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A seeming paradox of sickle cell disease is that patients do not suffer from a high prevalence of systemic hypertension in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, some patients do develop systolic hypertension and increased pulse pressure, an increasingly recognized major cardiovascular risk factor in other...
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Sickle cell anemia has many sequelae that result in emergency department (ED) use, but a minority of patients with sickle cell disease are frequent utilizers and make up the majority of ED visits. If patients who are likely to be frequent ED can be identified in steady state, they can be treated with disease modifying agents in an attempt to reduce...
Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation of hemolysis could be used as an objective outcome in clinical trials of new therapeutics for HbSS and would also enable better human studies of the pathogenesis of complications of HbSS that are ostensibly hemolysis-related, such as pulmonary hypertension. However, contem...
Citations
... Elevated pulse pressure is predominately attributed to arterial stiffness, lower diastolic blood pressure, and microvascular damage. 4,5 It is also an independent predictor of poor cardiovascular outcomes and endothelial dysfunction and has been linked to hemolysis in individuals with SCD. 5 Pulse pressure is associated with hemolytic biomarkers such as reticulocyte count and lactate dehydrogenase (LDH), and additional variables including hemoglobin, oxygen saturation, and creatinine. 5 To date, little attention has been devoted to pulse pressure in SCD, with no evidence of an association between pulse pressure and leg ulcers in individuals living with SCD. ...
... 4,5 It is also an independent predictor of poor cardiovascular outcomes and endothelial dysfunction and has been linked to hemolysis in individuals with SCD. 5 Pulse pressure is associated with hemolytic biomarkers such as reticulocyte count and lactate dehydrogenase (LDH), and additional variables including hemoglobin, oxygen saturation, and creatinine. 5 To date, little attention has been devoted to pulse pressure in SCD, with no evidence of an association between pulse pressure and leg ulcers in individuals living with SCD. ...
... 4,5 It is also an independent predictor of poor cardiovascular outcomes and endothelial dysfunction and has been linked to hemolysis in individuals with SCD. 5 Pulse pressure is associated with hemolytic biomarkers such as reticulocyte count and lactate dehydrogenase (LDH), and additional variables including hemoglobin, oxygen saturation, and creatinine. 5 To date, little attention has been devoted to pulse pressure in SCD, with no evidence of an association between pulse pressure and leg ulcers in individuals living with SCD. We set to examine pulse pressure, clinical, and laboratory parameters in a large, prospectively acquired, cohort of SCD adults with or without leg ulcers, in the United States. ...
Leg ulcers in individuals living with Sickle Cell Disease are evidence of systemic dysfunction. Data from a U.S. study link leg ulcers to wider pulse pressure and markers of chronic hemolysis, inflammation, renal, and liver dysfunction. image
... However, none of the PHT subjects in our study had proteinuria, suggesting there should be a more plausible explanation for the renal impairment, possibly because of chronic vaso-occlusive crises. Novelli et al 39 also found an association between elevated pulse pressure and renal impairment. However, we did not find any correlation or significant association between pulse pressure and eGFR in our study. ...
Pulmonary hypertension (PHT) is multifactorial in origin and a major cause of morbidity and mortality in the sickle cell populace. Its correlation with abnormal left ventricular geometric patterns has not been established. Subjects were sickle cell anemic patients of the hematology clinic of a tertiary hospital who gave informed consent. A modified Medical Research Council questionnaire was used to obtain the demographic, anthropometric, and clinical variables of the subjects. Blood samples were taken for hematologic and biochemical analysis. Spirometry, electrocardiography, and echocardiography were done for all subjects. SPSS version 25 was used for analysis. A p ≤0.05 was used for significance. In total 111 subjects with sickle cell anemia were recruited. Male:female ratio was 1:1.4. The prevalence of PHT was 8.1%. Those with PHT were older and had higher blood pressure, lower respiratory rate, higher body mass index, lower estimated glomerular filtration rate, and a higher prevalence of avascular necrosis of the head of femur, stroke, and chest pain. About 2/3 (66.7%) of those with PHT had concentric left ventricular hypertrophy (LVH) whereas none of those with eccentric LVH had PHT. Age, body mass index, systolic blood pressure, aortic root diameter, concentric LVH, serum creatinine, history of stroke, chest pain, and avascular necrosis of the head of femur correlated directly whereas eccentric LVH correlated inversely with PHT. Concentric LVH, relative systemic hypertension, history of chest pain, and respiratory rate were the independent correlates of PHT in subjects with sickle cell anemia. PHT is known to be of poor prognostic significance. Its association with relative systemic hypertension and concentric LVH suggests the need to initiate early treatment to reduce morbidity and mortality in this group.
... Blood pressure is a potential modulator of clinical severity in SCD patients, recent studies showed that relative systematic hypertension (RSH), defined as BP 120-139/70-89 mmHg, and Systemic Hypertension (BP >140/>90), considerably increased the risk of pulmonary hypertension and renal dysfunction (2). Previous studies have reported demographic, biological, anthropometric, and genetic factors to be associate with blood pressure in SCD patients (3)(4)(5)(6)(7)(8). Blood pressure is a heritable trait with estimates of heritability indicating that 30-70% of the trait variance is attributable to genetic variation and a recurrent deleterious and loss of functions mutation with genes associated with lowering BP has been recently associate with long survival in SCD in Africa (9). ...
Increased blood pressure (BP) has been associated with higher risk of stroke and mortality in Sickle Cell Disease (SCD). We investigated risk factors associated with Relative Systemic Hypertension (RSH) or systemic hypertension in SCD patients in Cameroon. Using R, Multivariate multinomial logistic regression modeling was used to examine the effects of the demographic, anthropometric, clinical, and laboratory factors to determine risk factors. A total of 815 individuals with SCD, including 380 (46.6%) males were analyzed. At baseline, the median age [interquartile range] was 18.0 [12.0–25.0] years, ranging from 3 to 66 years. Approximately three-quarters of the patients (n = 645; 79.1%) had normal BP, 151 (18.5%) had RSH and 19 (2.3%) had hypertension. Age (P < 0.001) and gender (P = 0.022) were significantly different across the BP categories. Weight (P < 0.001), height (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.020), history of stroke (P = 0.012), hemoglobin level (P = 0.002), red blood cell count (P = 0.031), creatinine (P < 0.001), and (estimated glomerular filtration rate) eGFR (P = 0.002) was also significantly different across the three BP categories. After adjustment, the significantly associated factors of RSH in the SCD patients were age [OR = 1.03, (95% CI = 1.01–1.06), P < 0.010], male gender [OR = 1.54, (95% CI = 1.04–2.27), P = 0.029], BMI [OR = 1.10, (95% CI = 1.04–1.17), P = 0.001]. After adjustment, the independent variables significantly associated factors of Hypertension in the SCD patients were age [OR = 1.05, (95% CI = 1.01–1.10), P = 0.034], male gender [OR = 3.31, (95% CI = 1.04–10.52), P = 0.042], BMI [OR = 1.14, (95% CI = 1.01–1.29), P = 0.027]. Creatinine was significantly associated with RSH [OR =1.31 (1.05–1.63), P = 0.016]. SCD patients with RSH or hypertension maybe at increased risk of renal dysfunction. We found relatively high prevalence of RSH and hypertension (20.8%) in SCD patients in Cameroon. Tailored Interventions that consider major risk factors (age, gender, and BMI) may lower BP pressure and prevent severe complications.
... DBP showed a positive correlation with age, body mass index in those over 17, hemoglobin concentration in women, blood urea nitrogen in males under 18, and a negative correlation with estimated glomerular filtration rate (eGFR) in patients under-age 18, SBP was negatively correlated with fetal hemoglobin in males over 17 [23]. Triglycerides increased hematocrit and higher blood viscosity were independent risk factors for RSH in SCD patients [24,25]. Furthermore, pulse pressure and a history of blood transfusion were independently associated with systemic hypertension in SCD patients [17]. ...
... Furthermore, pulse pressure and a history of blood transfusion were independently associated with systemic hypertension in SCD patients [17]. Markers of hemolysis are associated with a higher pulse pressure in SCD patients [25]. Augmentation index, a measure of arterial stiffness, was significantly higher in SCD patients compared with healthy controls (p < 0.050) [22]. ...
... Contrary to similar studies, Kuma et al., found a high prevalence of RSH and hypertension with a relatively low frequency of renal insufficiency, and no association between RSH and stroke [16]. Novelli et al., found that higher pulse pressure was associated with markers of hemolysis, elevated serum creatinine and with proteinuria in SCD patients [25]. Additionally, Kuma et al., found a higher pulse pressure in males of all ages compared to females [10]. ...
Objectives:
Blood pressure (BP) values ≥ 120/70 mmHg considerably increase the risk for pulmonary hypertension and renal dysfunction in Sickle Cell Disease (CSD) patients, and ultimately increased morbidity and mortality. This has led to the development of the term relative systemic hypertension (RSH). RSH was defined as Systolic BP 120-139 mm Hg or diastolic BP 70-89 mm Hg, whereas systemic hypertension is defined as Systolic BP ≥ 140 mm Hg or diastolic BP ≥90 mm Hg. Systematic identification of BP variations and risk factors in SCD patients could promote effective management. This review aimed to identify factors associated with BP variation among SCD patients.
Methods:
We searched PubMed, Scopus, Web of Science and Google Scholar up to December 2020 with no geographical or language restrictions. Two reviewers independently screened, and summarized data from eligible studies.
Results:
Advancing age, gender, higher body weight, haemoglobin, eGFR, triglycerides, greater heamatocrit, higher blood viscosity, history of blood transfusion, and targeted variants in DRD2 and MIR4301 genes were independently associated with the risk of hypertension in SCD patients.
Conclusion:
Interventions that consider these risk factors may potentially contribute to lower BP pressure in SCD patients and prevent developing severe complications.
... This is attributed to unbalanced fluid losses and possibly to a reduction in systemic vascular resistance [13]. Paradoxically, when present, hypertension has been shown to be predictive of poorer outcomes with increased incidences of both AKI and chronic kidney disease (CKD) [18]. The term "relative systemic hypertension" has been employed to describe relative elevations in blood pressure among patients with SCD. ...
... ESRD has been linked to risk factors such as older age, hypertension, proteinuria, hematuria, and deteriorating anemic state [16]. Notably, Yeruva et al [18] reported a 2-3-fold increase in the incidence of CKD in patients with SCD when compared with patients without SCD, based on a study performed over a 6-year period. Statistical variations between different studies have been noted and have been linked to discrepancies in the definition of renal failure as well as the different equations used to estimate GFR. ...
Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.
... Also, oxidative stress-induced haemodynamic disturbance and vascular dysfunction (Luangaram et al., 2007) as well as derangement in electrolytes (Berger, 2007;Beshel et al., 2019) have been reported to occur following PHZ intoxication. Decreased glomerular filtration rate (Haymann et al., 2010), albuminuria and proteinuria (Day et al., 2012;Novelli et al., 2014) have also been reported to occur following haemolysis. ...
Introduction: Phenylhydrazine (PHZ)-induced anaemia is associated with oxidative damage to
erythrocytes and impaired renal function. Fresh palm oil (FPO) is a rich source of antioxidants and preserves renal function. This study investigated the possible reno-protective effects of FPO in PHZ-induced anaemic Wistar rats.
Methods: Eighteen male Wistar rats (165 – 180 g) aged 8 – 9 weeks were randomly assigned into normal control (NC), anaemic control (AC) (60 mg/kg of PHZ i.p) and anaemic treated (A + FPO) (60 mg/kg of PHZ + 15 % FPO diet) groups. PHZ was administered twice consecutively at 48 h interval while FPO diet was given throughout the study period (14 days).
Results: Erythrocyte count, haemoglobin concentration and haematocrit were increased (p < 0.05) in A + FPO compared with AC. FPO improved imbalances in the levels of glucose and electrolytes (Na+, Cl-, K+, HCO3-) in serum and urine of the anaemic rats. Urea and creatinine concentrations were decreased (p < 0.05) in serum and increased (p < 0.05) in urine in the A + FPO relative to AC. Proteinuria was decreased (p < 0.05) in A + FPO compared with AC. The levels of malondialdehyde, pro-inflammatory cytokines and caspase-3 were downregulated (p < 0.05) in A + FPO compared with AC while interleukin-10 concentration, enzymatic antioxidants activities, and total antioxidant capacity were upregulated (p < 0.05) in A + FPO compared with AC.
Conclusion: FPO demonstrated anti-anaemic effect and improved the impaired renal function
associated with PHZ-induced anaemia.
... Although all children were normotensive, both systolic and diastolic BP were correlated positively with eGFR in the present study and elsewhere [7], while another study found no such association [10]. The pulse pressure was also found to be signi icantly elevated in hyper iltrating children in the present study, which is concur with results related pulse pressure to SCN and other cardiovascular complications, obtained from a large multisite study from the United States and the United Kingdom [29]. However, the signi icance of this inding in normotensive SCD patients needs to be con irmed and elaborated in further studies. ...
Background: Glomerular hyperfiltration (GH) is a common feature of sickle cell nephropathy (SCN) starting at infancy and represents an early marker of incipient glomerular injury and renal dysfunction. Methods: This study aimed to determine the prevalence and correlates of GH among children (≤ 16 years) with sickle cell disease (SCD) at their steady state, recruited over 6 months at the Pediatric Outpatient Clinic in Al-Sadaqa General Teaching Hospital, Aden, Yemen. Glomerular filtration rate (eGFR) was estimated using the Schwartz formula. Data on clinical history, anthropometry, blood pressure (BP) and laboratory investigations were collected. Results: Of 101 children (mean age 7.2 ± 3.9 years), 65 (64.4%) were males. The prevalence of GH was observed in 36 (35.6%) children, who were significantly older (10.7 ± 3.2 vs. 5.2 ± 2.7 years, p < 0.001) and had a lower fetal Hb level (5 ± 3.3 vs. 9 ± 7.1, p = 0.02). All children were normotensive, but hyperfiltrating children showed significantly higher systolic (97.2 ± 7.3 vs. 89.7 ± 5.2 mmHg) and diastolic pressure (55.1 ± 5.0 vs. 49 ± 4.3 mmHg) (all p < 0.001). Among evaluated children, 25.7% had hyperfiltration alone, whereas 9.9% had an associated microalbuminuria (MA), and no significant difference in eGFR between those with and without MA (158.4 ± 33.7 vs. 160.7 ± 29.8 ml/min/173m2, p = 0.84). Conclusion: This study demonstrated a relatively high prevalence of GH in Yemeni children with SCD that increased with age. Recognition of hyperfiltration and other early markers of nephropathy in this population could help to develop renal protective strategies to prevent progressive loss of kidney function.
... 8,9 Evidence on the prevalence of hypertension and subclinical vascular damage as assessed by arterial stiffness in SCD populations is relatively few and with inconsistent results. [9][10][11][12] Some studies showed low blood pressure (BP) levels in SCD patients and similar levels of pulse wave velocity (PWV) with healthy controls, 10 while others showed increased stiffness and an inverse association of PWV with BP. 9,11 The interaction of BP and arterial stiffness on the pathogenesis of cardiovascular disease in SCD could improve the understanding of underlying mechanisms and classification of cardiovascular risk in these patients. ...
Sickle cell disease (SCD) is associated with increased risk of cardiovascular disease, although blood pressure (BP) levels have been reported to be lower in SCD patients compared to general population. Aims of the present study were to investigate the prevalence of BP phenotypes and levels of arterial stiffness in pediatric patients with SCD and to assess the differences with children at risk for hypertension. We included in the study 16 pediatric SCD (HbS/β‐thalassemia, S/β‐thal) patients and 16 consecutive children at risk for hypertension referred to our hypertension clinic that served as high‐risk controls. All patients underwent ambulatory BP monitoring and measurement of carotid‐femoral pulse wave velocity (PWV). S/β‐thal patients had lower office systolic BP than the high‐risk control group (115.43 ± 10.03 vs 123.37 ± 11.92, P = .05) but presented similar levels of day and night ambulatory BP. Office hypertension was found in 12.5% of the S/β‐thal patients and in 43.8% of the high‐risk controls (P = .06), while 18.8% of the S/β‐thal patients and 25% of the high‐risk controls presented hypertension by ambulatory BP levels (P = .21). All of the S/β‐thal patients with ambulatory hypertension had night hypertension (one combined night and day hypertension) with office normotension (masked hypertension). S/β‐thal patients and high‐risk controls presented equal prevalence of masked hypertension (18.8%). Children and adolescents with S/β‐thal present similar prevalence of BP phenotypes and levels of PWV with children at risk for hypertension. A significant number of children and adolescents with S/β‐thal may have masked nighttime hypertension despite normal office BP levels.
... En nuestro estudio, la presencia de HP y/o dilatación de cavidades ventriculares fue observado más frecuentemente en los pacientes con NF. La coexistencia de complicaciones cardiovasculares y NF a causa de los cambios hemodinámicos producidos por hemólisis, anemia, hipoxemia crónica y posteriormente vasculopatía, es una interesante asociación descrita en adultos 27,28 , que no ha sido reportada en pediatría previamente. Futuros estudios debieran dilucidar las razones de esta asociación. ...
Introducción:
La nefropatía falciforme (NF) es una complicación poco estudiada en la edad pediátrica, que se manifiesta en diferentes formas, incluyendo la glomerulopatía y la tubulopatía.
Objetivo:
Descri bir las complicaciones renales agudas y crónicas de niños con anemia de células falciformes (ACF).
Pacientes y Método:
Estudio de cohorte restrospectiva. Se incluyeron pacientes pediátricos con diagnóstico confirmado de enfermedad de células falciformes que tuvieran estudio nefro-urológico. Se consignó patrón electroforético de hemoglobina, presencia y tipo de afectación renal, y presencia de compromiso cardiológico. Se realizó análisis bivariado para comparar pacientes con y sin NF.
Resultados:
Se incluyeron 79 pacientes, 59.5% hombres, siendo el patrón electroforético más fre cuente Hb-SS (60.9%). La NF se presentó en el 70% de ellos, con una edad de 114 meses (RIQ 65-157). Las alteraciones más frecuentemente encontradas fueron hiperfiltración glomerular, mi croalbuminuria, lesión renal aguda, hipertensión arterial e hipostenuria. En el análisis bivariado, un ecocardiograma anormal fue más frecuente en los pacientes con NF (84,8% vs 54,3% p = 0,01), así como tuvieron una tendencia a mayor uso de medicamentos nefrotóxicos (74,5% vs 54,2% p = 0,07).
Conclusiones:
Nuestros hallazgos sugieren que la nefropatía falciforme puede presentarse a tempra na edad, siendo muy frecuente la hiperfiltración glomerular. Las complicaciones cardiopulmonares en ACF se podrían asociar con la presencia NF.
... In SCD patients, not only overt hypertension is deleterious. Relative increments in systolic BP (resulting in elevated pulse pressure) have been associated with hemolysis and worse renal and cardiovascular outcomes, such as proteinuria, chronic kidney disease, pulmonary hypertension, diastolic heart dysfunction, stroke, and death [36,[38][39][40]. The term relative systemic hypertension (RSH) is currently being used to refer to SCD patients who do not present hypertension according to traditional criteria, but have increased risk for worse outcomes. ...
Sickle cell disease (SCD) is a hereditary condition characterized by homozygosis of the hemoglobin S (HbS) gene. Marked morbimortality is observed due to chronic hemolysis, endothelial injury, and episodes of vaso-occlusion, which leads to multi-organ damage. Renal impairment is common and may have different presentations, such as deficiency in urinary acidification or concentration, glomerulopathies, proteinuria, and hematuria, frequently resulting in end-stage renal disease (ESRD). Novel biomarkers of renal function, such as kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein 1 (MCP-1) are being studied in order to enable early diagnosis of kidney damage in SCD.
