Cognition Improvement in Taekwondo Novices Over 40. Results from the SEKWONDO Study.

Age-related cognitive decline is associated with increased risk of disability, dementia, and death. Recent studies suggest improvement in cognitive speed, attention, and executive functioning with physical activity. However, whether such improvements are activity specific is unclear. Therefore, we aimed to study the effect of 1 year age-adapted Taekwondo training on several cognitive functions, including reaction/motor time, information processing speed, and working and executive memory, in 24 healthy volunteers over 40. Reaction and motor time decreased with 41.2 and 18.4 s (p = 0.004, p = 0.015), respectively. Digit symbol coding task improved with a mean of 3.7 digits (p = 0.017). Digit span, letter fluency, and trail making test task-completion-time all improved, but not statistically significant. The questionnaire reported "better" reaction time in 10 and "unchanged" in 9 of the 19 study compliers. In conclusion, our data suggest that age-adapted Taekwondo training improves various aspects of cognitive function in people over 40, which may, therefore, offer a cheap, safe, and enjoyable way to mitigate age-related cognitive decline.

Higher ambulatory blood pressure relates to enlarged Virchow-Robin spaces in first-ever lacunar stroke patients.

Enlarged Virchow-Robin spaces (EVRS) are considered to be a sign of cerebral small vessel disease. Hypertension is an important risk factor for cerebral small vessel disease, whereas ambulatory blood pressure (BP) is the strongest predictor of hypertension-related brain damage. However, the association between ambulatory BP levels and EVRS has never been investigated. The aim of this study was to determine the association between ambulatory BP levels and EVRS. In 143 first-ever lacunar stroke patients, we performed 24-h ambulatory BP monitoring after the acute stroke phase. On brain MRI we counted EVRS in the basal ganglia and the centrum semiovale. We graded the number of EVRS at each level into a three-category severity scale. We assessed the association between BP levels and EVRS by ordinal regression analysis. After adjusting for age, sex, extensive white matter lesions, and asymptomatic lacunar infarcts, higher day systolic (OR 1.21; 95 % CI 1.00-1.46 per 10 mmHg), day diastolic (1.18; 95 % CI 1.02-1.37 per 5 mmHg) and 24-h diastolic (OR 1.18; 95 % CI 1.01-1.37 per 5 mmHg) ambulatory BP levels were associated with EVRS at the basal ganglia level. No relation was found between ambulatory BP levels and EVRS in the centrum semiovale. Higher day ambulatory BP levels are associated with EVRS in the basal ganglia. This association was independent of the presence of extensive white matter lesions and asymptomatic lacunar infarcts. Our results imply that basal ganglia EVRS should be regarded as a separate manifestation of BP-related brain damage.

Vascular inflammation in cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is considered to be caused by an increased permeability of the blood-brain barrier and results in enlargement of Virchow Robin spaces (VRs), white matter lesions, brain microbleeds, and lacunar infarcts. The increased permeability of the blood-brain barrier may relate to endothelial cell activation and activated monocytes/macrophages. Therefore, we hypothesized that plasma markers of endothelial activation (adhesion molecules) and monocyte/macrophage activation (neopterin) relate to CSVD manifestations. In 163 first-ever lacunar stroke patients and 183 essential hypertensive patients, we assessed CSVD manifestations on brain magnetic resonance imaging (MRI) and levels of C-reactive protein (CRP), neopterin, as well as circulating soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin). Neopterin, sICAM-1 and sVCAM-1 levels were higher in patients with extensive CSVD manifestations than in those without (p < 0.01). Neopterin levels independently related to higher numbers of enlarged Virchow Robin spaces (p < 0.001). An inflammatory process with activated monocytes/macrophages may play a role in the increased permeability of the blood brain barrier in patients with CSVD.

Angiogenic T-cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) may be caused by endothelial dysfunction, whereas endothelial progenitor cells (EPC) may attenuate endothelial dysfunction. Their vitality is lower in CSVD. A subset of lymphocytes, angiogenic T-cells, is capable to stimulate EPC function. The purpose of our study was to explore the relation between CSVD manifestations, angiogenic T-cells, and EPC in hypertensive patients with CSVD. METHODS: We compared 32 essential hypertensive patients with CSVD (white matter lesions, asymptomatic lacunar infarcts, or microbleeds on 1.5-Tesla MRI) to 29 age-matched and sex-matched hypertensive controls. We counted angiogenic T-cells (CD3(+)/CD31(+)/CD184(+)) and putative EPC (CD31(+)/CD34(+)/CD45(-)/KDR(+)) by flow cytometry and determined EPC vitality by in vitro cluster formation. RESULTS: Putative EPC numbers were lower in hypertensive individuals with CSVD than in those without (10±7(.)10(3)/mL versus 13±6(.)10(3)/mL [median±interquartile range]; P=0.011). Angiogenic T-cell numbers were also lower in hypertensive individuals with CSVD than in those without (0.56±0.25(.)10(9)/mL versus 0.78±0.50(.)10(9)/mL; P=0.008). Higher angiogenic T-cell numbers independently related to absence of CSVD (odds ratio, 0.088; 95% confidence interval, 0.012-0.627). CONCLUSIONS: Our data suggest that angiogenic T-cells and putative EPC independently relate to radiological CSVD manifestations in hypertensive patients.

Estimating the magnitude of genetic factors by calculating the genetic relative risk of stroke in first-ever lacunar stroke patients.

BACKGROUND: Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke. METHODS: By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated. PRINCIPAL FINDINGS: We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45-3.53) for overall first-degree relatives, 4.52 (95%CI 3.61-5.65) for patients' parents and 2.10 (95%CI 1.63-2.69) for patients' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size. CONCLUSIONS: We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke.

Family history of stroke is an independent risk factor for lacunar stroke subtype with asymptomatic lacunar infarcts at younger ages.

BACKGROUND AND PURPOSE: Results from case-control and case-case studies indicate that a positive family history of stroke (FHstroke) is an independent risk factor for lacunar stroke. Different lacunar stroke phenotypes can be distinguished on the basis of the presence of asymptomatic lacunar infarcts (aLACs), ischemic white-matter lesions, or brain microbleeds. The aim of the present study was to determine whether familial aggregation of stroke was different for lacunar stroke phenotypes. METHODS: In 157 patients with a first-ever lacunar stroke, a complete first-degree FHstroke was obtained by a standardized questionnaire and additional interview. Lacunar stroke patients were categorized successively into groups, depending on the presence of aLACs, ischemic white-matter lesions, and brain microbleeds on magnetic resonance imaging. RESULTS: Fifty-two percent of patients reported a positive FHstroke in at least one of their first-degree relatives. In younger (<65 years) probands, a high frequency of parental FHstroke (59% versus 20%, P<0.01) in those with aLACs compared with probands without aLACs was found. In multivariate analysis, the strongest associations were found for parental FHstroke (odds ratio=6.46; 95% CI=1.96 to 21.33), maternal FHstroke (odds ratio=4.00; 95% CI=1.18 to 13.56), and paternal FHstroke (odds ratio=5.40; 95% CI=1.14 to 25.61). CONCLUSIONS: A family history of stroke might be an independent risk factor for the lacunar stroke phenotype with aLACs at younger ages, suggesting a role for genetic factors in this phenotype caused by diffuse vasculopathy.

Subjective sleep disturbance increases the nocturnal blood pressure level and attenuates the correlation with target-organ damage.

OBJECTIVE: We aimed to investigate whether subjective sleep disturbance during overnight blood pressure (BP) monitoring results in higher night-time BP levels, and whether this affects the correlation between nocturnal BP and hypertensive target-organ damage. METHODS: In 203 untreated hypertensive patients (104 men) without a history of cardiovascular disease, with a mean age of 52.1 ± 12.5 years, and with office BP levels of 170 ± 23/104 ± 12 mmHg, we performed duplicate ambulatory BP monitoring (ABPM), assessed subjective sleep quality using the Groningen Sleep Quality Scale, and obtained information on hypertension-related cardiac damage by echocardiography. RESULTS: Overnight BP monitoring disturbed sleep significantly, but habituation to nocturnal measurements occurred on the second ABPM. Participants whose subjective sleep quality was less than usual on either ABPM did not have higher nocturnal BP levels than those who slept similar to usual (P > 0.05). When comparing the nocturnal BP levels between the first and second ABPM, we found that participants whose subjective sleep quality was less on the second ABPM had significantly higher pressure levels and a smaller BP dip than participants with a similar sleep quality for both ABPMs (P < 0.05). Accordingly, the correlations between the nocturnal BP and cardiac damage tended to be weaker based on the ABPM with the lowest sleep quality. CONCLUSIONS: Subjectively assessed sleep disturbance during overnight BP monitoring increases the nocturnal BP level and potentially attenuates the correlation with hypertension-related cardiac damage, even though habituation to overnight BP monitoring occurs.

Autoantibodies against oxidized low-density lipoprotein in cerebral small vessel disease.

BACKGROUND AND PURPOSE: Oxidized low-density lipoprotein (oxLDL) induces endothelial dysfunction and antibody formation. Because endothelial dysfunction is involved in cerebral small vessel disease (CSVD) (dilated Virchow Robin spaces, lacunar infarcts, and white matter lesions), oxLDL antibodies could play a role in CSVD pathogenesis. Therefore, we studied oxLDL antibodies in patients with high prevalence of CSVD: lacunar stroke patients and essential hypertensive patients. METHODS: A total of 158 lacunar stroke patients, 158 hypertensive patients, and 43 healthy controls were included. We determined levels of IgG and IgM against hypochlorite (HOCl) and malondialdehyde (MDA) oxLDL using ELISA (values in optical density). RESULTS: Patients with CSVD had higher levels of IgG-HOCl-oxLDL (0.77 versus 0.70; P<0.01), as well as lower levels of IgM-MDA-oxLDL (0.55 versus 0.65; P<0.05) than patients without such lesions. Higher IgG-HOCl-oxLDL levels were only independently associated with higher numbers of Virchow Robin spaces at the level of the basal ganglia (ß=0.218; P<0.001). CONCLUSIONS: An autoinflammatory process with lower levels of IgM antibodies and higher levels of IgG antibodies against oxLDL may be involved in CSVD.

Endothelial activation in lacunar stroke subtypes.

BACKGROUND AND PURPOSE: Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients. METHODS: In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA-PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors. RESULTS: In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA; P=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA; P=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98-1.00 per ng/mL change of PAI-1; P=0.04). CONCLUSIONS: We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.

Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: case report.

BACKGROUND: The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial. CASE PRESENTATION: We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved. CONCLUSIONS: This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.

The likelihood of decreasing strokes in atrial fibrillation patients by strict application of guidelines.

AIMS: Despite the known increased stroke risk associated with AF and the benefit of oral anticoagulation (OAC) in high-risk patients, still approximately 20% of all ischaemic strokes are atrial fibrillation (AF) related. We aimed to evaluate the frequency of inappropriate anticoagulation in all patients admitted with AF associated ischaemic stroke and calculate the theoretical number of preventable strokes in case of proper guideline adherence and assess secondary stroke prevention at discharge. METHODS AND RESULTS: In this cross-sectional study, all patients with ischaemic strokes admitted to our hospital during May 2003-August 2006 in whom the diagnosis AF was either known or established during hospital stay were identified. We studied if their admission and discharge antithrombotic therapy was in accordance with the published guidelines. Subsequently, we calculated the number of preventable strokes in case AF patients would have received adequate antithrombotic treatment on admission. On admission, in 51% of the OAC eligible known AF patients the drug was withheld. Improved antithrombotic guideline adherence potentially would have prevented 20 out of the 89 (22%) ischaemic strokes. At discharge at least 10% of the patients were still insufficiently protected against recurrent stroke. CONCLUSION: Many known AF patients admitted with ischaemic stroke lack adequate antithrombotic treatment on admission. Antithrombotic guideline adherence in these patients has the potential to prevent a substantial number strokes. Secondary stroke prevention at discharge is also suboptimal.

An unusual cause of transient neurologic deficits: compression of the carotid artery by a thyroid cystic nodule.

We report a case of a 93-year-old man, who presented with limb-shaking transient ischemic attacks (TIAs) after orthostatic position change or turning his head to the left. The limb-shaking TIAs resulted from external compression of the carotid artery. Contrast-enhanced magnetic resonance angiography of the head and neck and Doppler ultrasound examination of the thyroid gland revealed a large cystic nodule in the right thyroid lobe, resulting in compression and posterior displacement of the right common carotid artery. Clinicians should be aware that limb-shaking TIAs can not only result from obstructive extracerebral or intracerebral artery disease, but also from external compression of the carotid artery.

Haptoglobin phenotype correlates with the extent of cerebral deep white matter lesions in hypertensive patients.

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 of hypertensive deep white matter damage. One of the possibilities is that this is related to lower regenerating power against endothelial injury in Hp1-1 individuals.

Brain microbleeds relate to higher ambulatory blood pressure levels in first-ever lacunar stroke patients.

BACKGROUND AND PURPOSE: Hypertension is an important risk factor for brain microbleeds (BMBs) in lacunar stroke patients. However, beyond the qualitative label "hypertension," little is known about the association with ambulatory blood pressure (BP) levels. METHODS: In 123 first-ever lacunar stroke patients we performed 24-hour ambulatory BP monitoring after the acute stroke-phase. We counted BMBs on T2*-weighted gradient-echo MR images. Because a different etiology for BMBs according to location has been suggested, we distinguished between BMBs in deep and lobar location. RESULTS: BMBs were seen in 36 (29.3%) patients. After adjusting for age, sex, number of antihypertensive drugs, asymptomatic lacunar infarcts, and white matter lesions, we found 24-hour, day, and night systolic and diastolic BP levels to be significantly associated with the presence and number of BMBs (odds ratios 1.6 to 2.3 per standard deviation increase in BP). Distinguishing between different locations, various BP characteristics were significantly associated with the presence of deep (or combined deep and lobar) BMBs, but not with purely lobar BMBs. CONCLUSIONS: Our results underline the role of a high 24-hour BP load as an important risk factor for BMBs. The association of BP levels with deep but not purely lobar BMBs is in line with the idea that different vasculopathies might be involved. Deep BMBs may be a particular marker of BP-related small vessel disease, but longitudinal and larger studies are now warranted to substantiate these findings.

Associations of ambulatory blood pressure levels with white matter hyperintensity volumes in hypertensive patients.

OBJECTIVE: High daytime and nighttime blood pressure (BP) levels, and apparently also an abnormal nocturnal BP dip, coincide with a greater extent of cerebral white matter hyperintensities (WMHs). We assessed the relationship between ambulatory BP and volumes of WMH, and distinguished between periventricular and deep WMH because of their supposedly different cause. METHODS: A total of 210 hypertensive patients (106 men) without cardiovascular and cerebrovascular disease, with a mean age of 52.5 +/- 12.5 years, and untreated office BP levels of 170 +/- 24/104 +/- 12 mmHg underwent duplicate 24-h ambulatory blood pressure monitoring (off medication) and brain MRI to quantify the WMHs (total, periventricular, and deep) and brain volumes. We performed linear regression analyses to relate the mean 24-h, awake, and asleep BPs, and the relative nocturnal BP dip to the different volumes of WMHs, while adjusting for age, sex, brain volume, and vascular risk factors. RESULTS: Higher 24-h, awake, and asleep BP levels were continuously, without distinct thresholds, and independently associated with a greater volume of total (all P < 0.001), periventricular (P < 0.001), and, to a lesser extent, deep (P < 0.05) WMHs. Nocturnal BP dipping was not related to the volume of WMHs. CONCLUSION: Higher 24-h, daytime, and nighttime BP levels are independently associated with WMH volumes.

Endothelial dysfunction in lacunar stroke: a systematic review.

BACKGROUND: Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients. METHODS: We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunction in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and informative quality. The papers were categorized into subheadings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium. RESULTS: 29 articles were eligible for further analysis. We found 16 publications on regulation of vascular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilatation and CO2 reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular endothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion molecules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers. CONCLUSIONS: The current literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endothelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well-defined cases and combine multiple methods to evaluate endothelial function.

Periventricular white matter lucencies relate to low vitamin B12 levels in patients with small vessel stroke.

BACKGROUND AND PURPOSE: Blood-brain barrier dysfunction may be an early phenomenon in the development of the small vessel disease, which underlies white matter lesions. Because vitamin B12 plays a role in maintaining the integrity of the blood-brain barrier, we studied serum vitamin B12 level in relation to such lesions. METHODS: In 124 patients with first lacunar stroke, we measured serum vitamin B12 level and rated the degree of white matter lesions on MRI. RESULTS: Mean vitamin B12 level was 202 pmol/L (SD, 68.9). Thirty-nine patients (31.5%) had a vitamin B12 level less than the lower reference value of 150 pmol/L. Lower vitamin B12 level was (statistically significant) associated with more severe periventricular white matter lesions (odds ratio/100 pmol/L decrease, 1.773; 95% CI, 1.001-3.003), but not with deep white matter lesions (odds ratio/100 pmol/L decrease, 1.441; 95% CI, 0.881-2.358; ordered multivariate regression analysis). CONCLUSIONS: More severe periventricular white matter lesions in lacunar stroke patients relate to lower vitamin B12 levels. A possible causal relationship should now be studied prospectively.

Detection of silent cerebrovascular disease refines risk stratification of hypertensive patients.

OBJECTIVE: Detection of preclinical hypertension-related cardiorenal damage has been recommended in the identification of patients most at risk of cardiovascular complications. The inclusion of silent cerebrovascular disease (SCD) as an additional marker of hypertensive organ involvement might improve risk stratification. METHODS: In 192 hypertensive patients (98 men) without a history of cardiovascular and cerebrovascular disease, a mean age of 51.6 +/- 12.3 years and untreated office blood pressure levels of 170 +/- 23/104 +/- 12 mmHg, we obtained detailed information on preclinical cardiac (left ventricular hypertrophy), renal (microalbuminuria, impaired kidney function or both) and cerebrovascular damage (white matter hyperintensities, infarcts, microbleeds or all), and estimated the associated cardiovascular risk on the basis of the presence of common cardiovascular risk factors. RESULTS: Hypertensive target-organ damage involved the heart in 41 (21%), the kidneys in 50 (26%) and the brain in 84 (44%) participants. When considering only patients with demonstrable cardiac, renal damage or both (n = 72), 42 participants (58%) had also SCD. Of the remaining 120 participants without cardiorenal damage, 42 (35%) had brain damage. In other words, half of all patients with SCD were classified as having no target-organ (i.e., cardiorenal) involvement. The cardiovascular risk score of patients without cardiorenal but with brain damage was significantly higher than that of participants without any organ involvement (37 +/- 11 versus 27 +/- 11, P < 0.001), and similar to the risk score of those with cardiorenal damage (38 +/- 14, P > 0.05). CONCLUSION: These data suggest that SCD should be recognized as an additional, independent and prognostically relevant marker of preclinical hypertensive target-organ damage.

Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients.

Aortic stiffness predicts an excess risk of stroke, supposedly via cerebral small-vessel disease. White matter hyperintensities, silent lacunar infarcts, and brain microbleeds, manifestations of cerebral small-vessel disease on neuroimaging, may precede overt cerebrovascular disease. Therefore, we assessed whether aortic stiffness is also related to such lesions. In 167 hypertensive patients (85 men) without a history of cardiovascular or cerebrovascular disease, a mean age of 51.8+/-13.1 years, and untreated office blood pressure levels of 169+/-25/104+/-12 mm Hg, we determined aortic pulse wave velocity and office and ambulatory 24-hour pulse pressure (off medication), as well as the volume of white matter hyperintensities and the presence of lacunar infarcts and microbleeds using brain MRI. Linear and logistic regression analyses were performed to assess the relationships between the arterial stiffness measures and brain lesions. Aortic stiffness and pulse pressure were significantly related to each of the brain lesions in univariate analyses (P<0.05). Multivariate analyses, adjusted for age, sex, brain volume, mean arterial pressure, and heart rate, showed that a higher pulse wave velocity was significantly associated with a greater volume of white matter hyperintensities (unstandardized regression coefficient: 0.041; 95% CI: 0.005 to 0.078; P<0.05) and the presence of lacunar infarcts (odds ratio [per SD increase in pulse wave velocity]: 1.78; 95% CI: 1.06 to 2.99; P<0.05) but not with microbleeds. The models for pulse pressure failed to reach statistical significance in multivariate analyses. In conclusion, aortic stiffness is independently associated with manifestations of cerebral small-vessel disease in hypertensive patients, linking systemic large- to cerebral small-artery disease.

Haptoglobin polymorphism and lacunar stroke.

Haptoglobin (Hp) 2-2 phenotype has been associated with peripheral and coronary artery disease and risk of vascular complications in diabetic patients, but any association of Hp polymorphism with cerebrovascular disease has not been explored so far. We aimed to study Hp polymorphism in a sample of 124 patients with a rather homogeneous type of cerebrovascular disease, namely first symptomatic lacunar stroke due to small vessel disease, in comparison with a large (n=918) control group. Hp phenotypes were determined using starch gel electrophoresis. Hp1 allele frequency was significantly higher in patients than in controls (0.480 vs. 0.395, p<0.05), mainly due to a lower Hp2-2 phenotype frequency (25.0 vs. 36.3 %; OR 0.59; 95%CI 0.38-0.90; p<0.05). This was even more pronounced in younger (