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Journal ArticleDOI

Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease

TL;DR: In patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD, however, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor.
Abstract: Introduction Rheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown. Objective We aimed to estimate the impact of RA on the risk of adverse cardiovascular events in patients with and without CAD. Methods A population-based cohort of patients registered in the Western Denmark Heart Registry, who underwent coronary angiography (CAG) between 2003 and 2016, was stratified according to the presence of RA and CAD. Endpoints were myocardial infarction (MI), major adverse cardiovascular events (MACE; MI, ischaemic stroke and cardiac death) and all-cause mortality. Results A total of 125 331 patients were included (RA: n=1732). Median follow-up was 5.2 years. Using patients with neither RA nor CAD as reference (cumulative MI incidence 2.7%), the 10-year risk of MI was increased for patients with RA alone (3.8%; adjusted incidence rate ratio (IRRadj) 1.63, 95% CI 1.04 to 2.54), for patients with CAD alone (9.9%; IRRadj 3.35, 95% CI 3.10 to 3.62), and highest for patients with both RA and CAD (12.2%; IRRadj 4.53, 95% CI 3.66 to 5.59). Similar associations were observed for MACE an all-cause mortality. Conclusions In patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD. However, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor. Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalised treatment strategies
Citations
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Journal ArticleDOI
TL;DR: In this article, a review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with rheumatoid arthritis.
Abstract: Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA.

17 citations

Journal ArticleDOI
23 Nov 2020-BMJ Open
TL;DR: Those with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study.
Abstract: Objective To investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA). Design Population-based longitudinal cohort study. Setting UK Biobank. Participants UK Biobank participants (n=502 533) aged between 37 and 73 years old. Primary outcome measures Primary outcome measures were risk of all-cause mortality and MACE. Methods We examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox’s proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor. Results 75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports. Conclusion Those with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.

17 citations

Journal ArticleDOI
TL;DR: To assess the causality of the associations of rheumatoid arthritis with coronary artery disease (CAD) and stroke using the Mendelian randomization approach, a large number of patients with RA were diagnosed with at least some form of arthritis.
Abstract: To assess the causality of the associations of rheumatoid arthritis (RA) with coronary artery disease (CAD) and stroke using the Mendelian randomization approach.

5 citations

Journal ArticleDOI
TL;DR: In this paper, the effect of chloroquine and Hydroxychloroquine on QTc-interval and incidence of sudden cardiac death (SCD) was investigated, and the association was dose-dependent.
Abstract: Aims: Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD). Methods We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexpected and sudden death due to cardiac arrhythmia within one hour of the onset of acute symptoms, and in patients without cardiac symptoms within 24 hours before death. Results Among the study population of 14 594 individuals (58.8% women) with an average age of 65 years, 346 patients used [hydroxy]chloroquine at any time during follow-up. The total number of SCD cases was 609. In a multiple linear mixed model analysis, the current use of [hydroxy]chloroquine was associated with a significantly increased duration of the QTc-interval of 8.1 ms (95% CI: 3.6; 12.6) compared with non-users. The association was stronger among current-high daily dosage [15.3 (95%CI: 7.0; 23.6)] compared with current-low daily dosage [5.5 (95%CI: 0.4; 10.7)] users. In a Cox proportional hazard regression analysis, the risk of SCD was significantly higher in participants who were current users of [hydroxy]chloroquine than in non-users [adjusted hazard ratio; 3.7 (95%CI: 1.1; 12.6)]. Conclusions In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.

5 citations

Journal ArticleDOI
28 Sep 2021
TL;DR: A review of the possible mechanisms of sudden cardiac death in systemic sclerosis and their current understanding of how each of these mechanisms may contribute to cardiac death can be found in this article, highlighting the need for a future research agenda that addresses the underlying epidemiology of SCD in SSc and identifies opportunities for intervention to modify the disease course of heart disease.
Abstract: Cardiac disease is a leading cause of death in systemic sclerosis (SSc) and sudden cardiac death (SCD) is thought to occur more commonly in SSc than in the general population. Diffuse myocardial fibrosis, myocarditis and ischaemic heart disease are all prevalent in SSc and can be reasonably hypothesised to contribute to an increased risk of SCD. Despite this, SCD remains a relatively understudied area of SSc with little understood about SSc-specific risk factors and opportunities for primary prevention. In this review, we present an overview of the possible mechanisms of SCD in SSc and our current understanding of how each of these mechanisms may contribute to cardiac death. This review highlights the need for a future research agenda that addresses the underlying epidemiology of SCD in SSc and identifies opportunities for intervention to modify the disease course of heart disease in SSc.

4 citations

References
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Journal ArticleDOI
TL;DR: Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100, and the method is illustrated with two data sets.
Abstract: Relative risk is usually the parameter of interest in epidemiologic and medical studies. In this paper, the author proposes a modified Poisson regression approach (i.e., Poisson regression with a robust error variance) to estimate this effect measure directly. A simple 2-by-2 table is used to justify the validity of this approach. Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100. The method is illustrated with two data sets.

7,045 citations

Journal ArticleDOI
TL;DR: The principles of the method and how to impute categorical and quantitative variables, including skewed variables, are described and shown and the practical analysis of multiply imputed data is described, including model building and model checking.
Abstract: Multiple imputation by chained equations is a flexible and practical approach to handling missing data. We describe the principles of the method and show how to impute categorical and quantitative variables, including skewed variables. We give guidance on how to specify the imputation model and how many imputations are needed. We describe the practical analysis of multiply imputed data, including model building and model checking. We stress the limitations of the method and discuss the possible pitfalls. We illustrate the ideas using a data set in mental health, giving Stata code fragments. Copyright © 2010 John Wiley & Sons, Ltd.

6,349 citations

Journal ArticleDOI
TL;DR: Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid‐level lowering.
Abstract: BackgroundExperimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. MethodsWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. ResultsAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in t...

5,660 citations

Journal ArticleDOI
TL;DR: The Danish Civil Registration System (CRS) in connection with other registers and biobanks will continue to provide the basis for significant knowledge relevant to the aetiological understanding and possible prevention of human diseases.
Abstract: Introduction: The Danish Civil Registration System (CRS) was established in 1968, and all persons alive and living in Denmark were registered for administrative use. Content: CRS includes individual information on the unique personal identification number, name, gender, date of birth, place of birth, citizenship, identity of parents and continuously updated information on vital status, place of residence and spouses. Validity and coverage: Since 1968, CRS has recorded current and historical information on all persons living in Denmark. Among persons born in Denmark in 1960 or later it contains complete information on maternal identity. For women born in Denmark in April 1935 or later it contains complete information on all their children. CRS contains complete information on immigrations and emigrations from 1969 onwards, permanent residence in a Danish municipality from 1971 onwards, and full address in Denmark from 1977 onwards. Conclusion: CRS in connection with other registers and biobanks will continue to provide the basis for significant knowledge relevant to the aetiological understanding and possible prevention of human diseases.

3,724 citations

Journal ArticleDOI
TL;DR: The Danish National Patient Registry is a valuable tool for epidemiological research, however, both its strengths and limitations must be considered when interpreting research results, and continuous validation of its clinical data is essential.
Abstract: Background The Danish National Patient Registry (DNPR) is one of the world’s oldest nationwide hospital registries and is used extensively for research. Many studies have validated algorithms for identifying health events in the DNPR, but the reports are fragmented and no overview exists.

2,818 citations

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