Prevalence of Pulmonary Hypertension and Renal Dysfunction by Systemic Blood Pressure Categories in Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3169-3169 ◽  
Author(s):  
Victor R. Gordeuk ◽  
Mark T. Gladwin ◽  
Gregory Kato ◽  
Oswaldo Castro
Keyword(s):  
Blood Pressure ◽  
Pulmonary Hypertension ◽  
Renal Dysfunction ◽  
Sickle Cell ◽  
Systemic Blood Pressure ◽  
Systemic Hypertension ◽  
Cell Disease ◽  
Systemic Blood ◽  
Creatinine Concentration ◽  
Increased Risk

Abstract In an emerging paradigm of sickle cell disease (SCD) vasculopathy, the risk for pulmonary and systemic hypertension, renal dysfunction, proteinuria, stroke and early death may be related to the degree of hemolysis, nitric oxide scavenging and resultant damage to the vasculature (JAMA2005;293:1653). The systemic blood pressure (BP) in sickle cell anemia (SS) is lower than in normal subjects. Yet, the concept of relative systemic hypertension has been proposed because SS pts. Have higher BP than subjects with other forms of congenital anemias (Am J Med Sci 1993). Furthermore, apparently minor BP increases in SS are associated with stroke risk (Am J Med Sci1993;305:150, Am J Med1997;102:171). We hypothesized that in contrast to otherwise healthy individuals without SCD, systolic blood pressures (sBP) of 120 to 139 mm Hg define relative hypertension in SCD and identify patients at increased risk for vasculopathy and its complications. We analyzed entry data from 195 adult patients enrolled in the prospective Sickle Cell Pulmonary Hypertension Screening Study (NEJM2004;350:886), and stratified their ECHO-determined tricuspid regurgitant jet velocity (TRV) and serum creatinine concentration according to sBP categories. As shown in Figure 1, among Hb SS and S beta thal patients, the prevalence of pulmonary hypertension (PHTN, TRV 2.5 m/sec or greater) was 26% with sBP <120 mm Hg, 36% with sBP 120–139 mm Hg and 89% with sBP 140 mm Hg or higher (P <0.0005 for trend). Similarly, the prevalence of a serum creatinine concentration of 1.0 mg/dL or higher was 7% with sBP <120 mm Hg, 13% with sBP 120–139 mm Hg and 30% with sBP 140 mm Hg or higher (P = 0.002 for trend, Figure 2). The increasing prevalences of PHTN and renal dysfunction with the three progressively higher sBP categories are consistent with our hypothesis that sBP 120–139 represents relative hypertension and increased risk for vascular complications in patients with SCD. Whether treatment of relative hypertension in sickle patients would improve vasculopathy and lower their risk for PHTN, renal impairment or other complications such as stroke, is unknown. Consideration should be given to clinical trials to answer this important question. Figure Figure Figure Figure

Arginine Metabolite Profiling in Sickle Cell Disease: Abnormal Levels and Correlations with Pulmonary Hypertension, Desaturation, Hemolysis and Organ Dysfunction.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1205-1205
Author(s):  
Gregory J. Kato ◽  
Wang Zeneng ◽  
James G. Taylor ◽  
Roberto F. Machado ◽  
William C. Blackwelder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Renal Dysfunction ◽  
Sickle Cell ◽  
Early Mortality ◽  
Systemic Hypertension ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Arginine Transport

Abstract Pulmonary arterial hypertension (PAH) in patients with sickle cell disease (SCD) is linked to intravascular hemolysis, renal dysfunction, systolic hypertension, cholestasis, and early mortality. Although the pathophysiology of PAH in SCD is multifactorial, one important and fundamental factor is impaired nitric oxide bioavailability. Severe intravascular hemolysis releases hemoglobin and arginase into blood plasma, leading to consumption of nitric oxide and its plasma precursor L-arginine, the obligate substrate for the nitric oxide synthases (NOS). In order to explore other potential alterations in the arginine pathway that might affect arginine bioavailability and nitric oxide production, we used high-performance liquid chromatography-tandem mass spectrometry to determine the plasma concentrations for several key metabolites that may affect NOS activity or arginine transport: asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-L-arginine (MMA), and N-ω-hydroxy-L-arginine (NOHA). Plasma levels of ADMA, SDMA and MMA are significantly higher in all forms of SCD than in healthy African American control subjects (Table 1). NOHA, the intermediate species in nitric oxide synthesis from L-arginine, is significantly lower in sickle-β-thalassemia (Sβ-thal) patients and homozygous SCD (SS). L-arginine levels are significantly lower in all forms of SCD, as previously reported. PAH as assessed by echocardiography screening was correlated to SDMA (r=0.30, p<0.0001) and NOHA (r=0.23, p=0.002). Similar correlations were observed to NT-proBNP, another marker of PAH. Low oxygen saturations were linked to high levels of all four arginine metabolites. ADMA levels were elevated with severe hemolysis, and unexpectedly lower with renal dysfunction. Levels of SDMA and NOHA were significantly related to renal dysfunction (p<0.01), with an additional link of NOHA to systemic hypertension (p<0.001). In addition, Cox proportional hazard analysis showed a relationship of the arginine/SDMA ratio to early mortality (p<0.001). In summary, levels of the endogenous NOS inhibitor ADMA are highly elevated in SCD and linked to hemolysis, and may contribute to hemolysis-associated endothelial dysfunction. The levels of SDMA, a competitive inhibitor of arginine transport and intracellular bioavailability, are also elevated and linked to PAH, desaturation, renal dysfunction and early mortality risk. The low levels of arginine and NOHA in SCD are consistent with low substrate availability for NOS, and may also limit NO production. The role of arginine metabolites in dysregulation of the arginine-nitric oxide axis and pulmonary hypertension in SCD merits further investigation. Table 1. Arginine Metabolites in Sickle Cell Disease compared to controls. Metabolite Control (n=29) SC (n=34) Sβ-thal (n=11) SS (n=130) Values indicate median values in μM. *p<0.05; **p<0.01; ***p<0.001, Mann-Whitney test compared to controls. ADMA 0.31 0.82*** 0.92* 0.99*** SDMA 0.83 0.92* 1.03** 1.03*** MMA 0.13 0.15* 0.20** 0.18*** NOHA 2.50 2.23 2.15* 1.80** L-Arginine 78.3 51.5*** 41.6*** 45.5***

Prevalence of Relative Systemic Hypertension in Ghanaian Adults with Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3409-3409
Author(s):  
Amma A. Benneh ◽  
Amma T. Owusu-Ansah ◽  
Fredericka Sey ◽  
Mary A. Ampomah ◽  
Edeghonghon Olayemi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Significant Positive Correlation ◽  
Systemic Hypertension ◽  
Leg Ulcers ◽  
Cell Disease ◽  
Vascular Disorders ◽  
Positive Correlation ◽  
Increased Risk

Abstract Introduction: Sickle cell disease (SCD) is associated with an increased risk of premature death in adults. Relative systemic hypertension (RSH) is associated with increased risk of vascular disorders in SCD. While drugs targeting RSH may halt the development of sickle vascular disorders, the magnitude of this problem is unknown in many countries, including in Ghana, which has ~2% incidence rate of SCD. In this study, we examined the prevalence of relative hypertension in an adult SCD patient population of the Ghana Institute of Clinical Genetics (GICG), Korle-Bu, Accra, Ghana and described their demographic characteristics, genotypes and complications. Methods: With institutional ethics committee approval, we conducted a retrospective chart review of 1000 adults aged ≥ 18 years with SCD receiving regular care at the GICG. Charts were selected as patients visited the clinic for routine care over a ten month period. SCD patients 18 years or older who had 3 blood pressure (BP) measurements on separate clinic visits for at least one year were eligible for the study. RSH was defined as systolic BP (SBP) 120 mmHg to 139 mmHg and diastolic blood pressure (DBP) 70 mmHg to 89 mmHg on at least two consecutive routine visits or visits for mild illness. We collected data on demographics, genotypes, the three most recent consecutive BPs, blood counts done on days the BPs were recorded and documented complications of SCD. A data extraction manual was used to reduce inter-observer variability. Descriptive statistics were used for data analysis. The prevalence of relative systemic hypertension in the group was calculated. Results: There were 873 eligible cases involving 319 males (36.5%) and 554 females (63.5%). Homozygous SCD (SS) and Heterozygosity for sickle cell and hemoglobin D disease accounted for 56.9% of cases, Hb SC 39% and other genotypes (e.g. S-Beta Thalassemia, Hb SF) 4%. The overall prevalence of RSH was 40.4%; Hb SS 35.8% and Hb SC 47.7%. Among the 353 patients with RSH, 145 (41.1%) were male, and 208 (58.9%) were female. The predominant genotypes in the RSH group were SS (50.4%) and SC 46.2%. Other genotypes accounted for 3.4%. Median systolic BP (SBP) for the entire cohort was 116.6 (range 86.6 - 171.1) mmHg, and the median diastolic BP (DBP) was 70.3 (range 48 to 113.6) mmHg. Median blood pressures were higher in patients with Hb SC (males: 123/75, females: 122/76 mmHg) than those with Hb SS (males: 117.6/67, females 111/67mmHg). Complications were noted as follows; avascular necrosis (6.9%), other bone disease (1.1%) leg ulcers (6.3%), cholelithiasis (3.7%), cardiopulmonary 1%, and renal 1%. Pearson correlation coefficient showed associations between blood pressure, age, hemoglobin (Hb), and WBC. There was a positive correlation between SBP and age (r = 0.088, p = 0.009) and total Hb (r = 0.106, p = 0.002). Spearson's correlation revealed significant positive correlation between SBP and leg ulcers (r = 0.074, p ≤ 0.05); DBP and leg ulcers (r = 0.119, p ≤0.01); DBP and priapism (r = 0.075, p =0.026) and DBP and cholelithiasis (r = 0 .086, p=0.011). Conclusions: There is a 40.4% prevalence of RSH, which to the best of our knowledge represents the first estimate of this condition in the Ghanaian adult SCD population. The prevalence among Hb SS patients is 35.8% compared to the 44% previously reported in the US. There is significant positive correlation of BP with Hb, leg ulcers, priapism and cholelithiasis. Future prospective studies using standardized BP monitoring are warranted to validate preemptive treatment of RSH in SCD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Decades after the cooperative study: A re-examination of systemic blood pressure in sickle cell disease

2012 ◽  
Vol 87 (10) ◽  
pp. E65-E68 ◽  
Author(s):  
Payal C. Desai ◽  
Allison M. Deal ◽  
Julia E. Brittain ◽  
Susan Jones ◽  
Alan Hinderliter ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Systemic Blood Pressure ◽  
Cooperative Study ◽  
Cell Disease ◽  
Systemic Blood

scholarly journals Pulmonary hypertension in sickle cell disease: diagnosis and management

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 425-431 ◽  
Author(s):  
Kenneth I. Ataga ◽  
Elizabeth S. Klings
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Disease Diagnosis ◽  
Adult Patients ◽  
Heart Catheterization ◽  
Cell Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
High Prevalence

Abstract The increased survival of patients with sickle cell disease (SCD) into adulthood is associated with an increased incidence of multiorgan dysfunction and a progressive systemic and pulmonary vasculopathy. The high prevalence of an elevated tricuspid regurgitant jet velocity and its association with an increased risk of death in adult patients is well established. However, there has been controversy regarding the prevalence of pulmonary hypertension (PH) and its association with mortality in SCD. Multiple recently published reports demonstrate that PH as diagnosed by right heart catheterization is common in adult SCD patients, with a prevalence of 6%–11%. Furthermore, PH is associated with an increased risk of death in SCD patients. In this chapter, we provide evidence for the high prevalence of PH in SCD and its association with mortality and make recommendations for its evaluation and management. Finally, we provide the rationale for screening for this life-threatening complication in adult patients with SCD.

scholarly journals Intraocular pressure in postmenopausal Nigerian women with and without systemic hypertension

2011 ◽  
Vol 70 (3) ◽  
Author(s):  
J. A. Ebeigbe ◽  
P. N. Ebeigbe ◽  
A. D. A Ighoroje
Keyword(s):  
Blood Pressure ◽  
Intraocular Pressure ◽  
Postmenopausal Women ◽  
Systemic Blood Pressure ◽  
Systemic Hypertension ◽  
Systemic Blood ◽  
Nigerian Women ◽  
The Difference ◽  
Post Menopausal ◽  
The Right

Background: Mean intraocular pressure (IOP) in postmenopausal women has been reported higher than that in menstruating women. Also, intraocular pressure is said to be positively correlated with systemic blood pressure. No previous study in Nigeria has compared intraocular pressure in postmenopausal women with and without systemic hypertension. Purpose: To investigate the effects of menopause on intraocular pressure in subjects with and without high blood pressure. Methods: Normotensive and hypertensive premenopausal and postmenopausal subjects in the   same agerange of 45 to 55 years were studied. Intraocular pressure was measured with the hand-held Kowa applanation tonometer.  Blood pressure was taken in the sitting position at the right upper arm using a manual mercury sphygmomanometer with the right cuff size. The average of two readings was recorded. Results: Mean IOP for premenopausal normotensive women was 14.58 ± 2.56 mmHg whilethat of postmenopausal normotensive women was16.15 ± 1.80 mmHg (p<0.05).  Also, the difference in mean IOP between premenopausal hypertensive (16.58 ± 3.23 mmHg) and postmenopausal hypertensive women (18.24 ± 3.89 mmHg)was statistically significant (p<0.05). A statistically significant and positive correlation was observed between IOP and systemic blood pressure in postmenopausal hypertensive women, p<0.05.Conclusion: Menopause significantly increases intraocular pressure. Mean intraocular pressure of hypertensive postmenopausal women was significantly higher than that of normotensive post-menopausal women, (p<0.05). Knowledge of the normal level of intraocular pressure during various stages of the female reproductive cycle may help during glaucoma screening. (S Afr Optom 2011 70(3) 117-122)

Pulmonary Hypertension Is Not Associated with An Increased Risk of Death in Children with Sickle-Cell Disease Followed for a Mean of 3 Years.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1443-1443
Author(s):  
Margaret T. Lee ◽  
Tania Small ◽  
Muhammad Amar Khan ◽  
Erika Berman Rosenzweig ◽  
Robyn J. Barst ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Pulmonary Hypertension ◽  
Platelet Count ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of

Abstract To determine if pulmonary hypertension (PH) is associated with increased mortality in children with sickle-cell disease (SCD), we prospectively followed 88 pediatric patients for a mean of 3 years after echocardiographic screening for PH. Subjects (45 males, 43 females) were 5–20 years old (median 13) at initial screening and included 59 SS, 23 SC, 4 S/β0Thalassemia, 1 S/β+Thalassemia and 1 S/HPFH. PH was defined as tricuscipid regurgitant jet velocity (TRV) of ³2.5 m/s. Of the 88 subjects, 18 (20%) had TRV ³2.5 m/s (median 2.6, range 2.5–3.1). Subjects with PH ranged from 7 to 19 years old (median 15), were predominantly male (12 of 18) and included 14 (78%) SS, 2 SC, 2 S/β0Thalassemia. After a mean follow-up of 36.3 ± 9.4 (SD) months, all 18 patients with PH were alive. None had received specific treatment for PH; one had undergone a successful bone marrow transplant from a matched sibling donor. After a mean follow-up of 33.5 ± 13.3 months, 67 subjects with normal TRV were alive; 3 had been lost to follow-up. To compare risk factors for PH in our children with those reported for adults, we reviewed the clinical data for our subjects. Children with PH had significantly increased serum lactate dehydrogenase (LDH; P=0.04), higher platelet count (P=0.02), and, in males, a history of priapism (P=0.009). No significant differences were observed with respect to age, gender, sickle-cell type, white blood cell count, hemoglobin, reticulocyte count, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, ferritin, history of painful crisis, acute chest syndrome, asthma, splenectomy, or hydroxyurea therapy. To further examine the association of PH and hemolysis, a subanalysis was done excluding 18 chronically transfused patients because transfusion can alter laboratory indicators of hemolysis. Independent variables with P≤0.1 on univariate analysis (LDH, female gender, and platelet count) were entered into a logistic regression model. Only LDH was independently associated with PH (Odds Ratio=1.6, 95% CI=1.2–2.1, P=0.004). Our results show that PH diagnosed by Doppler echocardiography was not associated with an increased risk of death in children with SCD followed for a mean of 3 years. A greatly increased risk of death (rate ratio, 10.1) has been reported in adults followed for a mean of 1.5 years (N Eng J Med2004;350:886–95). In our children, as in the adults, increased LDH, a marker of hemolysis, and, in males, a history of priapism were associated with PH. By contrast, our children with PH did not have increases in serum creatinine, direct bilirubin, alkaline phosphatase and ferritin that have been linked epidemiologically to PH in adults with SCD (Pediatr Hematol Onc2007;24:159–70). These findings suggest that PH of itself may not be a direct cause of death in SCD. Rather, PH may be a manifestation of progressive, cumulative organ damage resulting from chronic hemolysis and systemic vasculopathy that ultimately leads to increased mortality in adulthood. Early recognition and preventive therapy for increased hemolysis may be needed to avert premature death in adults with SCD.

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