Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study—results at 5 years of follow-up

Rheumatology ◽  
2020 ◽  
Author(s):  
María A Martín-Martínez ◽  
Santos Castañeda ◽  
Fernando Sánchez-Alonso ◽  
Carmen García-Gómez ◽  
Carlos González-Juanatey ◽  
...  

Abstract Objectives To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. Methods This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. Results Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. Conclusions Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 2.2-2
Author(s):  
M. A. Martin-Martinez ◽  
S. Castañeda ◽  
F. Sánchez-Alonso ◽  
C. García Gomez ◽  
C. Gonzalez Juanatey ◽  
...  

Objectives:To determine the incidence and risk factors implicated in the development of first cardiovascular (CV) event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) attending Spanish rheumatology clinics after 5 years of follow-upMethods:Analysis of data of patients included in an observational prospective study [CARdiovascular in rheuMAtology (CARMA) project] after 5 years of follow-up. The study includes a cohort of 2234 patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), and another cohort of matched individuals (n=677) without CIRD from 67 hospitals in Spain. Cumulative incidence per 1000 patients of CVE was estimated in both cohorts at 5 years from the start. Weibull proportional hazard model was used to calculate the Hazard Ratio (HR) and 95% confidence intervals (CI) of the risk factors involved in the development of CV events. Losses to follow-up and their causes were also analyzed.Results:The total number patient who completed the follow-up visit at 5 years was 2.382 (81.9%). Fifteen patients died due to CVE and sixty due to non-CVE. The patients with CIRD showed higher cardiovascular cumulative incidence (40.5; 95% CI: 36.2-44.8) than controls (28.3; 95% CI: 21.8-34.8). The higher risk of developing a first CVE during the 5 years of follow-up was seen in patients with AS (HR: 4.60; 95% CI: 1.32-15.99; p=0.02), those with older age (HR:1.09; 95% CI: 1.05-1.13; p<0.001), higher systolic blood pressure (HR: 2.64; 95% CI: 1.32-5.25; p=0.006), and those with longer duration of the rheumatic disease (HR: 1.07; 95% CI: 1.03-1.12; p=0.002). In contrast, woman gender was a protective factor (HR: 0.45; 95% CI: 0.21-0.99; p=0.047).Conclusion:Patients with AS prospectively followed-up at rheumatology outpatient clinics showed higher risk of developing a first CVE than those without CIRD. Besides traditional CV disease risk factors, a longer time course of the disease is a risk factor for the development of CV disease in patients with CIRD.Acknowledgments:This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie.Disclosure of Interests:Maria Auxiliadora Martin-Martinez: None declared, Santos Castañeda: None declared, Fernando Sánchez-Alonso: None declared, Carmen García Gomez: None declared, Carlos Gonzalez Juanatey: None declared, Maria Angeles Belmonte: None declared, Jesús Tornero: None declared, José Santos Rey: None declared, CARMEN OLGA SANCHEZ GONZALEZ: None declared, Estefanía Quesada-Masachs: None declared, MARIA DELPUERTO MORENO GIL: None declared, Tatiana Cobo-Ibáñez: None declared, Jose Antonio Pinto Tasende: None declared, Jesús Babío: None declared, Gemma Bonilla: None declared, Antonio Juan Mas: None declared, Javier Manero: None declared, Montserrat Romera: None declared, Javier Bachiller-Corral: None declared, Eugenio Chamizo Carmona: None declared, Javier Calvo: None declared, Raimon Sanmarti: None declared, Maria Celia Erausquin: None declared, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi, Carmen Barbadillo: None declared, Sergio Ros Exposito: None declared, Javier del Pino Grant/research support from: Roche, Bristol, Consultant of: Gedeon, MARIA JOSE GONZALEZ: None declared, José Manuel Pina Salvador: None declared, Javier Llorca: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 775.2-776
Author(s):  
C. W. S. Chan ◽  
P. H. LI ◽  
C. S. Lau ◽  
H. Y. Chung

Background:Cardiovascular (CVS) diseases are the leading cause of death worldwide and patients with rheumatic diseases have an increased CVS risk including stroke and myocardial infarction (MI) (1-3). CVS risk factors and CVS events are common in SpA (4). Delineating the CVS risk and the association with medications in patients with SpA would be useful.Objectives:The objective of this study was to delineate the CVS risk and the association with medications in patients with SpA.Methods:Patients with SpA and patients with non-specific back pain (NSBP) were identified in rheumatology and orthopedics clinics respectively. Clinical information and CVS events were retrieved. Incidence rates were calculated. Association analysis was performed to determine the CVS risk of SpA and other modifiable risk factors.Results:A total of 5046 patients (SpA 2616 and NSBP 2430) were included from eight centers. Over 56 484 person-years of follow-up, 160 strokes, 84 MI and 262 major adverse cardiovascular events (MACE) were identified. Hypercholesterolemia was more prevalent in SpA (SpA 34.2%, NSBP 28.7%, P<0.01). Crude incidence rates of stroke and MI were higher in SpA patients. SpA was associated with a higher risk of MACE (HR 1.66, 95%CI 1.22-2.27, P<0.01) and cerebrovascular events (HR 1.42, 95%CI 1.01-2.00, p=0.04). The use of anti-tumor necrosis factor (TNF) drugs was associated with a reduced risk of MACE (HR 0.37, 95%CI 0.17-0.80, P=0.01) and cerebrovascular events (HR 0.21, 95%CI 0.06-0.78, P=0.02).Conclusion:SpA is an independent CVS risk factor. Anti-TNF drugs were associated with a reduced CVS risk in these patients.References:[1]Crowson CS, Liao KP, Davis JM, 3rd, Solomon DH, Matteson EL, Knutson KL, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622-8 e1.[2]Verhoeven F, Prati C, Demougeot C, Wendling D. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine. 2020;87(5):413-8.[3]Liew JW, Ramiro S, Gensler LS. Cardiovascular morbidity and mortality in ankylosing spondylitis and psoriatic arthritis. Best Pract Res Clin Rheumatol. 2018;32(3):369-89.[4]Molto A, Etcheto A, van der Heijde D, Landewe R, van den Bosch F, Bautista Molano W, et al. Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study. Ann Rheum Dis. 2016;75(6):1016-23.Disclosure of Interests:None declared.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4253-4253
Author(s):  
Hanne Rozema ◽  
Robby Kibbelaar ◽  
Nic Veeger ◽  
Mels Hoogendoorn ◽  
Eric van Roon

The majority of patients with myelodysplastic syndromes (MDS) require regular red blood cell (RBC) transfusions. Alloimmunization (AI) against blood products is an adverse event, causing time-consuming RBC compatibility testing. The reported incidence of AI in MDS patients varies greatly. Even though different studies on AI in MDS patients have been performed, there are still knowledge gaps. Current literature has not yet fully identified the risk factors and dynamics of AI in individual patients, nor has the influence of disease modifying treatment (DMT) been explored. Therefore, we performed this study to evaluate the effect of DMT on AI. An observational, population-based study, using the HemoBase registry, was performed including all newly diagnosed MDS patients between 2005 and 2017 in Friesland, a province of the Netherlands. All available information about treatment and transfusions, including transfusion dates, types, and treatment regimens, was collected from the electronic health records and laboratory systems. Follow-up occurred through March 2019. For our patient cohort, blood products were matched for AB0 and RhD, and transfused per the 'type and screen' policy (i.e. electronic matching of blood group phenotype between patient and donor). After a positive antibody screening, antibody identification and Rh/K phenotyping was performed and subsequent blood products were (cross)matched accordingly. The observation period was counted from first transfusion until last transfusion or first AI event. Univariate analyses and cumulative frequency distributions were performed to study possible risk factors and dynamics of AI. DMT was defined as hypomethylating agents, lenalidomide, chemotherapy and monoclonal antibodies. The effect of DMT as a temporary risk period on the risk of AI was estimated with incidence rates, relative risks (RR) and hazard ratios (HR) using a cox regression analysis. Follow-up was limited to 24 months for the cox regression analysis to avoid possible bias by survival differences. Statistical analyses were performed using IBM SPSS 24 and SAS 9.4. Out of 292 MDS patients, 236 patients received transfusions and were included in this study, covering 463 years of follow-up. AI occurred in 24 patients (10%). AI occurred mostly in the beginning of the observation period: Eighteen patients (75%) were alloimmunized after receiving 20 units of RBCs, whereas 22 patients (92%) showed AI after 45 units of RBCs (Figure 1). We found no significant risk factors for AI in MDS patients at baseline. DMT was given to 67 patients (28%) during the observation period. Patients on DMT received more RBC transfusions than patients that did not receive DMT (median of 33 (range: 3-154) and 11 (range: 0-322) RBC units respectively, p<0,001). Four AI events (6%) occurred in patients on DMT and 20 AI events (12%) occurred in patients not on DMT. Cox regression analysis of the first 24 months of follow-up showed an HR of 0.30 (95% CI: 0.07-1.31; p=0.11). The incidence rates per 100 person-years were 3.19 and 5.92 respectively. The corresponding RR was 0.54 (95% CI: 0.16-1.48; p=0.26). Based on our results, we conclude that the incidence of AI in an unselected, real world MDS population receiving RBC transfusions is 10% and predominantly occurred in the beginning of follow-up. Risk factors for AI at baseline could not be identified. Our data showed that patients on DMT received significantly more RBC transfusions but were less susceptible to AI. Therefore, extensive matching of blood products may not be necessary for patients on DMT. Larger studies are needed to confirm the protective effect of DMT on AI. Disclosures Rozema: Celgene: Other: Financial support for visiting MDS Foundation conference.


2020 ◽  
Vol 15 (12) ◽  
pp. 1749-1761
Author(s):  
Dorey A. Glenn ◽  
Candace D. Henderson ◽  
Michelle O’Shaughnessy ◽  
Yichun Hu ◽  
Andrew Bomback ◽  
...  

Background and objectivesInfections contribute to patient morbidity and mortality in glomerular disease. We sought to describe the incidence of, and identify risk factors for, infection-related acute care events among Cure Glomerulonephropathy Network (CureGN) study participants.Design, setting, participants, & measurementsCureGN is a prospective, multicenter, cohort study of children and adults with biopsy sample–proven minimal change disease, FSGS, membranous nephropathy, or IgA nephropathy/vasculitis. Risk factors for time to first infection-related acute care events (hospitalization or emergency department visit) were identified using multivariable Cox proportional hazards regression.ResultsOf 1741 participants (43% female, 41% <18 years, 68% White), 163 (9%) experienced infection-related acute care events over a median follow-up of 17 months (interquartile range, 9–26 months). Unadjusted incidence rates of infection-related acute care events were 13.2 and 6.2 events per 100 person-years among pediatric and adult participants, respectively. Among participants with versus without corticosteroid exposure at enrollment, unadjusted incidence rates were 50.6 and 28.6 per 100 person-years, respectively, during the first year of follow-up (adjusted hazard ratio for time to first infection, 1.31; 95% CI, 0.89 to 1.93), and 4.1 and 1.1 per 100 person-years, respectively, after 1 year of follow-up (hazard ratio, 2.99; 95% CI, 1.54 to 5.79). Hypoalbuminemia combined with nephrotic-range proteinuria (serum albumin ≤2.5 g/dl and urinary protein-creatinine ratio >3.5 mg/mg), compared with serum albumin >2.5 g/dl and urinary protein-creatinine ratio ≤3.5 mg/mg, was associated with higher risk of time to first infection (adjusted hazard ratio, 2.49; 95% CI, 1.51 to 4.12).ConclusionsAmong CureGN participants, infection-related acute care events were common and associated with younger age, corticosteroid exposure, and hypoalbuminemia with proteinuria.


Medicina ◽  
2020 ◽  
Vol 56 (8) ◽  
pp. 392
Author(s):  
Dalia Miltinienė ◽  
Giedrė Deresevičienė ◽  
Birutė Nakčerienė ◽  
Valerija Edita Davidavičienė ◽  
Edvardas Danila ◽  
...  

Background and objective: With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients’ population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population. Material and Methods: Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website. Results: Overall, 8779 patients with newly diagnosed RD were identified during the 2013–2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18–97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41–1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk. Conclusions: Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.


2019 ◽  
Vol 74 (12) ◽  
pp. 1903-1909 ◽  
Author(s):  
Meredith L Wallace ◽  
Daniel J Buysse ◽  
Susan Redline ◽  
Katie L Stone ◽  
Kristine Ensrud ◽  
...  

Abstract Background Sleep characteristics related to duration, timing, continuity, and sleepiness are associated with mortality in older adults, but rarely considered in health recommendations. We applied machine learning to: (i) establish the predictive ability of a multidimensional self-reported sleep domain for all-cause and cardiovascular mortality in older adults relative to other established risk factors and (ii) to identify which sleep characteristics are most predictive. Methods The analytic sample includes N = 8,668 older adults (54% female) aged 65–99 years with self-reported sleep characterization and longitudinal follow-up (≤15.5 years), aggregated from three epidemiological cohorts. We used variable importance (VIMP) metrics from a random survival forest to rank the predictive abilities of 47 measures and domains to which they belong. VIMPs > 0 indicate predictive variables/domains. Results Multidimensional sleep was a significant predictor of all-cause (VIMP [99.9% confidence interval {CI}] = 0.94 [0.60, 1.29]) and cardiovascular (1.98 [1.31, 2.64]) mortality. For all-cause mortality, it ranked below that of the sociodemographic (3.94 [3.02, 4.87]), physical health (3.79 [3.01, 4.57]), and medication (1.33 [0.94, 1.73]) domains but above that of the health behaviors domain (0.22 [0.06, 0.38]). The domains were ranked similarly for cardiovascular mortality. The most predictive individual sleep characteristics across outcomes were time in bed, hours spent napping, and wake-up time. Conclusion Multidimensional sleep is an important predictor of mortality that should be considered among other more routinely used predictors. Future research should develop tools for measuring multidimensional sleep—especially those incorporating time in bed, napping, and timing—and test mechanistic pathways through which these characteristics relate to mortality.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 591-591
Author(s):  
Girindra Raval ◽  
Anuj Mahindra ◽  
Xiaobo Zhong ◽  
Ruta Brazauskas ◽  
Robert Peter Gale ◽  
...  

Abstract Abstract 591 Background: Survival of patients with MM has improved over the past two decades, in part due to the use of AHCT. Increasingly, second primary malignancies (SPMs) are observed in MM survivors. Determining the baseline incidence and risk factors associated with SPMs after AHCT is important to assess risk and to evaluate the risk-benefit ratio of newer therapies. Methods: We analyzed the incidence of SPMs in 3784 MM patients receiving (“upfront”) AHCT for MM within 18 months of diagnosis between 1990 and 2010 and reported to the CIBMTR. Cumulative incidence rates of SPMs were estimated taking into account the competing risk of death. For each transplant recipient, the number of person-years at risk was calculated from the date of transplantation until date of last contact, death, or diagnosis of SPM, whichever occurred first. Incidence rates for all invasive cancers in the general population were obtained from the SEER database. Age-, sex-, and race- specific incidence rates for overall SPMs and particular anatomical sites were applied to the appropriate person-years at risk to compute the expected numbers of cancers. Observed–to –expected (O/E) ratios were calculated, and Poisson distribution 99% confidence intervals (CIs) were generated. Poisson regression model was used to analyze risk factors for overall SPMs and AML/MDS. Results: Pre-transplant therapy included novel agents in 56% including thalidomide (35%), lenalidomide (9%), bortezomib (16%) or their combinations (11%). Majority (80%) received high dose melphalan conditioning. Post-transplant maintenance therapy included thalidomide (16%), lenalidomide (8%), bortezomib (9%) and interferon (6%). Median follow-up of survivors was 52 months (range 3 to 192 months).With 12707 person years of follow up, 153 new malignancies were reported with a crude rate of 1.2 SPM per 100 person years of follow up. Observed/Expected [O/E] ratio for all SPMs was 0.99 (99% CI, 0.80–1.22). Cumulative incidence of SPM overall was 2.48% (95% CI, 1.96–3.05) at 3 years and 6.0% (95% CI, 4.96–7.10) at 7 years [Figure 1]. Individual SPMs observed significantly more frequently than expected are summarized in Table 1. The cumulative incidence of MDS/AML was 0.5% (95% CI, 0.28–0.78) at 3 years and 1.3 (95% CI, 0.85– 1.9%) at 7 years. Majority had MM progression prior to diagnosis of SPM (65 of 102 patients overall and 15 of 23 patients for MDS/AML). In multivariate analysis, significant risk factors for development of SPMs included: obesity [Hazard ratio = HR 1.89(95%CI, 1.21–2.93), p=0.0047 for BMI>30 vs. BMI<25], older age: [HR10.53 (95%CI, 1.46–75.82), p=0.0195] for 60–69 year olds and HR14.4 (95%CI, 1.89–109.75), p=0.01 for 70+ year olds compared to the 18–39 year old group. Specific conditioning regimens did not correlate with the risk of SPM. The low number of MDS/AML (33 events out of 3784 cases) limited the power of multivariate analysis. Increasing age was significantly associated with development of MDS (HR10.77, (95%CI,92.09–55.51), p=0.004 for 70+ year old vs. 40–49 year olds). Conclusion: In this large cohort of AHCT recipients for MM, the incidence of MDS/AML, melanoma and other skin cancers was significantly higher compared to age and sex matched general population. However the overall risk of SPM was similar to that expected for age and sex matched population. It was also similar to the placebo arms of recent reports by McCarthy Pl et al and Attal M et al (N Engl J Med. 10; 366(19):1770–91). Lenalidomide (8%) or thalidomide maintenance (16%) used in a small subset of patients with comparatively short follow up, was not associated with risk of SPM in the analysis of the overall cohort. Disclosures: Gale: Celgene: Employment. Brandenburg:Celgene: Employment, Equity Ownership. Lonial:Millennium, Celgene, Novartis, BMS, Onyx, Merck all Consultancy. Krishnan:Celgene and Millennium: Consultancy, Speakers Bureau. Dispenzieri:Celgene and Millennium: Research Funding. Hari:Celgene: Consultancy, Honoraria.


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