Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK

Conrad, Nathalie; Verbeke, Geert; Molenberghs, Geert; Goetschalckx, Laura; Callender, Thomas; Cambridge, Geraldine; Mason, Justin C; Rahimi, Kazem; McMurray, John J.V.; Verbakel, Jan Y

doi:10.1016/s0140-6736(22)01349-6

Cited by 204 publications

(163 citation statements)

References 31 publications

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“…Inflammation is a driver of CVD pathogenesis. Since 1997, a correlation has been identified between inflammatory marker C-reactive protein (CRP) and cardiovascular risk in patients regardless of blood lipid levels (Ridker et al, 1997), and increased risk of CVD has long been noted in patients with existing inflammatory conditions like rheumatoid arthritis (RA) (Hansildaar et al, 2021;Agca et al, 2022;Conrad et al, 2022). Furthermore, although current treatments for CVD primarily aim to reduce circulating lipid levels, some of the efficacy of statins has been attributed to their antiinflammatory action (Ridker, 2009).…”

Section: Introductionmentioning

confidence: 99%

Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities

2022

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Drug repurposing is an attractive, pragmatic approach to drug discovery that has yielded success across medical fields over the years. The use of existing medicines for novel indications enables dramatically reduced development costs and timescales compared with de novo drug discovery and is therefore a promising strategy in cardiovascular disease, where new drug approvals lag significantly behind that of other fields. Extensive evidence from pre-clinical and clinical studies show that chronic inflammation is a driver of pathology in cardiovascular disease, and many efforts have been made to target cardiovascular inflammation therapeutically. This approach has been met with significant challenges however, namely off-target effects associated with broad-spectrum immunosuppression, particularly in long-term conditions such as cardiovascular disease. Nevertheless, multiple anti-inflammatory medicines have been assessed for efficacy in cardiovascular clinical trials, with most of these being repurposed from their original indications in autoimmune conditions like rheumatoid arthritis. In this review, we discuss the mixed successes of clinical trials investigating anti-inflammatory drugs in cardiovascular disease, with examples such as anti-cytokine monoclonal antibodies, colchicine, and methotrexate. Looking to the future, we highlight potential new directions for drug repurposing in cardiovascular inflammation, including the emerging concepts of drug re-engineering and chrono-pharmacology.

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Section: Introductionmentioning

confidence: 99%

Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities

2022

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“…One of the main causes of death in these patients is cardiovascular disease. The excess of cardiovascular disease in SLE patients is not fully explained by a higher prevalence of classical cardiovascular risk factors [ 2 , 3 ]. Numerous efforts have been made to understand the pathogenesis behind this phenomenon and to develop therapeutic strategies that allow adequate management of cardiovascular disease in this group [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…It appears that obesity is associated with more severe cognitive and renal involvement, alteration of the quality of life, and contributes to the enhanced cardiovascular risk in SLE patients [ 8 ]. Additionally, SLE patients exhibit a high cardiovascular risk, having up to 3 times more risk of developing cardiovascular disease than the general population [ 2 , 9 , 10 , 11 ]. Systematic reviews focused on the impact of diabetes mellitus in SLE patients were not found in scientific literature.…”

Section: Introductionmentioning

confidence: 99%

Obesity, Diabetes, and Cardiovascular Risk Burden in Systemic Lupus Erythematosus: Current Approaches and Knowledge Gaps—A Rapid Scoping Review

Hernández-Negrín

Ricci

Mancebo-Sevilla

et al. 2022

IJERPH

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Obesity, diabetes mellitus, and cardiovascular risk are real challenges in systemic lupus erythematosus (SLE) clinical practice and research. The evidence of the burden of these health problems in SLE patients is determined by the methods used to assess them. Therefore, the aim of this scoping review is to map current approaches in assessing obesity, diabetes mellitus, and cardiovascular risk burden in SLE patients and to identify existing knowledge gaps in this field. This rapid scoping review was conducted according to the Joanna Briggs Institute methodology and identified 274 articles, of which 73 were included. Most studies were conducted at European institutions and patients were recruited from specialist hospital clinics, the majority of whom were women. The burden of obesity and diabetes mellitus for SLE patients was assessed mainly in terms of prevalence, impact on disease activity, and cardiometabolic risk. The burden of cardiovascular risk was assessed using multiple approaches, mainly imaging and laboratory methods, and risk factor-based scores, although there is great heterogeneity and uncertainty between the methods used. This review highlights the importance of improving and standardizing the approach to obesity, diabetes, and cardiovascular risk in SLE patients through a holistic assessment that includes lifestyle, clinical, biological, and social aspects.

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“…Cardiovascular diseases (CVDs) are mostly to blame for the elevated risk of early mortality in RA patients. Previous researches have demonstrated that RA patients are up to two times more likely to developed CVDs than the general population [ 2 ], including 2.0-fold risk of myocardial infarction, 1.7-fold risk of congestive heart failure, and 2.0-fold risk of venous thrombotic disease [ 3 , 4 ]. The European League Against Rheumatism (EULAR) suggests that RA patients should be estimated for CVD risk by using the risk score developed and validated in the general population [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…If we used the prediction score algorithms developed in generals, which only included the traditional risk factors, to estimate the CVD risk in RA patients, it would definitely underestimate the CVD risk in RA [ 7 ]. By taking the independent effect of RA on CVD risk into account [ 2 ], the EULAR guideline suggests that the 10-year CVD risk estimates for RA patients should be 1.5-fold of the risk score calculated by the predictive model developed in the general population [ 5 ]. Even so, it has been claimed that using this multiplication factor did not reclassify as many patients as was anticipated into a more appropriate risk category [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence and influence of hypouricemia on cardiovascular diseases in patients with rheumatoid arthritis

Zou

Zhu

et al. 2022

Eur J Med Res

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Background Serum uric acid (SUA) acts as an antioxidant and abnormally low SUA may raise the risk of developing atherosclerotic disorders. There is a U-shaped association between SUA with cardiovascular diseases (CVDs) in general population. However, the prevalence of hypouricemia and its influence on CVDs in rheumatoid arthritis (RA) remains unclear. Methods This cross-sectional study collected clinical data from a Chinese RA cohort. Hypouricemia was defined as SUA ≤ 3.0 mg/dL, and hyperuricemia was defined as SUA ≥ 7.0 mg/dL. CVDs were defined as a history of angina pectoris, myocardial infarction, heart failure, stroke and peripheral arterial disease. Restricted cubic spline regression and logistic regression analysis were conducted to evaluate the associations between SUA levels and CVDs. Results Among 1130 RA patients recruited, the mean age was 53.2 years and 79.0% were female. The prevalence of hypouricemia and hyperuricemia were 10.6% and 12.0%, respectively. RA patients with hyperuricemia had a higher rate of CVDs than normouricemic patients (27.9% vs. 7.1%, P < 0.05). Surprisingly, RA patients with hypouricemia also had a higher rate of CVDs (20.7% vs. 7.1%, P < 0.05) even without higher traditional cardiovascular risk factors. A U-shaped association between SUA levels and total CVDs was found (Pnon-linear < 0.001). Multivariate logistic regression analysis revealed that compared with normouricemia, both hypouricemia [adjusted OR (AOR) = 4.707, 95% CI 2.570–8.620] and hyperuricemia (AOR = 3.707, 95% CI 2.174–6.321) were associated with higher risk of CVDs. Conclusions Hypouricemia may be a potential risk factor of CVDs in RA patients

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Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK

Cited by 204 publications

References 31 publications

Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities

Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities

Obesity, Diabetes, and Cardiovascular Risk Burden in Systemic Lupus Erythematosus: Current Approaches and Knowledge Gaps—A Rapid Scoping Review

Prevalence and influence of hypouricemia on cardiovascular diseases in patients with rheumatoid arthritis

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