title: The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.
abstract: High concentrations of renin and aldosterone are risk factors for cardiovascular diseases (CVD) which are the leading cause of morbidity and mortality worldwide. Enhanced activation of the renin-angiotensin-aldosterone system (RAAS) by cigarette smoking has been reported. The aim of our study was to analyze the effect of cigarette smoking on parameters of the RAAS in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the utility of RAAS parameter for risk prediction. We determined the concentration of aldosterone, renin, angiotensin-I and angiotensin-II in participants of the LURIC study. Smoking status was assessed by a questionnaire and the measurement of plasma cotinine concentration. Parameters were log transformed before entering analyses, where appropriate. We used a multivariate Cox regression analysis to assess the effect of parameters on mortality. From the 3316 LURIC participants 777 were AS and 1178 NS. Within a median observation period of 10 years 221 (28.4 %) AS and 302 (25.6 %) NS died. After adjustment for age, gender, and the use of anti-hypertensive medication, only angiotensin-I was significantly different in AS compared to NS with an estimated marginal mean (95 % CI) of 1607 (1541-1673) ng/L and 1719 (1667-1772) ng/L, respectively. For both NS and AS renin and angiotensin-II were directly associated with mortality in the multivariate Cox regression analysis. Angiotensin-I was only associated with increased risk for mortality in NS (HR (95 % CI) of 0.69 (0.53-0.89)). We conclude that increased renin and angiotensin-II are independent predictors of mortality in AS and NS, while angiotensin-I was associated with reduced risk of death in NS only.
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
authors.forename: Graciela E
authors.initials: GE
authors.lastname: Delgado
authors.affiliation: Drug Regulatory Affairs, Pharmaceutical Institute, Bonn University, Bonn, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Siekmeier
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.affiliation: Swiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Grübler
authors.affiliation: Specialist Clinic for Rehabilitation PV Bad Aussee, Bad Aussee, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz Medical University, Graz, Austria.|Synlab Academy, Synlab Services LLC, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. marcus.kleber@medma.uni-heidelberg.de.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D012083:Renin
keywords: Aldosterone; Angiotensin; Cigarette smoking; Mortality; Renin; Smokers