Correspondence

Mortality in Sickle Cell Disease

N Engl J Med 1994; 331:1022-1023October 13, 1994

Article

To the Editor:

The article by Platt et al. (June 9 issue)1 described the risk factors associated with early death in patients with sickle cell disease -- specifically, they found that, of the 69 “healthy” patients with sickle cell anemia who died, approximately 22 percent had acute strokes. Recently, we reported that “relative” hypertension, defined by patient-based normative standards in a group of 89 patients homozygous for sickle cell disease, was significantly associated with stroke in patients older than 20 years of age.2 The elevated blood pressure in this group was in a range that would be considered normal on the basis of conventional standards, though inappropriately high on the basis of hemodynamic adjustments that had probably occurred as a result of the presence of chronic anemia; hence, the term “relative hypertension.”

Several clinical observations support the existence of relative hypertension in patients with sickle cell disease. First, concentric left ventricular hypertrophy, a frequent finding in long-standing hypertension, has been documented by echocardiography in up to 50 percent of unselected patients with hemoglobin SS or SC disease.3 Second, arteriolar vasoconstriction contributes to the pathogenesis of sickle cell retinopathy and nephropathy -- processes that have been shown to be ameliorated by calcium-channel blockers4 or angiotensin-converting-enzyme inhibitors.5 Finally, with a prevalence of hypertension among blacks of 20 to 25 percent,6 it would be anticipated that a sizable proportion of patients with sickle cell disease would be at risk for inheriting the putative genetic determinants for hypertension.

If the occurrence of relative hypertension can be substantiated in the analysis of larger populations, such as those in the Cooperative Study of Sickle Cell Disease,1 this factor should be tested for its contributions to the morbidity and mortality associated with the sickle cell syndromes. Abnormal blood pressure in this clinical context would provide the rationale for considering interventions aimed at normalizing the blood pressure, which might make a novel contribution to the treatment of these disorders.

Griffin P. Rodgers, M.D.
Elijah C. Walker, M.Sc.
Marvin J. Podgor, Ph.D.
National Institutes of Health, Bethesda, MD 20892

6 References

1. 1

   Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease -- life expectancy and risk factors for early death. N Engl J Med 1994;330:1639-1644
   Full Text | Web of Science | Medline

2. 2

   Rodgers GP, Walker EC, Podgor MJ. Is “relative” hypertension a risk factor for vaso-occlusive complications in sickle cell disease? Am J Med Sci 1993;305:150-156
   CrossRef | Web of Science | Medline

3. 3

   Lippman SM, Niemann JT, Thigpen T, Ginzton LE, Laks MM. Abnormal septal Q waves in sickle cell disease: prevalence and causative factors. Chest 1985;88:543-548
   CrossRef | Web of Science | Medline

4. 4

   Rodgers GP, Roy MS, Noguchi CT, Schechter AN. Is there a role for selective vasodilation in the management of sickle cell disease? Blood 1988;71:597-602
   Web of Science | Medline

5. 5

   Falk RJ, Scheinman J, Phillips G, Orringer E, Johnson A, Jennette JC. Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme. N Engl J Med 1992;326:910-915
   Full Text | Web of Science | Medline

6. 6

   Saunders E. Hypertension in blacks. Med Clin North Am 1987;71:1013-1029
   Web of Science | Medline

Author/Editor Response

Dr. Platt replies:

To the Editor: My colleagues and I agree with the comments concerning the importance of blood pressure as a potential risk factor for morbidity and mortality in sickle cell disease. This is an important area of investigation for the Cooperative Study of Sickle Cell Disease, which has issued a preliminary report on the age, sex, and hemoglobinopathy-specific normative data for the study group of over 4000 patients.1 We anticipate that the definitive analysis, including examination of risk factors for hypertension and hypotension and risk factors associated with these conditions, will be available soon.

Orah S. Platt, M.D.
Children's Hospital, Boston, MA 02115

1 References

1. 1

   Pegelow CH, Phillips G, Wright F. Blood pressure (BP) in sickle cell disease (SCD). Blood 1993;82:Suppl 1:473a-473a abstract.
   Web of Science

Citing Articles (2)

Citing Articles

1. 1

   Rajinder Prasad, Syed Hasan, Oswaldo Castro, Elliott Perlin, Kyungsook Kim. (2003) Long-Term Outcomes in Patients with Sickle Cell Disease and Frequent Vaso-Occlusive Crises. The American Journal of the Medical Sciences 325:3, 107-109
   CrossRef

2. 2

   L Foucan. (1998) A Randomized Trial of Captopril for Microalbuminuria in Normotensive Adults with Sickle Cell Anemia. The American Journal of Medicine 104:4, 339-342
   CrossRef