M Griffin

Cyprus University of Technology, Leymosun, Lemesos, Cyprus

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Publications (100)241.04 Total impact

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    ABSTRACT: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
    Nature Genetics 12/2014; · 35.21 Impact Factor
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    ABSTRACT: Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence-based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤ 2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤ 7.0%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.
    International angiology: a journal of the International Union of Angiology 06/2014; · 1.46 Impact Factor
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    ABSTRACT: Aim: The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events. Methods: Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models. Results: Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (Pfor trend=0.006 and P=0.001, respectively) and inflammatory factors (Pfor trend=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (ORadjusted=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >1000 ng/mL had a 75% reduced odds for CVD compared to the rest (ORadjusted=0.25; 95% CI=0.11 to 0.60; Pfor trend=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease. Conclusion: A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.
    International angiology: a journal of the International Union of Angiology 12/2013; 32(6):599-604. · 1.46 Impact Factor
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    ABSTRACT: The aim of this document is to provide a clear and concise account of the evidence regarding efficacy or harm for various methods available to prevent and manage venous thromboembolism (VTE).
    International angiology: a journal of the International Union of Angiology 04/2013; 32(2):111-260. · 1.46 Impact Factor
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    ABSTRACT: Carotid plaques have been associated with ipsilateral neurological symptoms. High-resolution ultrasound can provide information not only on the degree of carotid artery stenosis but also on the characteristics of the arterial wall including the size and consistency of atherosclerotic plaques. The aim of this study is to determine whether the addition of ultrasonic plaque texture features to clinical features in patients with asymptomatic internal carotid artery stenosis (ACS) improves the ability to identify plaques that will produce stroke. 1121 patients with ACS have been scanned with ultrasound and followed for a mean of 4 years. It is shown that the combination of texture features based on second-order statistics spatial gray level dependence matrices (SGLDM) and clinical factors improves stroke prediction (by correctly predicting 89 out of the 108 cases that were symptomatic). Here, the best classification results of 77 ±1.8% were obtained from the use of the SGLDM texture features with support vector machine classifiers. The combination of morphological features with clinical features gave slightly worse classification results of 76 ±2.6% . These findings need to be further validated in additional prospective studies.
    IEEE transactions on information technology in biomedicine: a publication of the IEEE Engineering in Medicine and Biology Society 04/2012; 16(5):966-73. · 1.69 Impact Factor
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    ABSTRACT: Electrical stimulation of calf muscles has been shown to be effective in prevention of DVT. The aim was to determine: (a) dependence of venous blood velocity and ejected volume on the rates of stimulated calf contractions: (b) clinical factors affecting efficacy in healthy individuals. The maximum intensity stimulus tolerated was applied to calves of 24 volunteers. In popliteal veins, peak systolic velocities (PSV), ejected volume per individual stimulus (stroke volume SV) and ejected total volume flow per minute (TVF) of expelled blood were determined using ultrasound. Stimulation rates from 2 to 120 beats per minute (bpm) were applied. Mean baseline popliteal PSV was 10 cm/s. For stimulation rates between 2 and 8 bpm, the PSV was 10 times higher and reached 96-105 cm/s. Stroke volume (SV) per individual stimulus decreased in a similar fashion. With increasing rates of stimulation the TVF increased by a factor of 12 times (from 20 ml/min to 240 ml/min). Electrical stimulation is an effective method of activating the calf muscle pump. Enhancements of popliteal blood velocity and volume flow are key factors in the prevention of venous stasis and DVT. Further studies are justified to determine the stimulation rates in those with a compromised venous system.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 12/2010; 40(6):766-71. · 2.92 Impact Factor
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    ABSTRACT: Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis.
    Current Vascular Pharmacology 09/2010; 8(5):673-81. · 2.91 Impact Factor
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    ABSTRACT: Different ultrasonic arterial wall measurements have been used as predictors of future myocardial infarction or stroke. The aim of the present study was to determine the relationship of total plaque area (TPA) (the sum of the atherosclerotic plaque area measurements from both carotid and both common femoral arteries) with prevalence of cardiovascular disease in a population-based cross-sectional study and compare it with intima-media thickness (IMT). Seven hundred sixty-two individuals (47% male) over the age of 40 were screened for cardiovascular risk factors. Evidence of clinical cardiovascular disease was present in 113 (14.8%). Both carotid and both common femoral bifurcations were scanned with ultrasound. After adjustment for conventional risk factors the association of IMT with prevalence of clinical cardiovascular disease was low (P=0.84, OR of upper IMT quintile 1.36; 95% CI 0.56 to 3.26) and of TPA high (P<0.001, OR of upper TPA quintile 8.38; 95% CI 2.57 to 27.32). TPA greater than 42 mm2 (cut-point derived from ROC curve analysis) identified 266 (34.9%) of the population that contained 87/113 (76.9%) of the clinical events (sensitivity: 77%; specificity: 73%; positive predictive value: 33%; negative predictive value: 94%; positive likelihood ratio of 2.79). In contrast, IMT greater than 0.07 mm had a sensitivity, specificity, positive and negative predictive value and positive likelihood ratio of 68%, 60%, 23%, 91% and 1.69 respectively. Total plaque area appears to be more strongly associated with the prevalence of cardiovascular disease than IMT. This finding warrants further prospective studies.
    International angiology: a journal of the International Union of Angiology 06/2010; 29(3):216-25. · 1.46 Impact Factor
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    ABSTRACT: Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. Cross-sectional study of consecutive patients with significant (>50%) ICA stenosis. Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (>50%) ICA stenosis. The asymptomatic and symptomatic groups did not differ in terms of gender distribution (P=0.76) and severity of stenosis (P=0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (P=0.004, OR=2.13, 95% CI=1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (P=0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation.
    The Journal of cardiovascular surgery 04/2010; 51(2):245-51. · 1.51 Impact Factor
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    ABSTRACT: Our aim was to test the association of mean leukocyte telomere length (LTL) with ultrasonic measures of subclinical atherosclerosis such as intima-media thickness in the common carotid (IMTcc) and sum of plaque areas (SPA) and with serological markers. Carotid and femoral bifurcations were scanned in 762 general population volunteers (46% men) over 40. Four features were considered: (a) IMTcc, (b) sum plaque areas of carotid plaques (SPAcar), (c) sum plaque area of common femoral plaques (SPAfem) and (d) sum plaque area (SPA--sum of the plaque areas of the largest plaques present in each of both carotid and femoral bifurcations). Mean LTL was determined with a quantitative real-time PCR-based method. IMTcc was strongly associated with mean LTL both before and after correction for traditional risk factors (B=-0.002; 95% CI=-0.004 to -0.00; p=0.014). In sex-specific analysis, the association was stronger in men (p for sex interaction<0.001). SPAfem was associated with LTL in women before and after correction (B=-0.195; 95% CI=-0.38 to -0.01; p=0.037) (p for sex interaction<0.001). LTL was also associated with age and sex-adjusted levels of hsCRP (p=0.012), sCD40L (p=0.042), homocysteine (p=0.006), creatinine (p=0.02), ApoA1 (p=0.01), Lp(a) (p=0.04) and HOMA-IR (p=0.008). Our results support the telomere hypothesis and highlight potential differences in the biological mechanisms leading to intima-media thickening and/or plaque formation between vascular beds. They may provide insights into a novel treatment of antisenescence to prevent atherosclerosis.
    Atherosclerosis 02/2010; 211(1):176-81. · 3.71 Impact Factor
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    ABSTRACT: Background: The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods: This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results: A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with <70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and <20% in 84 patients. Conclusion: Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone.
    Journal of Vascular Surgery 01/2010; 52(6):1486-1496. · 2.88 Impact Factor
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2010; 11(2):50-50.
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    ABSTRACT: Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis.
    Current Vascular Pharmacology 01/2010; 8(5):682-91. · 2.91 Impact Factor
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    ABSTRACT: The common carotid intima-media thickness (IMT) is considered as a marker of cardiovascular disease, while the value of the common femoral IMT is not well defined. The aim of the present study was to investigate the value of common femoral IMT alone or in combination with the common carotid IMT as a marker of cardiovascular disease in asymptomatic adults. Eighty-three individuals with no history of cardiovascular disease were subjected to IMT measurement of both common carotid and common femoral arteries with high-resolution ultrasonography. The Framingham Heart Study (FHS) risk score was calculated for each subject (according to gender) and was correlated with the carotid IMT, femoral IMT, and the combined IMT measured at both arterial sites. The carotid and femoral IMT separately and in combination were found to be correlated with the FHS risk score, calculated based on either the total cholesterol or low density lipoprotein plasma levels (carotid IMT: r = 0.28, p = 0.035, and r = 0.35, p = 0.007, respectively, femoral IMT: r = 0.38, p = 0.003, and r = 0.43, p = 0.001, respectively, carotid-femoral IMT: r = 0.37, p = 0.005, and r = 0.46, p = 0.0001, respectively). In addition, femoral IMT was found to be correlated with the carotid IMT (r = 0.41, p = 0.001). Common carotid and common femoral IMT showed similar correlation with the FHS risk score. Additionally, the combination of IMT from both arterial sites was found to have similar correlation with the FHS risk score to carotid IMT alone.
    VASA.: Zeitschrift für Gefässkrankheiten. Journal for vascular diseases 06/2009; 38(2):147-54. · 1.01 Impact Factor
  • Journal of Vascular Surgery 01/2009; 49(4-49):902-909. · 2.88 Impact Factor
  • Atherosclerosis 01/2009; 207(1). · 3.71 Impact Factor
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2009; 10(2).
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    ABSTRACT: Objectives: This study tested the hypothesis that silerit embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. Methods: In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. Results: During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with <60% stenosis, embolic infarcts were not associated with increased risk (log-rank P = .65). In patients with 60% to 99% stenosis, the cumulative stroke-free rate was 0.92 (1.0% annual stroke rate) when embolic infarcts were absent and 0.71 (3.6% annual stroke rate) when present (log-rank P = .002). In the subgroup of 216 with moderate 60% to 79% stenosis, the cumulative TIA or stroke-free rate in the absence and presence of embolic infarcts was 0.90 (1.3% annual rate) and 0.65 (4.4% annual rate), respectively (log-rank P = .005). Conclusion: The presence of silent embolic infarcts can identify a high-risk group for ipsilateral hemispheric neurologic events and stroke and may prove useful in the management of patients with moderate asymptomatic carotid stenosis.
    Journal of Vascular Surgery 01/2009; 49(4):902-909. · 2.88 Impact Factor
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    ABSTRACT: It has been demonstrated that an increased apolipoprotein B (ApoB)/apolipoprotein A-I (ApoA1) ratio is associated with atherogenic low density lipoprotein (LDL) particles and the development of clinical cardiovascular disease. The aim of this study was to test the hypothesis that ApoB/ApoA1 ratio is associated with early subclinical atherosclerosis as demonstrated by ultrasonic measurements. Both common carotid and common femoral bifurcations have been scanned with high-resolution ultrasound in 767 volunteers over the age of 40. The latter consisted of 95% of the population of two randomly selected areas. IMTcc, IMTmax (including plaques), total plaque thickness (TPT) (the sum of the thickest plaques present at each bifurcation in cm) and black plaque burden (BPB) (TPT means plaque type) using the Widder classification with type 1 being the most hyperechoic and calcified and type 5 the most hypoechoic plaque were recorded. A medical history was taken with emphasis on risk factors present and a fasting lipid profile including ApoB and ApoA1 was determined. In the total population (N.=767) the mean (+/-SD) ApoB/ApoA1 ratio was 0.85 (+/-0.22). In linear regression analysis, the Apob/ApoA1 ratio was significantly associated with all the ultrasonic measurements of early atherosclerosis (intima media thickness, IMTcc, IMTmax, TPT and BPB). These findings remained significant after correcting for age, gender, smoking, hypertension and diabetes (P<0.001 for all). The results indicate that a high ApoB/ApoA1 ratio is associated not only with early atherosclerosis but also with hypoechoic (BPB) and by inference unstable plaques.
    International angiology: a journal of the International Union of Angiology 02/2008; 27(1):74-80. · 1.46 Impact Factor

Publication Stats

1k Citations
241.04 Total Impact Points

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Institutions

  • 2013
    • Cyprus University of Technology
      Leymosun, Lemesos, Cyprus
  • 2009–2010
    • General University Hospital of Larissa
      Lárissa, Thessaly, Greece
  • 2008
    • University of Cyprus
      Lefkoşa, Lefkosia, Cyprus
  • 2001–2005
    • Imperial College London
      • Faculty of Medicine
      London, ENG, United Kingdom
    • Ealing Hospital NHS Trust
      Londinium, England, United Kingdom
  • 1996–2002
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Division of Oral Surgery
      Chieta, Abruzzo, Italy
  • 2000
    • Soroka Medical Center
      • Department of Vascular Surgery
      Be'er Sheva`, Southern District, Israel
    • WWF United Kingdom
      Londinium, England, United Kingdom