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1. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes

Author

Smith, Eric E., Shoamanesh, Ashkan, Xu, Lizhen, Heenan, Laura, Saad, Feryal, Colorado, Pablo, Chen, Chih-Hao, Lemmens, Robin, De Marchis, Gian Marco, Caso, Valeria, Masjuan, Jaime, Hirano, Teruyuki, Milanov, Ivan, Campbell, Bruce C.V., Mas, Jean-Louis, Connolly, Stuart J., Mundl, Hardi, Hart, Robert G., Bailey, P., Kleinig, T., Cordato, D., Choi, P., Garcia-Esperon, C., Chew, A., Cloud, G., Stanislaus, V., Krause, M., Priglinger, M., Grimley, R., Ghia, D., Sahathevan, R., Brown, H., Kwan, C., Devlin, M., Greisenegger, S., Bonelli-Nauer, S., Rath, J., Langer, A., Marko, M., Ferrari, J., Bernegger, A., Baumgartinger, M., Vigl, M., Krebs, S., Lang, W., Knoflach, M., Dejakum, B., Kiechl, S., Töll, T., Domig, L., Mutzenbach, J.S., Ganser, B., Hecker, C., Rösler, C., Bubel, N., Pikija, S., Zellner, T., Leitner, U., Berger, O., Surböck, B., Beirer, S., Staykov, D., Schrammel, D., Halilovic, A., Frattner, M., Barmherzigen, D., Lampl, C., Höfer, C., Nagl, S., Bocksrucker, C., Demeestere, J., Desfontaines, P., Ciobanu, C., De Pauw, A., Terwecoren, A., Hasenbroekx, M.C., Clement, F., De Klippel, N., Soors, P., Hermans, S., De Raedt, S., Vandervorst, F., Seynaeve, L., Fockaert, N., Smet, S., Rutgers, M., Del Gaudio, N., Paindeville, P., Staikov, I., Simeonova, A., Stoyanova, I., Cholakova, M., Mihnev, N., Petrova, T., Koralova, A., Dimov, D., Kuzev, Y., Danovska, M., Marinova, D., Marinova-Trifonova, D., Ovcharova, E., Mladenovski, I., Yanakieva, M., Stoev, P., Dimitrova, M., Todorova-Georgieva, S., Haralanov, L., Milkov, B., Solakov, D., Petkova, N., Ignatova-Valkova, V., Karabinov, V., Marinova, V., Miteva, Y., Andonova, V., Kasabova, D., Kostadinova, E., Shopova-Vrabcheva, Y., Gatev, D., Semova, D., Halil, E., Kaprelyan, A., Ivanov, B., Panov, G., Grudkova, M., Syuleyman, N., Kalpachki, R., Alexiev, F., Ivanova, I., Kancheva, K., Sakelarova, T., Maslarov, D., Drenska, D., Georgiev, V., Petrova, K., Petrova, N., Ivanova, I., Semerdjieva, N., Zhelyazkov, P., Spasova-Markova, S., Dong, X., Wang, D., Wang, S., Huang, W., Zhao, H., Wang, C., Jie, L., Xinyang, Y., Ping, Z., Dong, Q., Wang, Y., Fuling, Y., Yue, W., Liu, R., Yang, Y., Stetkarova, I., Mikulenka, P., Vasko, P., Peisker, T., Bar, M., Roubec, M., Mikulik, R., Cabukova, M., Vinklarek, J., Kovar, M., Pansky, M., Mencl, P., Skoda, O., Carek, M., Pernicka, M., Skodova, M., Geier, P., Cepkova, J., Drlik, J., Prax, T., Herzig, R., Krajickova, D., Vitkova, E., Haluskova, S., Vaclavik, D., Martinkova, J., Blejcharova, K., Tkacova, M., Pavlik, O., Nevšímalová, M., Rosol, J., Nevsimalova, M., Hruby, R., Iversen, H., Andersen, A.V., Rahimi, D., Christensen, H., Grundtvig, J., Hjort, N., Andersen, G., Sandal, B., Stilund, M., Modrau, B., Strade, A., Porobic, M., Andersen, S.D., Kruuse, C., Ölmestig, J., Kolmos, M., Parvez, A., Christensen, T., Stokholm, J., Jensen, H.B., Putaala, J., Strbian, D., Sibolt, G., Tiainen, M., Martinez-Majander, N., Curtze, S., Raty, S., Kraemer, Y., Roine, R., Aivo, J., Ruuskanen, J., Ylikotila, P., Roine, S., Hallikainen, M., Jakala, P., Kurl, S., Julkunen, V., Sibon, I., Olindo, S., Richard, S., Larrue, V., Gollion, C., Catala, H., Henon, H., Lucie, D.S., Nelly, D., Calvet, D., Malbranque, A., Mazé, B., Barbieux-Ghitu, C., Rosso, C., Samson, Y., Vannier, S., Moulin, T., Bonnet, L., Reiner, P., Buffon, F., Denier, C., Amri, K., Legris, N., Chassin, O., Selli, N., Mariana, S., Berrouschot, J., Stoll, A., Klunk, D., Keilitz, J., Neustadt, M., Zerrenner, S., Veltkamp, R., Hajjar, K., Heeger, A., Winezki, E., Apel, L., Pompsch, M., Mueller, P., Rappard, P., Auer, R., Ringleb, P.A., Berberich, A., Heyse, M., Mundiyanapurath, S., Reiff, T., Poli, S., Gomez-Exposito, A., Mengel, A., Tünnerhoff, J., Adeyemi, K., Poli, K., Kusch, V., Pelz, J., Michalski, D., Wartenberg, K., Althaus, K., Tavares, F., Mueller, S., Soda, H., Rascher, A., Hiermann, E., Weinhardt, R., Weissenborn, K., Leotescu, A., Grosse, G., Worthmann, H., Ernst, J., Gabriel, M., Schuppner, R., Schäfer, J.H., Charisse, D., Gruber, K., Kurka, N., Reitz, S.C., Pfeilschifter, W., Lee, J.I., Gliem, M., Moll, M., Steiner, T., Segura, L., Szegedi, N., Barandi, D., Uhrinakova, L., Czencz, M., Pasztor, M., Gyuker, N., Bartha, N.E., May, Z., Simony, Z., Szasz, G., Kakuk, I., Pető, N., Panczel, G.F., Olah, A., Racz, O., Balla, T., Horvath, B., Tuba, K., Czinderi, V., Klivenyi, P., Annus, A., Hertelendy, P., Szapary, L., Bosnyak, E., Kalmar, P., Karadi, Z., Cziba, L., Olah, L., Berki, A., Hudak, L., Kozák, M., Babel, S., Nemeth, L., Molnár, B., Simon, Z., Roveri, L., Cerri, F., Giacalone, G., Zini, A., Mauro, G., Asioli, G.M., Forlivesi, S., Arnone, G., Fiaccadori, A., Maria Fontana Francesca, E., Allegra, G., Mosconi, M.G., Longoni, M., Terlizzi, R., Paolucci, M., Tassi, R., Franci, B., Lucani, B., Domenichelli, C., Paoletti, D., Acampa, M., Zedde, M.L., Pezzella, F.R., Mangiardi, M., Galizia, P., Anticoli, S., Scalise, S., Lattanzi, S., Norata, D., Cannuccia, M., Cavallini, A., Federica, F., Denaro, M.F., Tosi, P., Sonoda, K., Kawajiri, M., Kusano, Y., Haraguchi, K., Kawano, H., Terasaki, T., Kaneko, C., Murase, S., Kumagai, M., Murai, N., Miyazaki, Y., Mori, T., Hatano, T., Kawanishi, M., Ochiai, J., Ishihara, S., Uehara, T., Yasaka, M., Nakagawa, H., Makino, M., Yonehara, T., Fukushima, Y., Hirotsune, N., Sakai, N., Yamasaki, M., Coutinho, J., Wouters, A., den Hertog, H., Zwartbol, R., Beumer, D., Kerklaan, J., Hilkens, P., Schreuder, T., Propper, D., Slowik, A., Wlodarczyk, E., Wrona, P., Pulyk, R., Lasek-Bal, A., Kosarz-Lanczek, K., Puz, P., Bilik, M., Magielska, A., Zamiela – Żółciak, A., Ochocinska, L., Bahdasaryan, S., Stępień, A., Dębiec, A., Joanna, K., Pawel, M., Jacek, S., Daniel, P., Marta, S., Rejdak, K., Wojczal, J., Luchowski, P., Fryze, W., Wisniewska, A., Krzyzanowska, M., Skowron, P., Wolosz, A., Galan, A., Grzymala, K., Krajewska, M., Nowak, R., Kłos, M., Cruz, V., Castro, P., Ferro, J., Canhão, P., Gouveia, R., Inácio, N., Rodrigues, M., Rachão, A., Ionel, C., Pereira, L., Viana-Baptista, M., Machado, C., Fernandes, C., Sargento, J., Inácio, N., Timchenko, L., Mironova, J., Zhadan, O., Torgashova, A., Bazhenova, O., Barashenkova, M., Kireeva, M., Romadina, N., Stepanova, I., Lenskaya, L., Lukinykh, L., Vorontsova, T., Agafina, A., Fedorova, A., Yashina, A., Alasheev, A., Smolkin, A., Prazdnichkova, E., Lutskovich, O., Gonysheva, Y., Mordvintseva, E., Nechaev, A., Martynova, E., Fedoraeva, N., Vishnyakova, T., Popov, D., Merzliakova, A., Margarita, K., Rechkalova, L., Ilyina, A., Kurenkova, N., Barbarash, O., Bazdyrev, E., Zvereva, T., Hromova, A., Morkvenas, A., Postnikova, E., Kovalenko, G., Taran, I., Pavlov, L., Ott, M., Chernitsova, N., Vodopyanova, N., Drozdova, E., Korebo, E., Lobanova, M., Lazareva, N., Snegova, N., Nikolaeva, O., Kolesnikov, Y., Kosheleva, Y., Krastev, G., Tomasova, K., Danis, M., Mako, M., Jankovicova, Z., Stevkova, Z., Kovacik, M., Kubikova, T., Jarosova, A., Serdahely, V., Cilingova, I., Pribulova, I., Sedlak, J., Slebodova, K., Paldaufova, M., Risnovsky, R., Berndtova, B., Urbanova, I., Junas, R., Karapetian, S., Gurcik, L., Vantrobova, A., Verbovsky, F., Vanacka, K., Ferenc, M., Galik, P., Bucakova, S., Ferencova, M., Kubalova, P., Boksanska, Z., Zacharova, E., Mahundi, E., Judita, H., Bachnak, M., Turcani, P., Kvasnicova Kamenska, A., Jurik, M., Vestenicka, V., Kycina, M., Sagatova, E., Dvorak, M., Hlubekova, A., Kucera, C., Gernath, L., Ferenc, M., Frimmelova, P., Slebodnikova, J., Aksteinerova, N., Horny, V., Gregova, Z., Segura, T., Romero, C., Ayo, O., Masjuan Vallejo, J., Cruz, A., De felipe, A, Matute, M.C., Garcia, S., Tembl Ferrairo, J., Vielba, I., Morales Caba, L., Molina, C., Garcia-Tornel García-Camba, Á., Requena Ruiz, M., Noelia, R., Rodriguez-Yañez, M., Rodriguez Castro, E., Lopez, I., Santamaria, M., Arias, S., Purroy García, F., Vázquez Justes, D., Mauri Capdevila, G., Vicente Pascual, M., Martí Fabregas, J., Camps Renom, P., Rodríguez Campello, A., Giralt, E., Krupinski, J., Molina, J., Trillo Senin, C. Ramos Martin, S., De La Fuente Sanz, E., Moniche, F., Manuel, M.R., Pardo, B., Martínez, I., Hernández Pérez, M., Arenillas Lara, J.F., De Lera, M., Egido, J.A., Gomez Escalonilla, C., Guillan, M., Martinez, J., Lindgren, A., Andsberg, G., Wictor, L., Leonidou, M., Stenman, M., Dalberg, N., Laska, A.C., Grünfeldt, A., Lundström, A., Nadzjafov, E., Rooth, E., Dalenbring, I., Sandén, P., Johansson, E., Thomas, G., Zietz, A.V., Rudin, S., Dittrich, T.D., Lilian, K., Kägi, G., Vehoff, J., Arnold, M., Scutelnic, A., Clénin, L., Beyeler, M., Madlaine, M., Maamari, B., Siepen, B., Vynckier, J., Tarnutzer, A., Bertschi, D., Luciani, M., Cereda, C., Maulucci, F., Bianco, G., Shairin, S., Pihan, H.A., Salmen, S., Quinn, T., McAlpine, C., Wright, F., Kalladka, D., Taylor, E., Sohaa, J., Brown, Z., Dawson, J., Cameron, A., Muir, S., Dima, S., Khan, U., Zhang, L., Warburton, E., Chatterjee, K., Nallasivan, A., Curran, D., Haider, S., Ghani, U., Kenton, A., Dallol, B., Mirza, M., Menezes, B., Davies, R., Robinson, T.G., Manning, L., Sztriha, L., Phinney, T., Sethi, P., Altafullah, I., Sharaf, A., Ostrander, M., Renati, S., Burgin, W.S., Olds, K., Delio, P., Malek, A., Dissin, J., Khatri, P., Flaherty, M., Demel, S., and Dofitas, S.

Published
2024
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3. Associations of serum n-3 and n-6 polyunsaturated fatty acids with plasma natriuretic peptides

Author

Daneshmand, R., Kurl, S., Tuomainen, T.-P., and Virtanen, J.K.

Subjects
Unsaturated fatty acids -- Health aspects, Natriuretic peptides -- Health aspects, Cardiovascular diseases -- Risk factors, Food/cooking/nutrition, Health
Abstract

BACKGROUND/OBJECTIVES: The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been associated with lower risk of cardiovascular disease (CVD), but little is known about their association with natriuretic peptides (NPs), a marker for CVD risk. The aim of this study was to investigate the association of serum n-3 and n-6 PUFAs with NPs. SUBJECTS/METHODS: A cross-sectional analysis of the association between serum n-3 and n-6 PUFAs with plasma N-terminal atrial (NT-proANP) and brain (NT-proBNP) NPs in a population-based sample of 985 men aged 46-65 years from Eastern Finland. RESULTS: After adjustment for age and examination year, only serum n-6 PUFA arachidonic acid (ARA) was inversely associated with NT-proANP (P-trend across quartiles = 0.02), but further adjustments for conventional risk factors (body mass index, smoking, alcohol intake, systolic blood pressure, low-density lipoprotein cholesterol and history of CVD) attenuated the association (P- trend =0.10). The associations with the other PUFAs were not statistically significant. Among the PUFAs, only serum n-3 PUFA docosapentaenoic acid (DPA; P-trend = 0.03) and ARA (P-trend = 0.02) had inverse associations with NT-proBNP after adjustment for age and examination years. The associations were again attenuated after further adjustments but remained statistically significant for DPA (P-trend = 0.05). Our results also suggested that the inverse associations may be more evident among those using beta-blockers. CONCLUSIONS: Our study suggests little overall impact of serum n-3 or n-6 PUFAs on plasma NPs. European Journal of Clinical Nutrition (2016) 70, 963-969; doi:10.1038/ejcn.2016.58; published online 13 April 2016, INTRODUCTION Cardiovascular disease is a major cause of death worldwide. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been associated with lower risk of cardiovascular disease. (1) The classification [...]

Published
2016
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5. Exercise cardiac power and the risk of heart failure in men:a population-based follow-up study

Author

Kurl, S. (Sudhir), Jae, S. Y. (Sae Young), Mäkikallio, T. H. (Timo H.), Voutilainen, A. (Ari), Hagnäs, M. J. (Magnus J.), Kauhanen, J. (Jussi), Laukkanen, J. A. (Jari A.), Kurl, S. (Sudhir), Jae, S. Y. (Sae Young), Mäkikallio, T. H. (Timo H.), Voutilainen, A. (Ari), Hagnäs, M. J. (Magnus J.), Kauhanen, J. (Jussi), and Laukkanen, J. A. (Jari A.)

Abstract

Background: Little is known about exercise cardiac power (ECP), defined as the ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, on heart failure (HF) risk. We examined the association of ECP and the risk of HF. Methods: This was a population-based cohort study of 2351 men from eastern Finland. The average time to follow-up was 25 years. Participants participated at baseline in an exercise stress test. A total of 313 cases of HF occurred. Results: Men with low ECP (<9.84 mL/mmHg, the lowest quartile) had a 2.37–fold (95% confidence interval (CI): 1.68–3.35, p<0.0001) hazards ratio of HF as compared with men with high ECP (>13.92 mL/mmHg, the highest quartile), after adjusting for age. Low ECP was associated with a 1.96-fold risk (95%CI: 1.38–2.78, p<0.001) of HF after additional adjustment for conventional risk factors. After further adjustment for left ventricular hypertrophy, the results hardly changed (hazards ratio=1.87, 95%CI: 1.31–2.66, p<0.001). One SD increase in ECP (3.16 mL/mmHg) was associated with a decreased risk of HF by 28% (95%CI: 17%–37%). Conclusions: ECP provides a noninvasive and easily available measure from cardiopulmonary exercise tests in predicting HF. However, ECP did not provide additional value over maximal oxygen uptake.

Published
2022

7. Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study

Author

Mannarino, M. R., Bianconi, V., Gigante, B., Strawbridge, R. J., Savonen, K., Kurl, S., Giral, P., Smit, A., Eriksson, P., Tremoli, E., Veglia, F., Baldassarre, D., Pirro, M., Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Università degli Studi di Perugia (UNIPG), Karolinska Institutet [Stockholm], University of Glasgow, University of Kuopio, University of Eastern Finland, 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), University Medical Center Groningen [Groningen] (UMCG), Maria Cecilia Hospital [Cotignola], 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), and Università degli Studi di Milano [Milano] (UNIMI)

Subjects
Carotid Artery Diseases, IMT, Neutrophils, cardiovascular, fungi, neutrophil, lymphocyte, prospective, Carotid Intima-Media Thickness, NLR, Primary Prevention, carotid, Cardiovascular Diseases, Risk Factors, cardiovascular system, Humans, cardiovascular diseases, Lymphocytes, Prospective Studies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.

Published
2022
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11. 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

21. Nat Commun

Author

Franceschini, N., GIAMBARTOLOMEI, C., DE VRIES, P. S., FINAN, C., BIS, J. C., HUNTLEY, R. P., LOVERING, R. C., TAJUDDIN, S. M., WINKLER, T. W., GRAFF, M., KAVOUSI, M., Dale, C., SMITH, A. V., Hofer, E., VAN LEEUWEN, E. M., Nolte, I. M., Lu, L., Scholz, M., Sargurupremraj, Muralidharan, PITKANEN, N., FRANZEN, O., Joshi, P. K., NOORDAM, R., MARIONI, R. E., Hwang, S. J., MUSANI, S. K., SCHMINKE, U., PALMAS, W., ISAACS, A., CORREA, A., ZONDERMAN, A. B., Hofman, A., TEUMER, A., COX, A. J., UITTERLINDEN, A. G., Wong, A., SMIT, A. J., NEWMAN, A. B., Britton, A., RUUSALEPP, A., Sennblad, B., HEDBLAD, B., PASANIUC, B., PENNINX, B. W., LANGEFELD, C. D., WASSEL, C. L., Tzourio, Christophe, Fava, C., BALDASSARRE, D., O'LEARY, D. H., TEUPSER, D., Kuh, D., TREMOLI, E., MANNARINO, E., Grossi, E., BOERWINKLE, E., SCHADT, E. E., INGELSSON, E., VEGLIA, F., Rivadeneira, F., BEUTNER, F., Chauhan, Ganesh, Heiss, G., SNIEDER, H., Campbell, H., VOLZKE, H., MARKUS, H. S., DEARY, I. J., JUKEMA, J. W., de Graaf, J., Price, J., POTT, J., HOPEWELL, J. C., Liang, J., Thiery, J., Engmann, J., GERTOW, K., Rice, K., TAYLOR, K. D., DHANA, K., KIEMENEY, Lalm, LIND, L., RAFFIELD, L. M., LAUNER, L. J., HOLDT, L. M., DORR, M., DICHGANS, M., TRAYLOR, M., SITZER, M., KUMARI, M., Kivimaki, M., Nalls, M. A., MELANDER, O., RAITAKARI, O., FRANCO, O. H., RUEDA-OCHOA, O. L., ROUSSOS, P., WHINCUP, P. H., Amouyel, P., Giral, P., ANUGU, P., WONG, Q., Malik, R., RAURAMAA, R., BURKHARDT, R., Hardy, R., Schmidt, R., DE MUTSERT, R., MORRIS, R. W., STRAWBRIDGE, R. J., WANNAMETHEE, S. G., HAGG, S., Shah, S., MCLACHLAN, S., TROMPET, S., SESHADRI, S., KURL, S., HECKBERT, S. R., Ring, S., HARRIS, T. B., LEHTIMAKI, T., GALESLOOT, T. E., Shah, T., DE FAIRE, U., Plagnol, V., ROSAMOND, W. D., Post, W., Zhu, X., Zhang, X., Guo, X., SABA, Y., DEHGHAN, A., SELDENRIJK, A., MORRISON, A. C., HAMSTEN, A., PSATY, B. M., VAN DUIJN, C. M., LAWLOR, D. A., MOOK-KANAMORI, D. O., BOWDEN, D. W., Schmidt, H., WILSON, J. F., ROTTER, J. I., WARDLAW, J. M., DEANFIELD, J., HALCOX, J., LYYTIKAINEN, L. P., Loeffler, M., EVANS, M. K., Debette, Stéphanie, HUMPHRIES, S. E., VOLKER, U., GUDNASON, V., HINGORANI, A. D., BJORKEGREN, J. L. M., CASAS, J. P., O'DONNELL, C. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
VINTAGE, cardiovascular system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, cardiovascular diseases, HEALTHY
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018
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24. Leisure-time cross-country skiing is associated with lower incidence of hypertension:a prospective cohort study

Author

Kunutsor, S. (Setor), Mäkikallio, T. (Timo), Kauhanen, J. (Jussi), Voutilainen, A. (Ari), Jae, S. (Sae), Kurl, S. (Sudhir), Laukkanen, J. A. (Jari A.), Kunutsor, S. (Setor), Mäkikallio, T. (Timo), Kauhanen, J. (Jussi), Voutilainen, A. (Ari), Jae, S. (Sae), Kurl, S. (Sudhir), and Laukkanen, J. A. (Jari A.)

Abstract

Objective: The prospective relationship between cross-country skiing and hypertension is uncertain. We aimed to assess the associations of leisure time cross-country skiing habits with incident hypertension in a general population. Methods: The frequency, average duration, and intensity of leisure cross-country skiing were assessed at baseline using a 12-month physical activity questionnaire in the Kuopio Ischemic Heart Disease prospective study of 1809 middle-aged men without hypertension. Hazard ratios [95% confidence intervals (CIs)] were calculated. Results: New onset diagnosis of hypertension was observed in 279 participants during a median (interquartile range) follow-up of 24.7 (18.1–26.8) years. Total volume and duration of cross-country skiing were continuously associated with hypertension risk. In analyses adjusted for hypertension risk factors, when compared with men with no cross-country skiing activity, the hazard ratios (95% CIs) of incident hypertension were 0.75 (0.57–0.99) and 0.57 (0.41–0.79) for men who did 1–200 and more than 200 MET hours/year of cross-country skiing, respectively. Compared with men with no cross-country skiing activity, the corresponding adjusted hazard ratios (95% CIs) for incident hypertension were 0.72 (0.55–0.94) and 0.62 (0.44–0.86) for men who did 1–60 min/week and more than 60 min/week of cross-country skiing, respectively. In subsidiary analyses, there were age-adjusted associations of cross-country skiing habits with risk of stroke and acute coronary events, but these were attenuated on further adjustment for several confounders. Cross-country skiing habits were associated with reduced risk of type 2 diabetes. Conclusion: Total volume as well as duration of leisure time cross-country skiing are each continuously, inversely, and independently associated with future risk of hypertension in a white male population.

Published
2019

25. Impact of a clinical decision support tool on prediction of progression in early-stage dementia:a prospective validation study

Author

Bruun, M. (Marie), Frederiksen, K. S. (Kristian S.), Rhodius-Meester, H. F. (Hanneke F. M.), Baroni, M. (Marta), Gjerum, L. (Le), Koikkalainen, J. (Juha), Urhemaa, T. (Timo), Tolonen, A. (Antti), van Gils, M. (Mark), Rueckert, D. (Daniel), Dyremose, N. (Nadia), Andersen, B. B. (Birgitte B.), Lemstra, A. W. (Afina W.), Hallikainen, M. (Merja), Kurl, S. (Sudhir), Herukka, S.-K. (Sanna-Kaisa), Remes, A. M. (Anne M.), Waldemar, G. (Gunhild), Soininen, H. (Hilkka), Mecocci, P. (Patrizia), van der Flier, W. M. (Wiesje M.), Lötjönen, J. (Jyrki), Hasselbalch, S. G. (Steen G.), Bruun, M. (Marie), Frederiksen, K. S. (Kristian S.), Rhodius-Meester, H. F. (Hanneke F. M.), Baroni, M. (Marta), Gjerum, L. (Le), Koikkalainen, J. (Juha), Urhemaa, T. (Timo), Tolonen, A. (Antti), van Gils, M. (Mark), Rueckert, D. (Daniel), Dyremose, N. (Nadia), Andersen, B. B. (Birgitte B.), Lemstra, A. W. (Afina W.), Hallikainen, M. (Merja), Kurl, S. (Sudhir), Herukka, S.-K. (Sanna-Kaisa), Remes, A. M. (Anne M.), Waldemar, G. (Gunhild), Soininen, H. (Hilkka), Mecocci, P. (Patrizia), van der Flier, W. M. (Wiesje M.), Lötjönen, J. (Jyrki), and Hasselbalch, S. G. (Steen G.)

Abstract

Background: In clinical practice, it is often difficult to predict which patients with cognitive complaints or impairment will progress or remain stable. We assessed the impact of using a clinical decision support system, the PredictND tool, to predict progression in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in memory clinics. Methods: In this prospective multicenter study, we included 429 patients with SCD (n = 230) and MCI (n = 199) (female 54%, age 67 ± 9, MMSE 28 ± 2) and followed them for at least 12 months. Based on all available patient baseline data (demographics, cognitive tests, cerebrospinal fluid biomarkers, and MRI), the PredictND tool provides a comprehensive overview of the data and a classification defining the likelihood of progression. At baseline, a clinician defined an expected follow-up diagnosis and estimated the level of confidence in their prediction using a visual analogue scale (VAS, 0–100%), first without and subsequently with the PredictND tool. As outcome measure, we defined clinical progression as progression from SCD to MCI or dementia, and from MCI to dementia. Correspondence between the expected and the actual clinical progression at follow-up defined the prognostic accuracy. Results: After a mean follow-up time of 1.7 ± 0.4 years, 21 (9%) SCD and 63 (32%) MCI had progressed. When using the PredictND tool, the overall prognostic accuracy was unaffected (0.4%, 95%CI − 3.0%; + 3.9%; p = 0.79). However, restricting the analysis to patients with more certain classifications (n = 203), we found an increase of 3% in the accuracy (95%CI − 0.6%; + 6.5%; p = 0.11). Furthermore, for this subgroup, the tool alone showed a statistically significant increase in the prognostic accuracy compared to the evaluation without tool (6.4%, 95%CI 2.1%; 10.7%; p = 0.004). Specifically, the negative predictive value was high. Moreover, confidence in the prediction increased significantly (∆VAS = 4%, p

Published
2019

34. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), Morris, R.W. (Richard), Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), and Morris, R.W. (Richard)

Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018
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35. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkanen, N, Franzen, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, S-J, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O'Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Voelzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Doer, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, de Mutsert, R, Morris, RW, Strawbridge, RJ, Wannamethee, SG, Hagg, S, Shah, S, McLachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, SR, Ring, S, Harris, TB, Lehtimaki, T, Galesloot, TE, Shah, T, de Faire, U, Plagnol, V, Rosamond, WD, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, AC, Hamsten, A, Psaty, BM, van Duijn, CM, Lawlor, DA, Mook-Kanamori, DO, Bowden, DW, Schmidt, H, Wilson, JF, Wilson, JG, Rotter, JI, Wardlaw, JM, Deanfield, J, Halcox, J, Lyytikainen, L-P, Loeffler, M, Evans, MK, Debette, S, Humphries, SE, Voelker, U, Gudnason, V, Hingorani, AD, Bjorkegren, JLM, Casas, JP, O'Donnell, CJ, Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkanen, N, Franzen, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, S-J, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O'Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Voelzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Doer, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, de Mutsert, R, Morris, RW, Strawbridge, RJ, Wannamethee, SG, Hagg, S, Shah, S, McLachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, SR, Ring, S, Harris, TB, Lehtimaki, T, Galesloot, TE, Shah, T, de Faire, U, Plagnol, V, Rosamond, WD, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, AC, Hamsten, A, Psaty, BM, van Duijn, CM, Lawlor, DA, Mook-Kanamori, DO, Bowden, DW, Schmidt, H, Wilson, JF, Wilson, JG, Rotter, JI, Wardlaw, JM, Deanfield, J, Halcox, J, Lyytikainen, L-P, Loeffler, M, Evans, MK, Debette, S, Humphries, SE, Voelker, U, Gudnason, V, Hingorani, AD, Bjorkegren, JLM, Casas, JP, and O'Donnell, CJ

Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

36. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author

Strawbridge, R.J., Silveira, A., Hoed, M. den, Gustafsson, S., Luan, J.A., Rybin, D., Dupuis, J., Li-Gao, R.F., Kavousi, M., Dehghan, A., Haljas, K., Lahti, J., Gadin, J.R., Backlund, A., Faire, U. de, Gertow, K., Giral, P., Goel, A., Humphries, S.E., Kurl, S., Langenberg, C., Lannfelt, L.L., Lind, L., Lindgren, C.C.M., Mannarino, E., Mook-Kanamori, D.O., Morris, A.P., Mutsert, R. de, Rauramaa, R., Saliba-Gustafsson, P., Sennblad, B., Smit, A.J., Syvanen, A.C., Tremoli, E., Veglia, F., Zethelius, B., Bjorck, H.M., Eriksson, J.G., Hofman, A., Franco, O.H., Watkins, H., Jukema, J.W., Florez, J.C., Wareham, N.J., Meigs, J.B., Ingelsson, E., Baldassarre, D., Hamsten, A., IMPROVE Study Grp, Medicum, Department of Psychology and Logopedics, University of Helsinki, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Developmental Psychology Research Group, Luan, Jian'an [0000-0003-3137-6337], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository

Subjects
Carotid Artery Diseases, Male, EXPRESSION, endocrine system, Genetic variants, endocrine system diseases, Quantitative Trait Loci, PATHOPHYSIOLOGY, DEPENDENT DIABETES-MELLITUS, Vascular Remodeling, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Gene Frequency, Risk Factors, Intima-media-thickness, Humans, Genetic Predisposition to Disease, CORONARY-HEART-DISEASE, COHORT, cardiovascular diseases, Mendelian randomisation, EUROPEAN POPULATION, COMMON, Genetic Association Studies, Chromosomes, Human, Pair 15, MEN, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Atherosclerosis, INSULIN, Europe, Phenotype, 3121 General medicine, internal medicine and other clinical medicine, Asymptomatic Diseases, Linear Models, Female, hormones, hormone substitutes, and hormone antagonists, Proinsulin
Abstract

Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

Published
2017

37. Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification

Author

Amato M, Veglia F, de Faire U, Giral P, Rauramaa R, Smit AJ, Kurl S, Ravani A, Frigerio B, Sansaro D, Bonomi A, Tedesco CC, Castelnuovo S, Mannarino E, Humphries SE, Hamsten A, Tremoli E, Baldassarre D, on behalf of the IMPROVE study group, School of Medicine / Biomedicine, and School of Medicine / Clinical Medicine

Abstract

Background and aims Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMTmean in cardiovascular risk prediction and risk stratification. Methods The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMTmax. PF CC-IMTmean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMTmax and PF CC-IMTmean versus their respective 1–3 quartiles were calculated using Cox regression. Results After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMTmax and PF CC-IMTmean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMTmax was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMTmean significantly adds to a model including both Framingham Risk Factors and cIMTmax (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). Conclusions cIMTmax and PF CC-IMTmean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification., published version, peerReviewed

Published
2017

38. Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

Author

Folkersen, L, Fauman, E, Sabater-Lleal, M, Strawbridge, R, Frånberg, M, Sennblad, B, Baldassarre, D, Veglia, F, Humphries, S, Rauramaa, R, de Faire, U, Smit, A, Giral, P, Kurl, S, Mannarino, E, Enroth, S, Johansson, Å, Gustafsson, S, Lind, L, Lindgren, C, Morris, A, Giedraitis, V, Silveira, A, Franco-Cereceda, A, Tremoli, E, group, IMPROVE study, Gyllensten, U, Ingelsson, E, Brunak, S, Eriksson, P, Ziemek, D, Hamsten, A, Mälarstig, A, School of Medicine / Biomedicine, Groningen Kidney Center (GKC), and Vascular Ageing Programme (VAP)

Subjects
Male, 0301 basic medicine, Medicin och hälsovetenskap, Cancer Research, GENOME-WIDE ASSOCIATION, INTIMA-MEDIA THICKNESS, GENETIC-VARIANTS, MENDELIAN RANDOMIZATION, EXPRESSION, RISK, POPULATION, CELLS, GWAS, LIFE, Gene Expression, Genome-wide association study, Coronary Artery Disease, Disease, Cardiovascular Medicine, Biochemistry, Vascular Medicine, Medical and Health Sciences, 0302 clinical medicine, Medicine and Health Sciences, Coronary Heart Disease, Genetics (clinical), Regulation of gene expression, Genetics, education.field_of_study, Blood Proteins, Genomics, Cardiovascular Diseases, Female, Research Article, lcsh:QH426-470, Quantitative Trait Loci, Population, Cardiology, Quantitative trait locus, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Mendelian randomization, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Gene Regulation, education, Molecular Biology, Genotyping, Ecology, Evolution, Behavior and Systematics, Plasma Proteins, Biology and Life Sciences, Proteins, Computational Biology, Human Genetics, Genome Analysis, lcsh:Genetics, 030104 developmental biology, Genetic Loci, Expression quantitative trait loci, Biomarkers, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p, published version, peerReviewed

Published
2017
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39. IDENTIFICATION OF APHID SPECIES (HOMOPTERA : APHIDIDAE) OF ECONOMIC IMPORTANCE FROM DELHI AND ITS NCR USING DNA BARCODES AND PCR-SSR BASED APPROACH.

Author

Lal, Archana and Kurl, S. P.

Subjects
COTTON aphid, GREEN peach aphid, APHIDS, HOMOPTERA, BAR codes, INTEGRATED pest control
Abstract

Aphids are among the most serious agricultural pests of tropical, subtropical and temperate regions. They infest almost every plant by feeding on its phloem (Clark et al, 1997) and acts as vectors of plant viruses. They constitute invasive threat to native and cultivated plants and cause very severe damage to crops. The reliable and accurate identification of aphid species is important for the effective integrated pest management strategies. However, the accurate identification of aphid is difficult because many species are morphologically similar and have higher level of intraspecific variation. The present paper deals with the identification and amplification of ten aphid species viz., Aphis gossypii, Aphis craccivora, Dactynotus compositae, Rhopalosiphum nymphaeae, Aphis nerii, Myzus persicae, Lipaphis erysimi, Toxoptera citricidus, Macrosiphum rosaeformis and Macrosiphonella sanborni. In the present study, polymerase chain reaction (PCR)-sequencing based on DNA barcoding and SSR were applied to identify aphid species collected from different areas of Delhi and its NCR. As both PCR and DNA barcoding provide quick and accurate tools for identification of these aphid species. [ABSTRACT FROM AUTHOR]

Published
2020

40. Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.

Author

Saliba‐Gustafsson, P., Pedrelli, M., Gertow, K., Werngren, O., Janas, V., Pourteymour, S., Baldassarre, D., Tremoli, E., Veglia, F., Rauramaa, R., Smit, A.J., Giral, P., Kurl, S., Pirro, M., Faire, U., Humphries, S.E., Hamsten, A., Gonçalves, I., Orho‐Melander, M., and Franco‐Cereceda, A.

Subjects
CAROTID intima-media thickness, DISEASE risk factors, MYOCARDIAL infarction, ATHEROSCLEROSIS, GLYCOGEN storage disease type II
Abstract

Background: Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development.Objective: We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts.Methods: A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central.Results: The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol.Conclusions: For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Published
2019
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47. Clustering of cardiovascular risk factors and carotid intima-media thickness: The USE-IMT study

Author

Wang, X., Dalmeijer, G.W., Ruijter, H.M. Den, Anderson, T.J., Britton, A.R., Dekker, J., Engstrom, G., Evans, G.W., Graaf, J. de, Grobbee, D.E., Hedblad, B., Holewijn, S., Ikeda, A., Kauhanen, J., Kitagawa, K., Kitamura, A., Kurl, S., Lonn, E.M., Lorenz, M.W., Mathiesen, E.B., Nijpels, G., Okazaki, S., Polak, J.F., Price, J.F., Rembold, C.M., Rosvall, M., Rundek, T., Salonen, J.T., Sitzer, M., Stehouwer, C.D., Tuomainen, T.P., Peters, S.A., Bots, M.L., Wang, X., Dalmeijer, G.W., Ruijter, H.M. Den, Anderson, T.J., Britton, A.R., Dekker, J., Engstrom, G., Evans, G.W., Graaf, J. de, Grobbee, D.E., Hedblad, B., Holewijn, S., Ikeda, A., Kauhanen, J., Kitagawa, K., Kitamura, A., Kurl, S., Lonn, E.M., Lorenz, M.W., Mathiesen, E.B., Nijpels, G., Okazaki, S., Polak, J.F., Price, J.F., Rembold, C.M., Rosvall, M., Rundek, T., Salonen, J.T., Sitzer, M., Stehouwer, C.D., Tuomainen, T.P., Peters, S.A., and Bots, M.L.

Abstract

Contains fulltext : 174717.pdf (publisher's version ) (Open Access), BACKGROUND: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. METHODS: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. RESULTS: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. CONCLUSION: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.

Published
2017

48. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author

Strawbridge, RJ, Silveira, A, den Hoed, M, Gustafsson, S, Luan, JA, Rybin, D, Dupuis, J, Li-Gao, RF, Kavousi, Maryam, Dehghan, A, Haljas, K, Lahti, J, Gadin, JR, Backlund, A, de Faire, U, Gertow, K, Giral, P, Goel, A, Humphries, SE, Kurl, S, Langenberg, C, Lannfelt, LL, Lind, L, Lindgren, CCM, Mannarino, E, Mook, Dennis, Morris, AP, de Mutsert, R, Rauramaa, R, Saliba-Gustafsson, P, Sennblad, B, Smit, AJ, Syvanen, AC, Tremoli, E, Veglia, F, Zethelius, B, Bjorck, HM, Eriksson, JG, Hofman, Bert, Franco Duran, OH, Watkins, H, Jukema, JW, Florez, JC, Wareham, NJ, Meigs, JB, Ingelsson, E, Baldassarre, D, Hamsten, A, Strawbridge, RJ, Silveira, A, den Hoed, M, Gustafsson, S, Luan, JA, Rybin, D, Dupuis, J, Li-Gao, RF, Kavousi, Maryam, Dehghan, A, Haljas, K, Lahti, J, Gadin, JR, Backlund, A, de Faire, U, Gertow, K, Giral, P, Goel, A, Humphries, SE, Kurl, S, Langenberg, C, Lannfelt, LL, Lind, L, Lindgren, CCM, Mannarino, E, Mook, Dennis, Morris, AP, de Mutsert, R, Rauramaa, R, Saliba-Gustafsson, P, Sennblad, B, Smit, AJ, Syvanen, AC, Tremoli, E, Veglia, F, Zethelius, B, Bjorck, HM, Eriksson, JG, Hofman, Bert, Franco Duran, OH, Watkins, H, Jukema, JW, Florez, JC, Wareham, NJ, Meigs, JB, Ingelsson, E, Baldassarre, D, and Hamsten, A

Published
2017

49. Glycated hemoglobin measurement and prediction of cardiovascular disease

Author

Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, Khan H, Butterworth AS, Wormser D, Kaptoge S, Kondapally Seshasai SR, Thompson A, Sarwar N, Willeit P, Ridker PM, Barr EL, Khaw KT, Psaty BM, Brenner H, Balkau B, Dekker JM, Lawlor DA, Daimon M, Willeit J, Njølstad I, Nissinen A, Brunner EJ, Kuller LH, Price JF, Sundström J, Knuiman MW, Feskens EJ, Verschuren WM, Wald N, Bakker SJ, Whincup PH, Ford I, Goldbourt U, Gómez de la Cámara A, Gallacher J, Simons LA, Rosengren A, Sutherland SE, Björkelund C, Blazer DG, Wassertheil Smoller S, Onat A, Marín Ibañez A, Casiglia E, Jukema JW, Simpson LM, Giampaoli S, Nordestgaard BG, Selmer R, Wennberg P, Kauhanen J, Salonen JT, Dankner R, Barrett Connor E, Kavousi M, Gudnason V, Evans D, Wallace RB, Cushman M, D'Agostino RB Sr, Umans JG, Kiyohara Y, Nakagawa H, Sato S, Gillum RF, Folsom AR, van der Schouw YT, Moons KG, Griffin SJ, Sattar N, Wareham NJ, Selvin E, Thompson SG, Danesh J. Collaborators Simpson LM, Coresh J, Wagenknecht L, Shaw JE, Zimmet PZ, Magliano D, Wannamethee SG, Morris RW, Kiechl S, Santer P, Bonora E, Casas JP, Ebrahim S, Ben Shlomo Y, Yarnell JW, Elwood P, Bachman DL, Nietert PJ, Håheim LL, Søgaard AJ, Tybjaerg Hansen A, Frikke Schmidt R, Benn M, Palmieri L, Vanuzzo D, Bonnet F, Copin N, Roussel R, Gómez Gerique JA, Rubio Herrera MA, Gutiérrez Fuentes JA, Friedlander Y, McCallum J, Simons J, Lee AJ, McLachlan S, Taylor JO, Guralnik JM, Phillips CL, Evans DA, Kohout F, Cohen H, George L, Fillenbaum G, McGloin JM, Khaw K., Schöttker B, Müller H, Rothenbacher D, Jansson J., Hallmans G, Tuomilehto J, Donfrancesco C, Woodward M, Oizumi T, Kayama T, Kato T, Danker R, Chetrit A, Wilhelmsen L, Eriksson H, Lappas G, Bengtsson C, Lissner L, Skoog I, Cremer P, Arima H, Ninomiya T, Hata J, Nijpels G, Stehouwer CD, Tuomainen T., Voutilainen S, Kurl S, de Boer IH, Bertoni AG, Veschuren WM, Dullaart RP, Lambers Heerspink HJ, Hilege HL, Trompet S, Stott DJ, Dagenais GR, Cantin B, Dehghan D, Hofman A, Franco OH, Tunstall Pedoe H, Lee E, Best L, Howard BV, Can G, Ademoğlu E, Sakurai M, Nakamura K, Morikawa Y, Løchen M., Mathiesen EB, Wilsgaard T, Byberg L, Cederholm T, Olsson E, Pradhan AD, Cook NR, Kromhout D, Walker M, Watson S, Burgess S, Gregson J, Harshfield E, Pennells L, Spackman S, Warnakula S, Wood AM, Danesh J., PANICO, SALVATORE, Emerging Risk Factors, Collaboration, Di Angelantonio, E, Gao, P, Khan, H, Butterworth, A, Wormser, D, Kaptoge, S, Kondapally Seshasai, Sr, Thompson, A, Sarwar, N, Willeit, P, Ridker, Pm, Barr, El, Khaw, Kt, Psaty, Bm, Brenner, H, Balkau, B, Dekker, Jm, Lawlor, Da, Daimon, M, Willeit, J, Njølstad, I, Nissinen, A, Brunner, Ej, Kuller, Lh, Price, Jf, Sundström, J, Knuiman, Mw, Feskens, Ej, Verschuren, Wm, Wald, N, Bakker, Sj, Whincup, Ph, Ford, I, Goldbourt, U, Gómez de la Cámara, A, Gallacher, J, Simons, La, Rosengren, A, Sutherland, Se, Björkelund, C, Blazer, Dg, Wassertheil Smoller, S, Onat, A, Marín Ibañez, A, Casiglia, E, Jukema, Jw, Simpson, Lm, Giampaoli, S, Nordestgaard, Bg, Selmer, R, Wennberg, P, Kauhanen, J, Salonen, Jt, Dankner, R, Barrett Connor, E, Kavousi, M, Gudnason, V, Evans, D, Wallace, Rb, Cushman, M, D'Agostino RB, Sr, Umans, Jg, Kiyohara, Y, Nakagawa, H, Sato, S, Gillum, Rf, Folsom, Ar, van der Schouw, Yt, Moons, Kg, Griffin, Sj, Sattar, N, Wareham, Nj, Selvin, E, Thompson, Sg, Danesh J., Collaborators Simpson LM, Coresh, J, Wagenknecht, L, Shaw, Je, Zimmet, Pz, Magliano, D, Wannamethee, Sg, Morris, Rw, Kiechl, S, Santer, P, Bonora, E, Casas, Jp, Ebrahim, S, Ben Shlomo, Y, Yarnell, Jw, Elwood, P, Bachman, Dl, Nietert, Pj, Håheim, Ll, Søgaard, Aj, Tybjaerg Hansen, A, Frikke Schmidt, R, Benn, M, Palmieri, L, Vanuzzo, D, Panico, Salvatore, Bonnet, F, Copin, N, Roussel, R, Gómez Gerique, Ja, Rubio Herrera, Ma, Gutiérrez Fuentes, Ja, Friedlander, Y, Mccallum, J, Simons, J, Lee, Aj, Mclachlan, S, Taylor, Jo, Guralnik, Jm, Phillips, Cl, Evans, Da, Kohout, F, Cohen, H, George, L, Fillenbaum, G, Mcgloin, Jm, Khaw, K., Schöttker, B, Müller, H, Rothenbacher, D, Jansson, J., Hallmans, G, Tuomilehto, J, Donfrancesco, C, Woodward, M, Oizumi, T, Kayama, T, Kato, T, Danker, R, Chetrit, A, Wilhelmsen, L, Eriksson, H, Lappas, G, Bengtsson, C, Lissner, L, Skoog, I, Cremer, P, Arima, H, Ninomiya, T, Hata, J, Nijpels, G, Stehouwer, Cd, Tuomainen, T., Voutilainen, S, Kurl, S, de Boer, Ih, Bertoni, Ag, Veschuren, Wm, Dullaart, Rp, Lambers Heerspink, Hj, Hilege, Hl, Trompet, S, Stott, Dj, Dagenais, Gr, Cantin, B, Dehghan, D, Hofman, A, Franco, Oh, Tunstall Pedoe, H, Lee, E, Best, L, Howard, Bv, Can, G, Ademoğlu, E, Sakurai, M, Nakamura, K, Morikawa, Y, Løchen, M., Mathiesen, Eb, Wilsgaard, T, Byberg, L, Cederholm, T, Olsson, E, Pradhan, Ad, Cook, Nr, Kromhout, D, Walker, M, Watson, S, Burgess, S, Gregson, J, Harshfield, E, Pennells, L, Spackman, S, Warnakula, S, Wood, Am, and Danesh, J.

Published
2014

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