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Association analysis of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) in cardiac and non-cardiac frailty
Authors : Q Li (Hong Kong,HK), L T Lui (Hong Kong,HK), X Yang (Hong Kong,HK), S Liu (Hong Kong,HK), K F Cheng (Hong Kong,HK), J Lupon (Barcelona,ES), A Bayes-Genis (Barcelona,ES), D Sahota (Hong Kong,HK), J Woo (Hong Kong,HK), E Fung (Hong Kong,HK)
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L T Lui1
K F Cheng1
1The Chinese University of Hong Kong, Medicine & Therapeutics - Hong Kong - Hong Kong
2Autonomous University of Barcelona, Department of Medicine - Barcelona - Spain
3The Chinese University of Hong Kong, Obstetrics & Gynaecology - Hong Kong - Hong Kong
Background/Introduction: Frailty is a clinical syndrome characterised by reduced physiologic reserve including easy fatigability, skeletal muscle wasting and weight loss that overlap with attributes of chronic heart failure (HF). Whereas elevated NT-proBNP can indicate ventricular stress and cardiac dysfunction, there remains no blood biomarker to discriminate between frailty subtypes. GDF-15 is increased in inflammatory states, chronic disease, and following tissue injury, and recent animal studies support its functional role in inhibiting muscle growth and body weight.
Purpose: To elucidate cardiac and non-cardiac frailty subtypes using echocardiography in combination with NT-proBNP and GDF-15.
Methods: Participant recruitment in the Undiagnosed heart Failure in frail Older individuals (UFO) study was purposeful sampling to target approx. one-third in each of 3 frailty subgroups using the 5-point multi-domain FRAIL scale: 0, robust (R); 1–2, pre-frail (PF); 3–5, frail (F). Cardiac structure and function were assessed by echocardiography, and serum NT-proBNP and GDF-15 levels were dichotomised at the median as ‘high’ or ‘low’ in a 2x2 matrix. Physical performance metrics including 6-minute walk distance (6MWD), gait speed (GS) and handgrip strength per body mass index (HGS) were assessed for strength of association using the method of polynomial contrasts for linear trend test; P <0.05 was considered statistically significant.
Results: FRAIL stratification of 306 individuals (mean age 74.7 y) resulted in classification of 34% R, 35% PF, and 31% F, with female-to-male ratios of 0.7, 4.4 and 5.3, respectively. The prevalence of diastolic (LVEF >50%) and systolic (=50%) dysfunction were 67% and 4.3%, respectively. Serum NT-proBNP levels in R, PF and F older adults were 181, 239 and 361 pg/ml, respectively, and GDF-15 levels were 1667, 2220, and 3206 pg/ml, respectively. NT-proBNP was not significantly associated with GDF-15 (r=0.09, adjusted P=0.13), suggesting complementary pathways. In association with FRAIL score, log10-NT-proBNP reached borderline significance (ß 0.33, adjusted P=0.046), whereas log10-GDF-15 was strongly associated (ß 1.18, adjusted P=3.1 x 10e-5).
In 2x2 analysis, physical performance ranking from worst to best (">") was as follows: NT-proBNP^high GDF-15^high (cardiac frailty; 6MWD, 265 m; GS, 0.72 m/s; HGS, 0.64) > NT-proBNP^low GDF-15^high (non-cardiac frailty; 6MWD, 320 m; GS, 0.85 m/s; HGS, 0.70) > NT-proBNP^high GDF-15^low (6MWD, 360 m; GS, 0.95 m/s; HGS, 0.79) > NT-proBNP^low GDF-15^low (6MWD, 376 m; GS, 0.96 m/s; HGS, 0.88). Age- and sex-adjusted P-values of linear trend pattern among the paired biomarker subgroups for 6MWD, GS and HGS were 3 x 10e-6, 5.6 x 10e-5, and 1.1 x 10e-4, respectively.
Conclusion: In combination with echocardiography, serum NT-proBNP and GDF-15 can be used to classify cardiac and non-cardiac frailty, as supported by statistically associated metrics of physical performance.
ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.
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