Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism in patients with inflammatory joint disease-results from the nationwide Norwegian Cardio-rheuma registry.

AIMS: Patients with inflammatory joint diseases (IJD), including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) have increased rates of pulmonary embolism (PE). Non-steroidal anti-inflammatory drugs (NSAIDs) use is associated with PE in the general population. Our aim was to evaluate the association between NSAIDs use and PE in IJD patients. METHODS AND RESULTS: Using individual-level registry data from the whole Norwegian population, including data from the Norwegian Patient Registry and the Norwegian Prescription Database, we: (1) evaluated PE risk in IJD compared to non-IJD individuals, (2) applied the self-controlled case series method to evaluate if PE risks were associated with use of traditional NSAIDs (tNSAIDs) and selective cox-2 inhibitors (coxibs). After a one-year wash-out period, we followed 4 660 475 adults, including 74 001 with IJD (RA: 39 050, PsA: 20 803, and axSpA: 18 591) for a median of 9.0 years. Crude PE incidence rates per 1000 patient years were 2.02 in IJD and 1.01 in non-IJD individuals. Age and sex adjusted hazard ratios for PE events were 1.57 for IJD patients compared to non-IJD. Incidence rate ratios (IRR) [95% confidence interval (CI)] for PE during tNSAIDs use were 0.78 (0.64-0.94, P = 0.010) in IJD and 1.68 (1.61-1.76, P < 0.001) in non-IJD. IRR (95% CI) for PE during coxibs use was 1.75 (1.10-2.79, P = 0.018) in IJD and 2.80 (2.47-3.18, P < 0.001) for non-IJD. CONCLUSION: Pulmonary embolism rates appeared to be higher in IJD than among non-IJD subjects in our study. Traditional NSAIDs may protect against PE in IJD patients, while coxibs may associated with increased PE risk.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus ß-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Associations between cardiovascular risk factors, disease activity and cardiorespiratory fitness in patients with inflammatory joint disease: a cross-sectional analysis.

BACKGROUND: Inflammatory joint diseases (IJD) are accompanied by an increased risk of cardiovascular disease (CVD). Cardiorespiratory fitness (CRF) is a modifiable CVD risk factor and low levels of CRF associate with an elevated CVD risk. This study aimed to investigate the associations between CVD risk factors, disease activity and CRF in patients with IJD and to explore differences between patients with normal versus low levels of CRF. METHODS: CRF was measured as peak oxygen uptake (VO2peak) with a cardiopulmonary exercise test. Participants were also evaluated for: Body composition, blood pressure, blood lipids, inflammatory markers and disease activity. Patient-reported use of cigarettes/snuff, medication, disease duration, pain, fatigue, CVD history, habitual physical activity and exercise beliefs and self-efficacy were collected by questionnaire. Cross-sectional associations between CVD risk factors, disease-related factors and CRF were analyzed by multiple linear regression. CRF was categorized to normal CRF (VO2peak ≥ 80%) or low CRF (VO2peak < 80%) according to age- and gender-stratified reference data. Differences in demographic, CVD and disease-related factors between patients with normal versus low CRF were explored. RESULTS: In 60 Norwegian patients with IJD [34 females, age 59 years (IQR: 52-63)], mean VO2peak was 30.2 (± 6.9) mL/kg/min, corresponding to 83% (± 18) of normative reference values. Age (coefficient: - 0.18 years, p = 0.01) and fat mass (coefficient: - 0.67 %, p < 0.001) were inversely associated with CRF, while physical activity index (coefficient: 0.13 points, p = 0.05) was positively associated with CRF (R2 = 0.66). There were no significant associations between CRF, classical CVD risk factors and disease-related variables. Compared to patients with low CRF (n = 30), patients with normal CRF (n = 30) had higher peak oxygen uptake (+ 9.4 mL/kg/min, p < 0.001), high-density lipoprotein cholesterol (+ 0.5 mmol L-1, p < 0.001), and exercise self-efficacy (+ 6.9, p < 0.01) as well as lower fat mass (- 8.7%, p < 0.001), resting heart rate (- 8.0 beats/min, p < 0.01) and triglycerides (- 0.5 mmol L-1, p < 0.01). CONCLUSIONS: In this sample of IJD-patients, age, fatmass and physical activity level were associated with CRF. CRF was lower than reference values and patients with normal CRF presented with a more favorable health profile. There is a continued need for exercise interventions to improve CRF in patients with IJD. TRIAL REGISTRATION: NCT04922840.

Long-term cardiovascular prognosis of patients with type 1 diabetes after myocardial infarction.

BACKGROUND: To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. METHODS: Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005-2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). RESULTS: Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74-2.17; p < 0.0001). Probabilities of cardiovascular death (sHR 1.81; p < 0.0001), recurrent MI (sHR 1.91; p < 0.0001), ischemic stroke (sHR 1.50; p = 0.0003), and heart failure hospitalization (sHR 1.98; p < 0.0001) were higher in patients with type 1 diabetes. Incidence of MACE was higher in diabetes patients than in controls in subgroups of men and women, patients aged < 60 and ≥ 60 years, revascularized and non-revascularized patients, and patients with and without atrial fibrillation, heart failure, or malignancy. CONCLUSIONS: Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.

All-cause and cause-specific mortality in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: a nationwide registry study.

OBJECTIVES: To explore mortality and causes of death among Norwegian patients with RA, PsA and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study. METHODS: Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10 codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan-Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted hazard ratios (HRs) for mortality were estimated using Cox regression models. RESULTS: We identified 36 095 RA, 18 700 PsA and 16 524 axSpA patients (70%, 53% and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI: 1.41, 1.48] and HR 1.38 [95% CI: 1.28, 1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI: 1.00, 1.21] among women and 1.02 [95% CI: 0.93, 1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases. CONCLUSION: Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities.

Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Population ageing has resulted in an increasing number of older people living with chronic diseases (multimorbidity) requiring five or more medications daily (polypharmacy). Ageing produces important changes in the cardiovascular system and represents the most potent single cardiovascular risk factor. Cardiovascular diseases (CVDs) constitute the greatest burden for older people, their caregivers, and healthcare systems. Cardiovascular pharmacotherapy in older people is complex because age-related changes in body composition, organ function, homeostatic mechanisms, and comorbidities modify the pharmacokinetic and pharmacodynamic properties of many commonly used cardiovascular and non-cardiovascular drugs. Additionally, polypharmacy increases the risk of adverse drug reactions and drug interactions, which in turn can lead to increased morbi-mortality and healthcare costs. Unfortunately, evidence of drug efficacy and safety in older people with multimorbidity and polypharmacy is limited because these individuals are frequently underrepresented/excluded from clinical trials. Moreover, clinical guidelines are largely written with a single-disease focus and only occasionally address the issue of coordination of care, when and how to discontinue treatments, if required, or how to prioritize recommendations for patients with multimorbidity and polypharmacy. This review analyses the main challenges confronting healthcare professionals when prescribing in older people with CVD, multimorbidity, and polypharmacy. Our goal is to provide information that can contribute to improving drug prescribing, efficacy, and safety, as well as drug adherence and clinical outcomes.

Incidence, sociodemographic factors and treatment penetration of rheumatoid arthritis and psoriatic arthritis in Norway.

OBJECTIVES: To evaluate nationwide incidence, sociodemographic associations and treatment penetration of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in Norway. METHODS: The study combined data from nationwide registries on the total Norwegian adult population (age ≥ 18). From the Norwegian Patient Registry, incident RA and PsA cases during 2011-2015 were identified with records of first and second healthcare episodes listing RA/PsA diagnostic codes, and ≥ 1 episode in an internal medicine or rheumatology unit with RA/PsA code during the two-year period after the first episode. Dispensed DMARD prescriptions were obtained from the Norwegian Prescription Database. Persons with dispensed DMARD prescriptions or biologic DMARDs given in hospitals > 12 months before the index date were excluded. RESULTS: Incidence of RA/PsA in Norway was 42/26 per 100,000 person-years (55/28 among women and 28/23 among men). RA peak incidence was observed at ages 70-79 in both sexes, whereas the peak incidence of PsA occurred at ages 50-59. Age- and sex-standardized incidences of RA and PsA were lower among persons with higher education levels. Within a year from the index date, 82.4/57.4% of RA/PsA patients used synthetic DMARDs while 9.4/9.5% used biologic DMARDs. CONCLUSIONS: Register-based incidence estimates for RA and PsA in Norway are similar to other Nordic countries, but slightly higher than in previous Norwegian studies. Furthermore, we found that higher socioeconomic status was associated with lower incidence of both RA and PsA. Although conventional synthetic DMARDs were less often used in early PsA than RA, frequency of biologic DMARD prescriptions was comparable.

Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment.

Patients with rheumatoid arthritis (RA) are at approximately 1.5-fold risk of atherosclerotic cardiovascular disease (CVD) compared with the general population, a phenomenon resulting from combined effects of traditional CVD risk factors and systemic inflammation. Rheumatoid synovitis and unstable atherosclerotic plaques share common inflammatory mechanisms, such as expression of proinflammatory cytokines interleukin (IL)-1, tumour necrosis factor (TNF)-α and IL-6. RA patients are undertreated in terms of CVD prevention, and structured CVD prevention programmes are warranted. Alongside management of traditional risk factors, suppressing systemic inflammation with antirheumatic medication is fundamental for the reduction of CVD risk among this high-risk patient group. Many antirheumatic drugs, especially methotrexate, TNF-α-inhibitors and IL-6-inhibitors are associated with reduced risk of CVD in observational studies among RA patients, but randomised controlled trials with hard CVD endpoints are lacking. In patients without rheumatic disease, anti-inflammatory therapies targeting nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome and the IL-1/IL-6 pathway arise as potential therapies after an atherosclerotic CVD event.

How do people with rheumatoid arthritis experience participation in a smoking cessation trial: a qualitative study.

Purpose: The aim of this study was to gain more knowledge on how people with rheumatoid arthritis (RA) experienced participation in a randomized controlled trial (RCT) testing the effect of a smoking cessation intervention since this intervention have not been tested on an RA population beforeMethods: We conducted a qualitative study with semi-structured individual interviews with 12 participants from the intervention group in the RCT.Results: Through thematic analysis we identified four themes: Instilling hope for smoking cessation, referring to the initial invitation to participate in the RCT; Various components of importance in the intervention, referring to cooperation with the smoking cessation counsellor, improved carbon monoxide levels, fear of becoming addicted to nicotine replacement therapy, and suggestions for additional components in the intervention which could promote motivation; Breaking habits, referring to ongoing reflection on quitting smoking; and Increased awareness of health, arthritis and smoking, referring to the lack of information on smoking and RA from health professionals, and the impact of smoking on RA symptoms and overall health.Conclusion: The results reflect the participants' perspective on what is meaningful to them when trying to quit smoking and adds important knowledge to future smoking cessation studies in this patient group.

Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients.

OBJECTIVES: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. METHODS: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. RESULTS: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. CONCLUSION: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.

Feasibility of cardiovascular disease risk assessments in rheumatology outpatient clinics: experiences from the nationwide NOCAR project.

OBJECTIVE: The European League Against Rheumatism recommends implementing cardiovascular disease (CVD) risk assessments for patients with inflammatory joint diseases (IJDs) into clinical practice. Our goal was to design a structured programme for CVD risk assessments to be implemented into routine rheumatology outpatient clinic visits. METHODS: The NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR) started in April 2014 as a quality assurance project including 11 Norwegian rheumatology clinics. CVD risk factors were recorded by adding lipids to routine laboratory tests, self-reporting of CVD risk factors and blood pressure measurements along with the clinical joint examination. The patients' CVD risks, calculated by the European CVD risk equation SCORE, were evaluated by the rheumatologist. Patients with high or very high CVD risk were referred to their primary care physician for initiation of CVD preventive measures. RESULTS: Data collection (autumn 2015) showed that five of the NOCAR centres had implemented CVD risk assessments. There were 8789 patients eligible for CVD risk evaluation (rheumatoid arthritis (RA), 4483; ankylosing spondylitis (AS), 1663; psoriatic arthritis (PsA), 1928; unspecified and other forms of spondyloarthropathies (SpA), 715) of whom 41.4 % received a CVD risk assessment (RA, 44.7%; AS, 43.4%; PsA, 36.3%; SpA, 30.6%). Considerable differences existed in the proportions of patients receiving CVD risk evaluations across the NOCAR centres. CONCLUSION: Patients with IJD represent a patient group with a high CVD burden that seldom undergoes CVD risk assessments. The NOCAR project lifted the offer of CVD risk evaluation to over 40% in this high-risk patient population.

Change in cardiovascular risk factors in patients who develop psoriatic arthritis: longitudinal data from the Nord-Trøndelag Health Study (HUNT).

OBJECTIVES: The aim of this population-based study was to compare changes in cardiovascular (CV) risk factors over a decade-long period in patients who developed psoriatic arthritis (PsA) and the background population. METHODS: Patients diagnosed with PsA (n=151) between 1998 and 2008 and matched controls (n=755) who participated in both the Nord-Trøndelag Health Study (HUNT) 2 (1995-1997) and HUNT3 (2006-2008) were included. Mixed linear and logistic models were used to analyse the difference in mean change between HUNT2 and HUNT3 in patients and controls for body mass index (BMI), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and blood pressure (BP). RESULTS: At baseline (HUNT2), the patients who developed PsA compared with controls had higher BMI (27.2 vs 25.9 kg/m2, p<0.001) and lower HDL-c (1.32 vs 1.40 mmol/L, p<0.03) and more were smokers (41.1 vs 28.5%, p<0.01). Seventy-eight per cent had skin psoriasis. The mean PsA disease duration at HUNT3 was 4.8 (+/-3.0) years. The patients who developed PsA gained less weight from HUNT2 to HUNT3 compared with the control group (2.1 vs 3.9 kg, difference in mean change -1.8 kg, 95% CI -3.9 to -0.5, p<0.01). TC, triglycerides, LDL-c or HDL-c values and BP declined in both groups, with no significant differences between groups. CONCLUSION: Longitudinal 10-year data did not show an increase in CV risk factors in patients who developed PsA compared with controls. This study implies that unfavourable CV risk factors in PsA were present before the diagnosis was established.

Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. METHODS: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. RESULTS: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). CONCLUSIONS: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

The effect of an intensive smoking cessation intervention on disease activity in patients with rheumatoid arthritis: study protocol for a randomised controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory rheumatic disease with the potential to induce significant disability. Patients with RA are at increased risk of cardiovascular diseases (CVD). Smokers with RA tend to experience more pain and fatigue, higher disease activity, more erosive joint destruction and a lower health-related quality of life (HR-QoL) than non-smokers. It remains to be determined whether these effects can be reduced by smoking cessation. This randomised controlled trial (RCT) in patients with RA aims to examine the effect of intensive smoking cessation intervention (motivational counselling combined with tailored nicotine replacement therapy) versus standard care on smoking cessation, and consequently on disease activity. Secondary objectives are to explore the effect on flare, risk factors for CVD, lung function, physical function, HR-QoL, pain and fatigue in patients with RA. METHODS: This will be a multicentre, open label, two arm, parallel group, RCT, including 150 daily smokers with RA, being in remission or having low-moderate disease activity (DAS28 ≤ 5.1). The intervention group (n = 75) will receive five counselling sessions with a trained smoking cessation counsellor based on the principles of motivational counselling. Furthermore, intervention patients will be offered nicotine replacement therapy tailored to individual needs. Participants randomised to the control group will receive standard care. The co-primary outcome is a hierarchical endpoint, which will be evaluated at 3 months follow-up and will include (1) self-reported smoking cessation biochemically validated by exhaled carbon monoxide and (2) achievement of EULAR clinical response (an improvement in DAS28 of > 0.6). Follow-up visits will be performed at 3, 6 and 12 months post-intervention. DISCUSSION: This trial will reveal whether intensive smoking cessation counselling helps smokers with RA to achieve continuous smoking cessation and whether, as a concomitant benefit, it will reduce their RA disease activity. The trial aims to generate high quality evidence for the feasibility of a health promotion intervention for smokers with RA. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02901886 . Registered on 10 September 2016. Recruitment status updated on 10th October 2016.

Bone mineral density in patients with psoriatic arthritis: data from the Nord-Trøndelag Health Study 3.

BACKGROUND: The risk of osteoporosis in patients with psoriatic arthritis (PsA) remains unclear. The aim of this study was to compare bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) in patients with PsA and controls. PATIENTS AND METHODS: Patients with PsA and controls were recruited from the Nord-Trøndelag Health Study (HUNT) 3. RESULTS: Patients with PsA (n=69) and controls (n=11 703) were comparable in terms of age (56.8 vs 55.3 years, p=0.32), gender distribution (females 65.2% vs 64.3%, p=0.87) and postmenopausal status (75.6% vs 62.8%, p=0.08). Body mass index (BMI) was higher in patients with PsA compared with controls (28.5 vs 27.2 kg/m2, p=0.01). After adjusting for potential confounding factors (including BMI), BMD was higher in patients with PsA compared with controls at lumbar spine 1-4 (1.213 vs 1.147 g/cm2, p=0.003) and femoral neck (0.960 vs 0.926 g/cm2, p=0.02), but not at total hip (1.013 vs 0.982 g/cm2, p=0.11). Controls had significantly higher odds of having osteopenia or osteoporosis based on measurements of BMD in both the femoral neck (p=0.001), total hip (p=0.033) and lumbar spine (p=0.033). CONCLUSION: Our population-based data showed comparable BMD in patients with PsA and controls. This supports that the PsA population is not at increased risk of osteoporosis.

Cardiovascular disease risk profiles in inflammatory joint disease entities.

BACKGROUND: Patients with inflammatory joint diseases (IJD) have increased risk of cardiovascular disease (CVD). Our aim was to compare CVD risk profiles in patients with IJD, including rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) and evaluate the future risk of CVD. METHODS: The prevalence and numbers of major CVD risk factors (CVD-RFs) (hypertension, elevated cholesterol, obesity, smoking, and diabetes mellitus) were estimated in patients with RA, axSpA and PsA. Relative and absolute risk of CVD according to Systematic Coronary Risk Evaluation (SCORE) was calculated. RESULTS: In total, 3791 patients were included. CVD was present in 274 patients (7.2%). Of those without established CVD; hypertension and elevated cholesterol were the most frequent CVD-RFs, occurring in 49.8% and 32.8% of patients. Patients with PsA were more often hypertensive and obese. Overall, 73.6% of patients had a minimum of one CVD-RF, which increased from 53.2% among patients aged 30 to <45 years, to 86.2% of patients aged 60 to ≤80 years. Most patients (93.5%) had low/moderate estimated risk of CVD according to SCORE. According to relative risk estimations, 35.2% and 24.7% of patients had two or three times risk or higher, respectively, compared to individuals with no CVD-RFs. CONCLUSIONS: In this nationwide Norwegian project, we have shown for the first time that prevalence and numbers of CVD-RFs were relatively comparable across the three major IJD entities. Furthermore, estimated absolute CVD risk was low, but the relative risk of CVD was markedly high in patients with IJD. Our findings indicate the need for CVD risk assessment in all patients with IJD.

Challenges of developing a cardiovascular risk calculator for patients with rheumatoid arthritis.

OBJECTIVE: Cardiovascular disease (CVD) risk calculators designed for use in the general population do not accurately predict the risk of CVD among patients with rheumatoid arthritis (RA), who are at increased risk of CVD. The process of developing risk prediction models involves numerous issues. Our goal was to develop a CVD risk calculator for patients with RA. METHODS: Thirteen cohorts of patients with RA originating from 10 different countries (UK, Norway, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico) were combined. CVD risk factors and RA characteristics at baseline, in addition to information on CVD outcomes were collected. Cox models were used to develop a CVD risk calculator, considering traditional CVD risk factors and RA characteristics. Model performance was assessed using measures of discrimination and calibration with 10-fold cross-validation. RESULTS: A total of 5638 RA patients without prior CVD were included (mean age: 55 [SD: 14] years, 76% female). During a mean follow-up of 5.8 years (30139 person years), 389 patients developed a CVD event. Event rates varied between cohorts, necessitating inclusion of high and low risk strata in the models. The multivariable analyses revealed 2 risk prediction models including either a disease activity score including a 28 joint count and erythrocyte sedimentation rate (DAS28ESR) or a health assessment questionnaire (HAQ) along with age, sex, presence of hypertension, current smoking and ratio of total cholesterol to high-density lipoprotein cholesterol. Unfortunately, performance of these models was similar to general population CVD risk calculators. CONCLUSION: Efforts to develop a specific CVD risk calculator for patients with RA yielded 2 potential models including RA disease characteristics, but neither demonstrated improved performance compared to risk calculators designed for use in the general population. Challenges encountered and lessons learned are discussed in detail.

On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study.

OBJECTIVE: To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. METHODS: Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. RESULTS: There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. CONCLUSIONS: Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.