Browsing by Author "Ronkainen, Kimmo"

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    ItemOpen Access
    Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.
    (Diabetes care, 2015-10) Lorenz, Matthias W; Price, Jackie F; Robertson, Christine; Bots, Michiel L; Polak, Joseph F; Poppert, Holger; Kavousi, Maryam; Dörr, Marcus; Stensland, Eva; Ducimetiere, Pierre; Ronkainen, Kimmo; Kiechl, Stefan; Sitzer, Matthias; Rundek, Tatjana; Lind, Lars; Liu, Jing; Bergström, Göran; Grigore, Liliana; Bokemark, Lena; Friera, Alfonsa; Yanez, David; Bickel, Horst; Ikram, M Arfan; Völzke, Henry; Johnsen, Stein Harald; Empana, Jean Philippe; Tuomainen, Tomi-Pekka; Willeit, Peter; Steinmetz, Helmuth; Desvarieux, Moise; Xie, Wuxiang; Schmidt, Caroline; Norata, Giuseppe D; Suarez, Carmen; Sander, Dirk; Hofman, Albert; Schminke, Ulf; Mathiesen, Ellisiv; Plichart, Matthieu; Kauhanen, Jussi; Willeit, Johann; Sacco, Ralph L; McLachlan, Stela; Zhao, Dong; Fagerberg, Björn; Catapano, Alberico L; Gabriel, Rafael; Franco, Oscar H; Bülbül, Alpaslan; Scheckenbach, Frank; Pflug, Anja; Gao, Lu; Thompson, Simon G

    Objective

    Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.

    Research design and methods

    In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.

    Results

    Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).

    Conclusions

    Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
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    Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.
    (PloS one, 2018-01) Lorenz, Matthias W; Gao, Lu; Ziegelbauer, Kathrin; Norata, Giuseppe Danilo; Empana, Jean Philippe; Schmidtmann, Irene; Lin, Hung-Ju; McLachlan, Stela; Bokemark, Lena; Ronkainen, Kimmo; Amato, Mauro; Schminke, Ulf; Srinivasan, Sathanur R; Lind, Lars; Okazaki, Shuhei; Stehouwer, Coen DA; Willeit, Peter; Polak, Joseph F; Steinmetz, Helmuth; Sander, Dirk; Poppert, Holger; Desvarieux, Moise; Ikram, M Arfan; Johnsen, Stein Harald; Staub, Daniel; Sirtori, Cesare R; Iglseder, Bernhard; Beloqui, Oscar; Engström, Gunnar; Friera, Alfonso; Rozza, Francesco; Xie, Wuxiang; Parraga, Grace; Grigore, Liliana; Plichart, Matthieu; Blankenberg, Stefan; Su, Ta-Chen; Schmidt, Caroline; Tuomainen, Tomi-Pekka; Veglia, Fabrizio; Völzke, Henry; Nijpels, Giel; Willeit, Johann; Sacco, Ralph L; Franco, Oscar H; Uthoff, Heiko; Hedblad, Bo; Suarez, Carmen; Izzo, Raffaele; Zhao, Dong; Wannarong, Thapat; Catapano, Alberico; Ducimetiere, Pierre; Espinola-Klein, Christine; Chien, Kuo-Liong; Price, Jackie F; Bergström, Göran; Kauhanen, Jussi; Tremoli, Elena; Dörr, Marcus; Berenson, Gerald; Kitagawa, Kazuo; Dekker, Jacqueline M; Kiechl, Stefan; Sitzer, Matthias; Bickel, Horst; Rundek, Tatjana; Hofman, Albert; Mathiesen, Ellisiv B; Castelnuovo, Samuela; Landecho, Manuel F; Rosvall, Maria; Gabriel, Rafael; de Luca, Nicola; Liu, Jing; Baldassarre, Damiano; Kavousi, Maryam; de Groot, Eric; Bots, Michiel L; Yanez, David N; Thompson, Simon G; PROG-IMT study group
    [This corrects the article DOI: 10.1371/journal.pone.0191172.].
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    Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration.
    (European journal of preventive cardiology, 2016-01) Willeit, Peter; Thompson, Simon G; Agewall, Stefan; Bergström, Göran; Bickel, Horst; Catapano, Alberico L; Chien, Kuo-Liong; de Groot, Eric; Empana, Jean-Philippe; Etgen, Thorleif; Franco, Oscar H; Iglseder, Bernhard; Johnsen, Stein H; Kavousi, Maryam; Lind, Lars; Liu, Jing; Mathiesen, Ellisiv B; Norata, Giuseppe D; Olsen, Michael H; Papagianni, Aikaterini; Poppert, Holger; Price, Jackie F; Sacco, Ralph L; Yanez, David N; Zhao, Dong; Schminke, Ulf; Bülbül, Alpaslan; Polak, Joseph F; Sitzer, Matthias; Hofman, Albert; Grigore, Liliana; Dörr, Marcus; Su, Ta-Chen; Ducimetière, Pierre; Xie, Wuxiang; Ronkainen, Kimmo; Kiechl, Stefan; Rundek, Tatjana; Robertson, Christine; Fagerberg, Björn; Bokemark, Lena; Steinmetz, Helmuth; Ikram, M Arfan; Völzke, Henry; Lin, Hung-Ju; Plichart, Matthieu; Tuomainen, Tomi-Pekka; Desvarieux, Moise; McLachlan, Stela; Schmidt, Caroline; Kauhanen, Jussi; Willeit, Johann; Lorenz, Matthias W; Sander, Dirk; PROG-IMT study group

    Background

    Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population.

    Methods

    Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses.

    Results

    Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015).

    Conclusion

    Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.
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    ItemOpen Access
    Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.
    (PloS one, 2018-01) Lorenz, Matthias W; Gao, Lu; Ziegelbauer, Kathrin; Norata, Giuseppe Danilo; Empana, Jean Philippe; Schmidtmann, Irene; Lin, Hung-Ju; McLachlan, Stela; Bokemark, Lena; Ronkainen, Kimmo; Amato, Mauro; Schminke, Ulf; Srinivasan, Sathanur R; Lind, Lars; Okazaki, Shuhei; Stehouwer, Coen DA; Willeit, Peter; Polak, Joseph F; Steinmetz, Helmuth; Sander, Dirk; Poppert, Holger; Desvarieux, Moise; Ikram, M Arfan; Johnsen, Stein Harald; Staub, Daniel; Sirtori, Cesare R; Iglseder, Bernhard; Beloqui, Oscar; Engström, Gunnar; Friera, Alfonso; Rozza, Francesco; Xie, Wuxiang; Parraga, Grace; Grigore, Liliana; Plichart, Matthieu; Blankenberg, Stefan; Su, Ta-Chen; Schmidt, Caroline; Tuomainen, Tomi-Pekka; Veglia, Fabrizio; Völzke, Henry; Nijpels, Giel; Willeit, Johann; Sacco, Ralph L; Franco, Oscar H; Uthoff, Heiko; Hedblad, Bo; Suarez, Carmen; Izzo, Raffaele; Zhao, Dong; Wannarong, Thapat; Catapano, Alberico; Ducimetiere, Pierre; Espinola-Klein, Christine; Chien, Kuo-Liong; Price, Jackie F; Bergström, Göran; Kauhanen, Jussi; Tremoli, Elena; Dörr, Marcus; Berenson, Gerald; Kitagawa, Kazuo; Dekker, Jacqueline M; Kiechl, Stefan; Sitzer, Matthias; Bickel, Horst; Rundek, Tatjana; Hofman, Albert; Mathiesen, Ellisiv B; Castelnuovo, Samuela; Landecho, Manuel F; Rosvall, Maria; Gabriel, Rafael; de Luca, Nicola; Liu, Jing; Baldassarre, Damiano; Kavousi, Maryam; de Groot, Eric; Bots, Michiel L; Yanez, David N; Thompson, Simon G; PROG-IMT study group

    Aims

    Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

    Methods and results

    From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C.

    Conclusions

    We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.