Research Article: P2X7 Receptor and APOE Polymorphisms and Survival from Heart Failure: A Prospective Study in Frail Patients in a Geriatric Unit

Date Published: July 21, 2017

Publisher: JKL International LLC

Author(s): Giuseppe Pasqualetti, Marta Seghieri, Eleonora Santini, Chiara Rossi, Edoardo Vitolo, Livia Giannini, Maria Giovanna Malatesta, Valeria Calsolaro, Fabio Monzani, Anna Solini.


Heart failure (HF) is one of the most frequent cause of hospitalization in elderly and often coexists with concurrent geriatric syndromes, like cognitive disturbances; various pathophysiological mechanisms are shared by HF and cognitive decline, notably a substrate of low-grade inflammation. We investigated whether SNPs in the purinergic receptor (P2X7R) and apolipoprotein (APO) E genes, both involved in a series of inflammatory responses, are associated to HF or cognitive impairment and are able to predict post-discharge mortality in the elderly. We prospectively analyzed 198 patients (age 85 ± 8 years, predominantly females) admitted to a Geriatric unit for acute HF, whose diagnosis was based on clinical signs, brain natriuretic peptide (BNP) values and ecocardiography in uncertain diagnosis (BNP values between 100 and 400 pg/mL); cognitive performance was assesed by Short Portable Mental Status Questionnaire (SPMSQ). In all the participants, SNPs rs208294 and rs3751143 for P2X7R gene and rs429558 and rs7412 for APOE gene were assessed. Information on all-cause mortality was adjudicated by medical records review 36 months after discharge. We found no relationship between P2X7R and APOE polymorphisms and 36-month post-discharge mortality; a better outcome for overall survival was observed in patients with BNP values below the median (281 pg/mL) (p=0.002) persisting after adjustment for renal function and age, and in those with cognitive impairment (p<0.001). Patients harboring APOE-ε4 genotype showed higher BNP concentrations than noncarriers (1289.9 ± 226.9 vs 580.5 ± 90.2 pg/mL respectively,p=0.004), whereas none of the studied SNPs were associated to impairment in cognitive performance. In conclusion, neither P2X7R or APOE genotype seem to predict long-term mortality in elderly patients. Interestingly, APOE-ε4 genotype was associated to higher BNP values, suggesting a putative interaction between genetic and biochemical markers in identifying people at risk for HF.

Partial Text

The main finding of the present study is a negative one: even though P2X7R (rs208294 and rs3751143) and APOE (rs429358 and rs7412) polymorphisms have been recognized as potential determinants of unfavorable prognosis in several and heterogeneous morbid conditions [29, 30], they were not independently associated to three-year post-discharge mortality in a cohort of older patients, admitted at emergency room for HF. Instead, our observation that higher BNP values and impairment in cognitive status tracked the poorest outcome deserves attention. Lastly, whilst P2X7R polymorphisms were linked neither to HF and cognitive decline, APOE-ε4 carriers showed significantly higher BNP values, indicative of a cardiac dysfunction.




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