RESUMO
AIMS: High serum phosphate is linked to cardiovascular morbidity and mortality in the general population. Fibroblast growth factor 23 (FGF-23) is a critical phosphate regulating hormone, potentially reflecting phosphate load better than a single serum phosphate measurement. Recent pioneering echocardiographic studies associated FGF-23 with left-ventricular morphology. However, the association between FGF-23 and left-ventricular function is unknown, prompting us to investigate this relationship in our HOM SWEET HOMe study. METHODS AND RESULTS: We studied the association between C-terminal FGF-23, coronary artery disease, and left-ventricular function in 885 subjects undergoing elective coronary angiography. Left-ventricular function was assessed with ventriculography. More, pro-brain natriuretic peptide (pro-BNP) plasma levels were measured. The presence of left-ventricular hypertrophy and atrial fibrillation was assessed by electrocardiography. Patients with an ejection fraction <40% had significantly higher FGF-23 levels compared with patients with the ejection fraction >40% (P< 0.001). In multivariable regression analysis, the observed relationship between FGF-23 and left-ventricular function remained significant after adjustment for estimated glomerular filtration rate, presence of left-ventricular hypertrophy, and other confounding variables. In accordance, FGF-23 significantly correlated with pro-BNP plasma levels (r = 0.31; P< 0.001). Prevalent atrial fibrillation was associated with elevated FGF-23 levels, while the presence of coronary artery disease was not. CONCLUSIONS: Fibroblast growth factor 23 levels are associated with left-ventricular function and atrial fibrillation even in the absence of renal function impairment. Of note, these cross-sectional data cannot prove causality; therefore, future studies will have to discern whether FGF-23 exerts a direct untoward effect on the myocardium, or rather represents an 'innocent bystander' which reflects a high phosphate burden.
Assuntos
Fibrilação Atrial/etiologia , Fosfatos de Cálcio/metabolismo , Doença da Artéria Coronariana/etiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Disfunção Ventricular Esquerda/etiologia , Fibrilação Atrial/sangue , Biomarcadores/metabolismo , Doença da Artéria Coronariana/sangue , Estudos Transversais , Eletrocardiografia , Fator de Crescimento de Fibroblastos 23 , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/etiologia , Nefropatias/complicações , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Disfunção Ventricular Esquerda/sangueRESUMO
AIMS: Monocytes and monocyte-derived macrophages have been recognised as the cellular hallmark of atherosclerosis decades ago. Recently, they have also been shown to play a pivotal role in obesity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. We initiated the I LIKE HOMe study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis. METHODS AND RESULTS: We assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14(++)CD16(-) and CD16(+) cells, which we further subdivided into CD14(++)CD16(+) and CD14((+))CD16(+) cells. Body mass index was significantly correlated with carotid IMT. High CD16(+) monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16(+) monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16(+) monocyte numbers in obesity may partly explain the association between obesity and IMT. CONCLUSION: Our results reveal a significant univariate association between CD16(+) monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16(+) monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.
Assuntos
Aterosclerose/patologia , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Macrófagos/patologia , Monócitos/patologia , Obesidade/patologia , Gordura Abdominal/patologia , Adiposidade/fisiologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de IgG/metabolismo , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
OBJECTIVES: The aim of this study was to analyze the yet ill-defined relationship of distinct human monocyte subsets with cardiovascular outcomes in a broad patient population at cardiovascular risk. BACKGROUND: Monocytes, the most abundant immune cell type found in atherosclerotic plaques, are crucial promoters of atherogenesis. Three distinct human monocyte subsets exist: classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Immunomodulation of distinct monocyte subsets has recently been discussed as a new therapeutic avenue in atherosclerosis. METHODS: Cardiovascular events in 951 subjects referred for elective coronary angiography were prospectively analyzed. Monocyte subset analysis was performed using flow cytometry, blinded to patients' clinical characteristics, and patients were categorized according to quartiles of total monocyte and monocyte subset counts. The primary endpoint was defined a priori as the first occurrence of cardiovascular death, acute myocardial infarction, or nonhemorrhagic stroke. Endpoint adjudication was done blinded to monocyte subset distribution. RESULTS: During a mean follow-up period of 2.6 ± 1.0 years, 93 patients experienced the primary endpoint. In univariate Kaplan-Meier analysis, counts of total (p = 0.010), classical CD14++CD16- (p = 0.024), and intermediate CD14++CD16+ (p < 0.001) monocytes predicted the primary endpoint, whereas nonclassical monocytes did not (p = 0.158). After full adjustment for confounders, CD14++CD16+ monocytes remained the only monocyte subset independently related to cardiovascular events (fourth vs. first quartile: hazard ratio: 3.019; 95% confidence interval: 1.315 to 6.928; p = 0.009). CONCLUSIONS: CD14++CD16+ monocytes independently predicted cardiovascular events in subjects referred for elective coronary angiography. Future studies will be needed to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies in atherosclerosis.