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Vol. 24, No. 2-3, 2007
Issue release date: August 2007
Cerebrovasc Dis 2007;24:202–209

Effect of the Ca Antagonist Nilvadipine on Stroke Occurrence or Recurrence and Extension of Asymptomatic Cerebral Infarction in Hypertensive Patients with or without History of Stroke (PICA Study)

1. Design and Results at Enrollment

Shinohara Y. · Tohgi H. · Hirai S. · Terashi A. · Fukuuchi Y. · Yamaguchi T. · Okudera T.
aFederation of National Public Service Personnel Mutual Aid Associations, Tachikawa Hospital, and bNippon Medical School, Tokyo, cDepartment of Neurology, Iwate Medical University, Morioka, dDepartment of Neurology, Gunma University School of Medicine, Maebashi, eAshikaga Red Cross Hospital, Ashikaga, fNational Cardiovascular Center, Suita, gCenter for Higher Brain Dysfunction, Haradoi Hospital, Fukuoka, Japan

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Background: We examined the effect of a Ca antagonist (nilvadipine) on the occurrence or recurrence of symptomatic stroke in hypertensive patients with MRI-defined asymptomatic cerebral infarction (ACI), periventricular hyperintensity (PVH), and deep and subcortical white matter hyperintensity (DSWMH), with or without a history of stroke, and evaluated the effect of long-term treatment on the lesions. Methods: Patients with hypertension and incidental ACI were divided into those with (group B, 235 patients) or without (group A, 181 patients) a history of symptomatic stroke, and were given nilvadipine 4–8 mg/day for 3 years. Primary evaluation points were occurrence of symptomatic ischemic stroke and development or extension of asymptomatic ischemic lesions. Results: Male sex, hyperuricemia, diabetes, maximum diameter of infarction and PVH severity were stronger risk factors for group B. Numbers of cerebral infarctions were 31 ± 28 (group A) and 42 ± 32 (group B) at enrollment (p < 0.001). Infarctions were larger and located more frequently on the internal capsule, putamen, thalamus and brainstem in group B. The severity of PVH and DSWMH paralleled the number of cerebral infarctions in both groups. Conclusion: The study design and status of asymptomatic ischemic brain lesions in hypertensive subjects at enrollment are presented.

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  1. Longstreth WT, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR: Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. Arch Neurol 1998;55:1217–1225.
  2. Bryan RN, Wells SW, Miller TJ, Elster AD, Jungreis CA, Poirier VC, Lind BK, Manolio TA: Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly:- data from the Cardiovascular Health Study. Radiology 1997;202:47–54.
  3. Shimada K, Kawamoto A, Matsubayashi K, Ozawa T: Silent cerebrovascular diseases in the elderly: correlation with ambulatory pressure. Hypertension 1990;16:692–699.
  4. Kobayashi S, Okada K, Yamashita K: Incidence of silent lacunar lesion in normal adults and its relation to cerebral blood flow and risk factors. Stroke 1991;22:1379–1383.
  5. Shinkawa A, Ueda K, Kiyohara Y, Kato I, Sueishi K, Tsuneyoshi M, Fujishima M: Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study. Stroke 1995;26:380–385.
  6. Breteler MM, van Swieten JC, Bots ML, Grobbee DE, Claus JJ, van den Hout JH, van Harskamp F, Tanghe HL, de Jong PT, van Gijn J, Hofman A: Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: The Rotterdam Study. Neurology 1994;44:1246–1252.
  7. Kario K, Shimada K, Schwartz JE, Matsuo T, Hoshide S, Pickering TG: Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension. J Am Coll Cardiol 2001;38:238–245.
  8. Leary MC, Saver JL: Annual incidence of first silent stroke in the United States: a preliminary estimate. Cerebrovasc Dis 2003;16:280–285.
  9. Sugiyama T, Lee JD, Shimizu H, Abe S, Ueda T: Influence of treated blood pressure on progression of silent cerebral infarction. J Hypertens 1999;17:679–684.
  10. Bernick C, Kuller L, Dulberg C, Longstreth WT, Manolio T, Beauchamp N, Price T: Silent MRI infarcts and the risk of future stroke. The Cardiovascular Health Study. Neurology 2001;57:1222–1229.
  11. Namba A, Hamano H, Kitagawa Y, Shinohara Y: Asymptomatic cerebral ischemic lesions on MRI in patients with first-ever stroke: characteristic features and relation to risk factors in ischemic stroke. Jpn J Stroke 1997;19:389–396.

    External Resources

  12. Vermeer SE, Koudastaal PJ, Oudkerk M, Hofman A, Breteler MM: Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2002;33:21–25.
  13. Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MMB: Silent brain infarcts and white matter lesions increase stroke risk in the general population. The Rotterdam Scan Study. Stroke 2003;34:1126–1129.
  14. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal P, Breteler MMB: Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215–1222.
  15. Tokuma Y, Fujiwara T, Noguchi H: Absorption, distribution and excretion of nilvadipine, a new dihydropyridine calcium antagonist, in rats and dogs. Xenobiotica 1987;17:1341–1349.
  16. Ogasawara K, Noda A, Yasuda S, Kobayashi M, Yukawa H, Ogawa A: Effect of calcium antagonist on cerebral blood flow and oxygen metabolism in patients with hypertension and chronic major cerebral artery occlusion: a positron emission tomography study. Nucl Med Commun 2003;24:71–76.
  17. Ishibashi H, Murai Y, Akaike N: Effect of nilvadipine on the voltage-dependent Ca2+ channels in rat hippocampal CA1 pyramidal neurons. Brain Res 1998;813:121–127.
  18. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1993;153:154–183.
  19. Mäntylä R, Erkinjuntti T, Salonen O, Aronen HJ, Peltonen T, Pohjasvaara T, Standertskjöld-Nordenstam CG: Variable agreement between visual rating scales for white matter hyperintensities on MRI: comparison of 13 rating scales in a poststroke cohort. Stroke 1997;28:1614–1623.
  20. Hypertension Detection and Follow-up Program Cooperative Group: Five-year finding of the Hypertension Detection and Follow-Up Program: reduction in stroke incidence among persons with high blood pressure. JAMA 1982;247:633–638.

    External Resources

  21. Medical Research Council Working Party: MRC trial of treatment of mild hypertension: principal results. BMJ 1985;291:97–104.
  22. SHEP Cooperative Research Group: Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the systolic hypertension in the elderly program (SHEP). JAMA 1991;265:3255–3264.

    External Resources

  23. MRC Working Party: Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ 1992;304:405–412.
  24. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O’Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A: Randomized double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997;350:757–763.
  25. Liu L, Wang JG, Gong L, Liu G, Staessen JA: Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. J Hypertens 1998;16:1823–1829.
  26. Hypertension-Stroke Cooperative Study Group: Effect of antihypertensive treatment on stroke recurrence. JAMA 1974;229:409–418.

    External Resources

  27. PROGRESS Collaborative Group: Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001;358:1033–1041.
  28. Blood Pressure Lowering Treatment Trialists’ Collaboration: Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomized trials. Lancet 2000;356:1955–1964.
  29. Staessen JA, Wang JG, Thijs L: Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 2001;358:1305–1315.

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