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Stroke. 2002;33:297-305

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(Stroke. 2002;33:297.)
© 2002 American Heart Association, Inc.

Case Report

Twenty-four–Hour Blood Pressure and MRI as Predictive Factors for Different Outcomes in Patients With Lacunar Infarct

Y. Yamamoto, PhD; I. Akiguchi, PhD; K. Oiwa, PhD; M. Hayashi, MD; T. Kasai, MD K. Ozasa, PhD

From the Department of Neurology, Kyoto Second Red Cross Hospital (Y.Y., K. Oiwa, T.K., M.H.); Department of Neurology, Kyoto University Hospital (I.A.); and Department of Social Medicine and Cultural Sciences, Kyoto Prefectural University of Medicine (K. Ozasa) (Japan).

Correspondence to Y. Yamamoto, PhD, Department of Neurology, Kyoto Second Red Cross Hospital, 355-5 Haruobicho Kamigyoku, Kyoto 602, Japan. E-mail yamamotoyasumasa{at}hotmail.com


*    Abstract
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 *Abstract
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Background and Purpose— A long-term follow-up study was conducted in patients with lacunar infarct to assess how 24-hour blood pressure monitoring values and MRI findings, in particular lacunar infarcts and diffuse white matter lesions, can predict subsequent development of dementia and vascular events, which include cerebrovascular and cardiovascular events.

Methods— One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up. Documented events comprise the development of dementia and the occurrence of vascular events. The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis.

Results— Twenty-six patients developed dementia (0.17/100 patient-years). Male sex (relative risk [RR], 4.2; 95% CI, 1.2 to 14.7), cognitive impairment (RR, 3.0; 95% CI, 1.0 to 8.5), confluent DWML (moderate: RR, 7.1; 95% CI, 1.6 to 31.5; severe: RR, 35.8; 95% CI, 7.2 to 177.3), and nondipping status (RR, 7.1; 95% CI, 2.2 to 22.0) were independent predictors for dementia. Forty-six patients suffered from vascular events (3.11/100 patient-years). Diabetes mellitus (RR, 5.7; 95% CI, 2.7 to 11.9), multiple lacunae (moderate: RR, 6.4; 95% CI, 2.5 to 15.8; severe: RR, 8.5; 95% CI, 3.1 to 23.3), and high 24-hour systolic blood pressure (>145 mm Hg versus <130 mm Hg) (RR, 10.3; 95% CI, 1.3 to 81.3) were independent predictors for vascular events.

Conclusions— Predictors for developing dementia and vascular events appear to differ. Male sex, confluent diffuse white matter lesions, and nondipping status were independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour systolic blood pressure were independent predictors for vascular events.


Key Words: blood pressure monitoring, ambulatory • dementia, vascular • lacunar infarction • white matter


*    Introduction
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 *Introduction
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Lacunar infarcts are small, deep infarcts caused by the obstruction of small penetrating arteries.1 Despite the fact that lacunar infarcts account for only 15% to 20% of all cerebral infarcts in Western countries,2–4 they probably constitute up to 30% to 40% of all cerebral infarcts in Japan.5,6 Compared with other stroke subgroups, lacunar infarcts are associated with low early-case fatality and recurrent stroke rates.4,6–9 Nonetheless, a certain percentage of vascular dementia that is due to small-vessel disease is believed to stem from the symptomatic lacunar infarct cohort.10,11 Although several studies have evaluated the prognosis of lacunar infarcts, very few studies have thoroughly analyzed long-term outcomes of lacunar infarction, which includes the risk of not only cerebrovascular and cardiovascular events but also the development of dementia.6

Hypertension, on the other hand, has been generally thought to be the most common cause of lacunar infarcts, although there remains much controversy over the risk factors for lacunar infarcts.12 Since the introduction of ambulatory blood pressure monitoring (ABPM) devices, it has been consistently reported that target organ damage and cardiovascular morbidity and mortality are more closely correlated with ambulatory blood pressure (ABP) than casual blood pressure (BP).13,14 Moreover, a nondipping status, that is, a state whereby patients exhibit either an absence of or a reduced nocturnal BP dip, was reported to correlate with more advanced target organ damage and worsened prognosis than patients who maintained dipping status.15 Accordingly, ABP values are of prognostic value for the prediction of subsequent morbid events in patients with essential hypertension.15–17 The prognostic value of ABP for cerebrovascular disease, however, has never been investigated, thus prompting us to pose the question of how ABP could potentially contribute to the prediction of long-term outcomes in patients with lacunar infarct.

In addition, it has also been previously noted that patients with silent lacunar infarcts18 and diffuse white matter lesions (DWML),6,19,20 as detected by MRI, might potentially be at greater risk for stroke recurrence or death. We thus conducted this prospective study to elucidate how the combination of ABP values and MRI findings can help to predict the long-term outcome of patients with lacunar infarct.


*    Subjects and Methods
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 *Subjects and Methods
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Patient Selection
Between January 1987 and December 1991, 623 patients were consecutively admitted to the Department of Neurology at the Kyoto Second Red Cross Hospital in Japan for first-ever symptomatic ischemic stroke. This group included 209 patients with symptomatic lacunar infarcts. Symptomatic lacunar infarct patients were defined as those patients who showed an acute onset of a focal neurological deficit lasting >24 hours that was consistent with a lacunar syndrome.1 Patients who showed cortical infarcts or subcortical infarcts in which diameters were >15 mm on MRI were excluded. Five patients who were diagnosed with dementia, 2 patients with severe renal failure, and 7 patients with lower basilar branch syndrome were excluded, leaving 195 patients. Of these 195 patients, 177 patients underwent both MRI and ABPM, without prior administration of antihypertensive agents for >4 weeks. Subsequently, either our outpatient clinic or family physicians tracked the 177 patients. All patients consented to participate in this study.

Conventional Risk Factors
Hypertension was defined as systolic BP (SBP) >=140 mm Hg and/or diastolic BP (DBP) >=90 mm Hg measured with the patient in a sitting position on at least 2 different occasions with no administration of antihypertensive agents for 2 weeks after ictus or previous use of antihypertensive agents. Diabetes mellitus was defined as fasting glucose level >=140 mg/dL or use of antidiabetic medication. Dyslipidemia was defined as fasting total cholesterol level >=220 mg/dL and/or fasting triglyceride level >=200 mg/dL without administration of any antihyperlipidemic agents. Cigarette smoking was defined as regularly smoking at the time of stroke. Complications of cardiac disease, including old myocardial infarctions, angina pectoris, congestive heart failure, atrial fibrillation, and cardiomyopathy, were also identified.

Magnetic Resonance Imaging
MRI scans were performed with the use of 1.5-T superconducting magnets (Shimazu, SMT 150X). MRIs were performed from 5 to 14 days after ictus. Transverse T2-weighted scans (repetition time, 2500 ms; echo time, 90 ms) and proton density images (repetition time, 2500 ms; echo time, 20 ms) were obtained at a slice thickness of 8 mm. Lacunae and DWML were then evaluated against baseline MRI. Lacunae were defined as penetrating artery occlusions 3 to 15 mm in diameter in horizontal sections with high intensity on both T2-weighted and proton density images. Lacunae were located within the basal ganglia, thalamus, internal capsule, corona radiata, and pons. DWML were defined as diffuse hyperintensities that were located in the subcortical and periventricular white matter with T2-weighted images and proton density images. For the baseline MRI, the number of lacunae was first counted and then graded as follows: grade 0, absent; grade 1, 1 to 2 lacunae; grade 2, 3 to 5 lacunae; and grade 3, 6 lacunae. DWML were defined and graded according to the classification of Schmidt et al21: grade 0, absent; grade 1, punctuate; grade 2, becoming confluent; and grade 3, confluent. Hyperintense periventricular caps and smooth halos were not counted as DWML. The baseline MRIs were evaluated by 2 authors (Y.Y. and I.A.), who were blinded to both the BP data and the results.

ABPM and Casual BP
The 24-hour BP data were recorded with a portable automatic recorder (ABPM-630, Nippon Corin Co) at 30-minute intervals, over a 24-hour period from 1 PM to 1 PM the following day. ABPM was performed from 14 to 30 days after ictus without administration of antihypertensive agents. Average values were calculated as follows. The SBP and DBP were averaged over successive 30-minute intervals throughout the 24-hour period. The mean daytime (6 AM to 10 PM) and nighttime (10:30 PM to 5:30 AM) values were also calculated.

The degree of the nocturnal BP dip (nocturnal dip) was calculated as follows: (mean daytime values-mean nighttime values)/mean daytime values. Nondippers were arbitrarily defined as essential hypertensive patients who did not exhibit a >10% nocturnal dip in SBP.13 Because a large number of lacunar infarct patients would be classified as nondippers on the basis of such criteria, we classified patients who did not exhibit a >5% nocturnal dip in SBP as nondippers; the remaining subjects were classified as dippers. According to recent guidelines,22,23 patients were divided into tertiles of ABP values for daytime SBP: 1, low tertile <135 mm Hg; 2, middle tertile 135 to 150 mm Hg; and 3, high tertile >150 mm Hg; for daytime DBP: 1, low tertile <80 mm Hg; 2, middle tertile 80 to 90 mm Hg; and 3, high tertile >90 mm Hg; for nighttime SBP: 1, low tertile <120 mm Hg; 2, middle tertile 120 to 140 mm Hg; and 3, high tertile >140 mm Hg; for nighttime DBP: 1, low tertile <70 mm Hg; 2, middle tertile 70 to 80 mm Hg; and 3, high tertile >80 mm Hg; for 24-hour average SBP: 1, low tertile <130 mm Hg; 2, middle tertile 130 to 145 mm Hg; and 3, high tertile >145 mm Hg; and for 24-hour average DBP: 1, low tertile <75 mm Hg; 2, middle tertile 75 to 85 mm Hg; and 3, high tertile >85 mm Hg.

BP was also measured with the patient in a sitting position by standard mercury sphygmomanometers in the morning when ABPM was performed. This was designated the casual BP. According to the World Health Organization/International Society of Hypertension guidelines, patients were divided into 3 tertiles of casual BP values for SBP: 1, low tertile <160 mm Hg; 2, middle tertile 160 to 180 mm Hg; and 3, high tertile >180 mm Hg; and for DBP: 1, low tertile <100 mm Hg; 2, middle tertile 100 to 110 mm Hg; and 3, high tertile >110 mm Hg.

Dementia Scale
At approximately the time when ABPM was performed, the overall severity of dementia was evaluated with the Clinical Dementia Rating Scale (CDR),24 with information from the neurological, neuropsychological, and functional examinations. The cognitive ability of all patients was also evaluated with Hasegawa’s Dementia Rating Scale Revised (HDSR).25 This evaluation scores cognitive impairment via 5 subtests that measure orientation, general information, calculation, memory recall, and memorization. The maximum score is 30 points, with low scores reflecting more extensive cognitive impairment. This test battery is widely used in Japan to evaluate cognitive impairment.10,18 The patients were diagnosed with dementia if either the CDR score was >=1 or the score on the HDSR was <=20 and the state of dementia met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition.26 Cognitive impairment was defined as CDR score of 0.5 or HDSR score of 21 to 26. Patients who could be diagnosed with dementia after a stroke recurrence with large cortical infarcts were not evaluated as dementia developed.

Patient Follow-Up
After the patients were discharged from the hospital, approximately half of the patients were followed on a monthly basis in our outpatient clinic; the remaining patients were tracked by their family physicians. Approximately 20% of those tracked by family physicians visited our clinic once a year for regular examination, including MRI and/or ultrasonography. When patients were referred to family physicians, the physicians were informed regarding patient characteristics, study protocol, and the method of evaluating dementia with the use of the CDR. The outcome of patients followed monthly in our outpatient clinic or readmitted to our hospital for subsequent stroke reoccurrence or cardiovascular events was identified directly by attending physicians. Patients who were tracked by their family physicians were intermittently reviewed over the years to record clinic BP, drug therapy, and the occurrence of cerebrovascular and cardiovascular events or the development of dementia. On occurrence of new events, family physicians and patients or family members were requested to notify our department. Finally, we performed telephone interviews directly for all patients or their families to confirm final outcomes on December 1999. Documented events consisted of development of dementia and the occurrence of cerebrovascular and cardiovascular events. Cerebrovascular and cardiovascular events were classified as vascular events. Cerebrovascular and cardiovascular deaths, which were classified as vascular deaths, and nonvascular death, which was defined as death due to causes other than cardiovascular and/or cerebrovascular diseases, such as cancer, pneumonia, or other unrelated diseases, were also identified. When patients were suspected to exhibit cognitive decline on an office visit, evaluation with CDR and HDSR was performed. Newly developed dementia was diagnosed according to the aforementioned definition. Recurrent stroke attack was diagnosed on rapid onset of a localized neurological deficit. Cardiovascular events included myocardial infarct, angina pectoris, ruptured aneurysm, and progressive heart failure. For patients followed in our outpatient clinic or by their family physicians, antihypertensive treatment was provided on the basis of office BP levels, with <=160/95 mm Hg as the goal for control. All patients were treated with 82 to 164 mg of acetylsalicylic acid or 200 mg of ticlopidine.

Statistical Analysis
Event rates are presented as the number of events per 100 patient-years based on the ratio of the observed number of events to the total number of patient-years of exposure. The study population was analyzed with 2 different models. In the first model, all patients were dichotomized into 2 groups: those with and without subsequent dementia. In the second model, all patients were dichotomized into 2 groups: those with and without subsequent vascular events. The follow-up period was defined as the time interval between the 24-hour BP monitoring and either the last follow-up in uncomplicated patients or the development of the first morbid event in the other groups. Different morbid events were separately counted for the same person, but only the first event was considered when vascular events occurred more than twice. In the 2 different models, variables were initially compared between 2 groups with and without events. Continuous variables were expressed as mean±SD, and categorized variables were given as the percentage of patients so affected. A comparison of clinical variables between the 2 groups was performed with a {chi}2 test; BP data were analyzed with Student’s t test. In both models, the effect of predictive factors on survival was evaluated by Cox proportional hazards analysis. Predictive factors included in the Cox proportional hazards analysis were age (<=50s versus 60s, <=50s versus 70s, <=50s versus 80s), sex (male and female), conventional risk factors (yes or no), cognitive impairment (yes or no), MRI findings (grade 0 to 1 versus grade 2 and grade 0 to 1 versus grade 3), and ABPM values, including daytime, nighttime, and 24-hour average BP (low tertile versus middle tertile and low tertile versus high tertile), nocturnal BP dip (dippers versus nondippers), and casual BP values (low tertile versus middle tertile and low tertile versus high tertile). Complications of cardiac disease were not included as a predictive factor because the number was small. Age and sex were simultaneously analyzed. Age- and sex-adjusted relative risks (RRs) and 95% CIs were calculated for individual factors by a Cox proportional hazards analysis with the use of Stat-View 5.0. Probability values <0.05 were considered significant. Predictive factors found to be significant by age- and sex-adjusted univariate analysis were examined with multivariate analysis. Among various ABP values such as daytime BP, nighttime BP, and 24-hour BP values, only the ABP value exhibiting highest RR by age- and sex-adjusted univariate analysis was used for multivariate Cox proportional hazards analysis.


*    Results
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 *Results
down arrowDiscussion
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General Data
The study population consisted of 177 patients. There were 110 men and 67 women aged 69.1±8.6 years (mean±SD), ranging from 47 to 86 years. Lacunar syndrome included pure motor hemiparesis (n=102), sensorimotor stroke (n=39), pure sensory stroke (n=18), dysarthria–clumsy hand syndrome (n=12), and miscellaneous (pure dysarthria; n=6). The study population was analyzed with 2 different outcomes, which include the development of dementia and the occurrence of vascular events. The demographics, conventional risk factors, MRI findings, number of cognitive impairments, casual BP values, and ABP values at baseline are displayed in Table 1 for the first model and in Table 2 for the second model.


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  		Table 1. Comparison of Baseline Characteristics, MRI Findings, and BP Values Between Subjects With and Without Subsequent Dementia


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  		Table 2. Comparison of Baseline Characteristics, MRI Findings, and BP Values Between Subjects With and Without Subsequent Vascular Events

Model 1: Newly Developed Dementia
Twenty-six patients developed dementia during a mean follow-up period of 8.7±3.0 years (0.17/100 patient-years). The average CDR score for these 26 patients was 0.27±0.15 at baseline and 1.73±0.4 at the time of diagnosis of dementia. Seventeen patients were diagnosed with dementia at our outpatient clinic. The HDSR scores for these 17 patients ranged from 26.8±3.4 at baseline to 16.4±3.4 at the time of diagnosis. These 17 patients also developed lacunae and DWML on the basis of follow-up MRI, suggesting that most patients could be classified with vascular dementia. Six patients showed evidence of cerebrovascular events, 3 died of cardiovascular events, and 4 died of nonvascular causes.

Table 3 presents the RRs and 95% CIs for developing dementia by Cox proportional hazards analysis. Developing dementia was significantly associated with male sex, cognitive impairment, confluent DWML (grade 0 to 1 versus grade 2 and grade 0 to 1 versus grade 3), and nondipping status by multivariate analysis.


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  		Table 3. Results of Cox Proportional Hazards Regression Analysis of Predictors of Subsequent Dementia

Model 2: Vascular Events
Forty-six patients suffered from vascular events during a mean follow-up period of 8.5±3.2 years (3.11/100 patient-years). Vascular events consisted of 35 cerebrovascular events and 11 cardiovascular events. Cerebrovascular events included 19 patients with lacunar infarcts, 5 patients with cerebral cortical infarcts, 2 patients with vertebrobasilar artery occlusive disease, 3 patients with cerebral hemorrhages, and 6 patients with unidentified acute stroke. Twenty-eight patients were identified on readmission to our hospital. Eleven patients died of cerebrovascular events. Cardiovascular events included myocardial infarction in 6, angina pectoris in 2, congestive heart failure in 1, ruptured aneurysm in 1, and unidentified acute heart disease in 1 patient. Seven patients were identified on readmission to our hospital. Eight patients died of cardiovascular events.

Table 4 presents the RRs and 95% CIs for developing dementia by Cox proportional hazards analysis. Because 24-hour SBP value exhibited the highest RR by age- and sex-adjusted univariate analysis, it was used for multivariate Cox proportional hazards analysis. Diabetes mellitus, multiple lacunae (grade 0 to 1 versus grade 2 and grade 0 to 1 versus grade 3), and 24-hour SBP (low tertile versus high tertile) emerged as independent predictors for vascular events after multivariate analysis.


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  		Table 4. Results of Cox Proportional Hazards Regression Analysis of Predictors of Subsequent Vascular Events

Nonvascular Death
Fifteen patients died of nonvascular causes, which included 4 patients who died of neoplastic diseases, 5 patients who died of pneumonia, 1 patient who died of asphyxia, and 5 patients who died of unknown causes. Four patients developed dementia, but no patients suffered from vascular events.


*    Discussion
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 up arrowAbstract
 up arrowIntroduction
 up arrowSubjects and Methods
 up arrowResults
 *Discussion
down arrowReferences
 
The present study identified different sets of predictive factors for different outcomes. It is of particular note that predictors for vascular events and dementia appear to differ. Diabetes mellitus, multiple lacunae, and high ambulatory SBP values were independent predictors for vascular events, while nondipping status, the highest degree of multiple lacunae, and confluent DWML were independently associated with the development of dementia.

The highest degree of 24-hour SBP exhibited higher RR for vascular events than casual BP, daytime and nighttime SBP, and diastolic ABP. Several studies have assessed the prognostic value of ABPM in essential hypertension.14–17,27,28 The present study is in agreement with these results, showing that higher ABP values at baseline can predict a higher rate of occurrence of vascular events. Our results are also consistent with these reports in that SBP appears to yield greater prognostic information than DBP.16,17 It is likely that a considerable proportion of treated patients have not achieved target BP levels, despite BP control during the follow-up period.29,30

In contrast, ABP values were not revealed to be a significant predictor for subsequent development of dementia, even by univariate analysis. The relationship between BP and cognitive function is controversial in the elderly.31 Some researchers found high BP to be related to dementia,32–34 while another researcher reported low BP to be linked with a higher prevalence of dementia in the elderly.35 Skoog et al36 demonstrated that a previously elevated BP tended to decline over time in patients who subsequently developed dementia. We have also recently reported that patients with lacunar infarct who subsequently develop both lacunae and DWML, together with a cognitive decline, exhibit a decline in the average 24-hour BP over the course of the disease.37,38 In consideration of such results, it might be postulated that an initially elevated BP may lead to multiple lacunae and DWML, followed by a gradual decline in cognitive abilities that occurs in conjunction with a decline in BP. It thus remains possible that before patients’ entry into the present study, BP values may have already begun to decline in patients who subsequently developed dementia. The possibility that vascular dementia progressed, regardless of BP level, is also not excluded.

There are increasing numbers of studies on ABPM in patients with lacunar infarct. The majority of previous studies using 24-hour BP measurements have demonstrated that nondipping status correlates with the occurrence and the extent of DWML or lacunar infarct.38–43 We reported by prospective study that the development of symptomatic or asymptomatic lacunar infarct and DWML was associated with a reduced nocturnal BP dip in patients with a history of lacunar infarct.39,44 In contrast, other studies suggested that excessive nighttime BP dip correlated with extensive DWML and lacunar infarct.45–47 On the other hand, short-term BP variability was reported as a risk factor for small-vessel disease or Binswanger’s disease.39,48

Nondipping status has been suggested to be a potential predictor of cerebrovascular and cardiovascular morbidity and mortality in hypertensive patients.14–17,27,28 In the present study, however, nondipping status was not shown to be independent marker of the risk for vascular events, although it was revealed to be significant by univariate analysis. It was found, however, that nondipping status independently predicted the subsequent development of dementia after adjustment for multiple lacunae and DWML. Nondipping status was reported to be associated with altered autonomic regulation44,49 and sodium-sensitive–type hypertension.50,51 It is conceivable that altered autonomic regulation can impair neurogenic control of cerebral circulation over time, resulting in a chronic ischemic state in the brain. Whether sodium-sensitive–type hypertension can facilitate the development of vascular dementia due to small-artery disease should also be investigated.44

The presence of multiple lacunae was found to be a significant predictor for vascular events, while confluent DWML was found to be an independent predictor for subsequent development of dementia. Multiple lacunae appeared to supersede the importance of confluent DWML for the risk for vascular events; on the other hand, DWML appeared to supersede multiple lacunae in the progression of dementia. Uehara et al52 reported that silent lacunar infarcts in the basal ganglia were associated with generalized atherosclerosis, including carotid and coronary artery disease, while silent infarcts in subcortical white matter were not associated with such a disease process. Previous reports53,54 have also demonstrated that silent lacunae occur in conjunction with a background of atherosclerosis. Consequently, patients with multiple lacunae appear to have both disseminated arteriolosclerosis, which may be caused by longstanding hypertension,1 and generalized atherosclerosis. Such patients are thus considered to be prone to recurrent stroke. Kobayashi et al18 conducted a prospective study demonstrating that although subcortical silent brain infarcts were identified as an independent predictor of subsequent symptomatic brain infarcts or brain hemorrhage, DWML were not found to be a predictor. The findings of the present study correlate well with those of Kobayashi et al.18

The nature of confluent DWML, in contrast, has typically been reported to be chronic white matter ischemia resulting from injury to the long penetrating arteries.55,56 Confluent DWML is speculated to be facilitated by excessive fall in BP,45–47,57,58 including orthostatic dysregulation59 and postprandial hypotension.60 Prospective studies, however, support the view that high BP may accelerate confluent DWML.44,61 The present study also suggests that nighttime BP increase rather than excessive nighttime BP dip correlates well with the development of dementia. Larger longitudinal studies to clarify the optimal BP level to prevent the development of DWML are necessary.

Reduced cerebral blood flow accompanied by an increased oxygen extraction fraction has also been observed in nondemented patients with confluent DWML.62,63 Misery perfusion might represent a predisposition for chronic ischemia in white matter over a long period, resulting in more extensive white matter ischemia and thus leading to Binswanger’s disease.64 Although confluent DWML has been reported to predict cerebrovascular and cardiovascular events or death,6,19,20,65 no study, to our knowledge, has ever demonstrated that confluent DWML can be used as an independent predictor for subsequent dementia. In addition, as previously suggested, cognitive impairment was also found to be an independent predictor for dementia.66,67

Diabetes mellitus was revealed to be an independent predictor for vascular events and nonvascular death. Diabetes mellitus has been established as an independent risk factor for ischemic stroke by prospective epidemiological studies.68,69 The widespread large-vessel atherosclerosis observed in the cerebral and general circulation of diabetic patients probably contributes to an enhanced risk of vascular events. It is also reasonable to state that diabetic patients may be prone to nonvascular deaths, such as those that result from infectious diseases.

Although the results of this study are encouraging, certain limitations should be addressed. First, the outcome for 56 patients (31.6%) was identified according to reports from family physicians. Nonetheless, our partnership with family physicians has been well established, and the information from family physicians and patients’ families corresponded well. Second, because the main purpose of this study was to thoroughly assess predictors for different outcomes after lacunar infarct, limited examinations, ie, CDR and HDSR, were used to assess cognitive function. It may be insufficient to diagnose dementia with the use of only the CDR at a family physician’s office. Additionally, identification of the time of dementia development by a family physician may have been ambiguous. Third, vascular workup was lacking because carotid Doppler ultrasonography and MR angiography were not performed for every patient.

The present study represents the first study to thoroughly analyze long-term outcomes of lacunar infarct patients with the use of ABPM and MRI. It is particularly noteworthy that distinct predictive factors were revealed for the development of dementia and vascular events. Confluent DWML and a nondipping status appear to represent independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour SBP value appear to be independent predictors for vascular events. Incidence of subsequent vascular events can be reduced by stricter BP control. The pathogenic mechanism of nondipping status should also be investigated further to reduce the risk of vascular dementia.


*    Acknowledgments
 
The authors are grateful to Christopher Hurt for reviewing the manuscript.

Received February 28, 2001; revision received September 4, 2001; accepted September 21, 2001.


*    References
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 up arrowAbstract
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 up arrowSubjects and Methods
 up arrowResults
 up arrowDiscussion
 *References
 

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