn low-risk/moderate-risk patients, phi values for SCORE+PDD, GCCVH (cut-off ≥11 g), LLDASno and aPLpos in antiplatelet-naïve antiphospholipid antibody-positive (aPLpos/APT-) cases were 0.06/0.13, 0.23/0.20, 0.07/0.16 and 0.06/0.33, respectively. Agreement for LLT eligibility to SCORE+cfUS was better for SCORE+PDD in moderate-risk patients and for SCORE+cUS in both groups of patients. SCORE+GCCVH and SCORE+aPLpos showed at least fair agreement (kappa ≥0.20) to SCORE+cfUS in low-risk or moderate-risk and in aPLpos/APT- moderate-risk patients, respectively. CONCLUSION: Disease-related and VUS features, in addition to SCORE, may help to improve LLT decision making in SLE. GCCVH and aPLpos improve LLT eligibility similarly and to a greater degree than PDD or LLDASno.

Application of EULAR and European Society of Cardiology recommendations with regard to blood pressure and lipid management in antiphospholipid syndrome.

BACKGROUND: To examine blood pressure (BP) and lipid treatment eligibility in antiphospholipid syndrome (APS) according to European Alliance of Associations for Rheumatology (EULAR) and European Society of Cardiology (ESC) recommendations. METHODS: Systematic Coronary Risk Evaluation (SCORE), modified-SCORE, diabetes mellitus (DM)-equivalent risk classifiers (DIME) and disease-related classifiers -type of thrombotic events (APSevents), antiphospholipid-antibody profile (aPLprofile) and adjusted Global APS Score for cardiovascular disease- were used to calculate predicted low-moderate, high and very-high cardiovascular risk (CVR) in 111 patients with APS without prior atherosclerotic cardiovascular events or DM. Actual CVR (AR) was determined according to ESC guidelines, including carotid/femoral plaque presence. In low-moderate SCORE-predicted risk patients, classification ability and agreement for BP or lipid treatment was tested with Matthews' correlation coefficient (MCC) and Cohen's kappa, respectively, using the AR classes as reference qualifiers. RESULTS: SCORE underestimated high/very-high-AR in >50% of cases. SCORE-guided BP/lipid treatment eligibility was 4.2%/12.6% for high, 10.5%/16.8% for very-high AR patients, while 5.3% of low-moderate AR cases were eligible for lipid-lowering therapy. For BP treatment, MCC was higher using DIME for low-moderate and very-high-risk (0.33 and 0.32, respectively), and using modified-SCORE+APSevents (MCC=0.25) for high-risk patients. Eligibility agreement was better with DIME+APSevents or aPLprofile (kappa=0.51) for high-risk, and DIME (kappa=0.31) for very-high-risk patients. For lipid treatment, both classification ability and eligibility agreement were stronger with SCORE (or modified-SCORE)+APSevents in low-moderate (MCC/kappa=0.43/0.41) and very-high risk (MCC/kappa=0.30/0.30), and with DIME+aPLprofile (MCC/kappa=0.50/0.50) in high-risk patients, respectively. CONCLUSION: Multimodal risk assessment including disease-related and cardiometabolic features used for high-risk diseases such as DM can improve CVR management in APS.

Generic and disease-adapted cardiovascular risk scores as predictors of atherosclerosis progression in SLE.

OBJECTIVE: Studies show that generic cardiovascular risk (CVR) prediction tools may underestimate CVR in SLE. We examined, for the first time to our knowledge, whether generic and disease-adapted CVR scores may predict subclinical atherosclerosis progression in SLE. METHODS: We included all eligible patients with SLE without a history of cardiovascular events or diabetes mellitus, who had a 3-year carotid and femoral ultrasound follow-up examination. Five generic (Systematic Coronary Risk Evaluation (SCORE), Framingham Risk Score (FRS), Pooled Cohort Risk Equation, Globorisk, Prospective Cardiovascular Münster) and three 'SLE-adapted' CVR scores (modified Systematic Coronary Risk Evaluation (mSCORE), modified Framingham Risk Score (mFRS), QRESEARCH Risk Estimator V.3 (QRISK3)) were calculated at baseline. The performance of CVR scores to predict atherosclerosis progression (defined as new atherosclerotic plaque development) was tested with Brier Score (BS), area under the receiver operating characteristic curve (AUROC) and Matthews correlation coefficient (MCC), while rank correlation was tested with Harrell's c-index. Binary logistic regression was also applied to examine determinants of subclinical atherosclerosis progression. RESULTS: Twenty-six (21%) of 124 included patients (90% female, mean age 44.4±11.7 years) developed new atherosclerotic plaques after a mean of 39.7±3.8 months' follow-up period. Performance analysis showed that plaque progression was better predicted by the mFRS (BS 0.14, AUROC 0.80, MCC 0.22) and QRISK3 (BS 0.16, AUROC 0.75, MCC 0.25). c-Index showed no superiority for discrimination between mFRS and QRISK3. In the multivariate analysis, QRISK3 (OR 4.24, 95% CI 1.30 to 13.78, p=0.016) among the CVR prediction scores and age (OR 1.13, 95% CI 1.06 to 1.21, p<0.001), cumulative glucocorticoid dose (OR 1.04, 95% CI 1.01 to 1.07, p=0.010) and antiphospholipid antibodies (OR 3.66, 95% CI 1.24 to 10.80, p=0.019) among disease-related CVR factors were independently associated with plaque progression. CONCLUSIONS: Application of SLE-adapted CVR scores such as QRISK3 or mFRS, as well as monitoring for glucocorticoid exposure and the presence of antiphospholipid antibodies, can help to improve CVR assessment and management in SLE.

Tahini consumption affects blood pressure and endothelial function in healthy males.

Sesame (Sesamum indicum L.) is rich in polyunsaturated fatty acids, proteins, vitamin E, and lignans. Recent studies have highlighted the antioxidant, antihypertensive, hypolipidemic, and appetite-control properties of sesame seeds and sesame oil. However, there is a gap in the literature regarding the effect of tahini (sesame paste) consumption on human health. Thus, the aim is to investigate the postprandial effect of tahini consumption on blood pressure, endothelial function, and arterial stiffness. Twenty healthy men with mean age of 28 y and mean BMI of 25.81 kg/m2 were included. After a 12-h fast, baseline blood was collected, participants consumed 50 g of tahini, and blood collection was repeated 4 h postprandially. Assessment of blood pressure, pulse rate, hemodynamic parameters, and endothelial function was performed at baseline and at the end of the trial. Blood samples were used for the quantification of intercellular cell-adhesion molecule-1, vascular cell-adhesion molecule-1, and E-selectin levels at baseline and 4 h postprandially. A statistically significant decrease in diastolic blood pressure (p = 0.010) and pulse rate (p = 0.002) was observed 4 h after tahini consumption. Significant increases in serum triglycerides (p < 0.001) and flow-mediated dilatation were observed (p = 0.022) 4 h postprandially. No changes were observed in other indices measured at the end of the intervention compared with baseline. This is the first study to report that tahini consumption can lower blood pressure and pulse rate and improve endothelial function, suggesting a healthy snack in place of others with a less desirable lipid profile.

Underperformance of clinical risk scores in identifying vascular ultrasound-based high cardiovascular risk in systemic lupus erythematosus.

AIMS: The aim of this study was to assess the performance of eight clinical risk prediction scores to identify individuals with systemic lupus erythematosus (SLE) at high cardiovascular disease (CVD) risk, as defined by the presence of atherosclerotic plaques. METHODS: CVD risk was estimated in 210 eligible SLE patients without prior CVD or diabetes mellitus (female: 93.3%, mean age: 44.8 ± 12 years) using five generic (Systematic Coronary Risk Evaluation (SCORE), Framingham Risk Score (FRS), Pooled Cohort Risk Equations (ASCVD), Globorisk, Prospective Cardiovascular Münster Study risk calculator (PROCAM)) and three 'SLE-adapted' (modified-SCORE, modified-FRS, QRESEARCH risk estimator, version 3 (QRISK3)) CVD risk scores, as well as ultrasound examination of the carotid and femoral arteries. Calibration, discrimination and classification measures to identify high CVD risk based on the presence of atherosclerotic plaques were assessed for all risk models. CVD risk reclassification was applied for all scores by incorporating ultrasound results. RESULTS: Moderate calibration (p-value range from 0.38 to 0.63) and discrimination (area under the curve 0.73-0.84), and low-to-moderate sensitivity (8.3-71.4%) and classification ability (Matthews correlation coefficient (MCC) 0.25-0.47) were observed for all risk models to identify patients with plaques at any arterial site as high-risk. MCC was improved for modified-FRS versus FRS (0.43 vs 0.36), but not for modified-SCORE versus SCORE (0.25 vs 0.25). Based on plaque presence, CVD risk was upgraded to high-risk in 10%, 16.1%, 20.5%, 21.5%, 24%, 28.2% and 28.6% of cases classified as non-high-risk by QRISK3, modified-FRS, Globorisk, FRS/PROCAM, ASCVD, modified-SCORE and SCORE, respectively. CONCLUSIONS: Most of the five generic and three 'SLE-adapted' clinical risk scores underestimated high CVD risk defined by atherosclerotic plaque presence in patients with SLE.