Haptoglobin Phenotype Correlates with the Extent of Cerebral Deep White Matter Lesions in Hypertensive Patients

Julie      Staals; Leon   H.G.   Henskens; Joris   R.   Delanghe; Robert   J.   van Oostenbrugge; Alfons   G.   Kessels; Abraham   A.   Kroon; Peter   W.   de Leeuw; Jan      Lodder

Abstract

Cerebral white matter lesions (WMLs), due to small vessel disease, can be regarded as an early “silent” sign of hypertensive cerebral end-organ damage. As haptoglobin (Hp) phenotype has earlier been associated with symptomatic vascular disease, we now examined the relationship between Hp phenotype and asymptomatic cerebral small vessel disease, manifested by deep and periventricular WMLs, in hypertensive patients. We determined Hp phenotype using starch gel electrophoresis in 152 hypertensive patients without symptomatic vascular disease. We found 26 (17.1%) Hp1-1, 89 (58.6%) Hp2-1 and 37 (24.3%) Hp2-2. Volumes of deep and periventricular WMLs were quantitatively measured on brain MR images. Patients were ranked in 5 categories according to ascending WMLs volumes. Compared to Hp2-2, Hp1-1 was associated with larger deep WMLs volumes when adjusted for age, gender, brain volume, 24-hour mean arterial pressure, duration of hypertension and previous antihypertensive treatment (ordinal regression analysis, OR 2.77, 95%CI 1.08-7.11, p=0.034). No association was found between Hp phenotype and periventricular WMLs. Hp1-1 phenotype correlates with the extent ofhypertensive deep white matter damage. One of the possibilities is that this is related to lower regenerating power against endothelial injury in Hp1-1 individuals.

Keywords: Cerebrovascular disease, haptoglobin phenotype, hypertension, small vessel disease, white matter lesions