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1. Prognostic relevance of the interaction between short-term, metronome-paced heart rate variability, and inflammation: Results from the population-based CARLA cohort study

Author

Medenwald, D. (Daniel), Swenne, C.A. (Cees), Loppnow, H. (Harald), Kors, J.A. (Jan), Pietzner, D. (Diana), Tiller, D. (Daniel), Thiery, J.P. (Joachim), Nuding, S. (Sebastian), Greiser, K.H. (Karin Halina), Haerting, J. (Johannes), Werdan, K. (Karl), Kluttig, A. (Alexander), Medenwald, D. (Daniel), Swenne, C.A. (Cees), Loppnow, H. (Harald), Kors, J.A. (Jan), Pietzner, D. (Diana), Tiller, D. (Daniel), Thiery, J.P. (Joachim), Nuding, S. (Sebastian), Greiser, K.H. (Karin Halina), Haerting, J. (Johannes), Werdan, K. (Karl), and Kluttig, A. (Alexander)

Abstract

Aims To determine the interaction between HRV and inflammation and their association with cardiovascular/all-cause mortality in the general population. Methods and results Subjects of the CARLA study (n = 1671; 778 women, 893 men, 45-83 years of age) were observed for an average follow-up period of 8.8 years (226 deaths, 70 cardiovascular deaths). Heart rate variability parameters were calculated from 5-min segments of 20-min resting electrocardiograms. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and soluble tumour necrosis factor-alpha receptor type 1 (sTNF-R1) were measured as inflammation parameters. The HRV parameters determined included the standard deviation of normal-to-normal intervals (SDNN), the root-mean-square of successive normal-interval differences (RMSSD), the low- and high-frequency (HF) power, the ratio of both, and non-linear pa

Published
2017
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2. Association between autonomic nervous dysfunction and cellular inflammation in end-stage renal disease

Author

Seibert, E. (Eric), Zohles, K. (Kristina), Ulrich, C. (Christof), Kluttig, A. (Alexander), Nuding, S. (Sebastian), Kors, J.A. (Jan), Swenne, C.A. (Cees), Werdan, K. (Karl), Fiedler, R. (Roman), Girndt, M. (Matthias), Seibert, E. (Eric), Zohles, K. (Kristina), Ulrich, C. (Christof), Kluttig, A. (Alexander), Nuding, S. (Sebastian), Kors, J.A. (Jan), Swenne, C.A. (Cees), Werdan, K. (Karl), Fiedler, R. (Roman), and Girndt, M. (Matthias)

Abstract

Background: Alterations in autonomic nervous function are common in hemodialysis (HD) patients. Sympathetic as well as paras

Published
2016
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3. Performance of Sokolow-Lyon index in detection of echocardiographically diagnosed left ventricular hypertrophy in a normal Eastern German population - results of the CARLA study

Author

Schröder, J. (Jochen), Nuding, S. (Sebastian), Müller-Werdan, U. (Ursula), Werdan, K. (Karl), Kluttig, A. (Alexander), Russ, M. (Martin), Greiser, K.H. (Karin Halina), Kors, J.A. (Jan), Haerting, J. (Johannes), Medenwald, D. (Daniel), Schröder, J. (Jochen), Nuding, S. (Sebastian), Müller-Werdan, U. (Ursula), Werdan, K. (Karl), Kluttig, A. (Alexander), Russ, M. (Martin), Greiser, K.H. (Karin Halina), Kors, J.A. (Jan), Haerting, J. (Johannes), and Medenwald, D. (Daniel)

Abstract

Background: Arterial hypertension is a common disease with high prevalence in the general population. Left ventricular hypertrophy (LVH) is an independent risk factor in arterial hypertension. Electrocardiographic indices like the Sokolow-Lyon index (SLI) are recommended as diagnostic screening methods for LVH. We assessed the diagnostic performance of the SLI in a cohort of a large general population. Methods: We used electrocardiographic and echocardiographic data from the prospective, population-based cohort study CARdio-vascular Disease, Living and Ageing in Halle (CARLA). Linear and logistic regression models were used to assess the association of SLI with LVH. To assess the impact of the body-mass-index (BMI), we performed interaction analyses. Results: AUC of SLI to predict LVH was 55.3 %, sensitivity of the SLI was 5 %, specificity 97 %. We found a significant association of SLI after covariate-adjustment with echocardiographically detected LVH (increase of left-ventricular mass index, LVMI 7.0 g/m2 per 1 mV increase of SLI, p < 0.0001). However, this association was mainly caused by an association of SLI with the left-ventricular internal diameter (LVIDd, increase of 0.06 cm/m2 per 1 mV increase of SLI, p < 0.0001). In obese (BMI > 30 kg/m2) we found the strongest association with an increase of 9.2 g/m2 per 1 mV. Conclusions: Although statistically significant, relations of SLI and echocardiographic parameters of LVH were weak and mainly driven by the increase in LVIDd, implicating a more eccentric type of LVH in the collective. The relations were strongest when obese subjects were taken into account. Our data do not favour the SLI as a diagnostic screening test to identify patients at risk for LVH, especially in non-obese subjects without eccentric LVH.

Published
2015
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4. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Arking, D.E. (Dan), Pulit, S.L. (Sara), Crotti, L. (Lia), Harst, P. (Pim) van der, Munroe, P. (Patricia), Koopmann, T.T. (Tamara), Sotoodehnia, N. (Nona), Rossin, E. (Elizabeth), Morley, M. (Michael), Wang, X. (Xinchen), Johnson, A.D. (Andrew), Lundby, A. (Alicia), Gudbjartsson, D.F. (Daniel), Noseworthy, P.A. (Peter), Eijgelsheim, M. (Mark), Bradford, Y. (Yuki), Tarasov, K.V. (Kirill), Dörr, M. (Marcus), Müller-Nurasyid, M. (Martina), Lahtinen, A.M. (Annukka), Nolte, I.M. (Ilja), Smith, A.V. (Davey), Bis, J.C. (Joshua), Isaacs, A.J. (Aaron), Newhouse, S.J. (Stephen), Evans, D.S. (Daniel), Post, W.S. (Wendy S.), Waggott, D. (Daryl), Lyytikäinen, L.-P. (Leo-Pekka), Hicks, A.A. (Andrew), Eisele, L. (Lewin), Ellinghaus, D. (David), Hayward, C. (Caroline), Navarro, P. (Pau), Ulivi, S. (Shelia), Tanaka, T. (Toshiko), Tester, D.J. (David), Chatel, S. (Stéphanie), Gustafsson, S. (Stefan), Kumari, M. (Meena), Morris, R.W. (Richard), Naluai, A.T. (Asa), Padmanabhan, S. (Sandosh), Kluttig, A. (Alexander), Strohmer, B. (Bernhard), Panayiotou, A.G. (Andrie), Torres, M. (Maria), Knoflach, M. (Michael), Hubacek, J.A. (Jaroslav A.), Slowikowski, K. (Kamil), Raychaudhuri, S. (Soumya), Kumar, R.D. (Runjun), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Shuldiner, A.R. (Alan), Alonso, A. (Alvaro), Bader, J.S. (Joel), Ehret, G.B. (Georg), Huang, H. (Hailiang), Kao, W.H.L. (Wen), Strait, J.B. (James), Macfarlane, P.W. (Peter), Brown, M.J. (Morris), Caulfield, M. (Mark), Samani, N.J. (Nilesh), Kronenberg, F. (Florian), Willeit, J. (Johann), Smith, J.G. (J. Gustav), Greiser, K.H. (Karin Halina), Zu Schwabedissen, H.M. (Henriette Meyer), Werdan, K. (Karl), Carella, C. (Cintia), Zelante, L. (Leopoldo), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), Kolcic, I. (Ivana), Polasek, O. (Ozren), Wright, A.F. (Alan), Griffin, M. (Maura), Daly, M.J. (Mark), Arnar, D.O. (David), Hólm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Denny, J.C. (Joshua), Roden, D.M. (Dan), Zuvich, R.L. (Rebecca), Emilsson, V. (Valur), Plump, A.S. (Andrew), Larson, M.G. (Martin), O'Donnell, C.J. (Christopher), Yin, X. (Xiaoyan), Bobbo, M. (Marco), Adamo, P. (Pio) d', Iorio, A. (Annamaria), Sinagra, G. (Gianfranco), Carracedo, A. (Angel), Cummings, S.R. (Steven), Nalls, M.A. (Michael), Jula, A. (Antti), Kontula, K.K. (Kimmo), Marjamaa, A. (Annukka), Oikarinen, L. (Lasse), Perola, M. (Markus), Porthan, K. (Kimmo), Erbel, R. (Raimund), Hoffmann, P. (Per), Jöckel, K.-H. (Karl-Heinz), Kälsch, H. (Hagen), Nöthen, M.M. (Markus), Hoed, M. (Marcel) den, Loos, R.J.F. (Ruth), Thelle, D.S. (Dag), Gieger, C. (Christian), Meitinger, T. (Thomas), Perz, S. (Siegfried), Peters, A. (Annette), Prucha, H. (Hanna), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Boer, R.A. (Rudolf) de, Franke, L. (Lude), Vleuten, P.A. (Pieter) van der, Beckmann, B.M. (Britt), Martens, E. (Eimo), Bardai, A. (Abdennasser), Hofman, N. (Nynke), Wilde, A.A.M. (Arthur), Behr, E.R. (Elijah), Dalageorgou, C. (Chrysoula), Giudicessi, J.R. (John), Medeiros-Domingo, A. (Argelia), Barc, J. (Julien), Kyndt, F. (Florence), Probst, V. (Vincent), Ghidoni, A. (Alice), Insolia, R. (Roberto), Hamilton, R.M. (Robert), Scherer, S.W. (Stephen), Brandimarto, J. (Jeffrey), Margulies, K. (Kenneth), Moravec, C.E. (Christine), Del Greco, F. (Fabiola), Fuchsberger, C. (Christian), O'Connell, J.R. (Jeffery), Lee, W.K. (Wai), Watt, G.C.M. (Graham), Campbell, H. (Harry), Wild, S.H. (Sarah), El Mokhtari, N.E. (Nour), Frey, N. (Norbert), Asselbergs, F.W. (Folkert), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Berg, M.P. (Maarten) van den, Veldhuisen, D.J. (Dirk) van, Kellis, M. (Manolis), Krijthe, B.P. (Bouwe), Franco, O.H. (Oscar), Hofman, A. (Albert), Kors, J.A. (Jan), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Kedenko, L. (Lyudmyla), Lamina, C. (Claudia), Oostra, B.A. (Ben), Abecasis, G.R. (Gonçalo), Lakatta, E. (Edward), Mulas, A. (Antonella), Orrù, M. (Marco), Schlessinger, D. (David), Uda, M. (Manuela), Markus, M.R.P. (Marcello R. P.), Völker, U. (Uwe), Snieder, H. (Harold), Spector, T.D. (Timothy), Ärnlöv, J. (Johan), Lind, L. (Lars), Sundstrom, J. (Johan), Syvanen, A.C., Kivimaki, M. (Mika), Kähönen, M. (Mika), Mononen, K. (Kari), Raitakari, O. (Olli), Viikari, J. (Jorma), Adamkova, V. (Vera), Kiechl, S. (Stefan), Brion, M.-J. (Maria), Nicolaides, A.N. (Andrew), Paulweber, B. (Bernhard), Haerting, J. (Johannes), Dominiczak, A. (Anna), Nyberg, F. (Fredrik), Whincup, P.H. (Peter), Hingorani, A. (Aroon), Schott, J.-J. (Jean-Jacques), Bezzina, C.R. (Connie), Ingelsson, E. (Erik), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Wilson, J.F. (James), Rudan, I. (Igor), Franke, A. (Andre), Mühleisen, T.W. (Thomas), Pramstaller, P.P. (Peter Paul), Lehtimäki, T. (Terho), Paterson, A.D. (Andrew), Parsa, A. (Afshin), Liu, Y. (YongMei), Duijn, C.M. (Cornelia) van, Siscovick, D.S. (David), Gudnason, V. (Vilmundur), Jamshidi, Y. (Yalda), Salomaa, V. (Veikko), Felix, S.B. (Stephan), Sanna, S. (Serena), Ritchie, M.D. (Marylyn), Stricker, B.H.Ch. (Bruno), Zwart, J-A. (John-Anker), Boyer, L.A. (Laurie), Cappola, T.P. (Thomas), Olsen, J.V. (Jesper), Lage, P. (Pedro), Schwartz, P.J. (Peter), Kääb, S. (Stefan), Chakravarti, A. (Aravinda), Ackerman, M. (Margaret), Pfeufer, A. (Arne), Bakker, P.I.W. (Paul) de, Newton-Cheh, C. (Christopher), Arking, D.E. (Dan), Pulit, S.L. (Sara), Crotti, L. (Lia), Harst, P. (Pim) van der, Munroe, P. (Patricia), Koopmann, T.T. (Tamara), Sotoodehnia, N. (Nona), Rossin, E. (Elizabeth), Morley, M. (Michael), Wang, X. (Xinchen), Johnson, A.D. (Andrew), Lundby, A. (Alicia), Gudbjartsson, D.F. (Daniel), Noseworthy, P.A. (Peter), Eijgelsheim, M. (Mark), Bradford, Y. (Yuki), Tarasov, K.V. (Kirill), Dörr, M. (Marcus), Müller-Nurasyid, M. (Martina), Lahtinen, A.M. (Annukka), Nolte, I.M. (Ilja), Smith, A.V. (Davey), Bis, J.C. (Joshua), Isaacs, A.J. (Aaron), Newhouse, S.J. (Stephen), Evans, D.S. (Daniel), Post, W.S. (Wendy S.), Waggott, D. (Daryl), Lyytikäinen, L.-P. (Leo-Pekka), Hicks, A.A. (Andrew), Eisele, L. (Lewin), Ellinghaus, D. (David), Hayward, C. (Caroline), Navarro, P. (Pau), Ulivi, S. (Shelia), Tanaka, T. (Toshiko), Tester, D.J. (David), Chatel, S. (Stéphanie), Gustafsson, S. (Stefan), Kumari, M. (Meena), Morris, R.W. (Richard), Naluai, A.T. (Asa), Padmanabhan, S. (Sandosh), Kluttig, A. (Alexander), Strohmer, B. (Bernhard), Panayiotou, A.G. (Andrie), Torres, M. (Maria), Knoflach, M. (Michael), Hubacek, J.A. (Jaroslav A.), Slowikowski, K. (Kamil), Raychaudhuri, S. (Soumya), Kumar, R.D. (Runjun), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Shuldiner, A.R. (Alan), Alonso, A. (Alvaro), Bader, J.S. (Joel), Ehret, G.B. (Georg), Huang, H. (Hailiang), Kao, W.H.L. (Wen), Strait, J.B. (James), Macfarlane, P.W. (Peter), Brown, M.J. (Morris), Caulfield, M. (Mark), Samani, N.J. (Nilesh), Kronenberg, F. (Florian), Willeit, J. (Johann), Smith, J.G. (J. Gustav), Greiser, K.H. (Karin Halina), Zu Schwabedissen, H.M. (Henriette Meyer), Werdan, K. (Karl), Carella, C. (Cintia), Zelante, L. (Leopoldo), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), Kolcic, I. (Ivana), Polasek, O. (Ozren), Wright, A.F. (Alan), Griffin, M. (Maura), Daly, M.J. (Mark), Arnar, D.O. (David), Hólm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Denny, J.C. (Joshua), Roden, D.M. (Dan), Zuvich, R.L. (Rebecca), Emilsson, V. (Valur), Plump, A.S. (Andrew), Larson, M.G. (Martin), O'Donnell, C.J. (Christopher), Yin, X. (Xiaoyan), Bobbo, M. (Marco), Adamo, P. (Pio) d', Iorio, A. (Annamaria), Sinagra, G. (Gianfranco), Carracedo, A. (Angel), Cummings, S.R. (Steven), Nalls, M.A. (Michael), Jula, A. (Antti), Kontula, K.K. (Kimmo), Marjamaa, A. (Annukka), Oikarinen, L. (Lasse), Perola, M. (Markus), Porthan, K. (Kimmo), Erbel, R. (Raimund), Hoffmann, P. (Per), Jöckel, K.-H. (Karl-Heinz), Kälsch, H. (Hagen), Nöthen, M.M. (Markus), Hoed, M. (Marcel) den, Loos, R.J.F. (Ruth), Thelle, D.S. (Dag), Gieger, C. (Christian), Meitinger, T. (Thomas), Perz, S. (Siegfried), Peters, A. (Annette), Prucha, H. (Hanna), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Boer, R.A. (Rudolf) de, Franke, L. (Lude), Vleuten, P.A. (Pieter) van der, Beckmann, B.M. (Britt), Martens, E. (Eimo), Bardai, A. (Abdennasser), Hofman, N. (Nynke), Wilde, A.A.M. (Arthur), Behr, E.R. (Elijah), Dalageorgou, C. (Chrysoula), Giudicessi, J.R. (John), Medeiros-Domingo, A. (Argelia), Barc, J. (Julien), Kyndt, F. (Florence), Probst, V. (Vincent), Ghidoni, A. (Alice), Insolia, R. (Roberto), Hamilton, R.M. (Robert), Scherer, S.W. (Stephen), Brandimarto, J. (Jeffrey), Margulies, K. (Kenneth), Moravec, C.E. (Christine), Del Greco, F. (Fabiola), Fuchsberger, C. (Christian), O'Connell, J.R. (Jeffery), Lee, W.K. (Wai), Watt, G.C.M. (Graham), Campbell, H. (Harry), Wild, S.H. (Sarah), El Mokhtari, N.E. (Nour), Frey, N. (Norbert), Asselbergs, F.W. (Folkert), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Berg, M.P. (Maarten) van den, Veldhuisen, D.J. (Dirk) van, Kellis, M. (Manolis), Krijthe, B.P. (Bouwe), Franco, O.H. (Oscar), Hofman, A. (Albert), Kors, J.A. (Jan), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Kedenko, L. (Lyudmyla), Lamina, C. (Claudia), Oostra, B.A. (Ben), Abecasis, G.R. (Gonçalo), Lakatta, E. (Edward), Mulas, A. (Antonella), Orrù, M. (Marco), Schlessinger, D. (David), Uda, M. (Manuela), Markus, M.R.P. (Marcello R. P.), Völker, U. (Uwe), Snieder, H. (Harold), Spector, T.D. (Timothy), Ärnlöv, J. (Johan), Lind, L. (Lars), Sundstrom, J. (Johan), Syvanen, A.C., Kivimaki, M. (Mika), Kähönen, M. (Mika), Mononen, K. (Kari), Raitakari, O. (Olli), Viikari, J. (Jorma), Adamkova, V. (Vera), Kiechl, S. (Stefan), Brion, M.-J. (Maria), Nicolaides, A.N. (Andrew), Paulweber, B. (Bernhard), Haerting, J. (Johannes), Dominiczak, A. (Anna), Nyberg, F. (Fredrik), Whincup, P.H. (Peter), Hingorani, A. (Aroon), Schott, J.-J. (Jean-Jacques), Bezzina, C.R. (Connie), Ingelsson, E. (Erik), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Wilson, J.F. (James), Rudan, I. (Igor), Franke, A. (Andre), Mühleisen, T.W. (Thomas), Pramstaller, P.P. (Peter Paul), Lehtimäki, T. (Terho), Paterson, A.D. (Andrew), Parsa, A. (Afshin), Liu, Y. (YongMei), Duijn, C.M. (Cornelia) van, Siscovick, D.S. (David), Gudnason, V. (Vilmundur), Jamshidi, Y. (Yalda), Salomaa, V. (Veikko), Felix, S.B. (Stephan), Sanna, S. (Serena), Ritchie, M.D. (Marylyn), Stricker, B.H.Ch. (Bruno), Zwart, J-A. (John-Anker), Boyer, L.A. (Laurie), Cappola, T.P. (Thomas), Olsen, J.V. (Jesper), Lage, P. (Pedro), Schwartz, P.J. (Peter), Kääb, S. (Stefan), Chakravarti, A. (Aravinda), Ackerman, M. (Margaret), Pfeufer, A. (Arne), Bakker, P.I.W. (Paul) de, and Newton-Cheh, C. (Christopher)

Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Published
2014
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5. Inflammation and prolonged QT time: Results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) study

Author

Medenwald, D. (Daniel), Kors, J.A. (Jan), Loppnow, H. (Harald), Thiery, J.P. (Joachim), Kluttig, A. (Alexander), Nuding, S. (Sebastian), Tiller, D. (Daniel), Greiser, K.H. (Karin Halina), Werdan, K. (Karl), Haerting, J. (Johannes), Medenwald, D. (Daniel), Kors, J.A. (Jan), Loppnow, H. (Harald), Thiery, J.P. (Joachim), Kluttig, A. (Alexander), Nuding, S. (Sebastian), Tiller, D. (Daniel), Greiser, K.H. (Karin Halina), Werdan, K. (Karl), and Haerting, J. (Johannes)

Abstract

Background: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. Objective: To determine the association between inflammation with an abnormally prolonged QT-time (APQT) in men and women of the elderly general population. Methods: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1), the high-sensitive C-reactive protein (hsCRP), and Interleukin 6 (IL-6). In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI) were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. Results: After covariate adjustment we found an odds ratio (OR) of 1.89 (95% CI: 1.13, 3.17) per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15) in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18), but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. Conclusion: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.

Published
2014
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6. Prevalence of Symptomatic Heart Failure with Reduced and with Normal Ejection Fraction in an Elderly General Population-The CARLA Study

Author

Tiller, D. (Daniel), Russ, M. (Martin), Greiser, K.H. (Karin Halina), Nuding, S. (Sebastian), Ebelt, H. (Henning), Kluttig, A. (Alexander), Kors, J.A. (Jan), Thiery, J.P. (Joachim), Bruegel, M. (Mathias), Haerting, J. (Johannes), Werdan, K. (Karl), Tiller, D. (Daniel), Russ, M. (Martin), Greiser, K.H. (Karin Halina), Nuding, S. (Sebastian), Ebelt, H. (Henning), Kluttig, A. (Alexander), Kors, J.A. (Jan), Thiery, J.P. (Joachim), Bruegel, M. (Mathias), Haerting, J. (Johannes), and Werdan, K. (Karl)

Abstract

Background/Objectives: Chronic heart failure (CHF) is one of the most important public health concerns in the industrialized world having increasing incidence and prevalence. Although there are several studies describing the prevalence of heart failure with reduced ejection fraction (HFREF) and heart failure with normal ejection fraction (HFNEF) in selected populations, there are few data regarding the prevalence and the determinants of symptomatic heart failure in the general population. Methods: Cross-sectional data of a population-based German sample (1,779 subjects aged 45-83 years) were analyzed to determine the prevalence and determinants of chronic SHF and HFNEF defined according to the European Society of Cardiology using symptoms, echocardiography and serum NT-proBNP. Prevalence was age-standardized to the German population as of December 31st, 2005. Results: The overall age-standardized prevalence of symptomatic CHF was 7.7% (95%CI 6.0-9.8) for men and 9.0% (95%CI 7.0-11.5) for women. The prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be shown in 48% (n = 78), symptomatic HFNEF in 52% (n = 85) of subjects with CHF. The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8) for women and 4.6 % (95%CI 3.6-6.3) for men. The age-standardized prevalence of HFNEF for women and men was 5.1 % (95%CI 3.8-7.0) and 3.0 % (95%CI 2.1-4.5), respectively. Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3) or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5). Conclusion: The prevalence of symptomatic CHF appears high in this population compared with other studies. While more women were affected by HFNEF than men, more male subjects suffered from HFREF. The high prevalence of symptomatic CHF seems likely to be mainly due to the high prevalence of cardiovascular risk factors in this population.

Published
2013
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7. Association of health behaviour with heart rate variability: A population-based study

Author

Kluttig, A. (Alexander), Schumann, B. (Barbara), Swenne, C.A. (Cees), Kors, J.A. (Jan), Kuss, O. (Oliver), Schmidt, H. (Helena), Werdan, K. (Karl), Haerting, J. (Johannes), Greiser, K.H. (Karin Halina), Kluttig, A. (Alexander), Schumann, B. (Barbara), Swenne, C.A. (Cees), Kors, J.A. (Jan), Kuss, O. (Oliver), Schmidt, H. (Helena), Werdan, K. (Karl), Haerting, J. (Johannes), and Greiser, K.H. (Karin Halina)

Abstract

Background: Reduced heart rate variability (HRV), a non-invasive marker of autonomic dysfunction, and an unhealthy lifestyle are associated with an increased morbidity and mortality of cardiovascular diseases (CVD). The autonomic dysfunction is a potential mediator of the association of behavioural risk factors with adverse health outcomes. We studied the association of HRV with behavioural risk factors in an elderly population.Methods: This analysis was based on the cross-sectional data of 1671 participants (age range, 45-83 years) of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. Physical activity, smoking habits, alcohol consumption and dietary patterns were assessed in standardized interviews. Time and frequency domain measures of HRV were computed from 5-min segments of highly standardized 20-min electrocardiograms. Their association with behavioural risk factors was determined by linear and non-parametric regression modelling.Results: There were only weak and inconsistent associations of higher physical activity, moderate consumption of alcohol, and non-s

Published
2010
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8. Genetic variants associated with cardiac structure and function: A meta-analysis and replication of genome-wide association data

Author

Vasan, R.S. (Ramachandran Srini), Glazer, N.L. (Nicole), Felix, J.F. (Janine), Lieb, W. (Wolfgang), Wild, P.S. (Philipp), Watzinger, N. (Norbert), Larson, M.G. (Martin), Smith, N.L. (Nicholas), Dehghan, A. (Abbas), Großhennig, A. (Anika), Schillert, A. (Arne), Teumer, A. (Alexander), Schmidt, R. (Reinhold), Kathiresan, S. (Sekar), Lumley, T. (Thomas), Aulchenko, Y.S. (Yurii), König, I.R. (Inke), Zeller, T. (Tanja), Homuth, G. (Georg), Struchalin, M.V. (Maksim), Aragam, J. (Jayashri), Bis, J.C. (Joshua), Rivadeneira Ramirez, F. (Fernando), Erdmann, J. (Jeanette), Schnabel, R. (Renate), Dörr, M. (Marcus), Zweiker, R. (Robert), Lind, L. (Lars), Rodeheffer, R.J. (Richard), Greiser, K.H. (Karin Halina), Levy, D. (Daniel), Haritunians, T. (Talin), Deckers, J.W. (Jaap), Stritzke, J. (Jan), Lackner, K.J. (Karl), Ingelsson, E. (Erik), Kullo, I. (Iftikhar), Haerting, J. (Johannes), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), Ziegler, A. (Andreas), Reffelmann, T. (Thorsten), Redfield, M.M. (Margaret), Mitchell, G.F. (Gary), Rice, K. (Kenneth), Arnett, D.K. (Donna), Hofman, A. (Albert), Gottdiener, J.S. (John), Uitterlinden, A.G. (André), Meitinger, T. (Thomas), Blettner, M. (Maria), Friedrich, N. (Nele), Wang, T.J. (Thomas), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Wichmann, H.E. (Erich), Munzel, T. (Thomas), Kroemer, H.K. (Heyo), Benjamin, E.J. (Emelia), Rotter, J.I. (Jerome), Witteman, J.C.M. (Jacqueline), Schunkert, H. (Heribert), Völzke, H. (Henry), Blankenberg, S. (Stefan), O'Donnell, C.J. (Christopher), Völker, U. (Uwe), Werdan, K. (Karl), Vasan, R.S. (Ramachandran Srini), Glazer, N.L. (Nicole), Felix, J.F. (Janine), Lieb, W. (Wolfgang), Wild, P.S. (Philipp), Watzinger, N. (Norbert), Larson, M.G. (Martin), Smith, N.L. (Nicholas), Dehghan, A. (Abbas), Großhennig, A. (Anika), Schillert, A. (Arne), Teumer, A. (Alexander), Schmidt, R. (Reinhold), Kathiresan, S. (Sekar), Lumley, T. (Thomas), Aulchenko, Y.S. (Yurii), König, I.R. (Inke), Zeller, T. (Tanja), Homuth, G. (Georg), Struchalin, M.V. (Maksim), Aragam, J. (Jayashri), Bis, J.C. (Joshua), Rivadeneira Ramirez, F. (Fernando), Erdmann, J. (Jeanette), Schnabel, R. (Renate), Dörr, M. (Marcus), Zweiker, R. (Robert), Lind, L. (Lars), Rodeheffer, R.J. (Richard), Greiser, K.H. (Karin Halina), Levy, D. (Daniel), Haritunians, T. (Talin), Deckers, J.W. (Jaap), Stritzke, J. (Jan), Lackner, K.J. (Karl), Ingelsson, E. (Erik), Kullo, I. (Iftikhar), Haerting, J. (Johannes), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), Ziegler, A. (Andreas), Reffelmann, T. (Thorsten), Redfield, M.M. (Margaret), Mitchell, G.F. (Gary), Rice, K. (Kenneth), Arnett, D.K. (Donna), Hofman, A. (Albert), Gottdiener, J.S. (John), Uitterlinden, A.G. (André), Meitinger, T. (Thomas), Blettner, M. (Maria), Friedrich, N. (Nele), Wang, T.J. (Thomas), Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Wichmann, H.E. (Erich), Munzel, T. (Thomas), Kroemer, H.K. (Heyo), Benjamin, E.J. (Emelia), Rotter, J.I. (Jerome), Witteman, J.C.M. (Jacqueline), Schunkert, H. (Heribert), Völzke, H. (Henry), Blankenberg, S. (Stefan), O'Donnell, C.J. (Christopher), Völker, U. (Uwe), and Werdan, K. (Karl)

Abstract

Context: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n=12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n=4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10-7to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Main Outcome Measures: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. Results: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1%of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). Conclusions: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these

Published
2009
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9. Cardiovascular disease, risk factors and heart rate variability in the elderly general population: Design and objectives of the CARdiovascular disease, Living and Ageing in Halle (CARLA) Study

Author

Greiser, K.H. (Karin Halina), Kluttig, A. (Alexander), Schumann, B. (Barbara), Kors, J.A. (Jan), Swenne, C.A. (Cees), Kuss, O. (Oliver), Werdan, K. (Karl), Haerting, J. (Johannes), Greiser, K.H. (Karin Halina), Kluttig, A. (Alexander), Schumann, B. (Barbara), Kors, J.A. (Jan), Swenne, C.A. (Cees), Kuss, O. (Oliver), Werdan, K. (Karl), and Haerting, J. (Johannes)

Abstract

Background: The increasing burden of cardiovascular diseases (CVD) in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic. In order to improve prevention, detection, therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany, it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality, potential causal mechanisms and prognostic factors in the elderly. Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient. A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age. Nevertheless, there is a lack of population-based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population. There also is a paucity of epidemiological data describing the health situation in Eastern Germany. Therefore, we conduct a population-based study to examine the distribution of CVD, heart rate variability and CVD risk factors and their associations in an elderly East German population. This paper describes the design and objectives of the CARLA Study. Methods/Design: For this study, a random sample of 45-80 year-old inhabitants of the city of Halle (Saale) in Eastern Germany was drawn from the population registry. By the end of the baseline examination (2002-2005), 1750 study participants will have been examined. A multi-step recruitment strategy aims at achieving a 70% response rate. Detailed information is collected on own and family medical history, socioeconomic, psychosocial, behavioural and biomedical factors. Medical examinations include anthropometric meagures, blood pressure of arm and ankle, a 10-second and a 20-minute electrocardiogram, a ge

Published
2005
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