Vasileios F. Panoulas

Hypertension in rheumatoid arthritis

RA associates with an increased burden of cardiovascular disease, which is at least partially attributed to classical risk factors such as hypertension (HT) and dyslipidaemia. HT is highly prevalent, and seems to be under-diagnosed and under-treated among patients with RA. In this review, we discuss the mechanisms that may lead to increased blood pressure in such patients, paying particular attention to commonly used drugs for the treatment of RA. We also suggest screening strategies and management algorithms for HT, specific to the RA population, although it is clear that these need to be formally assessed in prospective randomized controlled trials designed specifically for the purpose, which, unfortunately, are currently lacking.

Increased left ventricular trabeculation in highly trained athletes: do we need more stringent criteria for the diagnosis of left ventricular non-compaction in athletes?

Objective To investigate the prevalence and significance of increased left ventricular (LV) trabeculation in highly trained athletes. Design Cross sectional echocardiographic study. Setting Sports cardiology institutions in the UK and France. Subjects 1146 athletes aged 14–35u2005years (63.3% male), participating in 27 sporting disciplines, and 415 healthy controls of similar age. The results of athletes fulfilling conventional criteria for LV non-compaction (LVNC) were compared with 75 patients with LVNC. Main outcome measure Number of athletes with increased LV trabeculation and the number fulfilling criteria for LVNC. Results Athletes displayed a higher prevalence of increased LV trabeculation compared with controls (18.3% vs 7.0%; p≤0.0001) and 8.1% athletes fulfilled conventional criteria for LVNC. Increased LV trabeculation were more common in athletes of African/Afro-Caribbean origin. A small proportion of athletes (n=10; 0.9%) revealed reduced systolic function and marked repolarisation changes in association with echocardiographic criteria for LVNC raising the possibility of an underlying cardiomyopathy. Follow-up during the ensuing 48.6±14.6u2005months did not reveal adverse events. Conclusions A high proportion of young athletes exhibit conventional criteria for LVNC highlighting the non-specific nature of current diagnostic criteria if applied to elite athletic populations. Further assessment of such athletes should be confined to the small minority that demonstrate low indices of systolic function and marked repolarisation changes.

Pocket-size hand-held cardiac ultrasound as an adjunct to clinical examination in the hands of medical students and junior doctors

AIMSnWhile patient history taking and physical examination remain the cornerstones of patient evaluation in clinical practice, there has been a decline in the accuracy of the latter. Pocket-size hand-held echocardiographic (PHHE) devices have recently been introduced and could potentially improve the diagnostic accuracy of both medical students and junior doctors. The amount of training required to achieve optimal results remains a matter of debate. We hypothesized that the use of PHHE after limited training in the form of a tutorial can improve the clinical diagnosis even in the hands of medical students and inexperienced physicians.nnnMETHODS AND RESULTSnFive final-year medical students and three junior doctors without prior echocardiographic experience participated in a standardized 2 h PHHE bedside tutorial. Subsequently, they assessed 122 cardiology patients using history, physical examination, ECG and PHHE. Their final clinical diagnosis was compared against that of a consultant clinicians and also expert in echocardiography. A total of 122 PHHE were performed of which 64 (53%) by final-year medical students and 58 (47%) by junior doctors. Mean ± SD for diagnostic accuracy after history, physical examination, and ECG interpretation was 0.49 ± 0.22 (maximum = 1), whereas the addition of PHHE increased its value to 0.75 ± 0.28 (Z = -7.761, P<0.001). When assessing left ventricular systolic dysfunction by means of history and physical examination, specificity was 84.9% and sensitivity only 25.9%, whereas after including findings from PHHE, these figures rose to 93.6 and 74.1%, respectively.nnnCONCLUSIONnThe use of PHHE after brief bedside training in the form of a tutorial greatly improved the clinical diagnosis of medical students and junior doctors, over and above history, physical examination, and ECG findings.

The magnitude of sudden cardiac death in the young: a death certificate-based review in England and Wales

AIMSnIn the UK, the true impact of cardiac and sudden death in the young (<or=35 years) is speculative. The authors critically appraised the office of national statistics (ONS) data for causes of death in the 1-34 years age group in England and Wales in an attempt to present an estimate of the incidence of such deaths and their underlying causes.nnnMETHODS AND RESULTSnThe investigators analysed the ONS mortality data for 2002-2005, inclusive. International classification of diseases-10 codes representing possible cardiac deaths were selected and divided into four classes; A1: definite cardiac deaths with no structural heart disease identified at post-mortem, A2: definite cardiac deaths with structural heart disease identified at post-mortem, A3: definite cardiac deaths with indeterminate cause, and B: possible cardiac deaths. Analysis of the data revealed an average of 419 (SD 16.5) definite cardiac deaths per annum (Class A1 + A2 + A3) equating to 1.8 per 100,000 per year (SD 0.08) or 8 deaths/week. There were also 433 (SD 6.2) deaths per year in class B which comprised primarily of deaths from drowning and epileptic seizures. The most prevalent causes were ischaemic heart disease (33.5%), cardiomyopathies (27%), sudden arrhythmic death syndrome (14%), myocarditis (11%), valvular heart disease (5%), and hypertensive cardiomyopathy (2%).nnnCONCLUSIONnOur findings suggest that the number of cardiac and sudden deaths in the young identified is sufficiently high to command attention even without the inclusion of potential misclassifications (Class B). Awareness of such deaths among primary-care physicians, pathologists, and coroners should be raised to ensure that those at risk are identified and further tragedies are avoided.

Statin use in rheumatoid arthritis in relation to actual cardiovascular risk: evidence for substantial undertreatment of lipid-associated cardiovascular risk?

Background Cardiovascular disease (CVD) is partially attributed to traditional cardiovascular risk factors, which can be identified and managed based on risk stratification algorithms (Framingham Risk Score, National Cholesterol Education Program, Systematic Cardiovascular Risk Evaluation and Reynolds Risk Score). We aimed to (a) identify the proportion of at risk patients with rheumatoid arthritis (RA) requiring statin therapy identified by conventional risk calculators, and (b) assess whether patients at risk were receiving statins. Methods Patients at high CVD risk (excluding patients with established CVD or diabetes) were identified from a cohort of 400 well characterised patients with RA, by applying risk calculators with or without a ×1.5 multiplier in specific patient subgroups. Actual statin use versus numbers eligible for statins was also calculated. Results The percentage of patients identified as being at risk ranged significantly depending on the method, from 1.6% (for 20% threshold global CVD risk) to 15.5% (for CVD and cerebrovascular morbidity and mortality) to 21.8% (for 10% global CVD risk) and 25.9% (for 5% CVD mortality), with the majority of them (58.1% to 94.8%) not receiving statins. The application of a 1.5 multiplier identified 17% to 78% more at risk patients. Conclusions Depending on the risk stratification method, 2% to 26% of patients with RA without CVD have sufficiently high risk to require statin therapy, yet most of them remain untreated. To address this issue, we would recommend annual systematic screening using the nationally applicable risk calculator, combined with regular audit of whether treatment targets have been achieved.

Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study

IntroductionThe metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX.MethodsMetS prevalence was assessed cross-sectionally in 400 RA patients, using five MetS definitions (National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of the MetS. Further analysis established the nature of the association between MTX and the MetS.ResultsMetS prevalence rates varied from 12.1% to 45.3% in RA according to the definition used. Older age and higher HAQ scores associated with the presence of the MetS. MTX use, but not other disease modifying anti-rheumatic drugs (DMARDs) or glucocorticoids, associated with significantly reduced chance of having the MetS in RA (OR = 0.517, CI 0.33–0.81, P = 0.004).ConclusionsThe prevalence of the MetS in RA varies according to the definition used. MTX therapy, unlike other DMARDs or glucocorticoids, independently associates with a reduced propensity to MetS, suggesting a drug-specific mechanism, and makes MTX a good first-line DMARD in RA patients at high risk of developing the MetS, particularly those aged over 60 years.

Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: The role of obesity and smoking

BACKGROUNDnCardiovascular morbidity and mortality are increased in rheumatoid arthritis (RA). Interleukin-6 (IL-6) is high in RA and, together with smoking and obesity, an important contributor to the development of cardiovascular disease (CVD). The present study examined the potential association of IL-6-174 G/C polymorphism, together with obesity and smoking, with the presence of CVD in RA patients.nnnMETHODS AND RESULTSnDNA samples were collected from 383 RA patients (who also had extensive clinical and laboratory evaluations). IL-6-174 G/C was identified using real time PCR and melting curve analysis. Serum IL-6 levels were measured in a subgroup of 135 RA patients to examine the functionality of the polymorphism. Carriers of the IL6-174C-allele demonstrated increased prevalence of CVD (26.2% vs. 17.0%, p=0.041). There was a significant association with CVD, even after adjustment for traditional CVD risk factors (OR=1.92, 95%CI: 1.03 to 3.58, p=0.041). IL-6 levels were significantly increased in C-allele carriers [14.02 (3.21-38.81) vs. 4.48 (2.25-16.5), p=0.028]. No significant interactions were observed between adiposity and IL6-174G/C genotypes. There was only a trend for an interaction between ever smoking and IL6 C-allele carriers on CVD.nnnCONCLUSIONnThe IL-6-174C-allele may associate with CVD in RA patients and possibly exerts its effect via increased inflammation. This finding, if confirmed in future studies, may be used as a part of a genetic screening tool for RA patients at high CVD risk.

Lack of association between glucocorticoid use and presence of the metabolic syndrome in patients with rheumatoid arthritis: a cross-sectional study

IntroductionRheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality, attributed to both traditional and novel cardiovascular risk factors. The metabolic syndrome, a cluster of classical cardiovascular risk factors, including hypertension, obesity, glucose intolerance, and dyslipidaemia, is highly prevalent in RA. Reports suggest that long-term glucocorticoid (GC) use may exacerbate individual cardiovascular risk factors, but there have been no studies in RA to assess whether it associates with the metabolic syndrome. We examined whether GC exposure associates with the presence of metabolic syndrome in patients with RA.MethodsRA patients (n = 398) with detailed clinical and laboratory assessments were categorised into three groups according to GC exposure: no/limited (<3 months) exposure (NE), low-dose (<7.5 mg/day) long-term exposure (LE), and medium-dose (greater than or equal to 7.5 mg to 30 mg/day) long-term exposure (ME). The metabolic syndrome was defined using the National Cholesterol Education Programme III guidelines. The association of GC exposure with the metabolic syndrome was evaluated using binary logistic regression.ResultsThe metabolic syndrome was present in 40.1% of this population and its prevalence did not differ significantly between the GC exposure groups (NE 37.9% versus LE 40.7% versus ME 50%, P = 0.241). Binary logistic regression did not demonstrate any increased odds for the metabolic syndrome when comparing ME with LE (odds ratio = 1.64, 95% confidence interval 0.92 to 2.92, P = 0.094) and remained non significant after adjusting for multiple potential confounders.ConclusionsLong-term GC exposure does not appear to associate with a higher prevalence of the metabolic syndrome in patients with RA. The components of the metabolic syndrome may already be extensively modified by other processes in RA (including chronic inflammation and treatments other than GCs), leaving little scope for additive effects of GCs.

The South Asian genome.

The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the worlds population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

Physiological Right Ventricular Adaptation in Elite Athletes of African and Afro-Caribbean Origin

Background— Regular, intensive exercise results in physiological biventricular cardiac adaptation. Ethnicity is an established determinant of left ventricular remodeling; black athletes (BAs) exhibit more profound LV hypertrophy than white athletes (WAs). Right ventricular (RV) remodeling has not been characterized in BAs, although the issue is pertinent because BAs commonly exhibit ECG anomalies that resemble arrhythmogenic RV cardiomyopathy. Methods and Results— Between 2006 and 2012, 300 consecutive BAs (n=243 males) from 25 sporting disciplines were evaluated by use of ECG and echocardiography. Results were compared with 375 WAs and 153 sedentary control subjects (n=69 blacks). There were no ethnic differences between RV parameters in control subjects. Both BAs and WAs exhibited greater RV dimensions than control subjects. RV dimensions were marginally smaller in BAs than in WAs (proximal outflow tract, 30.9±5.5 versus 32.8±5.3 mm, P<0.001; longitudinal dimension, 86.6±9.5 versus 89.8±9.6 mm, P<0.001), although only 2.3% of variation was attributable to ethnicity. RV enlargement compatible with diagnostic criteria for arrhythmogenic RV cardiomyopathy was frequently observed (proximal outflow tract ≥32 mm; 45.0% of BAs, 58.5% of WAs). Anterior T-wave inversion was present in 14.3% of BAs versus 3.7% of WAs (P<0.001). Marked RV enlargement with concomitant anterior T-wave inversion was observed in 3.0% of BAs versus 0.3% of WAs (P=0.005). Further investigation did not diagnose arrhythmogenic RV cardiomyopathy in any athlete. Conclusions— Physiological RV enlargement is commonly observed in both black and white athletes. The impact of ethnicity is minimal, which obviates the need for race-specific RV reference values. However, in the context of frequent ECG repolarization anomalies in BAs, the potential for erroneous diagnosis of arrhythmogenic RV cardiomyopathy is considerably greater in this ethnic group.