title: Spontaneous baroreceptor reflex sensitivity for risk stratification of heart failure patients: optimal cut-off and age effects.
abstract: Baroreceptor reflex sensitivity (BRS) is an important prognostic factor because a reduced BRS has been associated with an adverse cardiovascular outcome. The threshold for a 'reduced' BRS was established by the ATRAMI study at BRS <3 ms/mmHg in patients with a previous myocardial infarction, and has been shown to improve risk assessment in many other cardiac dysfunctions. The successful application of this cut-off to other populations suggests that it may reflect an inherent property of baroreflex functioning, so our goal is to investigate whether it represents a 'natural' partition of BRS values. As reduced baroreflex responsiveness is also associated with ageing, we investigated whether a BRS estimate <3 ms/mmHg could be the result of a process of physiological senescence as well as a sign of BRS dysfunction. This study involved 228 chronic heart failure patients and 60 age-matched controls. Our novel method combined transfer function BRS estimation and automatic clustering of BRS probability distributions, to define indicative levels of different BRS activities. The analysis produced a fit clustering (cophenetic correlation coefficient 0.9 out of 1) and identified one group of homogeneous patients (well separated from the others by 3 ms/mmHg) with an increased BRS-based mortality risk [hazard ratio (HR): 3.19 (1.73, 5.89), P<0.001]. The age-dependent BRS cut-off, estimated by 5% quantile regression of log (BRS) with age (considering the age-matched controls), provides a similar mortality value [HR: 2.44 (1.37, 4.43), P=0.003]. In conclusion, the 3 ms/mmHg cut-off identifies two large clusters of homogeneous heart failure (HF) patients, thus supporting the hypothesis of a natural cut-off in the HF population. Furthermore, age was found to have no statistical impact on risk assessment, suggesting that there is no need to establish age-based cut-offs because 3 ms/mmHg optimally identifies patients at high mortality risk.
authors.affiliation: Institute of Electronics and Informatics Engineering of Aveiro (IEETA) and Center for R&D in Mathematics and Applications (CIDMA), Universidade de Aveiro (UA), Portugal sonia.gouveia@ua.pt.
authors.forename: Sónia
authors.initials: S
authors.lastname: Gouveia
authors.affiliation: CEMAT and Instituto Superior Técnico, Universidade de Lisboa, Portugal.
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Scotto
authors.affiliation: Department of Biomedical Engineering, Fondazione Salvatore Maugeri-IRCCS, Montescano, Italy.
authors.forename: Gian Domenico
authors.initials: GD
authors.lastname: Pinna
authors.affiliation: Department of Biomedical Engineering, Fondazione Salvatore Maugeri-IRCCS, Montescano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Maestri
authors.affiliation: Department of Cardiology, Fondazione Salvatore Maugeri-IRCCS, Montescano, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: La Rovere
authors.affiliation: Department of Electronics, Telecommunications and Informatics (DETI) and IEETA, Universidade de Aveiro (UA), Portugal.
authors.forename: Paulo J S G
authors.initials: PJ
authors.lastname: Ferreira
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D017704:Baroreflex; D001794:Blood Pressure; D002908:Chronic Disease; D016000:Cluster Analysis; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors
keywords: ageing; heart failure (HF); risk stratification; spectral analysis; spontaneous baroreceptor reflex sensitivity (BRS); transfer function (TF)