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Blood pressure and the brain

2003; Elsevier BV; Volume: 143; Issue: 6 Linguagem: Inglês

10.1067/s0022-3476(03)00625-5

1097-6833

Thomas R. Welch, Nancy Roizen, Stephen R. Daniels,

Cardiac, Anesthesia and Surgical Outcomes

Severe hypertension has well known, severe neurologic consequences. Persons with established hypertension are at increased risk of stroke, and acute blood pressure (BP) elevation can provoke hypertensive encephalopathy. What is less clear, however, is whether hypertension or even more mild elevation of BP could cause more subtle neurologic disorders. A study in the current issue of The Journal by Lande et al suggests that this is possible.1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar The investigators used data available from the National Health and Nutrition Examination III (NHANES III) for their study. NHANES III included 5398 children between 6 and 16 years of age in its population of 40,000 persons. As part of the NHANES protocol, these persons underwent a physical examination that included careful, precise BP determination. They also underwent some specific tests of cognitive functioning. In three specific subtests (Block Design, Digit Span, math), performance of children with systolic BP >90th percentile for age was below that of those whose systolic BP was 90th percentile was associated with reduced performance in the Block Design subtest. When adjustment was made for a large number of potentially confounding variables, the deficit in Digit Span persisted. Moreover, there was a suggestion of a “dose-response” effect in that children with systolic BP >95th percentile performed somewhat worse than those between the 90th and 95th percentiles. The importance of the findings of Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar can be judged in part in the context of similar findings in adults. Elias et al2.Elias M.F. Elias P.K. Sullivan L.M. Wolf P.A. D'Agostino R.B. Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study.Int J Obesity. 2003; 27: 260-268Crossref Scopus (534) Google Scholar showed that in the Framingham Heart Study, obesity and hypertension were associated with lower cognitive function in men measured after four to six years. Investigators in the Atherosclerosis Risk in Communities study also found that partially controlled or uncontrolled hypertension was associated with a less favorable cognitive profile.3.Alves de Moraes S. Szklo M. Knopman D. Sato R. The relationship between temporal changes in blood pressure and changes in cognitive function: atherosclerosis risk in communities (ARIC) Study.Prev Med. 2002; 35: 258-263Crossref PubMed Scopus (34) Google Scholar Adult studies are mixed in their findings in constructional function such as that measured in Block Design and negative in relation to general intelligence and verbal skills.4.Waldstein S. Manuck S. Ryan C. Muldoon M. Neuropsychological correlates of hypertension: review and methodologic considerations.Psychologic Bull. 1991; 110: 451-468Crossref PubMed Scopus (189) Google Scholar There have also been studies in adults with hypertension evaluating the effect of treatment on cognitive function. Muldoon et al found that antihypertensive treatment with a variety of agents did not affect mood or anxiety.5.Muldoon M.F. Waldstein S. Ryan C.M. Jennings J.R. Polefrone J.M. Shapiro A.P. et al.Effects of six anti-hypertensive medications on cognitive performance.J Hypertens. 2002; 20: 1643-1652Crossref PubMed Scopus (53) Google Scholar All of the antihypertensive medications favorably affected performance on tests of memory. In contrast, antihypertensive medications regardless of class reduced simple motor speed and slowed completion of tests measuring perceptual motor speed and mental flexibility. Metoprolol treatment resulted in a decline of manual dexterity. These effects were observed over a six-week treatment period. Murray et al showed in a longitudinal study of older African American adults that the use of antihypertensive medication was associated with preservation of cognitive function.6.Murray M.D. Lane K.A. Gao S. Evans R.M. Unverzagt F.W. Hall K.S. et al.Preservation of cognitive function with antihypertensive medications: a longitudinal analysis of a community-based sample of African Americans.Arch Intern Med. 2002; 162: 2090-2096Crossref PubMed Scopus (147) Google Scholar What do the types of cognitive deficits recognized by Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar mean? On the Wechsler Intelligence Scale for Children–Revised, the Vocabulary subtest is considered most predictive of overall cognitive function, specifically verbal function. In this survey, the Digit Span subtest, a measure of short-term memory and attention, which is not included in the IQ score, was used. The Block Design subtest is generally considered the most representative of the performance subtests and measures constructional skills. The Wide Range Achievement Test–Revised tests reading decoding skills as opposed to reading comprehension and computational arithmetic skills. Of the four measures, only a decreased Digit Span showed an association with an elevated systolic BP. This is consistent with studies of adults that show decrements in memory, abstract reasoning, and attention related to hypertension. This study does not enable us to determine the impact or potential impact on the short- and long-term function in the classroom and outside the classroom. The relationship with decreased Digit Span is intriguing, because problems with memory and attention are of concern in relation to success in the classroom.7.Trapani C. Psychoeducational assessment of children and adolescents with attention deficit hyperactivity disorder.in: Accardo P.J. Blondis T.A. Whitman B.Y Attention deficits and hyperactivity in children and adults: diagnosis, treatment, management. 2nd ed. Marcel Dekker, Inc, New York2000: 197-214Google Scholar These data indicate the need for a study of the neuropsychologic functioning of children with hypertension that includes a more comprehensive battery of tests that enable us to understand the type of memory and attention functions that are sensitive to BP. Ideally, these should include useful verbal measures, especially vocabulary, and tests of the broad base of cognitive function. The mechanisms by which BP elevation may worsen cognitive function, and antihypertensive treatment may improve it, are not known. Some mechanisms that have been suggested are metabolic factors, altered distribution of blood flow, silent stroke, atherogenesis, and demyelinization. The study by Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar demonstrates that cognitive decline may also occur in younger persons with less severe BP elevation and without the vascular changes that may occur with aging. These results support the concept that factors other than atherosclerosis and stroke may be operational in the cognitive decline observed with elevated BP. It should be remembered that the 90th percentile was used to define BP elevation in this study. Although this cutpoint might be expected to define the upper 10% of the population, in the study of Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar only 3.4% of subjects had systolic BP >90th percentile and only 1.6% had diastolic BP >90th percentile. The reason why BPs from NHANES III were lower than those found in previous epidemiologic investigations that were used to generate the percentiles for BP is unclear.8.National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program.Pediatrics. 1996; 98: 649-658PubMed Google Scholar The findings of Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar suggest that the relationship between BP and cognitive function is continuous and may not have a threshold of BP beyond which cognitive function declines. This may be important as the cutpoints for BP elevation are considered in the future. In adults, the level of BP that indicates the need for treatment to prevent cardiovascular disease may be lower than previously thought.9.Vasan R. Larson M.G. Leip E.P. Evans J.C. O'Donnell C.J. Kannel W.B. et al.Impact of high-normal blood pressure on the risk of cardiovascular disease.N Engl J Med. 2001; 345: 1291-1297Crossref PubMed Scopus (1639) Google Scholar This has led to suggestions of more aggressive treatment of hypertension to achieve lower targets. Cognitive function is an important target for consideration of end-organ disease in children and adolescents. The results of Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar suggest that pediatricians may need to lower the threshold for consideration of BP elevation in the future. Efforts directed at prevention of BP elevation should also be considered. It is important to remember that this study did not include a clinical population with hypertension. Future studies will be needed to evaluate the extent to which those patients have a decline in cognitive function. It will be necessary to explore whether the level of BP, the duration of hypertension, or both, lead to a decline in cognitive function. Are some patients more prone to a decline in cognitive function than others? It will also be important to evaluate the extent to which treatment of hypertension improves cognitive function. Children with end-stage renal disease have long been recognized to have developmental and cognitive deficits. Although there are clearly multifactorial in this population of complex children, suboptimal BP must be added to the list of potential modifiable causes. The study of Lande et al1.Lande M.B. Kaczorowski J.M. Auinger P. Schwartz G.J. Weitzman M. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States.J Pediatr. 2003; 143: 720-724Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar provides a beginning to the understanding of these issues.