scholarly journals Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies

2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

2021 ◽  
pp. postgradmedj-2021-139839
Author(s):  
Ione Swanepoel ◽  
April Roberts ◽  
Chelsea Brauns ◽  
Devahuti R Chaliha ◽  
Veronica Papa ◽  
...  

Cardiovascular disease (CVD) is one of the greatest disease burdens and takes the lives of many each year. There are many risk factors both modifiable and non-modifiable which contribute to the onset and progression of the disease. Trimethylamine N-oxide (TMAO) in recent years has been found to have a correlation with CVD onset. Those with increased levels of the metabolite have a markedly increased risk of future development of cardiometabolic disorders.This literature review aimed to critique past studies undertaken to find a consensus of the significance of the interrelationship between TMAO and cardiovascular risk. A definite link between TMAO levels and a CVD outcome was found. The majority of the literature stated the relationship with evidence; however, there is still some uncertainty as to why and how the correlation occurs. Further study needs to be done to further dissect and understand the relationship between TMAO and CVD risk.


2020 ◽  
Vol 18 (5) ◽  
pp. 431-446 ◽  
Author(s):  
George E. Fragoulis ◽  
Ismini Panayotidis ◽  
Elena Nikiphorou

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.


2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Romona D. Govender ◽  
Saif Al-Shamsi ◽  
Elpidoforos S. Soteriades ◽  
Dybesh Regmi

Abstract Background Individuals with established cardiovascular disease (CVD) and risk factors such as age, smoking, hypertension, and diabetes mellitus are at an increased risk of recurrent cardiovascular events and death. The incidence rate of recurrent CVD events varies between countries and populations. The United Arab Emirates (UAE) has one of the highest age-standardized death rates for CVD worldwide. The aim of our study was to estimate the incidence rates and determine the predictors of recurrent CVD events among UAE nationals. Methods We investigated an outpatient-based cohort of patients with a history of CVD visiting Tawam Hospital between April 1, 2008 and December 31, 2008. They were followed-up until July 31, 2018. Univariable and multivariable Cox proportional hazards regression models were used to determine the association between major CVD risk factors and the risk of CVD recurrence. Results A total of 216 patients (167 males, 49 females) with a history of CVD were included. They were followed for a median (interquartile range) of 8.1 (5.5–9.3) years, with a total of 1184 patient-years of follow-up. The overall incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. The 8-year cumulative incidence was 73.7%. Age, female sex, and diabetes mellitus were significant predictors of recurrent CVD events, where females had a 1.96 times higher risk of recurrent CVD events than males. Conclusion Significant predictors of recurrent CVD events are older age, female sex, and diabetes mellitus. The incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. Preventive measures, based on international guidelines for CVD management, may improve CVD morbidity and mortality in the UAE population.


2020 ◽  
pp. bjophthalmol-2019-315333
Author(s):  
Juan E Grunwald ◽  
Maxwell Pistilli ◽  
Gui-Shuang Ying ◽  
Maureen G Maguire ◽  
Ebenezer Daniel ◽  
...  

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.ConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.


2017 ◽  
Vol 44 (9) ◽  
pp. 1325-1330 ◽  
Author(s):  
Mike L.T. Berendsen ◽  
Marissa C. van Maaren ◽  
Elke E.A. Arts ◽  
Alfons A. den Broeder ◽  
Calin D. Popa ◽  
...  

Objective.To determine whether anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) are risk factors for 10-year cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).Methods.Analyses were performed using data from the Nijmegen early RA inception cohort, in which patients with newly diagnosed RA, consecutively included since 1985, were regularly followed up. Anti-CCP and RF were determined at baseline (diagnosis). Outcome was the first cardiovascular disease (CVD) event [ischemic heart disease, nonhemorrhagic cerebrovascular accident (CVA), or peripheral artery disease (PAD)] after baseline as retrieved from physician diagnosis. Fatality was checked against death certificates. Cox regression including correction for baseline confounders was performed to estimate the effect of anti-CCP, RF, and their interaction on 10-year CVD-free survival.Results.Of 929 patients included, 628 were anti-CCP–positive and 697 were RF-positive. During followup, with a median of 7.5 years, 162 CV events were observed (101 ischemic heart disease, 45 CVA, and 16 PAD), of which 15 were fatal. The HRadjusted for anti-CCP was 1.17 (95% CI 0.82–1.67) and the HRadjusted for RF was 1.52 (95% CI 1.00–2.30). The association of RF positivity with CVD was even stronger in the anti-CCP–negative patients: HRadjusted 2.09 (95% CI 1.18–3.71). There was no significant interaction (p = 0.098) between anti-CCP and RF.Conclusion.Rather than anti-CCP, presence of RF was associated with CVD in this cohort of patients with RA.


2017 ◽  
Vol 42 (3) ◽  
pp. 326-332 ◽  
Author(s):  
Parvin Mirmiran ◽  
Zahra Bahadoran ◽  
Azita Zadeh Vakili ◽  
Fereidoun Azizi

Limited data are available regarding the association of major dietary patterns and risk of cardiovascular disease (CVD) in Middle Eastern countries. We aimed to evaluate the association of major dietary patterns, using factor analysis, with the risk of CVD. Participants without CVD (n = 2284) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 4.7 years. Dietary intake of participants was assessed at baseline (2006–2008); biochemical variables were evaluated at baseline and follow-up examination. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary pattern scores. Linear regression models were used to indicate association of dietary pattern scores with changes of CVD risk factors over the study period. Two major dietary patterns, Western and traditional, were identified. During a mean 4.7 ± 1.4 years of follow-up, 57 participants experienced CVD-related events. In the fully adjusted model, we observed an increased risk of CVD-related events in the highest compared to the lowest tertile category of Western dietary pattern score (HR = 2.07, 95% CI = 1.03–4.18, P for trend = 0.01). Traditional dietary pattern was not associated with incidence of CVD or CVD risk factors. A significant association was observed between the Western dietary pattern and changes in serum insulin (β = 5.88, 95% CI = 0.34–11.4). Our findings confirm that the Western dietary pattern, characterized by higher loads of processed meats, salty snacks, sweets, and soft drinks, is a dietary risk factor for CVD in the Iranian population.


BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034145
Author(s):  
Anne B. Rohlfing ◽  
Gregory Nah ◽  
Kelli K. Ryckman ◽  
Brittney D. Snyder ◽  
Deborah Kasarek ◽  
...  

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.


2018 ◽  
Vol 24 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Peter Riis Hansen

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Aliza Hussain ◽  
VIJAY NAMBI ◽  
Elizabeth Selvin ◽  
Wensheng Sun ◽  
Kunihiro Matsushita ◽  
...  

Introduction: Cardiovascular disease (CVD) is the most common cause of death in nonalcoholic steatohepatitis (NASH). While these conditions share many cardio-metabolic risk factors including metabolic syndrome, diabetes and dyslipidemia, limited data exist on whether NASH is independently and prospectively associated with incident CVD beyond traditional risk factors. Fibrosis-4 (FIB-4) index is a scoring system based on platelet count, age, AST and ALT, shown to be comparable to magnetic resolution elastography for predicting advanced fibrosis in biopsy-proven NASH. We sought to evaluate the association of elevated FIB-4 with global CVD events and CVD mortality in the Atherosclerosis Risk in Communities (ARIC) Study Methods: We studied 5531 individuals, mean age of 76 (SD 5.2) years, 58% female, 22% black, at ARIC visit 5 (2011-2013). FIB-4 was categorized as low risk of advanced fibrosis for score <1.45, intermediate for 1.45-3.25 and high for >3.25. Cox regression was used to estimate the association of FIB-4 with time to first global CVD event (CHD, ischemic stroke or heart failure hospitalization) and CVD mortality adjusted for pooled cohort equation risk factors. Results: Over a median follow up of 6.2 (5.3-6.8) years, there were 1108 global CVD events and 457 CVD deaths. In adjusted models, compared to participants with low FIB-4 (<1.45), those with elevated FIB-4 >3.25, had significantly increased risk for global CVD events (HR 1.58, 95% CI 1.23-2.02) and CVD mortality (HR 1.70, 95% CI 1.16-2.50). Conclusions: In a large prospective cohort, presence of advanced liver fibrosis, as assessed by elevated FIB-4 index >3.25, was associated with increased risk for CVD events and CVD mortality, beyond traditional CVD risk factors. Future clinical trials of candidate medications under study for NASH should examine whether effective NASH treatment will impact CV outcomes.


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