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1. Matrix Metalloproteinases and Hypertension-Mediated Organ Damage: Current Insights

Author

Bisogni V, Cerasari A, Pucci G, and Vaudo G

Subjects
matrix metalloproteinases, arterial hypertension, hypertension-mediated organ damage, Internal medicine, RC31-1245
Abstract

Valeria Bisogni,1,* Alberto Cerasari,1,2,* Giacomo Pucci,1,2 Gaetano Vaudo1,2 1Unit of Internal Medicine, Terni University Hospital, Terni, Italy; 2Department of Medicine, University of Perugia, Perugia, Italy*These authors contributed equally to this workCorrespondence: Valeria BisogniUnit of Internal Medicine, Terni University Hospital, Via Tristano di Joannuccio, 1, Terni, TR 05100, ItalyTel +39 0744 205328Email valeria.bisogni@hotmail.itAbstract: Matrix metalloproteinases (MMPs) are important extracellular enzymes involved in many physiological and pathological processes. Changes in the activity and concentration of specific MMPs, as well as the unbalance with their inhibitors (tissue inhibitors of metalloproteinases – TIMPs), have been described as a part of the pathogenic cascade promoted by arterial hypertension. MMPs are able to degrade various protein substrates in the extracellular matrix, to influence endothelial cells function, vascular smooth muscle cells migration, proliferation and contraction, and to stimulate cardiomyocytes changes. All these processes can be activated by chronically elevated blood pressure values. Animal and human studies demonstrated the key function of MMPs in the pathogenesis of hypertension-mediated vascular, cardiac, and renal damage, besides age and blood pressure values. Thus, the role of MMPs as biomarkers of hypertension-mediated organ damage and potential pharmacological treatment targets to prevent further cardiovascular and renal complications in hypertensive population is increasingly supported. In this review, we aimed to describe the main scientific evidence about the behavior of MMPs in the development of vascular, cardiac, and renal damage in hypertensive patients.Keywords: matrix metalloproteinases, arterial hypertension, hypertension-mediated organ damage

Published
2020

4. Serum Myostatin is Associated With Central-to-Peripheral Arterial Stiffness Gradient in Healthy Adolescents: The MACISTE Study.

Author

Curcio, R, Nunziangeli, L, Migliola, E Nulli, Battista, F, D'Abbondanza, M, Anastasio, F, Crapa, M E, Sanesi, L, Pucci, G, and Vaudo, G

Subjects
PULSE wave analysis, VASCULAR smooth muscle, ARTERIAL diseases, ENZYME-linked immunosorbent assay, MYOKINES
Abstract

BACKGROUND Myostatin is a protein compound, structurally related to the transforming growth factor-beta protein, which plays a pivotal role in regulating muscle growth and extracellular matrix production. It exerts both profibrotic and antihypertrophic effects on vascular smooth muscle cells. Aim of the study was to explore the potential association between serum myostatin levels (sMSTN) and carotid-femoral pulse wave velocity (cf-PWV), carotid-radial pulse wave velocity (cr-PWV), and their ratio (PWVr), in a cohort of healthy adolescents. METHODS A cohort of 128 healthy subjects (mean age 17 ± 2 years, 59% male) was randomly selected from participants to the MACISTE (Metabolic And Cardiovascular Investigation at School, TErni) study. sMSTN was assessed utilizing an enzyme-linked immunosorbent assay. PWVs were measured in the supine position using high-fidelity applanation tonometry. RESULTS The mean cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s, and PWVr was 0.75 ± 0.12. PWVr exhibited a linear increase across increasing quartiles of sMSTN (0.71 ± 0.1, 0.74 ± 0.1, 0.7 ± 0.1, 0.77 ± 0.1, P for trend = 0.03), whereas the association between sMSTN and each single component of PWVr (cf-PWV, cr-PWV) did not attain statistical significance. Quartiles of sMSTN displayed a positive trend with serum HDL-cholesterol (P  = 0.01) and a negative one with LDL-cholesterol (P  = 0.01). In a multivariate linear model, the association between PWVr and sMSTN was independent of SBP values, age, sex, heart rate, BMI, HDL-cholesterol, and HOMA Index CONCLUSIONS In healthy adolescents, sMSTN showed independent associations with PWVr, a measure of central-to-peripheral arterial stiffness gradient. sMSTN may exert differential effects on the structural and functional properties of the arterial wall. [ABSTRACT FROM AUTHOR]

Published
2024
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7. OC 05.4 Defective Nitric Oxide Production and Increased Reactive Oxygen Species Generation by Platelets from COVID-19 Patients

Author

Petito, E., primary, Guglielmini, G., additional, De Robertis, E., additional, Giglio, E., additional, Becattini, C., additional, Falcinelli, E., additional, Franco, L., additional, Tondi, F., additional, Gori, F., additional, Vaudo, G., additional, Cerotto, V., additional, Paliani, U., additional, and Gresele, P., additional

Published
2023
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9. Quantitative near-infrared spectroscopy on patients with peripheral vascular disease

Author

Franceschini, MA, Fantini, S, Palumbo, R, Pasqualini, L, Vaudo, G, Franceschini, E, Gratton, E, Palumbo, B, Innocente, S, and Mannarino, E

Subjects
peripheral vascular disease, near-infrared spectroscopy, hemoglobin saturation, skeletal muscle
Abstract

We have used near-infrared spectroscopy to measure the hemoglobin saturation at rest and during exercise on patients affected by peripheral vascular disease (PVD). The instrument used in our study is a frequency-domain tissue oximeter which employs intensity modulated (110 MHz) laser diodes. We examined 9 subjects, 3 of which were controls and 6 were patients affected by stage II PVD. The optical probe was located on the calf muscle of the subjects. The measurement protocol consisted of: (1) baseline (∼5 min); (2) stationary bicycle exercise (∼5 min); (3) recovery (∼15 min). The change in hemoglobin saturation during exercise (ΔY) and the recovery time after exercise (trec) were significantly greater in the PVD patients (ΔY = -21±3%, trec= 5.9±3.8 min) than in the control subjects (ΔY = 2±3%, trec = 0.6±0.1 min).

Published
1997

13. Left atrial volume indexed for height2 is a new sensitive marker for subclinical cardiac organ damage in female hypertensive patients

Author

Airale, L, Paini, A, Ianniello, E, Mancusi, C, Moreo, A, Vaudo, G, Avenatti, E, Salvetti, M, Bacchelli, S, Izzo, R, Sormani, P, Arrivi, A, Muiesan, M, Esposti, D, Giannattasio, C, Pucci, G, De Luca, N, Milan, A, Airale L., Paini A., Ianniello E., Mancusi C., Moreo A., Vaudo G., Avenatti E., Salvetti M., Bacchelli S., Izzo R., Sormani P., Arrivi A., Muiesan M. L., Esposti D. D., Giannattasio C., Pucci G., De Luca N., Milan A., Airale, L, Paini, A, Ianniello, E, Mancusi, C, Moreo, A, Vaudo, G, Avenatti, E, Salvetti, M, Bacchelli, S, Izzo, R, Sormani, P, Arrivi, A, Muiesan, M, Esposti, D, Giannattasio, C, Pucci, G, De Luca, N, Milan, A, Airale L., Paini A., Ianniello E., Mancusi C., Moreo A., Vaudo G., Avenatti E., Salvetti M., Bacchelli S., Izzo R., Sormani P., Arrivi A., Muiesan M. L., Esposti D. D., Giannattasio C., Pucci G., De Luca N., and Milan A.

Abstract

Left atrial enlargement (LAe) is a subclinical marker of hypertensive-mediated organ damage, which is important to identify in cardiovascular risk stratification. Recently, LA indexing for height was suggested as a more accurate marker of defining LAe. Our aim was to test the difference in LAe prevalence using body surface area (BSA) and height2 definitions in an essential hypertensive population. A total of 441 essential hypertensive patients underwent complete clinical and echocardiographic evaluation. Left atrial volume (LAV), left ventricular morphology, and systolic-diastolic function were evaluated. LAe was twice as prevalent when defined using height2 (LAeh2) indexation rather than BSA (LAeBSA) (51% vs. 23%, p < 0.001). LAeh2, but not LAeBSA, was more prevalent in females (p < 0.001). Males and females also differed in left ventricular hypertrophy (p = 0.046) and left ventricular diastolic dysfunction (LVDD) indexes (septal Em/Etdi: p = 0.009; lateral Em/Etdi: p = 0.003; mean Em/Etdi: p < 0.002). All patients presenting LAeBSA also met the criteria for LAeh2. According to the presence/absence of LAe, we created three groups (Norm = BSA−/h2-; DilH = BSA−/h2+; DilHB = BSA+/h2+). The female sex prevalence in the DilH group was higher than that in the other two groups (Norm: p < 0.001; DilHB: p = 0.036). LVH and mean and septal Em/Etdi increased from the Norm to the DilH group and from the DilH to the DilHB group (p < 0.05 for all comparisons). These results show that LAeh2 identified twice as many patients as comparing LAe to LAeBSA, but that both LAeh2 and LAeBSA definitions were associated with LVH and LVDD. In female patients, the LAeh2 definition and its sex-specific threshold seem to be more sensitive than LAeBSA in identifying chamber enlargement.

Published
2021

17. Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants

Author

Laguzzi, Federica, Maitusong, Buamina, Strawbridge, Rona J., Baldassarre, Damiano, Veglia, Fabrizio, Humphries, Steve E., Rauramaa, Rainer, Kurl, Sudhir, Smit, Andries J., Giral, Philippe, Silveira, Angela, Tremoli, Elena, Hamsten, Anders, de Faire, Ulf, Gigante, Bruna, Leander, Karin, Sirtori, C. R., Calabresi, L., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Tedesco, C., Coggi, D., Capra, N., Bonomi, A., Eriksson, P., Cooper, J., Acharya, J., Savonen, K., Huttunen, K., Rauramaa, E., Penttila, I. M., Törrönen, J., van Gessel, A. I., van Roon, A. M., Nicolai, A., Mulder, D. J., Kontush, A., Carrié, A., Gallo, A., Karppi, J., Nurmi, T., Nyyssönen, K., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Sennblad, B., Pirro, M., Vaudo, G., Siepi, D., Lupattelli, G., Mannarino, M. R., Bianconi, V., Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Karolinska Institutet [Stockholm], Xinjiang University, University of Glasgow, Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University College of London [London] (UCL), University of Kuopio, University of Eastern Finland, University Medical Center Groningen [Groningen] (UMCG), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Cross-sectional study, Science, [SDV]Life Sciences [q-bio], Saturated fat, Cardiology, Disease, 030204 cardiovascular system & hematology, Logistic regression, Carotid Intima-Media Thickness, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Genetics, Medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Aged, Multidisciplinary, business.industry, Middle Aged, Atherosclerosis, Dietary Fats, 3. Good health, Endocrinology, Blood pressure, Intima-media thickness, Cohort, cardiovascular system, Dietary Fats/adverse effects, Female, Atherosclerosis/epidemiology, business, Biomarkers
Abstract

The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54–79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point > zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06–1.47), CC-IMTmean (OR:1.22;1.04–1.44) and ICA-IMTmean (OR:1.26;1.07–1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis.

Published
2021
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18. Association Between Uric Acid, Carotid Intima‐Media Thickness, and Cardiovascular Events: Prospective Results From the IMPROVE Study

Author

Mannarino, Massimo R., primary, Pirro, Matteo, additional, Gigante, Bruna, additional, Savonen, Kai, additional, Kurl, Sudhir, additional, Giral, Philippe, additional, Smit, Andries, additional, Veglia, Fabrizio, additional, Tremoli, Elena, additional, Baldassarre, Damiano, additional, Amato, M., additional, Frigerio, B., additional, Ravani, A., additional, Sansaro, D., additional, Coggi, D., additional, Tedesco, C., additional, Capra, N., additional, Bonomi, A., additional, Calabresi, Laura, additional, Sirtori, C. R., additional, Eriksson, Per, additional, Silveira, Angela, additional, Leander, Karin, additional, Laguzzi, Federica, additional, Hamsten, Anders, additional, de Faire, Ulf, additional, Humphries, Steve E., additional, Cooper, J., additional, Acharya, J., additional, Huttunen, K., additional, Rauramaa, E., additional, Penttila, I. M., additional, Törrönen, J., additional, van Gessel, A. I., additional, van Roon, A. M., additional, Nicolai, A., additional, Mulder, D. J., additional, Smeets, G. H., additional, Kontush, Anatole, additional, Carrié, Alain, additional, Gallo, Antonio, additional, Karppi, J., additional, Nurmi, T., additional, Nyyssönen, K., additional, Tuomainen, T. P., additional, Tuomainen, J., additional, Kauhanen, J., additional, Vaudo, G., additional, Bianconi, V., additional, Siepi, D., additional, and Lupattelli, G., additional

Published
2021
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19. Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study

Author

Bonomi, A., Veglia, F., Baldassarre, D., Strawbridge, R. J., Golabkesh, Z., Sennblad, B., Leander, K., Smit, A. J., Giral, P., Humphries, S. E., Tremoli, E., Hamsten, A., de Faire, U., Gigante, B., Sirtori, C. R., Castelnuovo, S., Calabresi, L., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Coggi, D., Tedesco, C. C., Eriksson, P., Silveira, A., Laguzzi, F., Cooper, J., Acharya, J., Huttunen, K., Rauramaa, E., Pekkarinen, H., Penttila, I. M., Torronen, J., Rauramaa, R., van Gessel, A. I., van Roon, A. M., Teune, G. C., Kuipers, W. D., Bruin, M., Nicolai, A., Haarsma-Jorritsma, P., Mulder, D. J., Bilo, H. J. G., Smeets, G. H., Beaudeux, J. L., Kahn, J. F., Carreau, V., Kontush, A., Karppi, J., Nurmi, T., Nyyssonen, K., Salonen, R., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Kurl, S., Vaudo, G., Alaeddin, A., Siepi, D., Lupattelli, G., Mannarino, E., Groningen Kidney Center (GKC), Lifestyle Medicine (LM), and Translational Immunology Groningen (TRIGR)

Subjects
Male, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Article, Gene Frequency, Risk Factors, Cytokine Receptor gp130, Humans, Genetic Predisposition to Disease, POPULATION, Aged, Medicinsk genetik, RISK, VASCULAR EVENTS, Interleukin-6, GENOME-WIDE, Genetic Variation, SIGNAL TRANSDUCER GP130, Middle Aged, Atherosclerosis, POLYMORPHISM, Genetic Loci, INTERLEUKIN-6 RECEPTOR, SOLUBLE GP130, Cytokines, Female, Medical Genetics, 4 SUBUNITS, Biomarkers
Abstract

The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–max β = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.

Published
2020

20. Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study

Author

Laguzzi, F., Baldassarre, D., Veglia, F., Strawbridge, R. J., Humphries, S. E., Rauramaa, R., Smit, A. J., Giral, P., Silveira, A., Tremoli, E., Hamsten, A., de Faire, U., Frumento, P., Leander, K., Sirtori, C. R., Castelnuovo, S., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Tedesco, C., Coggi, D., Bonomi, A., Eriksson, M. J., Cooper, J., Acharya, J., Huttunen, K., Rauramaa, E., Pekkarinen, H., Penttila, I. M., Torronen, J., van Gessel, A. I., van Roon, A. M., Teune, G. C., Kuipers, W. D., Bruin, M., Nicolai, A., Haarsma-Jorritsma, P., Mulder, D. J., Bilo, H. J. G., Smeets, G. H., Beaudeux, J. L., Kahn, J. F., Carreau, V., Kontush, A., Karppi, J., Nurmi, T., Nyyssonen, K., Salonen, R., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Vaudo, G., Alaeddin, A., Siepi, D., Lupattelli, G., Mannarino, E., Groningen Kidney Center (GKC), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Glasgow, Institute of Cardiovascular and Medical Sciences [Glasgow], University College of London [London] (UCL), University of Kuopio, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Karolinska University Hospital [Stockholm]

Subjects
Male, medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], Physical activity, Medicine (miscellaneous), Alcohol drinking, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine.artery, Internal medicine, medicine, Humans, 030212 general & internal medicine, Carotid intima-media thickness, Finland, Netherlands, Sweden, Nutrition and Dietetics, Progression, business.industry, Confounding, European population, Original Contribution, Atherosclerosis, 3. Good health, Italy, Subclinical atherosclerosis, Cardiology, Female, France, Internal carotid artery, business, Alcohol consumption, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background/Aim The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption. Methods Between 2002–2004, 1772 men and 1931 women aged 54–79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 − 5 g/d), low (> 5 to ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women, > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude. Results Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[− 0.17(95%CI − 0.32; − 0.02)], and Bif-IMTmean[− 0.07(95%CI − 0.13; − 0.01)] at baseline and decreasing C-IMTmean[− 0.006 (95%CI − 0.011; − 0.000)], Bif-IMTmean[− 0.016(95%CI − 0.027; − 0.005)], ICA-IMTmean[− 0.009(95% − 0.016; − 0.002)] and ICA-IMTmax[− 0.016(95%: − 0.032; − 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT. Conclusion In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.

Published
2020
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44. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

Author

Nicolaides, Andrew N, Kakkos, Stavros K., Kyriacou, Efthyvoulos, Griffin, Maura, Sabetai, Michael, Thomas, Dafydd J., Tegos, Thomas, Geroulakos, George, Labropoulos, Nicos, Dor, Caroline J., Morris, Tim P., Naylor, Ross, Abbott, Anne L., Adovasio, Roberto, Ziani, B., Alò, F. P., Cicilioni, C. G., Ambrosio, G., Andreev, A., Andreozzi, G. M., Verlato, F., Camporese, G., Arosio, E., Barkauskas, E., Barros D'Sa, A. A. B., Brannigan, P., Batchvarova, V., Dramov, A., Belardi, P., Novelli, Gp, Simoni, G., Bell, P., Biasi, G. M., Mingazzini, P., Bornstein, N. M., Bouchier Hayes, D., Fitzgerald, P., Cairols, M. A., Cao, P. G., Derango, P., Carboni, G. P., Geoffredo, C., Catalano, M., Chambers, B., Goetzmann, M., Dickinson, A., Clement, D., Bobelyn, M., Coccheri, S., Conti, E., Diamantopoulos, E., Andreadis, E. A., Dimakakos, P. B., Kotsis, T., Eikelboom, B., Entz, L., Ferrari Bardile, Null, Aloi, T., Salerno, M., Fernandes e. Fernandes, J., Pedro, L., Fitzgerald, D. E., O'Shaunnersy, Anne, Fletcher, J., Forconi, S., Cappeli, R., Bicchi, M., Arrigucci, S., Gallai, V., Cardaiolli, G., Geroulakos, G., Kakkos, S., Gomez Isaza, L. F., Gorgoyannis, G., Liasis, N., Graf, M., Guarini, P., Hardy, S., Harris, P., Aston, S., Iosa, G., Katsamouris, A., Giannoukas, A., Krzanowski, M., Ladurner, G., Leal Monedero, J., Lee, B. B., Liapis, C., Galanis, P., Liboni, W., Pavanelli, E., Mannarino, E., Vaudo, G., Mccollum, P., Levison, R., Micieli, G., Bosone, D., Middleton, L., Pantziaris, M., Tyllis, T., Minar, E., Willfort, A., Moggi, L., Nenci, G., Radicchia, S., Nicolaides, A., Thomas, D, Norgren, L., Ribbe, E., Novo, S., Tantillo, R., Olinic, D., Paaske, W., Pagnan, A., Pauletto, P., Pagliara, V., Pettina, G., Pratesi, C., Matticari, S., Polivka, J., Sevcik, P., Poredos, P., Blinc, A., Videcnik, V., Pujia, A., Raso, A., Rispoli, P., Conforti, M., Robinson, T., Dennis, M. S. J., Rosfors, S., Rudofsky, G., Schroeder, T., Gronholdt, M. L., Finocchi, C., Rodriguez, G., Spartera, C., Ventura, M., Scarpelli, P., Sprynger, M., Sadzot, B., Hottermans, C., Moonen, Null, Taylor, P. R., Tovar Pardo, A., Negreira, J., Vayssairat, M., Faintuch, J. M., Valaikiené, J., Walker, M. G., Wilkinson, A. R., Nicolaides, A, Kakkos, S, Kyriacou, E, Griffin, M, Sabetai, M, Thomas, D, Tegos, T, Geroulakos, G, Labropoulos, N, Dor, C, Morris, T, Naylor, R, Abbott, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardileah, N, Aloi, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbp, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A, Nicolaides, Andrew N, Kakkos, Stavros K., Kyriacou, Efthyvoulo, Griffin, Maura, Sabetai, Michael, Thomas, Dafydd J., Tegos, Thoma, Geroulakos, George, Labropoulos, Nico, Dor, Caroline J., Morris, Tim P., Naylor, Ro, Abbott, Anne L., Adovasio, Roberto, Ziani, B., Alò, F. P., Cicilioni, C. G., Ambrosio, G., Andreev, A., Andreozzi, G. M., Verlato, F., Camporese, G., Arosio, E., Barkauskas, E., Barros D'Sa, A. A. B., Brannigan, P., Batchvarova, V., Dramov, A., Belardi, P., Novelli, Gp, Simoni, G., Bell, P., Biasi, G. M., Mingazzini, P., Bornstein, N. M., Bouchier Hayes, D., Fitzgerald, P., Cairols, M. A., Cao, P. G., Derango, P., Carboni, G. P., Geoffredo, C., Catalano, M., Chambers, B., Goetzmann, M., Dickinson, A., Clement, D., Bobelyn, M., Coccheri, S., Conti, E., Diamantopoulos, E., Andreadis, E. A., Dimakakos, P. B., Kotsis, T., Eikelboom, B., Entz, L., Ferrari Bardile, Null, Aloi, T., Salerno, M., Fernandes e. Fernandes, J., Pedro, L., Fitzgerald, D. E., O'Shaunnersy, Anne, Fletcher, J., Forconi, S., Cappeli, R., Bicchi, M., Arrigucci, S., Gallai, V., Cardaiolli, G., Geroulakos, G., Kakkos, S., Gomez Isaza, L. F., Gorgoyannis, G., Liasis, N., Graf, M., Guarini, P., Hardy, S., Harris, P., Aston, S., Iosa, G., Katsamouris, A., Giannoukas, A., Krzanowski, M., Ladurner, G., Leal Monedero, J., Lee, B. B., Liapis, C., Galanis, P., Liboni, W., Pavanelli, E., Mannarino, E., Vaudo, G., Mccollum, P., Levison, R., Micieli, G., Bosone, D., Middleton, L., Pantziaris, M., Tyllis, T., Minar, E., Willfort, A., Moggi, L., Nenci, G., Radicchia, S., Nicolaides, A., Norgren, L., Ribbe, E., Novo, S., Tantillo, R., Olinic, D., Paaske, W., Pagnan, A., Pauletto, P., Pagliara, V., Pettina, G., Pratesi, C., Matticari, S., Polivka, J., Sevcik, P., Poredos, P., Blinc, A., Videcnik, V., Pujia, A., Raso, A., Rispoli, P., Conforti, M., Robinson, T., Dennis, M. S. J., Rosfors, S., Rudofsky, G., Schroeder, T., Gronholdt, M. L., Finocchi, C., Rodriguez, G., Spartera, C., Ventura, M., Scarpelli, P., Sprynger, M., Sadzot, B., Hottermans, C., Moonen, Null, Taylor, P. R., Tovar Pardo, A., Negreira, J., Vayssairat, M., Faintuch, J. M., Valaikiené, J., Walker, M. G., and Wilkinson, A. R.

Subjects
Male, Carotid Stenosi, carotid artery stenosis, Brain Ischemia, 80 and over, MED/22 - CHIRURGIA VASCOLARE, Carotid Stenosis, Cerebrovascular disease, cerebrovascular risk, Stroke, Ultrasonography, Aged, 80 and over, Middle Aged, cardiovascular system, Female, Radiology, Internal carotid artery, medicine.symptom, Cardiology and Cardiovascular Medicine, Carotid Artery, Internal, Adult, Aged, Amaurosis Fugax, Humans, ROC Curve, Risk Assessment, Surgery, Human, medicine.medical_specialty, Asymptomatic, Central nervous system disease, medicine.artery, medicine, Asymtomatic carotid stenosis, cardiovascular diseases, Risk factor, carotid surgery, Vascular disease, business.industry, Amaurosis fugax, medicine.disease, Internal, Stenosis, atherosclerosis, Carotid Artery, business
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

Published
2010
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45. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis

Author

Kakkos, Sk, Nicolaides, An, Charalambous, I, Thomas, D, Giannopoulos, A, Naylor, Ar, Geroulakos, G, Abbott, Al, Asymptomatic Carotid Stenosis, Risk of Stroke Study Group Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, A, Aloi, T, Salerno, M, Fernandes J, Fernandes e., Pedro, L, Fitzgerald, D, O'Shaughnessy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Kakkos, S, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Nicolaides, A, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, Pietro, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, M, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A. R., Kakkos, Stavros K., Nicolaides, Andrew N., Charalambous, Ioanna, Thomas, Dafydd, Giannopoulos, Argyrio, Naylor, A. Ro, Geroulakos, George, Abbott, Anne L., Adovasio, Roberto, Ziani, B., Alò, F. P., Cicilioni, C. G., Ambrosio, G., Andreev, A., Andreozzi, G. M., Verlato, F., Camporese, G., Arosio, E., Barkauskas, E., Barros D'Sa, A. A. B., Brannigan, P., Batchvarova, V., Dramov, A., Belardi, P., Novelli, G. P., Simoni, G., Bell, P., Biasi, G. M., Mingazzini, P., Bornstein, N. M., Bouchier Hayes, D., Fitzgerald, P., Cairols, M. A., Cao, P. G., Derango, P., Carboni, G. P., Geoffredo, C., Catalano, M., Chambers, B., Goetzmann, M., Dickinson, A., Clement, D., Bobelyn, M., Coccheri, S., Conti, E., Diamantopoulos, E., Andreadis, E. A., Dimakakos, P. B., Kotsis, T., Eikelboom, B., Entz, L., Ferrari Bardile, A., Aloi, T., Salerno, M., Fernandes E. Fernandes, J., Pedro, L., Fitzgerald, D. E., O'Shaughnessy, A. M., Fletcher, J., Forconi, S., Cappeli, R., Bicchi, M., Arrigucci, S., Gallai, V., Cardaiolli, G., Gomez Isaza, L. F., Gorgoyannis, G., Liasis, N., Graf, M., Guarini, P., Hardy, S., Harris, P., Aston, S., Iosa, G., Katsamouris, A., Giannoukas, A., Krzanowski, M., Ladurner, G., Leal Monedero, J., Lee, B. B., Liapis, C., Galanis, P., Liboni, W., Pavanelli, E., Mannarino, E., Vaudo, G., Mccollum, P., Levison, R., Micieli, G., Bosone, D., Middleton, L., Pantziaris, M., Tyllis, T., Minar, E., Willfort, A., Moggi, L., Nenci, G., Radicchia, S., Norgren, L., Ribbe, E., Novo, S., Tantillo, R., Olinic, D., Paaske, W., Pagnan, A., Pauletto, P., Pagliara, V., Pettina, G., Pratesi, C., Matticari, S., Polivka, J., Sevcik, P., Poredos, P., Blinc, A., Videcnik, V., Pujia, A., Raso, A., Rispoli, P., Conforti, M., Robinson, T., Dennis, M. S. J., Rosfors, S., Rudofsky, G., Schroeder, T., Gronholdt, M. L., Finocchi, C., Rodriguez, G., Spartera, C., Ventura, M., Scarpelli, P., Sprynger, M., Sadzot, B., Hottermans, C., Moonen, M., Taylor, P. R., Tovar Pardo, A., Negreira, J., Vayssairat, M., Faintuch, J. M., Valaikiené, J., Walker, M. G., and Wilkinson, A. R.

Subjects
Male, Time Factors, Cost effectiveness, medicine.medical_treatment, Carotid Stenosi, Predictive Value of Test, Kaplan-Meier Estimate, Carotid endarterectomy, Retinal Disease, Risk Factors, 80 and over, Carotid Stenosis, Plaque, Atherosclerotic, Ultrasonography, Aged, 80 and over, Ultrasonography, Doppler, Duplex, Incidence, Remission Induction, Doppler, Middle Aged, Prognosis, Plaque, Atherosclerotic, Duplex, Europe, Stroke, Predictive value of tests, Disease Progression, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Carotid Artery, Internal, Human, Adult, medicine.medical_specialty, Time Factor, Victoria, Prognosi, Asymptomatic, Retinal Diseases, Predictive Value of Tests, Internal medicine, medicine, Humans, Clinical significance, Aged, Asymptomatic Disease, business.industry, Risk Factor, medicine.disease, Internal, Confidence interval, Surgery, Stenosis, Asymptomatic Diseases, Relative risk, asymptomatic carotid artery stenosis, Carotid Artery, business
Abstract

OBJECTIVE: To determine baseline clinical and ultrasonographic plaque factors predictive of progression or regression of asymptomatic carotid stenosis and the predictive value of changes in stenosis severity on risk of first ipsilateral cerebral or retinal ischemic events (including stroke).METHODS: A total of 1121 patients with asymptomatic carotid stenosis of 50% to 99% in relation to the bulb diameter (European Carotid Surgery Trial [ECST] method) underwent six monthly clinical assessments and carotid duplexes for up to 8 years (mean follow-up, 4 years). Progression or regression was considered present if there was a change of at least one grade higher or lower, respectively, persisting for at least two consecutive examinations.RESULTS: Regression occurred in 43 (3.8%), no change in 856 (76.4%), and progression in 222 (19.8%) patients. Younger age, high grades of stenosis, absence of discrete white areas in the plaque, and taking lipid lowering therapy were independent baseline predictors of increased incidence of regression. High serum creatinine, male gender, not taking lipid lowering therapy, low grades of stenosis, and increased plaque area were independent baseline predictors of progression. One hundred and thirty first ipsilateral cerebral or retinal ischemic events, including 59 strokes, occurred. Forty (67.8%) of the strokes occurred in patients whose stenosis was unchanged, 19 (32.2%) in those with progression, and zero in those with regression. For the entire cohort, the 8-year cumulative ipsilateral cerebral ischemic stroke rate was zero in patients with regression, 9% if the stenosis was unchanged, and 16% if there was progression (average annual stroke rates of 0%, 1.1%, and 2.0%, respectively; log-rank, P = .05; relative risk in patients with progression, 1.92; 95% confidence interval, 1.14-3.25). For patients with baseline stenosis 70% to 99% in relation to the distal internal carotid (North American Symptomatic Carotid Endarterectomy Trial [NASCET] method), in the absence of progression (n = 349), the 8-year cumulative ipsilateral cerebral ischemic stroke rate was 12%. In the presence of progression (n = 77), it was 21% (average annual stroke rates of 1.5% and 2.6%, respectively; log-rank, P = .34). Only nine (30%) of the 30 strokes occurred in the progression group.CONCLUSIONS: Progressive asymptomatic carotid stenosis identified a subgroup with about twice the risk of ipsilateral stroke compared with those without progression. However, the clinical value of screening for progression simply for selecting patients for carotid procedures is limited because of the low frequency of progression and its relatively low associated stroke rate. The cost effectiveness of screening for change in stenosis severity to better direct current optimal medical treatment needs testing.

Published
2014
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46. Nuove terapie ipolipemizzanti per i pazienti con ipercolesterolemia familiare. Position paper della Società Italiana per lo studio dell'Arteriosclerosi

Author

Arca, M, Averna, M, Casula, M, Catapano, Al, Fellin, R, Angelico, F, Arosio, Enrico, Bernini, F, Calandra, S, Cipollone, F, Corsini, A, Marotta, A, Muntoni, S, Poli, A, Solini, A, Vaudo, G, and Zambon, A.

Subjects
therapy, atherosclerosis, familial hypercholesterolaemia, therapy, familial hypercholesterolaemia, atherosclerosis
Published
2016

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