Publications
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Webb CM, Collins P, 2021, Medical management of anginal symptoms in women with stable angina pectoris: A systematic review of randomised controlled trials, International Journal of Cardiology, Vol: 341, Pages: 1-8, ISSN: 0167-5273
BackgroundMedical therapies are used to improve stable anginal symptoms and quality of life in clinical practice however the evidence for the use of antianginal medication in women is largely unknown. We conducted a systematic review to investigate the extent of the evidence-base for the medical management of anginal symptoms in women with stable angina.MethodsMEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases were searched to the end of December 2019. Retrieved papers were hand searched. Included were randomised controlled trials with at least one week of follow-up that included women with stable angina pectoris, with or without significant coronary atherosclerosis, randomised to conventional antianginal medication or/and a comparator, with a primary or secondary endpoint of angina frequency or glyceryl trinitrate (GTN) consumption.ResultsA total of 397 eligible publications were included in a qualitative analysis, with women comprising up to 20–30% of the study populations. No publication that included women and men reported all data separately for each sex. Twenty-six publications reported any female data separately from male data but only 18 reported angina data for women, 12 of which included fewer than 10 women.ConclusionsSubstantially fewer women than men were included in randomised trials of antianginal medications reporting effects on anginal symptoms, and reporting of data by sex was infrequent. As a result, there is little evidence on which to base treatment recommendations for anginal symptoms in women. Our results provide a platform for future studies to fill this void in the evidence.
Gaudino M, Benedetto U, Fremes S, et al., 2020, Association of Radial Artery Graft vs Saphenous Vein Graft With Long-term Cardiovascular Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting, JAMA, Vol: 324, Pages: 179-179, ISSN: 0098-7484
Importance Observational studies have suggested that the use of radial artery grafts for coronary artery bypass grafting may improve clinical outcomes compared with the use of saphenous vein grafts, but this has not been confirmed in randomized trials.Objective To compare clinical outcomes between patients receiving radial artery vs saphenous vein grafts for coronary artery bypass grafting after long-term follow-up.Design, Setting, and Participants Patient-level pooled analysis comparing radial artery vs saphenous vein graft in adult patients undergoing isolated coronary artery bypass grafting from 5 countries (Australia, Italy, Serbia, South Korea, and the United Kingdom), with enrollment from 1997 to 2009 and follow-up completed in 2019.Interventions Patients were randomized to undergo either radial artery (n = 534) or saphenous vein (n = 502) grafts for coronary artery bypass grafting.Main Outcomes and Measures The primary outcome was a composite of death, myocardial infarction, or repeat revascularization and the secondary outcome was a composite of death or myocardial infarction.Results A total of 1036 patients were randomized (mean age, 66.6 years in the radial artery group vs 67.1 years in the saphenous vein group; 376 [70.4%] men in the radial artery group vs 351 [69.9%] in the saphenous vein group); 942 (90.9%) of the originally randomized patients completed 10 years of follow-up (510 in the radial artery group). At a median (interquartile range) follow-up of 10 (10-11) years, the use of the radial artery, compared with the saphenous vein, in coronary artery bypass grafting was associated with a statistically significant reduction in the incidence of the composite outcome of death, myocardial infarction, or repeat revascularization (220 vs 237 total events; 41 vs 47 events per 1000 patient-years; hazard ratio, 0.73 [95% CI, 0.61-0.88]; P < .001) and of the composite of death or myocardial infarction (188 vs
Gaudino M, Benedetto U, Fremes SE, et al., 2020, Angiographic outcome of coronary artery bypass grafts: Radial Artery Database International Alliance, Annals of Thoracic Surgery, Vol: 109, Pages: 688-694, ISSN: 0003-4975
BACKGROUND: We used a large patient-level dataset including six angiographic randomized trials (RCTs) on coronary artery bypass conduits to explore incidence and determinants of coronary graft failure. METHODS: Patient-level angiographic data of six RCTs comparing long-term outcomes of the radial artery and other conduits were joined. Primary outcome was graft occlusion at maximum follow-up. The analysis was divided as follows: 1) left anterior descending coronary (LAD) distribution, 2) non-LAD distribution (circumflex and right coronary artery). To identify predictors of graft occlusion, mixed model multivariable Cox regression including all baseline characteristics with stratification by individual trials was used. RESULTS: 1091 patients and 2281 grafts were included (921 left internal mammary arteries, 74 right internal mammary arteries, 710 radial artery and 576 saphenous veins; all left internal mammary arteries were used on the LAD, the other conduits were used on the non-LAD distribution; mean angiographic follow up: 65±29 months). Occlusion rate was 2.3%, 13.5%, 9.4%, 17.5% for the left internal mammary arteries, right internal mammary arteries, radial artery and saphenous veins, respectively. At multivariable analysis type of conduit used, age, female gender, left ventricular ejection fraction<50% and use of the Y graft were significantly associated with graft occlusion in the non-LAD distribution. CONCLUSIONS: Our analyses showed that failure of the left internal mammary arteries to LAD bypass is a very uncommon event. For the non-LAD distribution, the non-use of radial artery, age, female gender, left ventricular ejection fraction<50% and use of the Y graft configuration were significantly associated with mid-term graft failure.
Gaudino M, Benedetto U, Fremes S, et al., 2019, The RADial artery International ALliance (RADIAL) extended follow-up study: rationale and study protocol, European Journal of Cardio-Thoracic Surgery, Vol: 56, Pages: 1025-1030, ISSN: 1010-7940
It is generally accepted that radial artery (RA) grafts have better mid-term patency rate compared to saphenous vein grafts. However, the clinical correlates of the improved patency rate are still debated. Observational studies have suggested increased survival and event-free survival for patients who receive an RA rather than a saphenous vein, but they are open to bias and confounders. The only evidence based on randomized data is a pooled meta-analysis of 6 randomized controlled trial comparing the RA and the saphenous vein published by the RADial artery International Alliance (RADIAL). In the RADIAL database, improved freedom from follow-up cardiac events (death, myocardial infarction and repeat revascularization) was found at 5-year follow-up in the RA arm. The most important limitation of the RADIAL analysis is that most of the included trials had an angiographic follow-up in the first 5 years and it is unclear whether the rate of repeat revascularization (the main driver of the composite outcome) was clinically indicated due to per-protocol angiographies. Here, we present the protocol for the long-term analysis of the RADIAL database. By extending the follow-up beyond the 5th postoperative year (all trials except 1 did not have angiographic follow-up beyond 5 years), we aim to provide data on the role of RA in coronary artery bypass surgery with respect to long-term outcomes.
Taggart DP, Webb CM, Desouza A, et al., 2018, Long-term performance of an external stent for saphenous vein grafts: the VEST IV trial, Journal of Cardiothoracic Surgery, Vol: 13, ISSN: 1749-8090
BackgroundExternally stenting saphenous vein grafts reduces intimal hyperplasia, improves lumen uniformity and reduces oscillatory shear stress 1 year following surgery. The present study is the first to present the longer-term (4.5 years) performance and biomechanical effects of externally stented saphenous vein grafts.MethodsThirty patients previously implanted with the VEST external stent in the randomized, within-patient-controlled VEST I study were followed up for adverse events; 21 of these were available to undergo coronary angiography and intravascular ultrasound.ResultsTwenty-one stented and 29 nonstented saphenous vein grafts were evaluated by angiography and ultrasound at 4.5 ± 0.3 years. Vein graft failure rates were comparable between stented and nonstented grafts (30 and 23% respectively; p = 0.42). All failures were apparent at 1 year except for one additional nonstented failure at 4.5 years. In patent vein grafts, Fitzgibbon perfect patency remained significantly higher in the stented versus nonstented vein grafts (81 and 48% respectively, p = 0.002), while intimal hyperplasia area (4.27 mm2 ± 1.27 mm2 and 5.23 mm2 ± 1.83 mm2 respectively, p < 0.001) and thickness (0.36 mm ± 0.09 mm and 0.42 mm ± 0.11 mm respectively, p < 0.001) were significantly reduced. Intimal hyperplasia proliferation correlated with lumen uniformity and with the distance between the stent and the lumen (p = 0.04 and p < 0.001 respectively).ConclusionsExternal stenting mitigates saphenous vein graft remodeling and significantly reduces diffuse intimal hyperplasia and the development of lumen irregularities 4.5 years after coronary artery bypass surgery. Close conformity of the stent to the vessel wall appears to be an important factor.
Richards T, Collins P, Webb C, 2018, Factors affecting participation in cardiovascular clinical research – a comparison of men and women, British Association for Cardiovascular Prevention & Rehabilitation
Webb CM, Collins P, 2017, Role of testosterone in the treatment of cardiovascular disease, European Cardiology Review, Vol: 12, ISSN: 1758-3756
Cardiovascular disease (CVD) is the most prevalent non-communicable cause of death worldwide. Testosterone is a sex hormone that is predominant in males but also occurs in lower concentrations in females. It has effects directly on the blood vessels of the cardiovascular system and on the heart, as well as effects on risk factors for CVD. Serum testosterone concentrations are known to decrease with age and reduced testosterone levels are linked to premature coronary artery disease, unfavourable effects on CVD risk factors and increased risk of cardiovascular mortality independent of age. A significant number of men with heart failure demonstrate reduced serum testosterone concentrations and there is early evidence suggesting that low testosterone levels affect cardiac repolarisation. Any association between endogenous testosterone concentrations and CVD in women has yet to be established. Testosterone replacement is used to treat men with hypogonadism but also has cardiovascular effects. This review will present the current evidence, expert opinion and controversies around the role of testosterone in the pathophysiology of CVD and surrounding the use of testosterone treatment and its effects on the cardiovascular system and CVD.
Collins P, Webb CM, de Villiers TJ, et al., 2016, Cardiovascular risk assessment in women - an update, Climacteric, Vol: 19, Pages: 329-336, ISSN: 1473-0804
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in postmenopausal women. Although it is a disease of aging, vascular disease initiates much earlier in life. Thus, there is a need to be aware of the potential to prevent the development of the disease from an early age, and continue this surveillance throughout life. The menopausal period and early menopause presents an ideal opportunity to assess cardiovascular risk and plan accordingly. Generally in this period, women will be seen by primary health care professionals and non-cardiovascular specialists. This review addresses female-specific risk factors that may contribute to the potential development of CVD. It is important for all health care professionals dealing with women in midlife and beyond, to be cognisant of these risk factors and to initiate female specific preventative measures or to refer to a cardiovascular specialist.
Webb CM, Collins P, 2016, Syndrome X: how should it be investigated and treated?, Dialogues in Cardiovascular Medicine, Vol: 21, Pages: 191-195, ISSN: 1272-9949
Webb CM, Rosano GMC, Kaski J-C, et al., 2016, Twenty-five year follow-up of patients with chest pain and smooth, unobstructed epicardial coronary arteries, ESC Congress 2016, Publisher: Oxford University Press (OUP), ISSN: 1522-9645
Webb CM, Collins P, 2016, Coronary heart disease in women
Dr Carolyn Webb and Professor Peter Collins highlight common presenting symptoms in women with coronary heart disease (CHD) and reflects on the need to take a careful gynaecological history. Key learning points for healthcare professionals include the influence of female-specific factors on the development of CHD, and conditions that raise cardiovascular risk including polycystic ovary syndrome.
Webb CM, Orion E, Taggart DP, et al., 2015, OCT imaging of aorto-coronary vein graft pathology modified by external stenting: 1-year post-surgery, European Heart Journal Cardiovascular Imaging, Vol: 17, Pages: 1290-1295, ISSN: 2047-2412
Aims The Venous External Support Trial (VEST) evaluated whether a novel external stent attenuated saphenous vein graft (SVG) disease assessed with intravascular ultrasound 1 year following coronary artery bypass graft (CABG) surgery. This sub-study assessed SVGs with and without external stenting using optical coherence tomography (OCT). The aim of this study was to accurately compare quantitative and qualitative features of SVGs with and without a novel external stent using OCT.Methods and results Twenty-four of 30 patients (65 ± 8 years) enrolled in VEST underwent coronary angiography with OCT imaging using a non-occlusive technique. Quantitative analysis of lumen area was performed in one frame every 10 mm along the length of the graft, from distal to proximal anastomosis, and pathological features within the lumen were noted. Mean cross-sectional area was greater in unstented vs. stented grafts (8.4 ± 3 vs. 7.6 ± 2.7 mm; P = 0.005). The lumen of the stented grafts was more homogeneous (difference between maximum and minimum lumen diameter was significantly smaller in stented compared with unstented grafts, 0.28 ± 0.19 vs. 0.33 ± 0.23 mm, respectively, P = 0.006), and more circular (mean eccentricity index 0.08 ± 0.06 vs. 0.10 ± 0.06, stented vs. unstented; P = 0.019). Adherent thrombus was identified in three grafts (all unstented).Conclusion Our findings highlight the early changes occurring in SVGs after implantation of aorto-coronary bypass conduits, changes that may accelerate vein graft failure. External stenting resulted in a more homogeneous and less eccentric lumen with no thrombus formation.
Meirson T, Orion E, Di Mario C, et al., 2015, Flow patterns in externally stented saphenous vein grafts and development of intimal hyperplasia., Journal of Thoracic and Cardiovascular Surgery, Vol: 150, Pages: 871-879, ISSN: 1097-685X
BACKGROUND: Low and oscillatory wall shear stress promotes endothelial dysfunction and vascular disease. The aim of the study was to investigate the impact of an external stent on hemodynamic flow parameters in saphenous vein grafts (SVGs) and their correlation with the development of intimal hyperplasia. METHODS: We performed post hoc computational fluid dynamics analysis of the randomized Venous External Support Trial, in which angiography and intravascular ultrasound data were available for 29 patients, 1 year after coronary artery bypass grafting. Each patient received 1 external stent, to either the right or left coronary territories; ≥1 patients with nonstented SVGs served as control(s). Diffuse flow patterns were assessed using mean values of various hemodynamic parameters, including time-averaged wall shear stress and oscillatory shear index (OSI). Focal flow disturbances were characterized using percentile analysis of each parameter. RESULTS: Angiography and intravascular ultrasound data were available for 53 and 43 SVGs, respectively. The stented versus nonstented SVG failure rates were significantly lower in the left territory (17.6% vs 27.5%; P = .02), and significantly higher in the right territory (46.2% vs 13.4%; P = .01). In both diffuse and focal flow-pattern analyses, OSI was significantly lower in the stented versus nonstented SVG group (P = .009 and P < .003, respectively), whereas no significant differences were observed in time-averaged wall shear stress values. High OSI values were correlated with the development of intimal hyperplasia (P = .01). CONCLUSIONS: External stenting affects SVG's hemodynamics 1 year after coronary artery bypass grafting and may mitigate the progression of intimal hyperplasia by reducing oscillatory shear stress.
Taggart DP, Ben Gal Y, Lees B, et al., 2015, A randomized trial of external stenting for saphenous vein grafts in coronary artery bypass grafting, Annals of Thoracic Surgery, Vol: 99, Pages: 2039-2045, ISSN: 0003-4975
BackgroundExternal stents inhibit saphenous vein graft (SVG) intimal hyperplasia in animal studies. We investigated whether external stenting inhibits SVG diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery.MethodsThirty patients with multivessel disease undergoing coronary artery bypass graft surgery were enrolled. In addition to an internal mammary artery graft, each patient received one external stent to a single SVG randomly allocated to either the right or left coronary territories; and one or more nonstented SVG served as the control. Graft patency was confirmed at the end of surgery in all patients. The primary endpoint was SVG intimal hyperplasia (mean area) assessed by intravascular ultrasonography at 1 year. Secondary endpoints were SVG failure, ectasia (>50% initial diameter), and overall uniformity as judged by Fitzgibbon classification.ResultsOne-year follow-up angiography was completed in 29 patients (96.6%). All internal mammary artery grafts were patent. Overall SVG failure rates did not differ significantly between the two groups (30% stented versus 28.2% nonstented SVG, p = 0.55). The SVG mean intimal hyperplasia area, assessed in 43 SVGs, was significantly reduced in the stented group (4.37 ± 1.40 mm2) versus nonstented group (5.12 ± 1.35 mm2, p = 0.04). In addition, stented SVGs demonstrated marginally significant improvement in lumen uniformity (p = 0.08) and less ectasia (6.7% versus 28.2%, p = 0.05). There was some evidence that ligation of side branches with metallic clips increased SVG failure in the stented group.ConclusionsExternal stenting has the potential to improve SVG lumen uniformity and reduce diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery.
Webb CM, Collins P, 2012, Hormonal changes in cardiac syndrome X - Role of testosterone, Chest Pain with Normal Coronary Arteries: A Multidisciplinary Approach, Pages: 303-307, ISBN: 9781447148371
Cardiac Syndrome X occurs predominately in peri- or post-menopausal women. The onset of the chest pain associated with Cardiac Syndrome X coincides with the menopause or hysterectomy and the related decrease in circulating ovarian hormones. As well as estrogens and progestogens, testosterone is synthesized in the ovaries and adrenal glands of women, and has important physiological actions in women, either directly via androgen receptors or as precursors of estrogen production. Testosterone replacement can be given to menopausal women, with or without estrogen, to increase libido, relieve menopausal symptoms, increase bone density and improve quality of life. As well as chest pain, common symptoms of Cardiac Syndrome X include tiredness and lethargy, and it is feasible that reduced androgen concentrations may be involved in the pathophysiology of the syndrome. Relatively few studies have investigated the effects of testosterone replacement in women, and even fewer in women with Cardiac Syndrome X. Further studies are needed to better understand the role of testosterone in the pathophysiology and treatment of Cardiac Syndrome X.
Asbury EA, Webb CM, Probert H, et al., 2012, Cardiac Rehabilitation to Improve Physical Functioning in Refractory Angina: A Pilot Study, CARDIOLOGY, Vol: 122, Pages: 170-177, ISSN: 0008-6312
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- Citations: 30
Asbury EA, Webb CM, Probert H, et al., 2012, Exercise Training for Refractory Angina: Improving the Coronary Collateral Circulation Reply, CARDIOLOGY, Vol: 123, Pages: 80-80, ISSN: 0008-6312
Asbury E, Webb C, Probert H, et al., 2011, Cardiac Rehabilitation Improves Physical Functioning in Refractory Angina, CIRCULATION, Vol: 124, ISSN: 0009-7322
Webb CM, Collins P, Moat NE, et al., 2011, Response to Letters Regarding Article, "Vascular Reactivity and Flow Characteristics of Radial Artery and Long Saphenous Vein Coronary Bypass Grafts: A 5-Year Follow-Up", CIRCULATION, Vol: 123, Pages: E414-E414, ISSN: 0009-7322
Asbury EA, Webb CM, Collins P, 2011, Group support to improve psychosocial well-being and primary-care demands among women with cardiac syndrome X, CLIMACTERIC, Vol: 14, Pages: 100-104, ISSN: 1369-7137
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- Citations: 10
Webb CM, Collins P, 2010, Testosterone and coronary artery disease in men, MATURITAS, Vol: 67, Pages: 15-19, ISSN: 0378-5122
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- Citations: 17
Webb CM, Moat NE, Chong CF, et al., 2010, Vascular Reactivity and Flow Characteristics of Radial Artery and Long Saphenous Vein Coronary Bypass Grafts A 5-Year Follow-Up, CIRCULATION, Vol: 122, Pages: 861-867, ISSN: 0009-7322
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- Citations: 22
Collins P, Webb CM, Chong CF, et al., 2008, Radial artery versus saphenous vein patency randomized trial - Five-year angiographic follow-up, CIRCULATION, Vol: 117, Pages: 2859-2864, ISSN: 0009-7322
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- Citations: 222
Webb CM, Elkington AG, Kraidly MM, et al., 2008, Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease, AMERICAN JOURNAL OF CARDIOLOGY, Vol: 101, Pages: 618-624, ISSN: 0002-9149
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- Citations: 81
Webb CM, Hayward CS, Mason MJ, et al., 2008, Coronary vasomotor and blood flow responses to isoflavone-intact soy protein in subjects with coronary heart disease or risk factors for coronary heart disease, Clin. Sci. (Lond)., Vol: Epub ahead of print
Webb CM, Collins P, 2007, Androgens and arterial disease, Edition, Pages: 511-515, ISBN: 9780415425803
Historically androgens have been considered a risk factor for coronary artery disease in men, since postmenopausal women have a lower incidence of coronary heart disease and myocardial infarction than men of a similar age. However, there has been no direct evidence linking physiologic concentrations of androgens to an increased incidence of coronary heart disease and myocardial infarction, and recent evidence suggests that the reverse may be true. In a study examining the effect of risk factors (including estradiol and testosterone) on predicting myocardial infarction in males who had not had a previous myocardial infarction, Phillips and coworkers1 raised the possibility that hypotestosteronemia in men may be a risk factor for coronary atherosclerosis. Serum total and free testosterone levels were negatively correlated with degree of risk of coronary artery disease and with risk factors for myocardial infarction. These findings have been confirmed by other studies.2,3 Decreased total and free testosterone levels have been shown to be associated with ischemic stroke in men,4 further implicating testosterone in the pathophysiology of vascular diseases. Declining levels of the androgen dehydroepiandrosterone sulfate (DHEAS) have been associated with an increased risk of vascular disease.5 Confusion arises from data concerning the use of high doses of androgens (anabolic steroids) to increase muscle mass and athletic performance, where there is a well-documented increase in incidence of cardiovascular events.
Webb CM, Collins P, Chong CF, et al., 2006, A randomized trial of radial artery and saphenous vein grafts: 5-year patency, 79th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 433-433, ISSN: 0009-7322
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- Citations: 2
Chong WCF, Collins P, Webb CM, et al., 2006, Comparison of flow characteristics and vascular reactivity of radial artery and long saphenous vein grafts [NCT00139399], JOURNAL OF CARDIOTHORACIC SURGERY, Vol: 1, ISSN: 1749-8090
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- Citations: 24
Webb CM, Collins P, Di Mario C, 2005, Normal coronary physiology assessed by intracoronary Doppler ultrasound, HERZ, Vol: 30, Pages: 8-16, ISSN: 0340-9937
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- Citations: 5
Elkington AG, Webb CM, Gatehouse PD, et al., 2004, Chronic testosterone treatment in men with coronary artery disease: A study with perfusion cardiovascular magnetic resonance, 77th Scientific Meeting of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 573-573, ISSN: 0009-7322
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