N‐Terminal Pro‐B‐Type Natriuretic Peptide Levels in Parkinson's Disease

We read with interest the study by Choe and colleagues1 who increases emphasis on the heart–brain axis in Parkinson's disease (PD). They have studied the relation between subclinical cardiac markers and motor impairment (Unified Parkinson's Disease Rating Scale Part III and Hoehn and Yahr stage) and cognition (Montreal Cognitive Assessment [MoCA]) concluding that (1) patients with PD presented higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with healthy controls matched for age, sex, and cardiovascular risk factors; (2) increased levels of NT-proBNP and high-sensitivity troponin I were associated with worse motor impairment (Unified Parkinson's Disease Rating Scale Part III and Hoehn and Yahr stage); and (3) MoCA was inversely associated to high-sensitivity troponin I and NT-proBNP levels only in unadjusted models among patients with PD.1 The population included were patients with advanced-stage PD (12 years of disease duration in average).1 We have replicated these analyses in an independent population of patients with earlier stage PD (age 66 ± 9 years old, 56% male, disease duration 4.2 ± 2.62 years, Unified Parkinson's Disease Rating Scale Part III 24.5 ± 9.31) being evaluated for cardiovascular risk factors. We conducted a case-control study comparing patients with PD with non-PD controls. Patients with PD were recruited sequentially from the Movement Disorders Unit of the University Hospital of Santa Maria-Lisbon, and controls were recruited from 1 general practitioner list from a primary healthcare center in the same geographic region. All patients were diagnosed with PD by a movement disorders specialist according to the UK PD Brain Bank criteria2 and had <11 years of disease duration. Controls were randomly selected from a general practitioner's list of patients and matched to the patients with PD according to age and gender. All participants were evaluated by an internal medicine physician and movement disorders expert. Blood samples were taken and the MoCA test was performed by a trained nurse. Dysautonomy/orthostatic hypotension was defined as the decline of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure within 5 minutes of going from supine to standing. Participants with heart failure were excluded. All comparisons between patients with PD and matched controls did not reach significance (Table 1). In our analysis of the NT-proBNP marker among patients with PD, we only found higher significant results when comparing patients with PD with and without orthostatic hypotension (254 ng/L vs. 135 ng/L; P = 0.028). We also did not find a significant association of NT-proBNP with motor impairment or MoCA test in patients with PD. 158 ± 214 ng/mL (5; 1141) 143 ± 272 ng/mL (14; 1941) 135.3 ± 252.6 ng/mL (n = 89)**** P value = 0.44. Although our results are not conclusive, they go in the same direction of the conclusions of Choe and colleagues. The purpose of this letter is to add to the discussion the possibility that this association between subclinical cardiac markers and PD should be explored even at an earlier stage of the disease. (1) Research Project: A. Conception, B. Organization, C. Execution(2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. M.A.: 1A, 2A, 2B, 2C, 3A, 3B D.C.: 2A, 2B, 2C, 3B S.R.: 2C, 3B J.M.F.: 1A, 2C, 3B J.J.F.: 1A, 1B, 2A, 2C, 3B Dr Alves was awarded a scholarship from Fundação para a Ciência e Tecnologia (SFRH/BD/129700/2017); reports she has participated in educational meetings and/or attended conferences or symposia with Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Grünenthal,Tecnimede, Merck Sharp & Dohme. Prof Caldeira reports that he has participated in educational meetings and/or attended conferences or symposia with Bristol-Myers Squibb, Bayer, Boheringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis and Roche. Profª Reimão has nothing to report. Prof Ferro reports honoraria for speaker, clinical trial coordinator and advisory board from Boehringer Ingelheim. Prof. Ferreira has held consultancy functions with GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, Abbott, Abbvie, BIAL, Merck-Serono, Merz, Ipsen, Biogen, NeuroDerm, Zambon, Sunovion, Affiris, ONO; has received lecture fees from Biogen and BIAL, Sunovion, ONO, Zambon, Abbvie; has received grants from GlaxoSmithKline, Grunenthal, MSD, Allergan, Novartis, Fundação MSD (Portugal), Medtronic and Teva; has been employed by Faculdade de Medicina de Lisboa and CNS – Campus Neurológico Sénior.

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