Biomedical subjects

Alun H Davies

Publications and source records attributed to Alun H Davies.

7 recordsLinked to original sources

PubMed2025

Genome-wide association studies in chronic venous disease: A systematic review.

BACKGROUND: Chronic venous disease (CVD) arises from venous hypertension secondary to impaired venous return, causing significant morbidity and diminished quality of life. Genetic factors are likely important in the pathogenesis and susceptibility of a patient to develop CVD. This systematic review summarizes genome-wide association studies (GWASs) that investigate the link between genetic variants and CVD. METHODS: A systematic review was conducted in accordance with the PRISMA guidelines, with the search dates ranging from January 1, 1994, to July 17, 2025. Abstract and full-text screening were completed by two independent reviewers, with any conflicts referred to a third senior reviewer. GWASs in adults investigating links between genetic variants and CVD were included. Exclusion criteria included patients with venous thromboembolism, arterial or diabetic disease, or animal models. RESULTS: Thirteen studies were included after screening 517 studies from a search of PubMed, EMBASE, and Ovid. Database sources included UK Biobank, FinnGen, PopGen, and country- or hospital-specific databases with a majority Caucasian and European patient cohort. A total of 602,760 patients were identified with varicose veins and 3,664,604 control cases that were studied with GWASs and other statistical methods including a two-sample Mendelian randomization approach, functional mapping, and genetic correlations. A variety of statistically significant genetic polymorphisms were identified that can be attributed to the heritability of varicose veins affecting inflammation and immunity (eg, PPP3R1, EBF1, and GATA2), hypertension (eg, CASZ1), and vascular architecture (eg, CASZ1, PIEZO1, and STIM2). Protective variants (eg, GJD3, MMP10, and 4EBP1) were also identified in Finnish populations. However, replication studies showed that these genetic polymorphisms are not generalizable to specific populations. CONCLUSIONS: This systematic review highlights genes contributing to the development of CVD that have been identified in the literature. An improved understanding of genetic contributions to the pathogenesis of CVD may inform future diagnostics, prognostics, and personalized treatment. Further larger scale studies representative of global populations, including meta-analyses of genome-wide association datasets, are required owing to individual GWASs being statistically insufficient to draw generalizable conclusions.

Humans↗

PubMed2006

The potassium channel opener levcromakalim causes expansive remodelling of experimental vein grafts.

BACKGROUND: Maintenance of luminal area is essential for the optimal performance of venous bypass grafts. However, injury and response to the arterial circulation evoke vascular remodelling that favors intimal hyperplasia, with luminal encroachment and inward remodelling. Potassium channel-opening drugs reduce tissue workload and peripheral vascular resistance and through these mechanisms could favor outward or expansive remodelling of vein grafts. We tested the hypothesis that levcromakalim, a potassium channel opener, would enhance expansive remodelling in vein grafts. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 33 rats with vena cava-to-aorta bypass grafts. Drugs were administered via osmotic pump for 7 days after surgery. Half the cohort had bromodeoxyuridine (BrdU) infused at day 6. Morphometric analysis was conducted of pressure perfusion-fixed grafts harvested at 1 week and 4 weeks. RESULTS: At 1 week, lumen area was similar in both groups (1.82 +/- 0.39 mm(2) placebo vs 1.85 +/- 0.36 mm(2) levcromakalim), although medial cell density and BrdU staining were significantly increased in the placebo group. At 4 weeks, lumen area was unchanged in the placebo group (1.88 +/- 0.51 mm(2)) but had increased to 2.32 +/- 0.46 mm(2) in the levcromakalim group (P = .039 vs 1 week), with a very significant reduction in the intimal area (levcromakalim, 0.06 +/- 0.02 mm(2) vs placebo, 0.33 +/- 0.17 mm(2); P = .001). CONCLUSIONS: Early, short-term treatment with levcromakalim favors expansive remodelling of experimental vein grafts to mimic the effect of external stenting. This expansive remodelling was associated with a reduction in medial cell proliferation at 1 week. CLINICAL RELEVANCE: Critical limb ischemia can be treated by bypass surgery or angioplasty, but inward remodelling with restenosis is a common problem. There has been little previous experimental work to identify treatments associated with expansive remodelling, which would increase the chances of vessel patency. Here, in a randomized trial, we show that short-term treatment with a potassium channel opener (a class of drug that can be used to treat hypertension) results in strong, expansive remodelling, with increases the lumen area and graft size of experimental vein grafts by >25%.

Animals↗

PubMed2006

The ischaemic leg.

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Acute Disease↗

PubMed2005

Association between carotid artery intima-media thickness and cardiovascular risk factors in CKD.

BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) correlates with cardiovascular events in the general population and is an independent predictor of cardiovascular mortality in the hemodialysis population. It has not been evaluated extensively in patients with chronic kidney disease. METHODS: CCA-IMT was measured by using high-resolution B-mode ultrasonography, and glomerular filtration rate (GFR) was measured by means of EDTA clearance. Cardiovascular risk factors assessed included homocysteine and lipoprotein(a) levels, as well as smoking, blood pressure, and cholesterol level. RESULTS: One hundred fourteen patients were studied; mean measured GFR was 29.6 +/- 18.4 mL/min/1.73 m2 (0.49 +/- 0.31 mL/s). CCA-IMT was significantly elevated (0.59 +/- 0.22 cm) compared with a control group (0.44 +/- 0.08 cm; P = 0.0012). CCA-IMT increases with age (P < 0.0001) and low-density lipoprotein level (P = 0.048) and decreases with high-density lipoprotein level (P = 0.001) and being white (P = 0.014). CONCLUSION: This study suggests that arterial changes occur early in the course of renal disease progression and may be related to dyslipidemia in the early stages.

Adult↗

PubMed2002

Circumferential stretching of saphenous vein smooth muscle enhances vasoconstrictor responses by Rho kinase-dependent pathways.

OBJECTIVE: Surgical preparation and/or pulsatile arterial perfusion of saphenous vein increases the sensitivity of vein rings to calcium mobilising agonists such as phenylephrine. We have investigated the mechanism(s) underlying this effect. METHODS: We have used an ex vivo flow circuit, with simulated arterial or venous flows (mean pressure 100 and 20 mmHg, respectively), to investigate the sensitivity of human saphenous vein to phenylephrine, 5-hydroxytryptamine (5-HT) and KCl, using organ chamber pharmacology. RESULTS: After 90 min of pulsatile arterial perfusion the mean maximum tension induced by KCl had increased from 4.7 to 11.1 g (n=5), by phenylephrine had increased from 4.4 to 10.2 g (n=8) and by 5-HT had increased from 4.4 to 6.7 g (n=10), all P<0.01. Phenylephrine did not augment the tension in vein rings maximally precontracted with KCl (n=4). The EC(50) for KCl was unchanged after pulsatile arterial perfusion (n=5), but for phenylephrine and 5-HT there were significant reductions from 14+/-5 to 2+/-1 microM (n=8) and from 1.0+/-0.4 to 0.20+/-0.06 microM (n=10), respectively. The rate of contraction (in response to 3 microM phenylephrine) increased from 0.11 g/min to 0.37 g/min, P<0.02, after arterial perfusion (n=4). These changes in contractile properties (to phenylephrine) were endothelium-independent, evident within 5 min of simulated arterial perfusion. The changes in contractile properties could be abrogated by external stenting of the vein (to attenuate circumferential deformation) or inclusion in the perfusate of a vasodilator, e.g., cromakalim (5 microM) or the selective Rho kinase inhibitor Y-27632 (20 microM). The heightened sensitivity and contractility to phenylephrine was maintained after inclusion of adenosine (100 microM), gadolinium (10 microM) or cycloheximide (10 microM) in the vein perfusate. CONCLUSIONS: The circumferential deformations imposed by simulated arterial perfusion alter the vasomotor responses of saphenous vein smooth muscle. These effects are independent of new protein synthesis or the activation of stretch activated cation channels. The Rho kinase pathway appears to mediate the signalling mechanisms leading to increased agonist-induced tension and the increased sensitivity to vasoconstrictors.

Adenosine↗

PubMed2002

The intermittent claudication questionnaire: a patient-assessed condition-specific health outcome measure.

INTRODUCTION: As yet, there is no patient-assessed, condition-specific instrument for the assessment of health-related quality of life in intermittent claudication. We evaluated the intermittent claudication questionnaire (ICQ) for properties required of a measure of health outcome. METHODS AND RESULTS: Interviews with patients with intermittent claudication and vascular specialist opinion produced a pool of statements used to itemize a self-completed ICQ. This was piloted in 20 patients for practicality and then administered to 124 stable claudicants. Reliability was assessed through a retest in 63 (51%) patients at 14 days and analysis of Cronbach's alpha for internal consistency. Spearman's correlation coefficient was used to assess construct validity in comparisons between the ICQ and ankle brachial pressure index, treadmill-walking distances, the walking impairment questionnaire, the EuroQol, and the Short Form-36. Responsiveness of the ICQ to changes in health was assessed in 60 patients treated conservatively and 40 patients undergoing angioplasty. The standardized response mean was used to identify the most responsive instrument in the study. A 16-item ICQ with a test-retest intraclass correlation of 0.95 and Cronbach's alpha of.94 was produced. One hundred twenty-one (98%) patients completed the ICQ (mean time, 3.7 minutes). The ICQ correlated better with the EuroQol (r = 0.58) and 7 out of 8 subscales of the Short Form-36 (r = 0.33-0.68) compared with the walking impairment questionnaire. The ICQ demonstrated the largest standardized response mean in relation to health transition compared with the other instruments. CONCLUSIONS: The patient-assessed ICQ is a practical, reliable, valid, and responsive measure of patient health-related quality of life in intermittent claudication.

Adult↗

PubMedDate not supplied

Clinical outcome following infra-inguinal percutaneous transluminal angioplasty for critical limb ischemia.

OBJECTIVE: The aim of this study was to assess the efficacy and durability of infra-inguinal PTA in patients with CLI, in terms of clinical outcome. DESIGN: Retrospective study of 50 consecutive patients with CLI that were exclusively treated by infra-inguinal PTA. METHODS: The indications for intervention were rest pain in seven (14%) patients, non-healing ulcers in 27 (54%), and gangrenous lesions in 16 (32%). Thirty-three (66%) of these patients presented with a single arterial lesion, and the remaining 17 (34%) with multilevel arterial lesions. Kaplan-Meier analysis was used to assess survival, patency, limb-salvage rates, and amputation-free survival. RESULTS: A total of 67 endovascular procedures were performed and 59 (88.1%) of them were considered to be technically successful. The median follow-up period was 12 months (interquartile range: 17 months). The 30-day mortality was 4%, while the cumulative survival rates at 12, 24, and 36 months were 73%, 67%, and 59%, respectively. The cumulative primary patency rates at 12 and 24 months were 63% and 52%, respectively, and remained unchanged thereafter. The estimated secondary patency rate was 72% at 36 months. There was only one below-knee amputation in the patients that were treated exclusively with infra-inguinal PTA. The cumulative amputation-free survival at the same period was estimated at 60%. CONCLUSIONS: Infra-inguinal PTA had a good early and late outcome in this series of patients with a limited life expectancy. These results are comparable to historical results of surgical revascularization in the treatment of CLI. There is need for a randomized study to determine the primary optimal interventional approach for patients with CLI.

Aged↗