Associations of plasma renin with 10-year cardiovascular mortality, sudden cardiac death, and death due to heart failure
Abstract
AIMS: Renin is the key regulator of the renin-angiotensin-aldosterone system. Previous studies have reported conflicting results on the relation of plasma renin with fatal cardiovascular events. This study in a large cohort of patients sought to evaluate the association between plasma renin concentration (PRC) and cardiovascular mortality after long-term follow-up of almost 10 years. METHODS AND RESULTS: Plasma renin concentration [median: 11.4 (6.0-24.6) pg/mL] was measured in 3303 patients (mean age: 62.7 ± 10.6 years; 30.3% women) referred to coronary angiography. After a median follow-up of 9.9 years, 554 participants (16.8%) with PRC measurement at baseline had died due to fatal cardiovascular events. Multivariable-adjusted Cox analysis revealed that when compared with participants in the lowest PRC quartile, those in the highest quartile were at increased risk of cardiovascular mortality (hazard ratio: 1.79, 95% CI 1.28-2.48). Analyses of specific causes of cardiovascular death showed that for each standard deviation increase in log-PRC there was a 22% (P = 0.006) increase in risk of sudden cardiac death and a 23% (P = 0.033) greater risk of death due to heart failure. The association of PRC with cardiovascular mortality remained stable after adjustment for established cardiovascular risk factors, ongoing antihypertensive medication, immunoreactive angiotensin II, and aldosterone levels. Age, N-terminal pro-B-type natriuretic peptide levels, coronary artery disease, the use of angiotensin-converting enzyme-inhibitors, beta-blockers, diuretics, and kidney function were important effect modifiers. CONCLUSIONS: Plasma renin concentration is associated with long-term cardiovascular mortality in patients referred to coronary angiography. Further intervention studies should determine whether renin is a potential therapeutic target or only a marker of mortality risk in various cardiovascular risk groups.
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Cites
(1992) · New England Journal of Medicine · doi:10.1056/nejm199209033271003 · Cited by 3,725 · see citing works
A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure
Cohn, J. N., & Tognoni, G. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010713 · Cited by 3,108 · see citing works
McMurray, J. J., Östergren, J., Swedberg, K., Granger, C. B., Held, P., Michelson, E. L., Olofsson, B., Yusuf, S., & Pfeffer, M. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14283-3 · Cited by 2,604 · see citing works
Available, N. (2000) · JAMA · doi:10.1001/jama.284.23.3043 · Cited by 2,344 · see citing works
Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death
Wang, T. J., Gona, P. N., Larson, M. G., Tofler, G. H., Levy, D. A., Newton‐Cheh, C., Jacques, P. F., Rifai, N., Selhub, J., Robins, S. J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055373 · Cited by 1,342 · see citing works
Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy
Parving, H., Persson, F., Lewis, J. B., Lewis, E. J., & Hollenberg, N. K. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708379 · Cited by 1,092 · see citing works
McMurray, J. J. V., Östergren, J., Swedberg, K. B., Granger, C. B., Held, P., Michelson, E. L., Olofsson, B., Yusuf, S., & Pfeffer (2003) · The Lancet · Cited by 1,043 · see citing works
Chugh, S. S., Jui, J., Gunson, K., Stecker, E. C., John, B. T., Thompson, B., Ilias-Khan, N. A., Vickers, C. A., Dogra, V., Daya, M. R., et al. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.06.029 · Cited by 793 · see citing works
Alderman, M. H., Madhavan, S., Ooi, W. L., Cohen, H. W., Sealey, J. E., & Laragh, J. H. (1991) · New England Journal of Medicine · doi:10.1056/nejm199104183241605 · Cited by 726 · see citing works
Huang, Y., Wongamorntham, S., Kasting, J., McQuillan, D. J., Owens, R. T., Yu, L. H., Noble, N. A., & Border, W. A. (2005) · Kidney International · doi:10.1038/sj.ki.5000011 · Cited by 423 · see citing works
Winkelmann, B. R., März, W., Boehm, B. O., Zotz, R. B., Hager, J., Hellstern, P., & Senges, J. (2001) · Pharmacogenomics · doi:10.1517/14622416.2.1.s1 · Cited by 368 · see citing works
Self-citationEffects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure
McMurray, J. J. V., Pitt, B., Latini, R., Maggioni, A. P., Solomon, S. D., Keefe, D. L., Ford, J. H., Verma, A., & Lewsey, J. (2008) · Circulation Heart Failure · doi:10.1161/circheartfailure.107.740704 · Cited by 354 · see citing works
Latini, R. (2004) · European Heart Journal · doi:10.1016/j.ehj.2003.10.030 · Cited by 344 · see citing works
Solomon, S. D., Appelbaum, E. A., Manning, W. J., Verma, A. K., Berglund, T., Lukashevich, V., Papst, C. C., Smith, B. A., & Dahlöf, B. (2009) · Circulation · doi:10.1161/circulationaha.108.826214 · Cited by 301 · see citing works
Aliskiren, a Human Renin Inhibitor, Ameliorates Cardiac and Renal Damage in Double-Transgenic Rats
Pilz, B., Shagdarsuren, E., Wellner, M., Fiebeler, A., Dechend, R., Gratze, P., Meiners, S., Feldman, D. L., Webb, R. L., Garrelds, I. M., et al. (2005) · Hypertension · doi:10.1161/01.hyp.0000179573.91016.3f · Cited by 243 · see citing works
Plasma Renin Activity: A Risk Factor for Myocardial Infarction in Hypertensive Patients
Alderman, M. H. (1997) · American Journal of Hypertension · doi:10.1016/s0895-7061(96)00301-9 · Cited by 194 · see citing works
Campbell, D. J., Nussberger, J., Stowasser, M., Danser, A. H. J., Morganti, A., Frandsen, E., & Ménard, J. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2008.118000 · Cited by 187 · see citing works
Self-citationTomaschitz, A., Pilz, S., Ritz, E., Meinitzer, A., Boehm, B. O., & Marz, W. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq019 · Cited by 171 · see citing works
Self-citationRenin, (pro)renin and receptor: an update
Nguyen, G. (2010) · Clinical Science · doi:10.1042/cs20100432 · Cited by 168 · see citing works
Aldosterone and arterial hypertension
Tomaschitz, A., Pilz, S., Ritz, E., Obermayer-Pietsch, B. M., & Pieber, T. R. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.263 · Cited by 155 · see citing works
Self-citationSchirpenbach, C., Seiler, L., Maser‐Gluth, C., Beuschlein, F., Reincke, M., & Bidlingmaier, M. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2006.068502 · Cited by 146 · see citing works
Plasma Renin Activity and Ischemic Heart Disease
Meade, T. W., Cooper, J. A., & Peart, W. S. (1993) · New England Journal of Medicine · doi:10.1056/nejm199308263290905 · Cited by 107 · see citing works
Plasma Renin Levels and Vascular Complications in Hypertension
Doyle, A. E., Jerums, G., Johnston, C. I., et al. (1973) · BMJ · doi:10.1136/bmj.2.5860.206 · Cited by 76 · see citing works
Macfelda, K. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2002.2117 · Cited by 73 · see citing works
Masson, S., Solomon, S. D., Angelici, L., Latini, R., Anand, I. S., PRESCOTT, M. F., Maggioni, A. P., Tognoni, G., & Cohn, J. N. (2010) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2010.06.417 · Cited by 70 · see citing works
Trenkel, S., Seifarth, C., Schobel, H.-P., Hahn, E. G., & Hensen, J. (2002) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2002-23491 · Cited by 65 · see citing works
Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study
Parikh, N. I., Gona, P. N., Larson, M. G., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm399 · Cited by 60 · see citing works
Managing cardiovascular and renal risk: the potential of direct renin inhibition
Sever, P., Gradman, A. H., & Azizi, M. (2009) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320309104662 · Cited by 59 · see citing works
Aldosterone/Renin Ratio Determines Peripheral and Central Blood Pressure Values Over a Broad Range
Tomaschitz, A., Maerz, W., Pilz, S., Ritz, E., Scharnagl, H., Renner, W., Boehm, B. O., Fahrleitner‐Pammer, A., Weihrauch, G., & Dobnig, H. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.01.032 · Cited by 55 · see citing works
Self-citationAldosterone to Renin Ratio – A Reliable Screening Tool for Primary Aldosteronism?
Tomaschitz, A., & Pilz, S. (2010) · Hormone and Metabolic Research · doi:10.1055/s-0030-1248326 · Cited by 47 · see citing works
Self-citationTomaschitz, A., Pilz, S., Ritz, E., Grammer, T. B., Drechsler, C., Boehm, B. O., & März, W. (2010) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2010.10.047 · Cited by 45 · see citing works
Self-citationBalakumar, P., & Jagadeesh, G. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181f21576 · Cited by 42 · see citing works
Application of Direct Renin Inhibition to Chronic Kidney Disease
Mende, C. W. (2010) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-010-6232-1 · Cited by 38 · see citing works
Volpe, M., Francia, P., Tocci, G., Rubattu, S., Cangianiello, S., Rao, M. A. E., Trimarco, B., & Condorelli, M. (2010) · Clinical Cardiology · doi:10.1002/clc.20813 · Cited by 37 · see citing works
Immunoradiometric versus enzymatic renin assay
Morganti, A., Pelizzola, D., Mantero, F., et al. (1995) · Journal of Hypertension · doi:10.1097/00004872-199501000-00004 · Cited by 37 · see citing works
Self-citationRole of the Renin-Angiotensin System in Cardiovascular Disease
Cohn, J. N. (2010) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-010-6230-3 · Cited by 29 · see citing works
Role of pro renin receptor in cardiovascular cells from the aspect of signaling
Hitom, H. (2010) · Frontiers in Bioscience-Elite · doi:10.2741/e185 · Cited by 15 · see citing works
Review: Plasma renin and the incidence of cardiovascular disease
Meade, T. (2010) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320310365015 · Cited by 14 · see citing works
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- Authors
- Tomaschitz, A., Pilz, S., Ritz, E., Morganti, A., Grammer, T., Amrein, K., Boehm, B. O., & Marz, W.
- Affiliations
- Medical University of Graz (AT)
- Heidelberg University (DE)
- University of Milan (IT)
- Synlab (Germany) (DE)
- Universität Ulm (DE)
- Corresponding author
- Tomaschitz, A.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-05-23
- Volume
- 32
- Issue
- 21
- Pages
- 2642-2649
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2129610631
- Cited by
- 64
- References
- 38
- Citations by year
- 2025: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 8
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- European Commission (201668)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- plasma renin concentration, cardiovascular mortality, sudden cardiac death, heart failure mortality, renin-angiotensin-aldosterone system, coronary angiography patients, effect modifiers, N-terminal pro-brain natriuretic peptide, ACE inhibitors, beta-blockers, diuretics, renal function
- MeSH terms
- Aged, Cardiovascular Diseases, Female, Heart Failure, Humans, Male, Middle Aged, Prospective Studies, Renin, Risk Factors, Biomarkers, Death, Sudden, Cardiac, Kaplan-Meier Estimate
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