Jan Lodder

Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus or aortic valve

Aims To determine whether mitral annular calcification and aortic valve calcification, with or without stenosis, are expressions of atherosclerotic disease. Methods The incidence of atherosclerotic risk factors was analysed in patients with mitral annular calcification and aortic valve calcification and in control patients from a prospective echocardiographic database of 8160 consecutive patients; 657 patients (8%) were identified with mitral annular calcification and 815 (9%) with a calcified aortic valve, of whom 515 (6.3%) had stenosis with a minimal aortic valve gradient of 16 mm Hg. In these patients, cardiac and vascular risk factors were compared with 568 control patients using multiple logistic regression analysis. Results Age (odds ratio (OR) varying from 5.78 to 104, depending on age class), female sex (OR 1.75), hypertension (OR 2.38), diabetes mellitus (OR 2.85), and hypercholesterolaemia (OR 2.95) were strongly and significantly associated with aortic valve calcification without stenosis, as were age (OR varying from 8.82 to 67, depending on age class), female sex (OR 2.22), hypertension (OR 2.72), diabetes mellitus (OR 2.49), and hypercholesterolaemia (OR 2.86) with mitral annular calcification. Age (OR varying from 1.11 to 7.7), hypertension (OR 1.91), and hypercholesterolaemia (OR 2.55) were strongly and significantly associated with stenotic aortic valve calcification. Conclusions Mitral annular calcification and stenotic or non-stenotic aortic valve calcification have a high incidence of atherosclerotic risk factors, suggesting they should be considered as manifestations of generalised atherosclerosis.

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.

Cognitive Functioning after Stroke: A One-Year Follow-Up Study

Cognitive disorders after stroke are one of the main causes of disability in daily activities. The main aim of this study was to investigate the frequency of post-stroke dementia, post-stroke mild cognitive impairment (MCI) and post-stroke amnestic MCI at different times after first-ever stroke; 196 patients were included in the study. In addition, cognitive disorders and their clinical course were studied. Frequency of post-stroke dementia was about 10% at all evaluation times; most patients had post-stroke MCI. Of the cognitive functions investigated, mental speed and calculation were most frequently affected. Performance on almost all cognitive tests was improved 6 and 12 months after stroke. Thus, while the frequency of post-stroke dementia is low, the frequency of post-stroke MCI is high, but improvement of cognitive function is possible.

Stroke subtype and mortality. a follow-up study in 998 patients with a first cerebral infarct.

The aim of this article was to study mortality following a first-ever cerebral infarct, accounting for ischemic stroke subtypes (lacunar, cardioembolic, atherothrombotic) and relevant prognostic variables. This study was done from s a hospital-based prospective registry of all patients with a first cerebral infarct, with a high case ascertainment of first and recurrent stroke by CT. We used a cross-sectional follow-up, using standardized methods. Analyses were performed using crude comparison of mortality data and death causes between stroke subtypes. We analyzed 30-day case fatality and 1-year mortality in 30-day survivors by means of logistic regression analysis, and mortality in 1-year survivors by means of Cox proportional hazard modeling. We also constructed Kaplan-Meier survival curves, and used log-rank testing for differences between stroke subtypes. Thirty-day case fatality was 10%, 1-year mortality 15%, and after 1-year mortality 16%. Mean follow-up was 691, SD 521 days. At the end of follow-up 36% of all patients had died. Mortality was at all three time points lowest in lacunar stroke (2, 12, and 14%, respectively), intermediate in atherothrombotic stroke (10, 16, and 15%, respectively), and highest in cardioembolic stroke (23, 22, and 21%, respectively). Death related to recurrent stroke was similar in all three stroke subtypes (13-16%). Although 30-day case fatality rate was low in lacunar stroke, a quarter of lacunar stroke patients had died at the end of follow-up. Diabetes mellitus, age, stroke subtype, and initial stroke severity were independent predictors of 30-day case fatality, but only diabetes and age were consistent independent predictors for later mortality. Recurrent stroke and heart failure were important death causes. Prognosis for (future) death following a first cerebral infarct differs between stroke subtypes; lacunar stroke patients have the lowest mortality. However, lacunar stroke cannot be regarded as a mild stroke type, as after 2 years more than a quarter of such stroke patients had died. Cardioembolic stroke patients have the grimmest prognosis: more than half of them had died within 1.5 years. Better prognosis for long-term survival following stroke may be achieved by therapies which lower the risk of stroke recurrence, provide better treatment of heart failure, or both.

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.

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.

Endothelial progenitor cell research in stroke: a potential shift in pathophysiological and therapeutical concepts.

Background and Purpose— Stroke is the leading cause of disability in the Western world; however, few therapies are at hand to decrease this burden. Summary of Review— Endothelial progenitor cells (EPCs) have been introduced in cardiovascular medicine as factotums. EPCs can repair damaged endothelium and attenuate the development and progression of atherosclerosis. Also, EPCs can form new vessels in ischemic areas and thus promote recovery after ischemic events. In stroke, however, EPC research is limited. In our overview, we provide background information on EPC use as a risk marker and as a potential therapeutic agent. Conclusion— In our opinion, the lack of EPC studies in stroke should instigate vascular neurologists to participate in EPC research, as EPCs could also change pathophysiological concepts and improve clinical treatments in vascular neurology.

Risk of Stroke in a Cohort of 815 Patients With Calcification of the Aortic Valve With or Without Stenosis

BACKGROUND AND PURPOSE We sought to establish the possible role of calcification of the aortic valve with or without stenosis as a risk factor for stroke. METHODS Occurrences of stroke, stroke subtypes, and concomitant cardiovascular risk factors were prospectively analyzed in 300 patients with echocardiographic evidence of aortic valve calcification, 515 patients with calcified aortic valve stenosis, and 562 control subjects. RESULTS Twenty-four patients with aortic valve calcification, 24 patients with calcified aortic valve stenosis, and 27 control subjects had a stroke during follow-up. Using Cox proportional hazards models, we found that strokes were not significantly associated with aortic valve calcification with or without stenosis, but hypertension and any carotid stenosis were associated. On multiple logistic regression analysis, we did not find any association between one of the two valve lesions and indirect possible indications of cardiogenic embolism such as territorial as opposed to small deep brain infarcts or the presence of silent brain infarcts. CONCLUSIONS Aortic valve calcification with or without stenosis is not a risk factor for stroke.

Is there a side predilection for cerebrovascular disease

Abstract—In studies on carotid artery intima-media thickness and stroke, researchers implicitly assume that cerebrovascular abnormalities show a symmetrical distribution. To evaluate whether there is a difference in intima-media thickness between the 2 carotids, we compared left and right common carotid artery intima-media thickness as measured by B-mode ultrasonography in a group of 102 untreated hypertensive patients. This yielded a significant difference between both sides (left, 0.75±0.11 mm; right, 0.71±0.11 mm; P <0.001). This was associated with a higher cross-sectional area of the intima-media complex and a higher flow velocity at the left side. Arterial diameters, however, were not different. We also assessed whether there is a side preference with respect to cerebrovascular accidents. To this end, we explored our population-based Stroke Registry of 1843 subjects and indeed found a significantly higher incidence of nonlacunar cerebrovascular stroke at the left side, whereas lacunar infarcts were symmetrically distributed. Our findings suggest a predilection for cerebrovascular disease at the left side, which may be related to greater hemodynamic stress and intimal damage in the left carotid artery.

Different classifications of nocturnal blood pressure dipping affect the prevalence of dippers and nondippers and the relation with target-organ damage.

Objective We assessed how different definitions of the awake and asleep periods and use of various blood pressure (BP) indices affect the extent of the nocturnal BP dip, the prevalence of dippers and nondippers, their respective reproducibilities and the relation of nondipping with target-organ damage. Methods We performed 24-h ambulatory BP monitoring twice and determined the left ventricular mass index and urinary albumin excretion as indices of target-organ damage in 150 hypertensive patients (off-medication). Awake and asleep periods were assessed using fixed and diary time methods, covering all readings available (wide) or excluding morning and evening transition hours (narrow). Nondipping (BP dip < 10%) was established for systolic BP and diastolic BP, their combinations (and/or), and mean arterial pressure. Results The different awake–asleep definitions caused significant variation in both the extent of the BP dip and the number of dippers and nondippers in comparison with the wide diary definition (i.e. use of actual awake and sleep periods). The prevalences of dippers and nondippers also varied significantly with the BP index. Reproducibility analyses of the BP dip and the dipping status yielded repeatability coefficients (expressed as percentages of nearly maximal variation) between 42.39 and 48.71%, and kappa values between 0.323 and 0.459, respectively. Some classifications, but not all, discriminated significantly between consistent dippers and nondippers in terms of left ventricular mass index or urinary albumin excretion. Conclusions Use of different definitions of awake–asleep and BP indices affects significantly the classification of nocturnal BP dipping and its relation with hypertensive target-organ damage.