scholarly journals Cardiac Dysfunction in Rheumatoid Arthritis: The Role of Inflammation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 881
Author(s):  
Jianmin Chen ◽  
Lucy V. Norling ◽  
Dianne Cooper

Rheumatoid arthritis is a chronic, systemic inflammatory disease that carries an increased risk of mortality due to cardiovascular disease. The link between inflammation and atherosclerotic disease is clear; however, recent evidence suggests that inflammation may also play a role in the development of nonischemic heart disease in rheumatoid arthritis (RA) patients. We consider here the link between inflammation and cardiovascular disease in the RA community with a focus on heart failure with preserved ejection fraction. The effect of current anti-inflammatory therapeutics, used to treat RA patients, on cardiovascular disease are discussed as well as whether targeting resolution of inflammation might offer an alternative strategy for tempering inflammation and subsequent inflammation-driven comorbidities in RA.

Author(s):  
Paddy Ssentongo ◽  
Anna E. Ssentongo ◽  
Emily S. Heilbrunn ◽  
Djibril M Ba ◽  
Vernon M. Chinchilli

Background Exploring the association of coronavirus-2019 disease (COVID-19) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic to optimize survival. The objective of this systematic review and meta-analysis is to explore the association of pre-existing conditions with COVID-19 mortality. Methods We searched MEDLINE, OVID databases, SCOPUS, and medrxiv.org for the period December 1, 2019, to May 1, 2020. The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing conditions. Comorbidities explored were cardiovascular diseases (coronary artery disease, hypertension, cardiac arrhythmias, and congestive heart failure), chronic obstructive pulmonary disease, type 2 diabetes, cancer, chronic kidney disease, chronic liver disease, and stroke. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. Results Ten chronic conditions from 19 studies were included in the meta-analysis (n = 61,455 patients with COVID-19; mean age, 61 years; 57% male). Overall the between-study study heterogeneity was medium and studies had low publication bias and high quality. Coronary heart disease, hypertension, congestive heart failure, and cancer significantly increased the risk of mortality from COVID-19. The risk of mortality from COVID-19 in patients with coronary heart disease was 2.4 times as high as those without coronary heart disease (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension as high as that compared to those without hypertension (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer also were at twice the risk of mortality from COVID-19 compared to those without cancer (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure were at 2.5 times the risk of mortality compared to those without congestive heart failure (RR=2.66, 95%CI 1.58-4.48, n=3). Conclusions COVID-19 patients with all any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer have an increased risk of mortality. Tailored infection prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Elizabeth J Bell ◽  
Jennifer L St. Sauver ◽  
Veronique L Roger ◽  
Nicholas B Larson ◽  
Hongfang Liu ◽  
...  

Introduction: Proton pump inhibitors (PPIs) are used by an estimated 29 million Americans. PPIs increase the levels of asymmetrical dimethylarginine, a known risk factor for cardiovascular disease (CVD). Data from a select population of patients with CVD suggest that PPI use is associated with an increased risk of stroke, heart failure, and coronary heart disease. The impact of PPI use on incident CVD is largely unknown in the general population. Hypothesis: We hypothesized that PPI users have a higher risk of incident total CVD, coronary heart disease, stroke, and heart failure compared to nonusers. To demonstrate specificity of association, we additionally hypothesized that there is not an association between use of H 2 -blockers - another commonly used class of medications with similar indications as PPIs - and CVD. Methods: We used the Rochester Epidemiology Project’s medical records-linkage system to identify all residents of Olmsted County, MN on our baseline date of January 1, 2004 (N=140217). We excluded persons who did not grant permission for their records to be used for research, were <18 years old, had a history of CVD, had missing data for any variable included in our model, or had evidence of PPI use within the previous year.We followed our final cohort (N=58175) for up to 12 years. The administrative censoring date for CVD was 1/20/2014, for coronary heart disease was 8/3/2016, for stroke was 9/9/2016, and for heart failure was 1/20/2014. Time-varying PPI ever-use was ascertained using 1) natural language processing to capture unstructured text from the electronic health record, and 2) outpatient prescriptions. An incident CVD event was defined as the first occurrence of 1) validated heart failure, 2) validated coronary heart disease, or 3) stroke, defined using diagnostic codes only. As a secondary analysis, we calculated the association between time-varying H 2 -blocker ever-use and CVD among persons not using H 2 -blockers at baseline. Results: After adjustment for age, sex, race, education, hypertension, hyperlipidemia, diabetes, and body-mass-index, PPI use was associated with an approximately 50% higher risk of CVD (hazard ratio [95% CI]: 1.51 [1.37-1.67]; 2187 CVD events), stroke (hazard ratio [95% CI]: 1.49 [1.35-1.65]; 1928 stroke events), and heart failure (hazard ratio [95% CI]: 1.56 [1.23-1.97]; 353 heart failure events) compared to nonusers. Users of PPIs had a 35% greater risk of coronary heart disease than nonusers (95% CI: 1.13-1.61; 626 coronary heart disease events). Use of H 2 -blockers was also associated with a higher risk of CVD (adjusted hazard ratio [95% CI]: 1.23 [1.08-1.41]; 2331 CVD events). Conclusions: PPI use is associated with a higher risk of CVD, coronary heart disease, stroke and heart failure. Use of a drug with no known cardiac toxicity - H 2 -blockers - was also associated with a greater risk of CVD, warranting further study.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Vitor M Rocha ◽  
Maria Guadalupe B Pippa

Backgroung: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, that appear to be responsible for 50% of mortality for thrombotic events such as Myocardial Infarction (MI) and Ischemic Stroke (SI) in RA patients. Occur approximately a decade earlier in these patients compared with the normal population. Objectives: To determine the risk of developing cardiovascular disease in patients with Rheumatoid Arthritis according to the classification criteria of the American College of Rheumatology. Methods: To assess the risk of cardiovascular diseases we studied 78 patients diagnosed with Rheumatoid Arthritis. For this we used the criteria of the risk score of Acute Coronary Disease in 10 years according to the Framingham Heart Study. A control group consisted of 21 patients with osteoarthritis and fibromyalgia was also assessed using the same criteria, where age, sex, systolic blood pressure values, total cholesterol, cholesterol HDL, presence of smoking and diagnosis of diabetes, were scored. Results: Patients with rheumatoid arthritis had a mean disease duration of 12.8 years (SD=7.4), age 58.6 years (SD=10.3) and the control group 59.3 years (SD=10,0). The old values of total cholesterol, HDL, blood pressure and being with Diabetes Mellitus showed positive correlations with the Cardiovascular Risk, and Blood Pressure in the index this correlation was stronger (r=+0.593) in Rheumatoid Arthritis and age (r=+0.702) in the control group. The Global Cardiovascular Risk in each group were considered low (7,8 points to Rematoid Artrhrits and 9,3 points to the control group). Conclusion: The results showed no increased risk of cardiovascular disease when compared to control group. Remember that control group fact be constituted by a larger number of diabetics, which likely impact these results.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marie Jakobsen ◽  
Christophe Kolodziejczyk ◽  
Morten Sall Jensen ◽  
Peter Bo Poulsen ◽  
Humma Khan ◽  
...  

Abstract Background There is increasing concern about cardiovascular disease (CVD) after breast cancer (BC). The aim of this study was to estimate the prevalence of different types of CVD in women diagnosed with BC compared to cancer-free controls as well as the incidence of CVD after BC diagnosis. Methods We performed a cohort study based on data from national registries covering the entire Danish population. We followed 16,505 cancer-naïve BC patients diagnosed from 2003 to 2007 5 years before and up to 10 years after BC diagnosis compared to 165,042 cancer-free controls. Results We found that 15.6% of BC patients were registered with at least one CVD diagnosis in hospital records before BC diagnosis. Overall, BC patients and controls were similar with regard to CVD comorbidity before BC diagnosis. After BC diagnosis, the incidence of all CVD diagnoses combined was significantly higher in BC patients than controls up to approximately 6 years after the index date (BC diagnosis). After 10 years, 28% of both BC patients and controls (without any CVD diagnosis up to 5 years before the index date) had at least one CVD diagnosis according to hospital records. However, the incidence of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism remained higher in BC patients than controls during the entire 10-year follow-up period. After 10 years, 2.7% of BC patients compared to 2.5% of controls were diagnosed with heart failure, 2.7% of BC patients compared to 1.5% of controls were diagnosed with thrombophlebitis/thrombosis, and 1.5% of BC patients compared to 1.0% of controls were diagnosed with pulmonary heart disease according to hospital records. Furthermore, we found that the risk of heart failure and thrombophlebitis/thrombosis was higher after chemotherapy. Conclusions Focus on CVD in BC patients is important to ensure optimum treatment with regard to BC as well as possible CVD. Strategies to minimise and manage the increased risk of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism in BC patients are especially important.


Author(s):  
Rajeev Malhotra ◽  
Christopher J. Nicholson ◽  
Dongyu Wang ◽  
Vijeta Bhambhani ◽  
Samantha Paniagua ◽  
...  

Objective: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction. MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp +/− mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident heart failure with preserved ejection fraction. Aortic PWV was increased in older, but not young, female Mgp +/− mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. Conclusions: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future heart failure with preserved ejection fraction in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in heart failure with preserved ejection fraction.


2021 ◽  
Author(s):  
Dasan Mary Cibi ◽  
Reddemma Sandireddy ◽  
Hanumakumar Bogireddy ◽  
Nicole Tee ◽  
Siti Aishah Binte Abdul Ghani ◽  
...  

Diabetes patients have an increased risk of heart failure (HF). Diabetes is highly prevalent in HF with preserved ejection fraction (HFpEF), which is on the rise worldwide. The role of diabetes in HF is less established and available treatments of HF are not effective in HFpEF patients. Tissue factor (TF), a transmembrane receptor, plays an important role in immune-cell inflammation and atherothrombosis in diabetes. However, its role in diabetes-induced cardiac inflammation, hypertrophy, and HF has not been studied. Here, we have utilized Wildtype (WT), heterozygous, and Low-TF (with 1% human TF) mice to determine TF’s role in <i>Type1 diabetes</i>-induced HF. We found significant upregulation of cardiac TF mRNA and protein levels in diabetic WT hearts compared to non-diabetic controls. WT diabetic hearts also exhibited increased inflammation and cardiac hypertrophy versus controls. However, these changes in cardiac inflammation and hypertrophy were not found in diabetic Low-TF mice compared to their non-diabetic controls. TF deficiency was also associated with improved cardiac function parameters suggestive of HFpEF, which was evident in diabetic WT mice. The TF regulation of inflammation and cardiac remodeling was further dependent on downstream ERK1/2 and STAT3 pathways. In summary, our study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HF with preserved ejection fraction.


Author(s):  
Hao Chen ◽  
Michael Chhor ◽  
Benjamin Rayner ◽  
Kristine McGrath ◽  
Lana McClements

ABSTRACTAimsCirculating biomarkers are commonly used in diagnosis and prognosis of heart failure with preserved ejection fraction (HFpEF) in clinical practice. However, the diagnostic and prognostic potential of current biomarkers in HFpEF remain unclear.Methods and resultsWe conducted a search of the PubMed, Web of Science, MEDLINE and SCOPUS (1900 to January 2020) databases of all diagnostic (n=1,104) and prognostic (n=53,497) biomarkers investigated in people with HFpEF. B-type natriuretic peptide (BNP) displayed satisfactory sensitivity (0.81, 95% CI: 0.76 to 0.85; I2=0) and specificity (0.86, 95% CI: 0.82 to 0.89; I2=16.9%) for the diagnosis of HFpEF. Natriuretic peptides (NPs), including N-terminal pro BNP (NT-proBNP) and BNP, were associated with over two-fold increased risk of mortality (NT-proBNP: HR=2.27, 95% CI: 1.69 to 3.06, I2=87.6%; BNP: HR=3.01, 95% CI: 1.27 to 7.21, I2=97.2%), hospitalisation (NT-proBNP: HR=3.54, 95% CI: 2.83 to 4.43, I2=83.4%), and a composite event of both (NT-proBNP: HR=2.55, 95% CI: 2.13 to 3.05, I2=78.1%; BNP: HR=2.28, 95% CI: 1.42 to 3.69, I2=75.8%) in people with HFpEF. Interestingly, Galectin-3 (Gal-3) (sensitivity: 0.70, 95% CI: 0.63 to 0.75, I2=86.7%; specificity: 0.78, 95% CI: 0.69 to 0.85, I2=68.6%) and soluble suppression of tumorigenicity 2 (sST2) (sensitivity: 0.58, 95% CI: 0.52 to 0.64, I2=88.1%; specificity: 0.59, 95% CI: 0.49 to 0.68, I2=69.5%) showed limited diagnostic potential of HFpEF.ConclusionAmongst currently available biomarkers, BNP remains the most reliable diagnostic marker of HFpEF. Although there was high heterogeneity between the studies included, BNP or NT-proBNP could also have promising prognostic potential in HFpEF.


2019 ◽  
Vol 24 (46) ◽  
pp. 5525-5527 ◽  
Author(s):  
Achilleas Papagiannis ◽  
Stelina Alkagiet ◽  
Konstantinos Tziomalos

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with increased risk for hospitalization and all-cause mortality. Currently, there is no established treatment to improve the survival of these patients. Aldosterone appears to play a role in the pathogenesis of HFpEF. Objective: To discuss the findings of studies that evaluated the effects of mineralocorticoid receptor (MR) antagonists on the outcome of patients with HFpEF. Methods: PubMed was searched for relevant papers. References of retrieved articles were also evaluated for pertinent material. Results: Accumulating data suggest that MR antagonists might be useful in the management of patients with HFpEF. However, existing evidence is limited and conflicting. Conclusions: More studies are needed to clearly define the therapeutic potential of MR antagonists in HFpEF. Given the heterogeneity of this disease and the low specificity of the criteria used for its diagnosis, it is also important to improve the definition of HFpEF and include appropriately selected patients in these studies.


2019 ◽  
Vol 19 (4) ◽  
pp. 330-338
Author(s):  
Anne Vinggaard Christensen ◽  
Jakob Bue Bjorner ◽  
Ola Ekholm ◽  
Knud Juel ◽  
Lars Thrysoee ◽  
...  

Background: The SF-12v2 health survey (SF-12) is widely used as a generic measure of health-related quality of life. However, interpretation of score differences can be difficult. Aim: To estimate benchmarks for interpretation of score differences on the SF-12 for readmission and all-cause mortality in cardiac patients. Methods: Data from the DenHeart study, a national cross-sectional survey including one year follow-up register data, were used. Patients with ischaemic heart disease, arrhythmia, heart failure and heart valve disease answered the survey at hospital discharge. Cox proportional hazards models were used to regress readmission and all-cause mortality. Results: A total of 10,813 cardiac patients completed the SF-12. For patients with ischaemic heart disease and arrhythmia, a one point lower physical component summary score was associated with a 2% increase in risk in readmission (hazard ratio (HR) 1.022 (95% confidence interval 1.017;1.027) and HR 1.024 (1.018; 1.029), respectively) and a 3% increase in risk for patients with heart failure (HR 1.027 (1.015; 1.038)). A one point lower mental component summary score was associated with a 2% increase in the risk of readmission (HR 1.017 (1.013; 1.022)) across diagnoses. For both the physical and mental component summary score, a one point lower score meant a 5% increase in the risk of all-cause mortality (HR 1.046 (1.031; 1.060) and HR 1.046 (1.029; 1.065), respectively) across diagnoses. Conclusion: In a large group of cardiac patients, a one point lower physical or mental component summary score was associated with an up to 3% increased risk of readmission and a 5% increased risk of mortality in the first year after discharge.


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