Cardiovascular disease risk profiles among 'healthy' siblings of patients with early-onset cardiovascular disease:Application of the new SCORE system

BACKGROUND: Cardiovascular disease (CVD) occurs more frequently in individuals with a family history of premature CVD. Within families the demographics of CVD are poorly described. DESIGN: We examined the risk estimation based on the Systematic Coronary Risk Evaluation (SCORE) system and the Joint British Guidelines (JBG) for older unaffected siblings of patients with premature CVD (onset ≤55 years for men and ≤60 years for women). METHODS: Between August 1999 and November 2003 laboratory and demographic details were collected on probands with early-onset CVD and their older unaffected siblings. Siblings were screened for clinically overt CVD by a standard questionnaire and 12-lead electrocardiogram (ECG). RESULTS: A total of 790 siblings was identified and full demographic details were available for 645. The following siblings were excluded: 41 with known diabetes mellitus; seven with random plasma glucose of 11.1 mmol/l or greater; and eight with ischaemic ECG. Data were analysed for 589 siblings from 405 families. The mean age was 55.0 years, 43.1% were men and 28.7% were smokers. The mean total serum cholesterol was 5.8 mmol/l and hypertension was present in 49.4%. Using the SCORE system, when projected to age 60 years, 181 men (71.3%) and 67 women (20.0%) would be eligible for risk factor modification. Using JBG with a 10-year risk of 20% or greater, 42 men (16.5%) and four women (1.2%) would be targeted. CONCLUSIONS: Large numbers of these asymptomatic individuals meet both European and British guidelines for the primary prevention of CVD and should be targeted for risk factor modification. The prevalence of individuals defined as eligible for treatment is much higher when using the SCORE system. © 2007 European Society of Cardiology.

Intermedin (Adrenomedullin-2) a novel counter-regulatory peptide in the cardiovascular and renal systems

Intermedin (IMD) is a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (AM). Proteolytic processing of a larger precursor yields a series of biologically active C-terminal fragments, IMD1–53, IMD1–47 and IMD8–47. IMD shares a family of receptors with AM and CGRP composed of a calcitonin-receptor like receptor (CALCRL) associated with one of three receptor activity modifying proteins (RAMP). Compared to CGRP, IMD is less potent at CGRP1 receptors but more potent at AM1 receptors and AM2 receptors; compared to AM, IMD is more potent at CGRP1 receptors but less potent at AM1 and AM2 receptors. The cellular and tissue distribution of IMD overlaps in some aspects with that of CGRP and AM but is distinct from both. IMD is present in neonatal but absent or expressed sparsely, in adult heart and vasculature and present at low levels in plasma. The prominent localization of IMD in hypothalamus and pituitary and in kidney is consistent with a physiological role in the central and peripheral regulation of the circulation and water-electrolyte homeostasis. IMD is a potent systemic and pulmonary vasodilator, influences regional blood flow and augments cardiac contractility. IMD protects myocardium from the deleterious effects of oxidative stress associated with ischaemia-reperfusion injury and exerts an anti-growth effect directly on cardiomyocytes to oppose the influence of hypertrophic stimuli. The robust increase in expression of the peptide in hypertrophied and ischaemic myocardium indicates an important protective role for IMD as an endogenous counter-regulatory peptide in the heart.

Statins in Heart Failure-Where Do We Stand?

HMG Co-A reductase inhibitors (statins) are a group of drugs which lower cholesterol by inhibiting the conversion of HMG Co-A to mevalonate early in the cholesterol synthetic pathway. They are used in the primary and secondary prevention of cardiovascular events in patients deemed to be at increased risk and their benefit in patients with ischaemic heart disease is well supported. Their use in patients with heart failure (HF) however, is controversial. Evidence from observational and mechanistic studies suggests that statins should benefit patients with HF. However, larger randomised controlled trials have failed to demonstrate these expected benefits. The aim of this review article is to summarise the data from trials of statin use in patients with HF and attempt to explain the apparent conflict between recent placebo controlled trials and earlier observational and mechanistic studies.

Recurrent lower gastrointestinal bleeding secondary to cytomegalovirus-associated colonic ulcer in a non human immunodeficiency virus infected patient:Timely diagnosis and treatment averted surgery

Mr C, a 68-year-old Chinese male with diabetes mellitus, previous stroke and ischaemic cardiomyopathy on clopidogrel, presented with haematochezia. Colonoscopy showed a sigmoid ulcer, which was treated endoscopically. Histology of the biopsy from the ulcer revealed non-specific changes. However, he presented with recurrent bleeding from this non-healing sigmoid ulcer. A review of the histologic specimen revealed CMV intranuclear inclusion bodies. He was treated with intravenous ganciclovir, with no further hematochezia.

Keywords Hematochezia, cytomegalovirus, ulcer

Improved detection of acute myocardial infarction in patients with chest pain and significant left main stem coronary stenosis.

Background: Non-invasive diagnosis of acute myocardial infarction (AMI) associated with significant left main stem (LMS) stenosis remains challenging.

Methods: Consecutive patients presenting with acute ischaemic-type chest pain from 2000 to 2010 were analysed. Entry criteria: 12-lead ECG and Body Surface Potential Map (BSPM) at presentation, cardiac troponin T (cTnT) =12?h and coronary angiography during admission. cTnT =0.03?µg/l defined AMI. ECG abnormalities assessed: STEMI by Minnesota criteria; ST elevation (STE) aVR =0.5?mm; ST depression (STD) =0.5?mm in =2 contiguous leads (CL); T-wave inversion (TWI) =1?mm in =2 CL. BSPM STE was =2?mm in anterior, =1?mm in lateral, inferior, right ventricular or high right anterior and =0.5?mm in posterior territories. Significant LMS stenosis was =70%.

Results: Enrolled were 2810 patients (aged 60?±?12 years; 71% male). Of these, 116 (4.1%) had significant LMS stenosis with AMI occurring in 92 (79%). STEMI by Minnesota criteria occurred in 13 (11%) (sensitivity 12%, specificity 92%), STE in lead aVR in 23 (20%) (sensitivity 23%, specificity 92%), TWI in 38 (33%) (sensitivity 34%, specificity 71%) and STD in 51 (44%) (sensitivity 49%, specificity 75%). BSPM STE occurred in 85 (73%): sensitivity 88%, specificity 83%, positive predictive value 95% and negative predictive value 65%. Of those with AMI, 74% had STE in either the high right anterior or right ventricular territories not identified by the 12-lead ECG. C-Statistic for AMI diagnosis using BSPM STE was 0.800 (P?<?0.001).

Conclusion: In patients with significant LMS stenosis presenting with chest pain, BSPM STE has improved sensitivity (88%), with specificity 83%, over 12-lead ECG in the diagnosis of AMI.

Endothelial Progenitors as Tools to Study Vascular Disease

Endothelial progenitor cells (EPCs) have great clinical value because they can be used as diagnostic biomarkers and as a cellular therapy for promoting vascular repair of ischaemic tissues. However, EPCs also have an additional research value in vascular disease modelling to interrogate human disease mechanisms. The term EPC is used to describe a diverse variety of cells, and we have identified a specific EPC subtype called outgrowth endothelial cell (OEC) as the best candidate for vascular disease modelling because of its high-proliferative potential and unambiguous endothelial commitment. OECs are isolated from human blood and can be exposed to pathologic conditions (forward approach) or be isolated from patients (reverse approach) in order to study vascular human disease. The use of OECs for modelling vascular disease will contribute greatly to improving our understanding of endothelial pathogenesis, which will potentially lead to the discovery of novel therapeutic strategies for vascular diseases.

Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Retinopathy is a major complication of diabetes mellitus and this condition remains a leading cause of blindness in the working population of developed countries. As diabetic retinopathy progresses a range of neuroglial and microvascular abnormalities develop although it remains unclear how these pathologies relate to each other and their net contribution to retinal damage. From a haemodynamic perspective, evidence suggests that there is an early reduction in retinal perfusion before the onset of diabetic retinopathy followed by a gradual increase in blood flow as the complication progresses. The functional reduction in retinal blood flow observed during early diabetic retinopathy may be additive or synergistic to pro-inflammatory changes, leucostasis and vaso-occlusion and thus be intimately linked to the progressive ischaemic hypoxia and increased blood flow associated with later stages of the disease. In the current review a unifying framework is presented that explains how arteriolar dysfunction and haemodynamic changes may contribute to late stage microvascular pathology and vision loss in human diabetic retinopathy.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection):a randomised placebo-controlled trial

Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients.

Comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland from 2003 to 2008: national and centre-specific analyses

Introduction: The prevalence of comorbidities in incident renal replacement therapy (RRT) patients changes with age and varies between ethnic groups. This study describes these associations and the independent effect of comorbidities on outcomes. Methods: Adult patients starting RRT between 2003 and 2008 in centres reporting to the UK Renal Registry (UKRR) with data on comorbidity (n ¼ 14,909) were included. The UKRR studied the association of comorbidity with patient demographics, treatment modality, haemoglobin, renal function at start of RRT and subsequent listing for kidney transplantation. The relationship between comorbidities and mortality at 90 days and one year after 90 days from start of RRT was explored using Cox regression. Results: Completeness of comorbidity data was 40.0% compared with 54.3% in 2003. Of patients with data, 53.8% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions seen in 30.1% and 22.7% of patients respectively. Current smoking was recorded for 14.5% of incident RRT patients in the 6-year period. Comorbidities became more common with increasing age in all ethnic groups although the difference between the 65–74 and 75+ age groups was not significant. Within each age group, South Asians and Blacks had lower rates of comorbidity, despite higher rates of diabetes mellitus. In multivariate survival analysis, malignancy and ischaemic/neuropathic ulcers were the strongest independent predictors of poor survival at 1 year after 90 days from the start of RRT. Conclusion: Differences in prevalence of comorbid illnesses in incident RRT patients may reflect variation in access to health care or competing risk prior to commencing treatment. At the same time, smoking rates remained high in this ‘at risk’ population. Further work on this and ways to improve comorbidity reporting should be priorities for 2010–11.

Comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland: national and centre-specific analyses

Introduction: The prevalence of 13 comorbid conditions and smoking status at the time of starting renal replacement therapy (RRT) in England, Wales and Northern Ireland are described. Methods: Adult patients starting RRT between 2002 and 2007 in centres reporting to the UK Renal Registry (UKRR) and with data on comorbidity (n¼13,293) were included. The association of comorbidity with patient demographics, treatment modality, haemoglobin, renal function at start of RRT and subsequent listing for kidney transplantation were studied. Association between comorbidities and mortality at 90 days and one year after 90 days from start of RRT was explored using Cox regression. Results: Completeness of data on comorbidity returned to the UKRR remained poor. Of patients with data, 52% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions seen in 28.9% and 22.5% of patients respectively. Comorbidities became more common with increasing age (up to the 65–74 age group), were more common amongst Whites and were associated with a lower likelihood of pre-emptive transplantation, a greater likelihood of starting on haemodialysis (rather than peritoneal dialysis) and a lower likelihood of being listed for kidney transplantation. In multivariable survival analysis, malignancy and ischaemic/neuropathic ulcers were the strongest predictors of poor survival at 1 year after 90 days from start of RRT. Conclusions: The majority of patients had at least one comorbid condition and comorbidity is an important predictor of early mortality on RRT.

Urban greenways have the potential to increase physical activity levels cost-effectively

BACKGROUND: For many, physical activity has been engineered out of daily life, leading to high levels of sedentariness and obesity. Multi-faceted physical activity interventions, combining individual, community and environmental approaches, have the greatest potential to improve public health, but few have been evaluated. METHODS: Approximately 100 000 people may benefit from improved opportunities for physical activity through an urban regeneration project in Northern Ireland, the Connswater Community Greenway. Using the macro-simulation PREVENT model, we estimated its potential health impacts and cost-effectiveness. To do so, we modelled its potential impact on the burden from cardiovascular disease, namely, ischaemic heart disease, type 2 diabetes mellitus and stroke, and colon and breast cancer, by the year 2050, if feasible increases in physical activity were to be achieved. RESULTS: If 10% of those classified as 'inactive' (perform less than 150 minutes of moderate activity/week) became 'active', 886 incident cases (1.2%) and 75 deaths (0.9%) could be prevented with an incremental cost-effectiveness ratio of £4469/disability-adjusted life year. For effectiveness estimates as low as 2%, the intervention would remain cost-effective (£18 411/disability-adjusted life year). Small gains in average life expectancy and disability-adjusted life expectancy could be achieved, and the Greenway population would benefit from 46 less years lived with disability. CONCLUSION: The Greenway intervention could be cost-effective at improving physical activity levels. Although the direct health gains are predicted to be small for any individual, summed over an entire population, they are substantial. In addition, the Greenway is likely to have much wider benefits beyond health.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.

Radiation retinopathy--clinical, histopathological, ultrastructural and experimental correlations

Clinical, pathological and experimental studies of radiation retinopathy confirm that the primary vascular event is endothelial cell loss and capillary closure. Pericytes are less susceptible, but typically atrophy as the capillaries become non-functional. The immediate effects of radiation reflect interphase and early mitotic death of injured endothelial cells, whereas later changes may be attributed to delayed mitotic death of compromised endothelial cells as they attempt division in the ordinary course of repair and replacement. Capillary occlusion leads to the formation of dilated capillary collaterals which may remain serviceable and competent for years. Microaneurysms develop in acellular and poorly supported capillaries, predominantly on the arterial side of the circulation and adjacent to regions of poorly perfused retina. Alterations in haemodynamics produce large telangiectatic-like channels which, typically develop a thick collagenous adventitia and may become fenestrated. Limited capillary regeneration occurs, usually evident as recanalisation of arterioles or venules by new capillaries. Vitreo-retinal neovascularisation may occur where retinal ischaemia is widespread. Radiation produces an exaggerated vasculopathy in patients with diabetes mellitus, and five month streptozotocin-induced diabetic rats develop a severe ischaemic retinopathy with vitreoretinal neovascularisation when exposed to 1500 cGy of radiation. Later photocoagulation is useful in containing or reversing microvascular incompetence and vasoproliferation in some patients with advanced radiation retinopathy.

High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort

Aims
Our aim was to test the prediction and clinical applicability of high-sensitivity assayed troponin I for incident cardiovascular events in a general middle-aged European population.

Methods and results
High-sensitivity assayed troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340) with 2171 cardiovascular events (including acute coronary heart disease and probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by the high-sensitivity method was associated with future cardiovascular risk after full adjustment such as that individuals in the fourth category had 2.5 times the risk compared with those without detectable troponin I (P < 0.0001). These associations remained significant even for those individuals in whom levels of contemporary-sensitivity troponin I measures were not detectable. Addition of troponin I levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (P < 0.0001) and net reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in men is suggested to detect individuals at high risk for future cardiovascular events.

Conclusion
Troponin I, measured with a high-sensitivity assay, is an independent predictor of cardiovascular events and might support selection of at risk individuals.