Les facteurs régulant l’hématopoïèse en contexte de vieillissement s’avèrent incomplètement compris. Nous avons étudié les déterminants de la variabilité des traits de la formule sanguine complète dans une cohorte de 2996 femmes apparentées et non-apparentées d’ascendance française du Québec âgées de 55 à 101 ans. Les déterminants héréditaires ont été évalués par étude d’association pan-génomique. Des facteurs acquis, incluant comorbidités et hématopoïèse clonale, ont aussi été évalués. Des analyses multivariées ont été réalisées avec des modèles linéaires mixtes généralisés. Nous avons identifié des variants dans la région de GSDMA et PSMD3-CSF3 significativement associés au décompte de neutrophiles et un polymorphisme intronique à ARHGEF3 associé au décompte plaquettaire. L’effet de certains variants diminuait avec l’âge. Avec l’âge, les décomptes de neutrophiles et monocytes augmentaient tandis que le décompte des lymphocytes décroissait. Les valeurs de neutrophiles (4,1x109/L vs 3,83x109/L, valeur-p <0,001), monocytes (0,50x109/L vs 0,45x109/L, valeur-p <0,001) et plaquettes (259x109/L vs 243x109/L, valeur-p <0,001) étaient augmentées lors de comorbidités cardiométaboliques (maladie coronarienne, hypertension, diabète, dyslipidémie). L’hématopoïèse clonale ne modifiait pas les décomptes. En conclusion, nous identifions des déterminants génétiques héréditaires contribuant à la variabilité des décomptes cellulaires sanguins dans une cohorte vieillissante. De plus, le vieillissement est associé à des niveaux accrus de neutrophiles et monocytes et une diminution des lymphocytes indiquant un biais myéloïde, lequel est majoré lors de comorbidités métaboliques. L’hématopoïèse clonale ne contribue pas à ce biais myéloïde. Ces résultats supportent le fait que des facteurs extrinsèques, possiblement via un effet inflammatoire, promeuvent le biais myéloïde relié à l’âge. / Our understanding of the factors regulating peripheral blood cell traits in the setting of aging remains incomplete. We investigated the determinants underlying blood cell trait variability in a cohort of 2996 related and unrelated women of French ancestry from Québec aged 55 to 101 years. We performed a genome-wide association study to assess for genetic variants. We also assessed the impact of acquired factors such as chronic comorbidities and clonal hematopoiesis. Multivariate analyses were subsequently performed using generalized linear mixed models. We identify variants in the region of GSDMA and PSMD3-CSF3 that meet genome-wide requirements for neutrophil counts and a variant intronic to ARHGEF3 for platelet counts. With aging, the effect of certain variants decreased. Aging was associated with increasing neutrophil and monocyte counts and decreasing lymphocyte counts. We also document that individuals with cardiometabolic comorbidities (diabetes, coronary heart disease, hypertension and dyslipidemia) exhibit significantly higher neutrophil (4.1x109/L vs 3.83x109/L, p-value <0.001), monocyte (0.50x109/L vs 0.45x109/L p-value <0.001), and platelet (259x109/L vs 243x109/L, p-value <0.001) counts. Clonal hematopoiesis did not contribute significantly to these traits. In conclusion, germline variants related to GSDMA and PSMD3-CSF3 contribute to neutrophil counts and a SNP intronic to ARHGEF3 contributes to platelet counts. Aging is associated with a myeloid shift with increased levels of neutrophils and monocytes, and reduced lymphocyte counts. This myeloid-biased skewing is further increased with cardiometabolic comorbidities. Clonal hematopoiesis does not contribute to this phenomenon. These findings support that cellextrinsic factors may contribute to the myeloid shift possibly through low-grade inflammation.

Some CBC parameters have been implicated in individual susceptibility to death, both in heart disease and cardiac surgery populations. The cellular elements of blood are widely affected during cardiopulmonary bypass (CPB), technique used in cardiac surgery. A Complete Blood Count called Risk Score (CBC-RS) was calculated from the average of the deviations of the various elements of the CBC and has been previously validated and published. The CBC-RS showed as excellent predictor of death from all causes in large healthy and cardiovascular risk populations. Despite the effect of CPB on the blood cells, there is no acknowledgement from the prior assessment of this score in the surgical setting. The aim of this study was to evaluate the role of CBC-RS in the surgical risk prediction (mortality and morbidity) in patients undergoing cardiac surgery with CPB. For this, it was evaluated a historical cohort of 428 patients undergoing cardiac surgery with CPB. The individual CBC-RS was calculated using the collected blood count of patients preoperatively. Logistic regression and statistical C analyzed the predictive accuracy of this score. The primary endpoint was in-hospital mortality (all-cause) and secondary outcomes included the majors and bleeding complications. In our study, CBC-RS was a predictor of hospital mortality (OR = 1.28 for each score increments, 95% CI = 1123-1458, p <0.001) and secondary outcomes (OR = 1.208, 95% CI = 1.103 to 1.323, p <0.001). The areas under the curve (AUC) was 0.697 (p <0.001) and 0.636 (p <0.001) for both the primary and secondary endpoints, respectively. In multivariate analysis, after adjustment for other risk predictors (EuroSCORE II and CPB time), the CBC-RS remained significant and was the strongest predictor of mortality. Therefore, the CBC-RS proved to be an independent predictor of mortality and surgical complications during hospitalization. It may be a useful tool in risk assessment of patients undergoing cardiac surgery. / Dentre os diversos parâmetros fornecidos pelo hemograma, alguns já foram implicados em aumento da suscetibilidade individual à morte, tanto em pacientes com patologias cardíacas quanto os submetidos à cirurgia cardíaca. Os elementos celulares do sangue são amplamente afetados durante a circulação extracorpórea (CEC), técnica usada nas cirurgias cardíacas. Um escore calculado a partir dos desvios da média dos diversos componentes do hemograma foi previamente validado, publicado e chamado de Complete Blood Count Risk Score (CBC-RS). O CBC-RS se mostrou excelente preditor de morte por todas as causas em grandes populações saudáveis ou com fatores de risco cardiovascular. Apesar do efeito da CEC sobre as células sanguíneas, não se tem conhecimento da avaliação prévia deste escore no contexto cirúrgico. O objetivo do presente trabalho foi avaliar o papel do CBC-RS na predição de risco cirúrgico (mortalidade e morbidade hospitalar) em pacientes submetidos à cirurgia cardíaca com CEC. Para isso, uma coorte histórica de 428 pacientes submetidos à cirurgia cardíaca com CEC foi avaliada. O CBC-RS individual foi calculado utilizando o hemograma coletado dos pacientes no pré-operatório. A acurácia preditora deste escore foi analisada através regressão logística e estatística C. O desfecho primário avaliado foi a mortalidade hospitalar (por todas as causas) e os desfechos secundários incluíram as complicações maiores e sangramento. Em nosso estudo, o CBC-RS foi um preditor de mortalidade hospitalar (OR = 1,28 por cada aumento de pontuação do CBC-RS, IC 95% = 1.123 - 1.458, p <0,001) e dos desfechos secundários (OR = 1,208, IC 95% = 1,103 - 1,323, p <0,001). As áreas sob a curva (AUC) foram 0,697 (p <0,001) e 0,636 (p <0,001) para os desfechos primário e secundário, respectivamente. Na análise multivariada, após ajuste para preditores de risco pré-operatório (EuroSCORE II) e transoperatório (tempo de CEC) conhecidos, o CBC-RS permaneceu significativo e foi o preditor de mortalidade mais forte. Sendo assim, o CBC-RS se mostrou um preditor independente da mortalidade e complicações cirúrgicas no período hospitalar, podendo representar uma ferramenta útil na avaliação de risco de pacientes submetidos à cirurgia cardíaca.