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1. Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Author

Seekircher, Lisa, primary, Tschiderer, Lena, additional, Lind, Lars, additional, Safarova, Maya S, additional, Kavousi, Maryam, additional, Ikram, M Arfan, additional, Lonn, Eva, additional, Yusuf, Salim, additional, Grobbee, Diederick E, additional, Kastelein, John J P, additional, Visseren, Frank L J, additional, Walters, Matthew, additional, Dawson, Jesse, additional, Higgins, Peter, additional, Agewall, Stefan, additional, Catapano, Alberico, additional, de Groot, Eric, additional, Espeland, Mark A, additional, Klingenschmid, Gerhard, additional, Magliano, Dianna, additional, Olsen, Michael H, additional, Preiss, David, additional, Sander, Dirk, additional, Skilton, Michael, additional, Zozulińska-Ziółkiewicz, Dorota A, additional, Grooteman, Muriel P C, additional, Blankestijn, Peter J, additional, Kitagawa, Kazuo, additional, Okazaki, Shuhei, additional, Manzi, Maria V, additional, Mancusi, Costantino, additional, Izzo, Raffaele, additional, Desvarieux, Moise, additional, Rundek, Tatjana, additional, Gerstein, Hertzel C, additional, Bots, Michiel L, additional, Sweeting, Michael J, additional, Lorenz, Matthias W, additional, and Willeit, Peter, additional

Published
2023
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2. Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque : Individual Participant Data Meta-Analysis of 20 Prospective Studies

Author

Tschiderer, Lena, Seekircher, Lisa, Izzo, Raffaele, Mancusi, Costantino V., Manzi, Maria, Baldassarre, Damiano, Amato, Mauro, Tremoli, Elena, Veglia, Fabrizio, Tuomainen, Tomi-Pekka, Kauhanen, Jussi, Voutilainen, Ari, Iglseder, Bernhard, Lind, Lars, Rundek, Tatjana, Desvarieux, Moise, Kato, Akihiko, de Groot, Eric, Asci, Guelay, Ok, Ercan, Agewall, Stefan, Beulens, Joline W. J. D., Byrne, Christopher C., Calder, Philip C., Gerstein, Hertzel, Gresele, Paolo, Klingenschmid, Gerhard, Nagai, Michiaki H., Olsen, Michael, Parraga, Grace S., Safarova, Maya, Sattar, Naveed, Skilton, Michael, Stehouwer, Coen D. A., Uthoff, Heiko A., van Agtmael, Michiel A., van der Heijden, Amber A., Zozulinska-Ziolkiewicz, Dorota, Park, Hyun-Woong, Lee, Moo-Sik, Bae, Jang-Ho, Beloqui, Oscar F., Landecho, Manuel, Plichart, Matthieu, Ducimetiere, Pierre, Empana, Jean Philippe, Bokemark, Lena, Bergstroem, Goeran, Schmidt, Caroline, Castelnuovo, Samuela, Calabresi, Laura D., Norata, Giuseppe, Grigore, Liliana, Catapano, Alberico, Zhao, Dong, Wang, Miao, Liu, Jing, Ikram, M. Arfan, Kavousi, Maryam L., Bots, Michiel J., Sweeting, Michael W., Lorenz, Matthias, Willeit, Peter, Tschiderer, Lena, Seekircher, Lisa, Izzo, Raffaele, Mancusi, Costantino V., Manzi, Maria, Baldassarre, Damiano, Amato, Mauro, Tremoli, Elena, Veglia, Fabrizio, Tuomainen, Tomi-Pekka, Kauhanen, Jussi, Voutilainen, Ari, Iglseder, Bernhard, Lind, Lars, Rundek, Tatjana, Desvarieux, Moise, Kato, Akihiko, de Groot, Eric, Asci, Guelay, Ok, Ercan, Agewall, Stefan, Beulens, Joline W. J. D., Byrne, Christopher C., Calder, Philip C., Gerstein, Hertzel, Gresele, Paolo, Klingenschmid, Gerhard, Nagai, Michiaki H., Olsen, Michael, Parraga, Grace S., Safarova, Maya, Sattar, Naveed, Skilton, Michael, Stehouwer, Coen D. A., Uthoff, Heiko A., van Agtmael, Michiel A., van der Heijden, Amber A., Zozulinska-Ziolkiewicz, Dorota, Park, Hyun-Woong, Lee, Moo-Sik, Bae, Jang-Ho, Beloqui, Oscar F., Landecho, Manuel, Plichart, Matthieu, Ducimetiere, Pierre, Empana, Jean Philippe, Bokemark, Lena, Bergstroem, Goeran, Schmidt, Caroline, Castelnuovo, Samuela, Calabresi, Laura D., Norata, Giuseppe, Grigore, Liliana, Catapano, Alberico, Zhao, Dong, Wang, Miao, Liu, Jing, Ikram, M. Arfan, Kavousi, Maryam L., Bots, Michiel J., Sweeting, Michael W., Lorenz, Matthias, and Willeit, Peter

Abstract

Background: The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results: We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions: Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent

Published
2023
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3. Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Author

Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Abstract

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

Published
2023

4. Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque:Individual Participant Data Meta-Analysis of 20 Prospective Studies

Author

Tschiderer, Lena, Seekircher, Lisa, Izzo, Raffaele, Mancusi, Costantino, Manzi, Maria V., Baldassarre, Damiano, Amato, Mauro, Tremoli, Elena, Veglia, Fabrizio, Tuomainen, Tomi Pekka, Kauhanen, Jussi, Voutilainen, Ari, Iglseder, Bernhard, Lind, Lars, Rundek, Tatjana, Desvarieux, Moise, Kato, Akihiko, de Groot, Eric, Aşçi, Gülay, Ok, Ercan, Agewall, Stefan, Beulens, Joline W.J., Byrne, Christopher D., Calder, Philip C., Gerstein, Hertzel C., Gresele, Paolo, Klingenschmid, Gerhard, Nagai, Michiaki, Olsen, Michael H., Parraga, Grace, Safarova, Maya S., Sattar, Naveed, Skilton, Michael, Stehouwer, Coen D.A., Uthoff, Heiko, van Agtmael, Michiel A., van der Heijden, Amber A., Zozulińska-Ziółkiewicz, Dorota A., Park, Hyun Woong, Lee, Moo Sik, Bae, Jang Ho, Beloqui, Oscar, Landecho, Manuel F., Plichart, Matthieu, Ducimetiere, Pierre, Empana, Jean Philippe, Bokemark, Lena, Bergström, Göran, Schmidt, Caroline, Castelnuovo, Samuela, Calabresi, Laura, Norata, Giuseppe D., Grigore, Liliana, Catapano, Alberico, Zhao, Dong, Wang, Miao, Liu, Jing, Ikram, M. Arfan, Kavousi, Maryam, Bots, Michiel L, Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Tschiderer, Lena, Seekircher, Lisa, Izzo, Raffaele, Mancusi, Costantino, Manzi, Maria V., Baldassarre, Damiano, Amato, Mauro, Tremoli, Elena, Veglia, Fabrizio, Tuomainen, Tomi Pekka, Kauhanen, Jussi, Voutilainen, Ari, Iglseder, Bernhard, Lind, Lars, Rundek, Tatjana, Desvarieux, Moise, Kato, Akihiko, de Groot, Eric, Aşçi, Gülay, Ok, Ercan, Agewall, Stefan, Beulens, Joline W.J., Byrne, Christopher D., Calder, Philip C., Gerstein, Hertzel C., Gresele, Paolo, Klingenschmid, Gerhard, Nagai, Michiaki, Olsen, Michael H., Parraga, Grace, Safarova, Maya S., Sattar, Naveed, Skilton, Michael, Stehouwer, Coen D.A., Uthoff, Heiko, van Agtmael, Michiel A., van der Heijden, Amber A., Zozulińska-Ziółkiewicz, Dorota A., Park, Hyun Woong, Lee, Moo Sik, Bae, Jang Ho, Beloqui, Oscar, Landecho, Manuel F., Plichart, Matthieu, Ducimetiere, Pierre, Empana, Jean Philippe, Bokemark, Lena, Bergström, Göran, Schmidt, Caroline, Castelnuovo, Samuela, Calabresi, Laura, Norata, Giuseppe D., Grigore, Liliana, Catapano, Alberico, Zhao, Dong, Wang, Miao, Liu, Jing, Ikram, M. Arfan, Kavousi, Maryam, Bots, Michiel L, Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Abstract

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid p

Published
2023

5. Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Author

Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Interne Geneeskunde Vasculaire, Nefro Vasculaire Geneeskunde, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Interne Geneeskunde Vasculaire, Nefro Vasculaire Geneeskunde, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, Seekircher, Lisa, Tschiderer, Lena, Lind, Lars, Safarova, Maya S., Kavousi, Maryam, Ikram, M. Arfan, Lonn, Eva, Yusuf, Salim, Grobbee, Diederick E., Kastelein, John J.P., Visseren, Frank L.J., Walters, Matthew, Dawson, Jesse, Higgins, Peter, Agewall, Stefan, Catapano, Alberico, De Groot, Eric, Espeland, Mark A., Klingenschmid, Gerhard, Magliano, Dianna, Olsen, Michael H., Preiss, David, Sander, Dirk, Skilton, Michael, Zozulińska-Ziółkiewicz, Dorota A., Grooteman, Muriel P.C., Blankestijn, Peter J., Kitagawa, Kazuo, Okazaki, Shuhei, Manzi, Maria V., Mancusi, Costantino, Izzo, Raffaele, Desvarieux, Moise, Rundek, Tatjana, Gerstein, Hertzel C., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Published
2023

6. Associations of proteins of the Wnt signalling pathway with cardiovascular disease risk

Author

Klingenschmid, Gerhard and Klingenschmid, Gerhard

Abstract

Einleitung: Der Wnt Signalweg, seine Modulatoren Dickkopf-1 und Sclerostin sowie Osteoprotegerin, welches vom Wnt Signalweg reguliert wird, werden mit der Pathogenese von Herz-Kreislauferkrankungen (HKE) in Verbindung gebracht. Vorherige Studien zeigten eine Assoziation zwischen Osteoprotegerin und dem Auftreten von HKE in der Allgemeinbevölkerung, die Datenlage bei Patient*innen mit hohem HKE-Risiko ist jedoch nicht ausreichend geklärt. Das Ziel dieser Arbeit war, den Zusammenhang zwischen Dickkopf-1 und Sclerostin und HKE in der bevölkerungsbasierten Bruneck Studie, sowie die Assoziation zwischen Osteoprotegerin und HKE mittels Meta-Analyse in bereits publizierten Studien bei Patient*innen mit Erkrankungen mit hohem HKE-Risiko, zu untersuchen. Methoden: In der ersten Studie wurden Assoziationen von Dickkopf-1 und Sclerostin, welche im Jahr 2000 in der Bruneck Studie gemessen wurden, mit dem Auftreten eines kombinierten kardiovaskulären Endpunktes über einen Beobachtungszeitraum von 16 Jahren mittels Cox Regressionsanalyse quantifiziert. In der zweiten Studie wurde in der Literatur systematisch nach Studien über die Assoziation von Osteoprotegerin und inzidenten HKE bei Patient*innen mit hohem HKE-Risiko gesucht und Studien-spezifische Schätzer mittels random-effects Meta-Analyse gepoolt. Ergebnisse: Die durchschnittliche Serum-Konzentration von Dickkopf-1 lag bei 44,5 pmol/L (Standardabweichung [SD] 14,7), die für Sclerostin betrug 47,1 pmol/L (SD 17,5). Über einen medianen Beobachtungszeitraum von 15,6 Jahren traten 179 HKE-Ereignisse auf. Die multivariat-adjustierten hazard ratios (HRs) für das Auftreten eines HKE-Ereignisses pro SD-höherer Konzentration betrugen 1,20 für Dickkopf‐1 (95 % Konfidenzintervall [CI], 1,02–1,42; P = 0,028) und 0,92 für Sclerostin (95 % CI, 0,78–1,08; P = 0,286). Die Assoziation zwischen Dickkopf-1 und inzidenten HKE konnte vorwiegend durch eine starke Assoziation mit cerebrovaskulären Ereignissen erklärt werden (67 Ereignisse; HR, 1, Introduction: Wnt signalling, its modulatory proteins dickkopf-1 and sclerostin, and the Wnt-regulated protein osteoprotegerin have been implicated in the pathogenesis of cardiovascular disease (CVD). Osteoprotegerin has been associated with incident CVD in the general population, however its relevance as a biomarker among populations at high vascular risk is less clear. The thesis aims to evaluate the relationship of dickkopf‐1 and sclerostin with CVD risk based on data of the population‐based Bruneck Study, and to assess the relationship between osteoprotegerin and incident CVD in patients with conditions conveying a high CVD-risk by conducting a meta-analysis of studies reporting on this association. Methods: For the first study, we quantified associations between serum dickkopf-1 and sclerostin measured in the 2000 examination of the prospective Bruneck Study with a combined CVD endpoint during a 16-year follow-up interval using Cox regression analysis. For the second study, we systematically searched prospective studies reporting associations of osteoprotegerin with incident CVD in high-risk patient populations and pooled study‐specific risk ratios using random‐effects meta‐analysis. Results: Among 706 participants of the Bruneck Study, mean±standard deviation (SD) of serum levels were 44.5±14.7 pmol/L for dickkopf‐1 and 47.1±17.5 pmol/L for sclerostin. Over a median follow‐up duration of 15.6 years, 179 CVD events occurred. For the primary CVD outcome, multivariable‐adjusted hazard ratios (HRs) per SD-higher level were 1.20 for dickkopf‐1 (95 % confidence interval [CI], 1.02–1.42; P = 0.028) and 0.92 for sclerostin (95 % CI, 0.78–1.08; P = 0.286). Secondary outcome analyses revealed that the association of dickkopf‐1 was primarily driven by stroke (67 events; HR, 1.37; 95 % CI, 1.06–1.78; P = 0.017). In the second study, we included a total of 19 prospective studies reporting on 27,450 patients. Over a mean follow‐up of 4.2 years, 4,066 CVD events were recorde, Gerhard Klingenschmid, Zusammenfassung in deutscher Sprache, Dissertation Medical University of Innsbruck 2023

Published
2023

7. Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk

Author

Willeit, Peter, Tschiderer, Lena, Allara, Elias, Reuber, Kathrin, Seekircher, Lisa, Gao, Lu, Liao, Ximing, Lonn, Eva, Gerstein, Hertzel C, Yusuf, Salim, Brouwers, Frank P, Asselbergs, Folkert W, Van Gilst, Wiek, Anderssen, Sigmund A, Grobbee, Diederick E, Kastelein, John JP, Visseren, Frank LJ, Ntaios, George, Hatzitolios, Apostolos I, Savopoulos, Christos, Nieuwkerk, Pythia T, Stroes, Erik, Walters, Matthew, Higgins, Peter, Dawson, Jesse, Gresele, Paolo, Guglielmini, Giuseppe, Migliacci, Rino, Ezhov, Marat, Safarova, Maya, Balakhonova, Tatyana, Sato, Eiichi, Amaha, Mayuko, Nakamura, Tsukasa, Kapellas, Kostas, Jamieson, Lisa M, Skilton, Michael, Blumenthal, James A, Hinderliter, Alan, Sherwood, Andrew, Smith, Patrick J, Van Agtmael, Michiel A, Reiss, Peter, Van Vonderen, Marit GA, Kiechl, Stefan, Klingenschmid, Gerhard, Sitzer, Matthias, Stehouwer, Coen DA, Uthoff, Heiko, Zou, Zhi-Yong, Cunha, Ana R, Neves, Mario F, Witham, Miles D, Park, Hyun-Woong, Lee, Moo-Sik, Bae, Jang-Ho, Bernal, Enrique, Wachtell, Kristian, Kjeldsen, Sverre E, Olsen, Michael H, Preiss, David, Sattar, Naveed, Beishuizen, Edith, Huisman, Menno V, Espeland, Mark A, Schmidt, Caroline, Agewall, Stefan, Ok, Ercan, Aşçi, Gülay, De Groot, Eric, Grooteman, Muriel PC, Blankestijn, Peter J, Bots, Michiel L, Sweeting, Michael J, Thompson, Simon G, Lorenz, Matthias W, PROG-IMT And The Proof-ATHERO Study Groups, Group, PROG-IMT Study, Group, Proof-ATHERO Study, Vascular Medicine, Medical Psychology, APH - Mental Health, APH - Personalized Medicine, Experimental Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Global Health, APH - Aging & Later Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Pulmonary hypertension & thrombosis, Ege Üniversitesi, MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, MUMC+: HVC Pieken Maastricht Studie (9), Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), Allara, Elias [0000-0002-1634-8330], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Internal medicine, Nephrology, and ACS - Diabetes & metabolism

Subjects
Male, medicine.medical_specialty, Carotid Artery, Common, carotid intima-media thickness, LDL TREATMENT STRATEGIES, Myocardial Infarction, surrogate marker, TYPE-2 DIABETES-MELLITUS, HIV-INFECTED PATIENTS, 030204 cardiovascular system & hematology, Impaired glucose tolerance, EXTENDED-RELEASE NIACIN, 03 medical and health sciences, 0302 clinical medicine, IMPAIRED GLUCOSE-TOLERANCE, ESTROGEN PLUS PROGESTIN, cardiovascular disease, Physiology (medical), Internal medicine, BASE-LINE CHARACTERISTICS, medicine, Humans, CORONARY-HEART-DISEASE, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Stroke, Randomized Controlled Trials as Topic, clinical trials as topic, business.industry, Surrogate endpoint, Middle Aged, medicine.disease, Common, Clinical trial, meta-analysis, ARTERIAL-WALL THICKNESS, Intima-media thickness, JAPAN STATIN TREATMENT, Heart Disease Risk Factors, Relative risk, Meta-analysis, Cardiology, cardiovascular system, Female, Carotid Artery, Cardiology and Cardiovascular Medicine, business
Abstract

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. the primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 mu m/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 mu m/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: the extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials., Austrian Science Fund (FWF)Austrian Science Fund (FWF) [P 32488]; Dr-Johannes-and-Hertha-Tuba Foundation; German Research FoundationGerman Research Foundation (DFG) [DFG Lo 1569/2-1, DFG Lo 1569/2-3]; excellence initiative "Competence Centers for Excellent Technologies" (COMET) of the Austrian Research Promotion Agency (FFG) "Research Center of Excellence in Vascular Ageing: Tyrol, VAS-Cage" - Bundesministerium fur Verkehr, Innovation und Technologie (B [843536]; Bundesministerium fur Bildung, Wissenschaft und Forschung (BMWFW); Wirtschaftsagentur Wien; Standortagentur Tirol, This work was supported by the Austrian Science Fund (FWF; P 32488); the Dr-Johannes-and-Hertha-Tuba Foundation; the German Research Foundation (DFG Lo 1569/2-1 and DFG Lo 1569/2-3); and the excellence initiative "Competence Centers for Excellent Technologies" (COMET) of the Austrian Research Promotion Agency (FFG) "Research Center of Excellence in Vascular Ageing: Tyrol, VAS-Cage" (K-Project No. 843536), funded by Bundesministerium fur Verkehr, Innovation und Technologie (BMVIT), Bundesministerium fur Bildung, Wissenschaft und Forschung (BMWFW), Wirtschaftsagentur Wien, and Standortagentur Tirol.

Published
2020
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9. The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium : Design and Rationale

Author

Tschiderer, Lena, Seekircher, Lisa, Klingenschmid, Gerhard, Izzo, Raffaele, Baldassarre, Damiano, Iglseder, Bernhard, Calabresi, Laura, Liu, Jing, Price, JackieF., Bae, Jang-Ho, Brouwers, FrankP., de Groot, Eric, Schmidt, Caroline, Bergstroem, Goeran, Asci, Guelay, Gresele, Paolo, Okazaki, Shuhei, Kapellas, Kostas, Landecho, ManuelF., Sattar, Naveed, Agewall, Stefan, Zou, Zhi-Yong, Byrne, Christopher D., Nanayakkara, Prabath W. B., Papagianni, Aikaterini, Witham, Miles D., Bernal, Enrique, Ekart, Robert, van Agtmael, Michiel A., Neves, Mario F., Sato, Eiichi, Ezhov, Marat, Walters, Matthew, Olsen, Michael H., Stolic, Radojica, Zozulinska-Ziolkiewicz, DorotaA., Hanefeld, Markolf, Staub, Daniel, Nagai, Michiaki, Nieuwkerk, Pythia T., Huisman, Menno V., Kato, Akihiko, Honda, Hirokazu, Parraga, Grace, Magliano, Dianna, Gabriel, Rafael, Rundek, Tatjana, Espeland, Mark A., Kiechl, Stefan, Willeit, Johann, Lind, Lars, Empana, Jean Philippe, Lonn, Eva, Tuomainen, Tomi-Pekka, Catapano, Alberico, Chien, Kuo-Liong, Sander, Dirk, Kavousi, Maryam, Beulens, Joline W. J., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., Willeit, Peter, Tschiderer, Lena, Seekircher, Lisa, Klingenschmid, Gerhard, Izzo, Raffaele, Baldassarre, Damiano, Iglseder, Bernhard, Calabresi, Laura, Liu, Jing, Price, JackieF., Bae, Jang-Ho, Brouwers, FrankP., de Groot, Eric, Schmidt, Caroline, Bergstroem, Goeran, Asci, Guelay, Gresele, Paolo, Okazaki, Shuhei, Kapellas, Kostas, Landecho, ManuelF., Sattar, Naveed, Agewall, Stefan, Zou, Zhi-Yong, Byrne, Christopher D., Nanayakkara, Prabath W. B., Papagianni, Aikaterini, Witham, Miles D., Bernal, Enrique, Ekart, Robert, van Agtmael, Michiel A., Neves, Mario F., Sato, Eiichi, Ezhov, Marat, Walters, Matthew, Olsen, Michael H., Stolic, Radojica, Zozulinska-Ziolkiewicz, DorotaA., Hanefeld, Markolf, Staub, Daniel, Nagai, Michiaki, Nieuwkerk, Pythia T., Huisman, Menno V., Kato, Akihiko, Honda, Hirokazu, Parraga, Grace, Magliano, Dianna, Gabriel, Rafael, Rundek, Tatjana, Espeland, Mark A., Kiechl, Stefan, Willeit, Johann, Lind, Lars, Empana, Jean Philippe, Lonn, Eva, Tuomainen, Tomi-Pekka, Catapano, Alberico, Chien, Kuo-Liong, Sander, Dirk, Kavousi, Maryam, Beulens, Joline W. J., Bots, Michiel L., Sweeting, Michael J., Lorenz, Matthias W., and Willeit, Peter

Abstract

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, ankle-brachial index, pulse wave velocity, and coronary artery calcium. The Prospective Studies of Atherosclerosis (Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.

Published
2020
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10. The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale

Author

Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Tschiderer, Lena, Seekircher, Lisa, Klingenschmid, Gerhard, Izzo, Raffaele, Baldassarre, Damiano, Iglseder, Bernhard, Calabresi, Laura, Liu, Jing, Price, Jackie F., Bae, Jang Ho, Brouwers, Frank P., De Groot, Eric, Schmidt, Caroline, Bergström, Göran, Aşçi, Gülay, Gresele, Paolo, Okazaki, Shuhei, Kapellas, Kostas, Landecho, Manuel F., Sattar, Naveed, Agewall, Stefan, Zou, Zhi Yong, Byrne, Christopher D., Nanayakkara, Prabath W.B., Papagianni, Aikaterini, Witham, Miles D., Bernal, Enrique, Ekart, Robert, Van Agtmael, Michiel A., Neves, Mario F., Sato, Eiichi, Ezhov, Marat, Walters, Matthew, Olsen, Michael H., Stolić, Radojica, Zozulińska-Ziółkiewicz, Dorota A., Hanefeld, Markolf, Staub, Daniel, Nagai, Michiaki, Nieuwkerk, Pythia T., Huisman, Menno V., Kato, Akihiko, Honda, Hirokazu, Parraga, Grace, Magliano, Dianna, Gabriel, Rafael, Rundek, Tatjana, Espeland, Mark A., Beulens, Joline W.J., Bots, Michiel L., Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Tschiderer, Lena, Seekircher, Lisa, Klingenschmid, Gerhard, Izzo, Raffaele, Baldassarre, Damiano, Iglseder, Bernhard, Calabresi, Laura, Liu, Jing, Price, Jackie F., Bae, Jang Ho, Brouwers, Frank P., De Groot, Eric, Schmidt, Caroline, Bergström, Göran, Aşçi, Gülay, Gresele, Paolo, Okazaki, Shuhei, Kapellas, Kostas, Landecho, Manuel F., Sattar, Naveed, Agewall, Stefan, Zou, Zhi Yong, Byrne, Christopher D., Nanayakkara, Prabath W.B., Papagianni, Aikaterini, Witham, Miles D., Bernal, Enrique, Ekart, Robert, Van Agtmael, Michiel A., Neves, Mario F., Sato, Eiichi, Ezhov, Marat, Walters, Matthew, Olsen, Michael H., Stolić, Radojica, Zozulińska-Ziółkiewicz, Dorota A., Hanefeld, Markolf, Staub, Daniel, Nagai, Michiaki, Nieuwkerk, Pythia T., Huisman, Menno V., Kato, Akihiko, Honda, Hirokazu, Parraga, Grace, Magliano, Dianna, Gabriel, Rafael, Rundek, Tatjana, Espeland, Mark A., Beulens, Joline W.J., and Bots, Michiel L.

Published
2020

11. Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100,667 Patients

Author

Team Medisch, Circulatory Health, Global Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Interne Geneeskunde Vasculaire, MS Nefrologie, Cardiovasculaire Epidemiologie, Willeit, Peter, Tschiderer, Lena, Allara, Elias, Reuber, Kathrin, Seekircher, Lisa, Gao, Lu, Liao, Ximing, Lonn, Eva, Gerstein, Hertzel C, Yusuf, Salim, Brouwers, Frank P, Asselbergs, Folkert W, van Gilst, Wiek, Anderssen, Sigmund A, Grobbee, Diederick E, Kastelein, John J P, Visseren, Frank L J, Ntaios, George, Hatzitolios, Apostolos I, Savopoulos, Christos, Nieuwkerk, Pythia T, Stroes, Erik, Walters, Matthew, Higgins, Peter, Dawson, Jesse, Gresele, Paolo, Guglielmini, Giuseppe, Migliacci, Rino, Ezhov, Marat, Safarova, Maya, Balakhonova, Tatyana, Sato, Eiichi, Amaha, Mayuko, Nakamura, Tsukasa, Kapellas, Kostas, Jamieson, Lisa M, Skilton, Michael, Blumenthal, James A, Hinderliter, Alan, Sherwood, Andrew, Smith, Patrick J, van Agtmael, Michiel A, Reiss, Peter, van Vonderen, Marit G A, Kiechl, Stefan, Klingenschmid, Gerhard, Sitzer, Matthias, Stehouwer, Coen D A, Blankestijn, Peter J, Bots, Michiel L, PROG-IMT and the Proof-ATHERO Study Groups, Team Medisch, Circulatory Health, Global Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Interne Geneeskunde Vasculaire, MS Nefrologie, Cardiovasculaire Epidemiologie, Willeit, Peter, Tschiderer, Lena, Allara, Elias, Reuber, Kathrin, Seekircher, Lisa, Gao, Lu, Liao, Ximing, Lonn, Eva, Gerstein, Hertzel C, Yusuf, Salim, Brouwers, Frank P, Asselbergs, Folkert W, van Gilst, Wiek, Anderssen, Sigmund A, Grobbee, Diederick E, Kastelein, John J P, Visseren, Frank L J, Ntaios, George, Hatzitolios, Apostolos I, Savopoulos, Christos, Nieuwkerk, Pythia T, Stroes, Erik, Walters, Matthew, Higgins, Peter, Dawson, Jesse, Gresele, Paolo, Guglielmini, Giuseppe, Migliacci, Rino, Ezhov, Marat, Safarova, Maya, Balakhonova, Tatyana, Sato, Eiichi, Amaha, Mayuko, Nakamura, Tsukasa, Kapellas, Kostas, Jamieson, Lisa M, Skilton, Michael, Blumenthal, James A, Hinderliter, Alan, Sherwood, Andrew, Smith, Patrick J, van Agtmael, Michiel A, Reiss, Peter, van Vonderen, Marit G A, Kiechl, Stefan, Klingenschmid, Gerhard, Sitzer, Matthias, Stehouwer, Coen D A, Blankestijn, Peter J, Bots, Michiel L, and PROG-IMT and the Proof-ATHERO Study Groups

Published
2020

13. Osteoprotegerin and Cardiovascular Events in High-Risk Populations: Meta-Analysis of 19 Prospective Studies Involving 27450 Participants

Author

Tschiderer, Lena, Klingenschmid, Gerhard, Nagrani, Rajini, Willeit, Johann, Laukkanen, Jari, Schett, Georg, Kiechl, Stefan, and Willeit, Peter

Subjects
cardiovascular disease, osteoprotegerin, riskiryhmät, meta-analyysi, prospective cohorts, sydän- ja verisuonitaudit, proteiinit, high-risk population
Abstract

Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (CVD) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066 CVD events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50; P

Published
2018

15. Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Author

Tschiderer L, Seekircher L, Izzo R, Mancusi C, Manzi MV, Baldassarre D, Amato M, Tremoli E, Veglia F, Tuomainen TP, Kauhanen J, Voutilainen A, Iglseder B, Lind L, Rundek T, Desvarieux M, Kato A, de Groot E, Aşçi G, Ok E, Agewall S, Beulens JWJ, Byrne CD, Calder PC, Gerstein HC, Gresele P, Klingenschmid G, Nagai M, Olsen MH, Parraga G, Safarova MS, Sattar N, Skilton M, Stehouwer CDA, Uthoff H, van Agtmael MA, van der Heijden AA, Zozulińska-Ziółkiewicz DA, Park HW, Lee MS, Bae JH, Beloqui O, Landecho MF, Plichart M, Ducimetiere P, Empana JP, Bokemark L, Bergström G, Schmidt C, Castelnuovo S, Calabresi L, Norata GD, Grigore L, Catapano A, Zhao D, Wang M, Liu J, Ikram MA, Kavousi M, Bots ML, Sweeting MJ, Lorenz MW, and Willeit P

Subjects
Humans, Female, Middle Aged, Male, Carotid Intima-Media Thickness, Prospective Studies, Risk Factors, Carotid Artery, Common diagnostic imaging, Plaque, Atherosclerotic, Carotid Artery Diseases diagnostic imaging, Carotid Artery Diseases epidemiology
Abstract

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I 2 =63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I 2 =59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I 2 =57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Published
2023
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