G. Y. H. Lip

A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice.

Summary.  Background:  Anticoagulation management of patients with atrial fibrillation (AF) should be tailored individually on the basis of ischemic stroke risk. The objective of this study was to compare the predictive ability of 15 published stratification schemes for stroke risk in actual clinical practice in the UK. Methods:  AF patients aged ≥ 18 years in the General Practice Research Database, which contains computerized medical records, were included. The c‐statistic was estimated to determine the predictive ability for stroke for each scheme. Outcomes included stroke, hospitalizations for stroke, and death resulting from stroke (as recorded on death certificates). Results:  The study cohort included 79 844 AF patients followed for an average of 4 years (average of 2.4 years up to the start of warfarin therapy). All risk schemes had modest discriminatory ability in AF patients, with c‐statistics for predicting events ranging from 0.55 to 0.69 for strokes recorded by the general practitioner or in hospital, from 0.56 to 0.69 for stroke hospitalizations, and from 0.56 to 0.78 for death resulting from stroke as reported on death certificates. The proportion of patients assigned to individual risk categories varied widely across the schemes, with the proportion categorized as moderate risk ranging from 12.7% (CHA2DS2‐VASc) to 61.5% (modified CHADS2). Low‐risk subjects were truly low risk (with annual stroke events < 0.5%) with the modified CHADS2, National Institute for Health and Clinical Excellence and CHA2DS2‐VASc schemes. Conclusion:  Current published risk schemes have modest predictive value for stroke. A new scheme (CHA2DS2‐VASc) may discriminate those at truly low risk and minimize classification of subjects as intermediate/moderate risk. This approach would simplify our approach to stroke risk stratification and improve decision‐making for thromboprophylaxis in patients with AF.

Quality of life in adults with congenital heart disease

Objective: To examine the quality of life of adults with congenital heart disease. Design and setting: Observational, cross sectional study conducted at one general hospital in Birmingham, UK. Patients: All 471 patients registered at the adult congenital heart disease clinic were sent the 36 item short form health survey (SF-36) to assess their quality of life. Questionnaires were completed by 276 (58.6%) patients (41.7% men; median (interquartile range) age 31.0 (26.3–36.0) years, range 16–85 years). Results: Surprisingly, patients deemed surgically cured (for example, atrial septal defect repair) had significantly poorer quality of life in all domains (all p < 0.05), except for pain, than the general population, as determined from population normative data. Patients who had received palliative treatment reported quality of life scores similar to those who had never required cardiac surgery and to the general population, although both patient groups had significantly poorer physical functioning and overall general health perception than the general population (all p < 0.01). Patients with inoperable conditions had significantly poorer physical functioning (all p < 0.01) and overall general health perception (all p < 0.05) than all other patients, and significantly worse quality of life in all domains than the similarly aged general population. Patients with cyanotic conditions had significantly worse quality of life than age and sex matched acyanotic patients (all p < 0.01). Conclusions: Patients with inoperable or cyanotic conditions and, paradoxically, those deemed surgically cured, had the poorest quality of life among adults with congenital heart disease. However, all adults with congenital heart disease had significantly poorer levels of physical functioning and overall general health perception then similarly aged people in the general population.

Angiogenesis: basic pathophysiology and implications for disease

The development of new blood vessels is essential to embryonic growth and throughout life for physiological repair processes such as wound healing, post-ischaemic tissue restoration, and the endometrial changes of the menstrual cycle. However, abnormal development of new blood vessels has been implicated in numerous pathophysiological processes. For example, inhibited growth of blood vessels is associated with bowel atresia and peptic ulcers.1–3 Furthermore, although generally focussing on tumour growth, increased vascular growth has been demonstrated in many other non-malignant diseases such rheumatoid arthritis, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis.3–5 It is therefore clear that the subject is currently attracting considerable research energies as tools are becoming available to assess possible therapeutic options. The formation of the vascular system is fashioned by three processes. During embryogenesis, there is differentiation of embryonic mesenchymal cells (the endothelial precursor cells or angioblasts) into endothelial cells resulting in de novo development of blood vessels (vasculogenesis).6 Secondly, angiogenesis refers to the formation of new blood vessels by sprouting from pre-existing small vessels in adult and embryonic tissue (sprouting angiogenesis) or by intravascular subdivision (intussusception). The existing vasculature can betransformed into a mature network by processes of pruning and remodelling. Thirdly, arteriogenesisis defined as rapid proliferation of pre-existingcollateral vessels.7 Angiogenesis also seems to bean organ-specific process reliant on the stage of microvascular network.8 Since angiogenesis seems to play a key role inthe pathophysiology of various disease processes,recent attempts have been made to utilize this knowledge in the development of new therapeutic approaches. For example, inhibition of angiogenesis has been used in the restriction of tumour growth and the seeding of metastases, as well asin rheumatoid arthritis, where an aim is to reduce the infiltration of inflammatory cells and soluble mediators.9–11 Angiogenesis related research in cardiovascular medicine has initially been …

Abnormal angiopoietins 1&2, angiopoietin receptor tie-2 and vascular endothelial growth factor levels in hypertension : relationship to target organ damage [a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)]

Background.  The increased risk of target organ damage (TOD) in hypertension may be related to a prothrombotic or hypercoagulable state, with abnormalities in platelet activation. Altered angiogenesis, possibly related to increased plasma vascular endothelial growth factor (VEGF) is also a feature of hypertension. We hypothesized a link between altered angiogenesis and TOD in hypertension. Accordingly, the angiogenic growth factors VEGF, angiopoietin 1 and 2 (Ang 1 & 2) and soluble angiopoietin receptor Tie‐2 in plasma and in platelets were assessed in terms of the presence or absence of hypertensive TOD.

Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study

Summary.  Background:  Female sex has been suggested as a risk factor for stroke/thromboembolism in patients with non‐valvular atrial fibrillation (AF) and has therefore been included within risk scores, e.g. the CHA2DS2‐VASc score, and guidelines.

Ethnic differences in blood pressure and the prevalence of hypertension in England

The objective of this study was to examine the prevalence of hypertension and mean blood pressures among Afro-Caribbeans and South-Asians in England compared with Caucasians. Data from the Birmingham Factory Screen, Birmingham INTERSALT volunteers, and four West Midlands churches were combined into a single database (n = 2853), since all three studies employed identical methods. The cohort comprised 2169 (76%) Caucasians (71% men); 453 (16%) Afro-Caribbean (60% men); and 231 (8%) South-Asian men. The results were that overall prevalence of hypertension (⩾160/95 mm Hg or taking antihypertensives) was greater in both Afro-Caribbean men (31%) and women (34%) (both P < 0.001), compared with Caucasians (19% and 13% respectively), while South-Asian men had a similar overall prevalence to Caucasians (16%). Compared with Caucasians, Afro-Caribbeans had significantly higher mean systolic blood pressure, with higher mean diastolic blood pressures evident among Afro-Caribbean women. After adjustment for age, body mass index, smoking, and weekly alcohol intake, the odds ratios (95% CI) for being hypertensive were 1.56 (1.14 to 2.13; P = 0.005) and 2.40 (1.51 to 3.81; P = 0.0002) for Afro-Caribbean men and women, respectively and 1.31 (0.88 to 1.97; P = 0.19) for South-Asian men, compared with Caucasians. In conclusion the prevalence of hypertension and mean blood pressures are higher among Afro-Caribbeans compared with Caucasians. South-Asian men had similar rates of hypertension and mean blood pressures to Caucasians.

Oxidative stress in malignant and non-malignant phase hypertension

Malignant hypertension (MHT) is a rare and severe form of hypertension characterised by arteriolar necrosis and severe vascular damage, leading to stroke, myocardial infarction and death. We hypothesised that in addition to endothelial damage, MHT may be associated with increased oxidative stress. Lipid hydroperoxides (LHP, an index of oxidative damage) and plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction) were measured in 16 patients with MHT and compared with 16 non-malignant essential hypertensives and 32 normotensive controls. vWf was greater in MHT (mean 117 iU/dL) than in non-malignant hypertensives (97 iU/dL) or normotensive controls (100 iU/dL) (ANOVA P = 0.017). However, although LHP were greater in MHT (mean 10.6 μmol/L) than in normotensives (4.5 μmol/L, P < 0.001), the levels in MHT were similar to those in non-malignant hypertension (12.3 μmol/L). In conclusion endothelial damage (raised vWf) was more evident in MHT compared with both normotensive controls and with non-malignant hypertension, whilst oxidative stress (raised LHP) was increased to a similar extent in both hypertension groups when compared with normotensive controls. These observations raise the possibility abnormal oxidative stress is probably not the mechanism responsible for the endothelial damage seen in malignant phase hypertension.

Peripheral vascular disease and hypertension: a forgotten association?

Peripheral vascular disease (PVD) is associated with a high cardiovascular morbidity and mortality. Intermittent claudication is the most common symptomatic manifestation of PVD, but is also an important predictor of cardiovascular death, increasing it by three-fold, and increasing all-cause mortality by two to five-fold. Hypertension is a common and important risk factor for vascular disorders, including PVD. Of hypertensives at presentation, about 2–5% have intermittent claudication, with this prevalence increasing with age. Similarly, 35–55% of patients with PVD at presentation also have hypertension. Patients who suffer from hypertension with PVD have a greatly increased risk of myocardial infarction and stroke. Apart from the epidemiological associations, hypertension contributes to the pathogenesis of atherosclerosis, the basic underlying pathological process underlying PVD. Hypertension, in common with PVD, is associated with abnormalities of haemostasis and lipids, leading to an increased atherothrombotic state. Nevertheless, none of the large antihypertensive treatment trials have adequately addressed whether a reduction in blood pressure causes a decrease in PVD incidence. There is therefore an obvious need for such outcome studies, especially since the two conditions are commonly encountered together.

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary.  There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS2 score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS2 and CHA2DS2‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.

Angiogenesis, thrombogenesis, endothelial dysfunction and angiographic severity of coronary artery disease

Background: Thrombogenesis, angiogenesis, and endothelial damage/dysfunction are components in the pathogenesis of atherosclerosis. Objective: To investigate the relation of these variables to atherosclerotic disease severity and the possible interrelations between the three. Methods: 111 patients attending for coronary angiography were studied (85 male, 26 female; mean (SD) age, 61.6 (10.0) years). Plasma concentrations of von Willebrand factor (vWf, a marker of endothelial damage/dysfunction), vascular endothelial growth factor (VEGF, associated with angiogenesis), soluble VEGF receptor Flt-1 (sFlt-1), and tissue factor (TF, a key component of coagulation) were measured by an enzyme linked immunosorbent assay. Following angiography, disease severity was assessed by the number of coronary vessels diseased (> 50% stenosis) and by a coronary atheroma score. Results: All indices were raised in the patients compared with 34 healthy controls except sFlt-1, which was lower in the patients. No significant correlations were found between the coronary atheroma score and values of vWf (Spearman correlations: r  =  0.21, p  =  0.83), VEGF (r  =  0.11, p = 0.27), or TF (r  =  −0.04, p  =  0.68). However, there was an inverse correlation between plasma sFlt-1 and coronary atheroma score (r  =  −0.19, p  =  0.049). The number of vessels diseased had no relation to any marker. Correlations were found between TF and VEGF (r  =  0.25, p  =  0.008) and between TF and sFlt-1 (r  =  0.42, p < 0.001) in the patients. Conclusions: Despite evidence of abnormal angiogenesis (VEGF and sFlt-1), thrombogenesis (TF), and endothelial damage/dysfunction (vWf) in the patients with coronary artery disease, there was no correlation between VEGF, sFlt-1, vWf, or TF and angiographically defined disease severity.