Background and Purpose:
Stroke, which remains the third leading cause of death after heart disease and cancer in developed countries, is a disorder causing permanent neurologic disability. Even though, hemorrhagic strokes are seen less than the ischemic type, they are more fatal. We studied the risk factors for spontaneous intra-cerebral hemorrhage (ICH) to direct the proper preventive treatment modalities and the effects of these factors on mortality as well as applied therapeutic strategies on survival.
Materials and Methods:
The archive records of 106 patients (60 male, 46 female) who were diagnosed with spontaneous ICH in Baskent University Hospital, Ankara, between January 2003 and September 2008, were assessed retrospectively.
The mean age was found as 62.5. The most frequent risk factor was hypertension (73.5%); 69.2% of these hypertensive patients had uncontrolled blood pressure levels. The mortality rate was detected as 34.9% and patients were found to die approximately within 9 days after ICH. Older age, increased hemorrhage volume, ventricular extension of hemorrhage, and the presence of midline shift were found to significantly correlate with increased mortality (P < 0.05). Patients who underwent surgical therapy showed a longer survival rate (P = 0.016); however, no association was found between medical and surgical therapy in terms of mortality (P = 0.555).
The results of this study suggest that effective control of blood pressure is important in the prevention of spontaneous ICH; clinical and radiological findings with treatment modalities influencing mortality should be carefully managed.
Mortality; risk factors; spontaneous intra-cerebral hemorrhage; treatment
Ischemic Heart Disease (IHD) is the leading cause of death worldwide. The Global Burden of Diseases, Injuries and Risk Factors (GBD) 2010 Study estimated IHD mortality and disability burden for 21 world regions for the years 1990 to 2010.
Data sources for GBD IHD epidemiology estimates were mortality surveillance, verbal autopsy, and vital registration data (for IHD mortality) and systematic review of IHD epidemiology literature published 1980–2008 (for non-fatal IHD outcomes). An estimation and validation process led to an ensemble model of IHD mortality by country for all 21 world regions, adjusted for country-level covariates. Disease models were developed for the nonfatal sequelae of IHD: myocardial infarction, stable angina pectoris, and ischemic heart failure.
Country level covariates including metabolic and nutritional risk factors, education, war, and annual income per capita contributed to the ensemble model for the analysis of IHD death. In the acute myocardial infarction model, inclusion of troponin in the diagnostic criteria of studies published after the year 2000 was associated with a 50% higher incidence. Self-reported diagnosis of angina significantly overestimated stable angina prevalence compared with “definite” angina elicited by the Rose angina questionnaire. For 2010, Eastern Europe and Central Asia had the highest rates of IHD death and the Asia Pacific High-Income, East Asia, Latin American Andean, and sub-Saharan Africa regions had the lowest.
Global and regional IHD epidemiology estimates are needed for estimating the worldwide burden of IHD. Using descriptive meta-analysis tools, the GBD 2010 standardized and pooled international data by adjusting for region-level mortality and risk factor data, and study level diagnostic method. Analyses maximized internal consistency, generalizability, and adjustment for known sources of bias. The GBD IHD analysis nonetheless highlights the need for improved IHD epidemiology surveillance in many regions and the need for uniform diagnostic standards.
Stroke is the leading cause of disability in developed countries and the third cause of mortality. Up to 15-30% of ischemic strokes are caused by cardiac sources of emboli being associated with poor prognosis and high index of fatal recurrence. In order to establish an adequate preventive strategy it is crucial to identify the cause of the embolism. After a complete diagnostic workup up to 30% of strokes remain with an undetermined cause, and most of them are attributed to an embolic mechanism suggesting a cardiac origin.
There is no consensus in the extent and optimal approach of cardiac workup of ischemic stroke. Clinical features along with brain imaging and the study of the cerebral vessels with ultrasonography or MRI/CT based angiography can identify other causes or lead to think about a possible cardioembolic origin.
Atrial fibrillation is the most common cause of cardioembolic stroke. Identification of occult atrial fibrillation is essential. Baseline ECG, serial ECG(’s), cardiac monitoring during the first 48 hours, and Holter monitoring have detection rates varying from 4 to 8% each separately. Extended cardiac monitoring with event loop recorders has shown higher rates of detection of paroxysmal atrial fibrillation.
Cardiac imaging with echocardiography is necessary to identify structural sources of emboli. There is insufficient data to determine which is the optimal approach. Transthoracic echocardiography has an acceptable diagnostic yield in patients with heart disease but transesophageal echocardiography has a higher diagnostic yield and is necessary if no cardiac sources have been identified in patients with cryptogenic stroke with embolic mechanism.
Ambulatory electrocardiography; atrial fibrillation; cardiac workup; cardioembolic stroke; cryptogenic stroke; echocardiography; electrocardiography; stroke.
Standard procedures carried out at a stroke department in patients after a cerebral event may prove insufficient for monitoring hemodynamic indices. Impedance cardiography enables hemodynamic changes to be monitored non-invasively. The aim of the work was to describe hemodynamic parameters in patients with acute phase of ischemic and hemorrhagic stroke and to analyse the correlation between the type of hemodynamic response and long-term prognosis.
Material and methods
The 45 consecutive subjects with ischemic stroke and 16 with a hemorrhagic stroke were examined additionally with impedance cardiography during the first day of hospitalization. The heart contractility, pump performance, afterload and preload indices were recorded and calculated automatically and the data analyzed in terms of 6-month mortality.
We found a significant association between the systemic vascular resistance index, Heather index, stroke index, heart rate, systolic and diastolic and mean arterial blood pressure and mortality in patients with ischemic stroke (p = 0.002, p = 0.008, p = 0.012, p = 0.005, p = 0.007, p = 0.009, p = 0.002 respectively). Logistic regression analysis identified the thoracic fluid content as the most significant variable correlating with the non-survival of the patients with ischemic stroke and in the whole group (ischemic and hemorrhagic stroke). The significant parameters were also mean arterial pressure and stroke index in ischemic stroke (the correct answer ratio was 86.67%) and heart rate in the whole group (the correct answer ratio was 80.33%). There were no significant associations in hemorrhagic stroke.
The hemodynamic parameters correlate with long term prognosis in patients with ischemic brain stroke.
ischaemic stroke; hemorrhagic; hemodynamics; impedance cardiography
Cerebral ischemia and ischemic heart diseases, common entities nowadays, are the main manifestation of circulatory diseases. Cardiovascular diseases, followed by stroke, represent the leading cause of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. However, each entity has its own particularities. Ischemic stroke shows a variety of pathogenic mechanisms not present in ischemic heart disease. An ischemic stroke increases the risk of suffering a coronary heart disease, and viceversa. The aim of this chapter is to review data on epidemiology, pathophisiology and risk factors for both entities, considering the differences and similarities that could be found in between them. We discuss traditional risk factors, obtained from epidemiological data, and also some novel ones, such as hyperhomocisteinemia or sleep apnea. We separate risk factors, as clasically, in two groups: nonmodifiables, which includes age, sex, or ethnicity, and modifiables, including hypertension, dyslipidemia or diabetis, in order to discuss the role of each factor in both ischemic events, ischemic stroke and coronary heart disease.
Coronary heart disease; ischemic stroke; epidemiology; risk factors.
Information on the leading causes of mortality will continue to rely on verbal autopsy (VA) in developing countries. The accuracy of VA methods in correctly ascertaining the cause for each individual death is crucial in order to have confidence in the data collected through the procedure. Accuracy of the VA procedure is generally established by carrying out validation studies involving a comparison of the underlying cause of death derived from the VA with a reference underlying cause from medical records. Such validation is only possible in cases for which clinical records are available, and this is clearly not the case for most deaths in developing countries. We attempt to verify the accuracy of VA evidence by reviewing the responses to specific symptom questions and other information recorded in verbal autopsy questionnaires that were assigned cerebrovascular conditions (stroke) as causes of death upon physician review in Vietnam.
Materials and Methods:
A national sample mortality surveillance activity identified deaths and causes of death that had occurred during 2008 in selected communes in 16 provinces distributed across Vietnam. All cases from the northern provinces of Hanoi, Hai Duong, Quang Ninh and Thanh Hoa with ICD codes pertaining to cerebrovascular diseases were identified. A total of 326 VA questionnaires for deaths from cerebrovascular diseases were reviewed and analysed in detail for the presence of symptoms pertaining to stroke. The respondents’ narration of the chronological disease history and the hospital diagnosis was also examined with an aim to explore supporting signs for diagnosis and to verify the quality of VA interview. Differences between responses among cases with and without hospital admission were examined using Chi-squared test of statistical significance.
Ninty percent of the cases diagnosed as stroke were found to have positive response to the key symptoms; viz., paralysis (in structured question or free text) and history of stroke. For the remaining 10% of cases, stroke was assigned as a cause-of-death based on other suggestive cardiac signs and symptoms such as hypertension, unconsciousness, or headache, etc. Community had different perspectives of “paralysis” and “stroke” which might have affected the diagnosis of stroke in some aspects. Respondents of cases with hospital admission or visit were found to have a better recall of disease symptoms than those without hospital admission.
The results of this study suggest the possible utility of VA content analysis method to back up the low coverage of conventional validation studies in developing countries owing to nonavailability of medical records. The understanding of the VA content would also form the basis for improvement in the quality of interviews and collection of data to achieve better quality information in future.
Cause-of-death; stroke; validation; verbal autopsy
Cardiovascular disease (CVD) mortality increased in developed countries until the 1970s then started to decline. Turkey is about to complete its demographic transition, which may also influence mortality trends. This study evaluated trends in coronary heart disease (CHD) and stroke mortality between 1988 and 2008.
The number of deaths by cause (ICD-8), age and sex were obtained from the Turkish Statistical Institute (TurkStat) annually between 1988 and 2008. Population statistics were based on census data (1990 and 2000) and Turkstat projections. European population standardised mortality rates for CHD and stroke were calculated for men and women over 35 years old. Joinpoint Regression was used to identify the points at which a statistically significant (p < 0.05) change of the trend occurred.
The CHD mortality rate increased by 2.9% in men and 2.0% in women annually from 1988 to 1994, then started to decline. The annual rate of decline for men was 1.7% between 1994–2008, whilst in women it was 2.8% between 1994–2000 and 6.7% between 2005–2008 (p < 0.05 for all periods).
Stroke mortality declined between 1990–1994 (annual fall of 3.8% in both sexes), followed by a slight increase between 1994–2004 (0.6% in men, 1.1% in women), then a further decline until 2008 (annual reduction of 4.4% in men, 7.9% in women) (p < 0.05 for all periods).
A decrease in CVD mortality was observed from 1995 onwards in Turkey. The causes need to be explored in detail to inform future policy priorities in noncommunicable disease control.
Coronary heart disease mortality; Stroke mortality; Cardiovascular mortality; Trends; Turkey
To compare nosologist coding of death certificate’s underlying cause of death with adjudicated cause of death for subjects age 65+ in the Cardiovascular Health Study (CHS).
Four communities: Forsyth County North Carolina (Wake Forest University), Sacramento County California (University of California at Davis), Washington County Maryland (Johns Hopkins University), and Pittsburgh Pennsylvania (University of Pittsburgh).
Men and women ages 65 and over participating in CHS, a longitudinal study of coronary heart disease and stroke, and who died through June 2004.
The CHS centrally adjudicated underlying cause of death for 3194 fatal events from 6/1989–6/2004 using medical records, death certificates, proxy interviews and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only.
Comparison of 3194 CHS vs. nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95% CI:0.89–0.93). Kappas varied by category: CHD=0.61 (95% CI:0.58–0.64), stroke=0.59 (95% CI:0.54–0.64), COPD=0.58 (95% CI:0.51–0.65), dementia=0.40 (95% CI:0.34–0.45), and pneumonia=0.35 (95% CI:0.29–0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in both sex and race categories. CHS classified 340 (10.6%) of deaths due to dementia, while nosologist coding classified only 113 (3.5%) with dementia as the underlying cause.
Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality.
death certificates; mortality; vital statistics
We investigated the relationship between dietary iron intake and mortality from cardiovascular disease (CVD) in a population-based sample of Japanese adults.
The study cohort consisted of 58 615 healthy Japanese (23 083 men and 35 532 women), aged between 40 and 79 years, who had no history of stroke, coronary heart disease (CHD), or cancer at baseline. Dietary iron intake was assessed at baseline by a validated food frequency questionnaire administered between 1988 and 1990 as part of the Japan Collaborative Cohort (JACC) Study.
We documented 2690 (1343 men and 1347 women) deaths from CVD: 1227 (607 men and 620 women) deaths from total stroke, 651 from ischemic stroke (355 men and 296 women), 459 (196 men and 263 women) from hemorrhagic stroke, and 557 (311 men and 246 women) from CHD. Dietary intake of total iron was positively associated with mortality from total and ischemic stroke and total CVD in men. The multivariable hazard ratio for the highest versus the lowest quintile of total iron intake was 1.43 (95% CI, 1.02–2.00; P for trend = 0.009) for total stroke and 1.27 (1.01–1.58; 0.023) for total CVD in men. Dietary total iron intake was not associated with mortality from other endpoints in men, and was not associated with any endpoints in women.
Dietary intake of total iron was positively associated with mortality from stroke and total CVD in Japanese men.
dietary iron; mortality; stroke; coronary heart disease; cardiovascular disease; follow-up studies
STUDY OBJECTIVE--The study investigated the joint effect of body mass index and systolic blood pressure on cardiovascular and total mortality. DESIGN--This was a prospective cohort study. The main outcome measures were age adjusted mortality and relative risks estimated from survival models. SETTING--The population of the city of Bergen, Norway. PARTICIPANTS--Subjects were 21,145 men and 30,330 women aged 30-79 years at the time of examination in 1963. MAIN RESULTS--Both cause specific and all cause mortality increased with systolic blood pressure within each category of body mass index. Stroke mortality was not significantly associated with body mass index when adjusted for systolic blood pressure in either age group of men or women. Coronary heart disease mortality increased on average 30% per 5 kg/m2 increase in body mass index in men and women aged 30-59 years at baseline. Adjusted for systolic blood pressure, the relative risks were reduced to 1.20 (95% confidence interval (CI) 1.12, 1.29) in men and 1.10 (95% CI 1.03, 1.18) in women. They were similar at each level of systolic blood pressure. For coronary heart disease mortality in men and women aged 60-79 years at measurement a negative interaction between body mass index and systolic blood pressure was suggested in the first five years. Excluding the first five years, adjusted relative risks per 5 kg/m2, were 1.05 (95% CI 0.96, 1.15) in men and 1.11 (95% CI 1.04, 1.17) in women in the older age group. There was an upturn in cardiovascular mortality at low levels of body mass index in both age groups of women, but not in men. CONCLUSIONS--Hypertension is an important risk factor for cardiovascular and all cause mortality even in the obese. Body mass index is generally a weak predictor of cardiovascular mortality in this population. It is a stronger risk factor of coronary death in men when measured at a younger age. Thin people with hypertension are not at particularly high risk of death from coronary heart disease compared with their obese counterparts, except possibly in the first few years after measurement in the elderly. Being underweight is associated with increased risk of death from all cardiovascular causes in women, but not in men.
The relationship between dietary glycemic index, glycemic load and risk of coronary heart disease (CHD), stroke, and stroke-related mortality is inconsistent.
We systematically searched the MEDLINE, EMBASE, and Science Citation Index Expanded databases using glycemic index, glycemic load, and cardiovascular disease and reference lists of retrieved articles up to April 30, 2012. We included prospective studies with glycemic index and glycemic load as the exposure and incidence of fatal and nonfatal CHD, stroke, and stroke-related mortality as the outcome variable. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models.
Fifteen prospective studies with a total of 438,073 participants and 9,424 CHD cases, 2,123 stroke cases, and 342 deaths from stroke were included in the meta-analysis. Gender significantly modified the effects of glycemic index and glycemic load on CHD risk, and high glycemic load level was associated with higher risk of CHD in women (RR = 1.49, 95%CI 1.27−1.73), but not in men (RR = 1.08, 95%CI 0.91−1.27). Stratified meta-analysis by body mass index indicated that among overweight and obese subjects, dietary glycemic load level were associated with increased risk of CHD (RR = 1.49, 95%CI 1.27−1.76; P for interaction = 0.003). Higher dietary glycemic load, but not glycemic index, was positively associated with stroke (RR = 1.19, 95% CI 1.00−1.43). There is a linear dose-response relationship between dietary glycemic load and increased risk of CHD, with pooled RR of 1.05 (95%CI 1.02−1.08) per 50-unit increment in glycemic load level.
High dietary glycemic load is associated with a higher risk of CHD and stroke, and there is a linear dose-response relationship between glycemic load and CHD risk. Dietary glycemic index is slightly associated with risk of CHD, but not with stroke and stroke-related death. Further studies are needed to verify the effects of gender and body weight on cardiovascular diseases.
OBJECTIVES--To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over. DESIGN--A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded. SETTING--Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS--730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4. RESULTS--Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease. CONCLUSION--In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease.
There is limited evidence regarding the relationship between serum tocopherol levels and cardiovascular disease.
We conducted a nested case-control study as part of the Japan Collaborative Cohort Study for evaluation of cancer risk (JACC Study). Baseline serum samples were collected from 39 242 participants (age range, 40–79 years) between 1988 and 1990. During the 13-year follow-up, there were 530 stroke deaths (302 ischemic strokes and 210 hemorrhagic strokes) and 211 deaths from coronary heart disease. Controls were matched for sex, age, and area of residence.
Serum α-tocopherol level was not associated with any type of cardiovascular death in men; however, in women, it was inversely associated with total stroke mortality and hemorrhagic stroke mortality. The multivariate odds ratio (95% CI) for the highest versus the lowest quintile of serum α-tocopherol levels among women was 0.35 (0.16–0.77; P for trend = 0.009) for total stroke and 0.26 (0.07–0.97; P for trend = 0.048) for hemorrhagic stroke. Serum γ-tocopherol was inversely associated with ischemic stroke mortality in men but positively associated with hemorrhagic stroke mortality in women. The respective multivariate odds ratios (95% CI) for the highest versus the lowest quintile and for a 1-standard deviation increment in γ-tocopherol level were 0.48 (0.22–1.06; P for trend = 0.07) and 0.77 (0.58–1.02), respectively, for ischemic stroke in men and 3.10 (0.95–10.12; P for trend = 0.052) and 1.49 (1.04–2.13) for hemorrhagic stroke in women.
Among women, hemorrhagic stroke mortality was inversely associated with serum α-tocopherol and positively associated with serum γ-tocopherol. These findings are due in part to the antioxidative and antithrombotic activities of these tocopherols.
α-tocopherol; γ-tocopherol; vitamin E; prospective study; stroke; cardiovascular disease; nested case-control study
Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions.
The effects of habitual dairy consumption and the risk of 15-year cardiovascular disease (CVD) mortality in a cohort of older Australians were investigated. Participants (n = 2900) completed a validated 145-item semi-quantitative food frequency questionnaire. Cox proportional hazards regression models were used to investigate associations between tertiles of the dairy consumption, including low/reduced fat dairy, whole fat dairy and their ratio (ratioLF/WF), and risk of mortality from coronary heart disease (CHD), stroke or combined CVD. There were 548 recorded cases of CVD mortality in this cohort. For total dairy intake, a reduction in risk of CVD was only seen in tertile 2 (adjusted hazard ratio, AHR: 0.71; 95% CI: 0.55–0.93), and for CHD both tertile 2 and tertile 3 were associated with a reduced risk (both with AHR: 0.71). However there were no linear trends between total dairy consumption and any of the three outcomes. There were no associations or trends between low/reduced fat dairy or whole fat dairy consumption, or ratioLF/WF and any of the three outcomes in the fully adjusted model (all p > 0.05). This study found no consistent association between baseline consumption of dairy foods and the risk of CHD, stroke and combined CVD mortality.
dairy; cardiovascular disease; older Australian; Blue Mountains Eye Study; population
Most studies providing data on survival in patients with atherosclerosis only address a single disease site: heart, brain or legs. Therefore, our objective was to determine risk of death after first hospital admission for atherosclerotic disease located at different sites.
A nationwide cohort of patients hospitalized for the first time for acute myocardial infarction (AMI), peripheral arterial disease of the lower extremities (PAD) or ischemic stroke was identified through linkage of national registers. The mortality rate in AMI patients was compared to mortality rate in ischemic stroke and PAD patients by estimating relative risks (with 95%CI). Cox's proportional hazard models were used to estimate sex differences in risk of death.
Case fatality was high for ischemic stroke patients (men:21.0%, women:23.8%) and AMI patients (men:12.7%, women:20.9%) though low for PAD patients (men:2.4%, women:3.5%). The five-year risk of death was similar for male AMI compared to PAD patients (men: RR1.04; 95%CI 0.98-1.11). The risk of death for ischemic stroke patients remained the highest though the differences with AMI and PAD patients attenuated.
The dynamics of mortality over follow-up time clearly differ between atherosclerotic diseases, located at different vascular beds. The risk of death increases considerably over follow-up time for PAD patients, and 5 years after first hospital admission the differences in risks of death between AMI- and PAD patients and between AMI- and ischemic stroke patients have largely attenuated. Clinicians should be aware of these dynamics of mortality over follow-up time to provide optimal secondary prevention treatment.
Ischemic stroke is a serious disease leading to significant morbidity and mortality. Multifocal and recurrent strokes are usually caused by embolic diseases, i.e. atrial fibrillation, but rare causes like cerebral vasculitis and clotting disorders are also well known. Here we report on two patients suffering from the very rare intravascular large B-cell lymphoma leading to multifocal and recurrent strokes in the brain and spinal cord as the prominent neurological symptom. The difficulties and the need for diagnostic brain biopsy in making an ‘in vivo’ diagnosis in this particular disease are outlined. Furthermore, the prerequisite for an interdisciplinary approach in these patients is strongly emphasized. Delayed diagnosis for several reasons was the most probable cause for cerebral relapse leading to death in one patient a few months after diagnosis. Conversely, early initiation of immunochemotherapy with a classical lymphoma schedule (R-CHOP) led to long-lasting remission of the disease in the other patient. With this report we like to improve alertness to intravascular large B-cell lymphoma as a cause for multifocal and recurrent strokes.
Intravascular large B-cell lymphoma; Stroke; Cerebral vasculitis; Brain biopsy; R-CHOP
Multiple cause-of-death data--that is, records of all medical conditions listed on death certificates--are used to study hypertension mortality in New York State during 1968-82. Mortality rates based on underlying causes for ischemic heart disease (IHD) and stroke are selected for comparison. During 1968-78, white women showed the largest age-adjusted decline of all race-sex groups for hypertension, as white men did for stroke and nonwhite men did for IHD. White men showed the largest age-adjusted decline for all three diseases for 1979-82. In general, declines in hypertension death rates are more comparable to declines in stroke mortality than to IHD mortality.
Cardiovascular diseases are the main cause of death in women and men in Brazil, but the trends for the death ratios for ischemic heart disease and stroke in women and men remain unknown.
In this study, the trends for the death ratios among women and men who were over 30 years of age were analyzed from 1980 to 2005. Data were collected for both the Brazilian population and the metropolitan area of São Paulo. Estimates of the population size and data for mortality were then obtained from the Brazilian Institute of Geography and Statistics and the Ministry of Health. The risk for death was adjusted using a direct method.
Death rates due to cardiovascular disease, ischemic heart disease, and stroke have declined in both Brazil and the metropolitan region of São Paulo. A linear regression analysis revealed a similar trend for ischemic heart disease and demonstrated a male/female ratio of 1.653 ± 0.001 (r = 0.228; p = 0.262) in Brazil and 1.763 ± 0.008 (r = 0.863; p<0.001) in São Paulo. Comparisons between the slopes of the linear regressions showed an increased ischemic heart disease ratio in men/women in São Paulo in comparison to those in Brazil (p<0.0001). The linear regression showed an increasing trend for the male/female stroke ratio of 1.252 ± 0.004 (r = 0.776; p<0.0001) in Brazil and 1.331 ± 0.006 (r = 0.580; p = 0.002) in São Paulo. Comparisons between the regressions for the stroke ratio were similar for men/women in São Paulo compared to Brazil (p = 0.244).
We observed an increased trend in the ratio for ischemic heart disease death in men compared to women. Improvements in the control of risk factors and treatments for both men and women are mandatory to reduce the number of ischemic heart disease‐related deaths in Brazil.
Brain Ischemia; Myocardial Ischemia; Mortality; São Paulo; Brazil
Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality.
Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates.
There was no relationship between CHD and stroke mortality rates (r = 0.04; p = 0.78), but there was between CHD and stroke risk scores at the individual (r = 0.68; p < 0.0001) and state (r = 0.64, p < 0.0001) level. There was a stronger (p < 0.0001) association between state-level FCRS and state-level CHD mortality (r = 0.28, p = 0.18), than between FSRS and stroke mortality (r = 0.12, p = 0.56).
Weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest geographic variation in risk factors may not underlie geographic variations in stroke and CHD mortality. The relationship between risk factor scores and mortality was stronger for CHD than stroke.
Stroke; Coronary Heart Disease; Geography; Risk Factors; Mortality
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), induces endothelial dysfunction. Although elevated ADMA has been associated with an increased risk of cardiovascular disease (CVD) events and mortality in referral samples, the prognostic significance of ADMA in the community has not been adequately evaluated.
Methods and Results
We related plasma ADMA, L-arginine, and the Arg/ADMA ratio to the incidence of CVD (fatal or non-fatal myocardial infarction, coronary insufficiency, angina pectoris, stroke or transient ischemic attack, intermittent claudication, or heart failure) and death in 3319 Framingham Offspring participants (1769 women; mean age 59 years). Over a follow-up period of 10.9 years, 281 individuals of 2956 free of CVD at baseline developed incident CVD, and 285 participants died. In multivariable models adjusting for established risk factors and other biomarkers (B-type natriuretic peptide, renin, homocysteine, urine albumin excretion and C-reactive protein), ADMA and the Arg/ADMA ratio were significantly associated with all-cause mortality (adjusted-hazard ratio [HR] per SD increment 1.21, 95% CI 1.07-1.37, and 0.80, 95% CI 0.69-0.93, respectively), whereas L-arginine was not (HR per SD 0.89, 95% CI 0.77-1.02). We noted effect modification by diabetes status: ADMA was associated with mortality in individuals without diabetes (adjusted-HR per SD increment 1.30, 95% CI 1.13-1.50), but not in individuals with diabetes (adjusted-HR per SD increment 0.85, 95% CI 0.62-1.16). ADMA, L-arginine and the Arg/ADMA ratio were not associated with CVD incidence (p >0.10).
In our large community-based sample, ADMA was significantly associated with all-cause mortality, particularly in non-diabetic individuals.
nitric oxide; l-arginine; ADMA; cardiovascular disease; epidemiology
We developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established.
The Rotterdam Ischemic Heart Disease and Stroke Computer Simulation (RISC) model was developed using data covering 5 years of follow-up from the Rotterdam Study. To prove 1) internal and 2) predictive validity, the incidences of coronary heart disease (CHD), stroke, CVD death, and non-CVD death simulated by the model over a 13-year period were compared with those recorded for 3,478 participants in the Rotterdam Study with at least 13 years of follow-up. 3) External validity was verified using 10 years of follow-up data from the European Prospective Investigation of Cancer (EPIC)-Norfolk study of 25,492 participants, for whom CVD and non-CVD mortality was compared.
At year 5, the observed incidences (with simulated incidences in brackets) of CHD, stroke, and CVD and non-CVD mortality for the 3,478 Rotterdam Study participants were 5.30% (4.68%), 3.60% (3.23%), 4.70% (4.80%), and 7.50% (7.96%), respectively. At year 13, these percentages were 10.60% (10.91%), 9.90% (9.13%), 14.20% (15.12%), and 24.30% (23.42%). After recalibrating the model for the EPIC-Norfolk population, the 10-year observed (simulated) incidences of CVD and non-CVD mortality were 3.70% (4.95%) and 6.50% (6.29%). All observed incidences fell well within the 95% credibility intervals of the simulated incidences.
We have confirmed the internal, predictive, and external validity of the RISC model. These findings provide a basis for analyzing the effects of modifying cardiovascular disease risk factors on the burden of CVD with the RISC model.
Cardiovascular disease prevention; Simulation modeling; Model validation
Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.
Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance.
On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections.
PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections.
Acute ischemic stroke is a leading cause of mortality and disability in the elderly. Age is the most important non-modifiable risk factor for stroke, yet many preclinical models continue to examine only young male animals. In addition, the majority of stroke deaths now occur in older women, who also shoulder the burden of stroke-related disability, yet no preclinical studies have examined the effect of aging on stroke outcome in female mice. It remains unclear how experimental stroke outcomes change with aging and with biological sex. If sex differences are present, it is not known if these reflect an intrinsic differing sensitivity to stroke or are secondary to the loss of estrogen with aging. To address these questions, we subjected both young and aging C57BL/6 mice of both sexes to middle cerebral artery occlusion (MCAO). Young female mice had smaller strokes compared to age-matched males, an effect that was reversed by ovariectomy. Interestingly, stroke damage increased with aging in female mice whereas male mice had decreased damage after MCAO. Blood Brain Barrier (BBB) permeability changes correlated with infarct size. However edema formation exhibited a striking age-dependent effect that was independent of sex and histological damage, with a significant decrease in edema formation in the aging brains of both sexes. Differences in the cellular response to stroke occur across the lifespan in both male and female mice. These differences need to be considered when developing relevant therapies for stroke patients, the vast majority of whom are elderly.
age; blood brain barrier; cerebral edema; inflammation; sex difference; focal cerebral ischemia
Pathologists' opinions of cause of death given at the end of post-mortem (PM) reports have often been used to validate clinicians' death certificates. Information about strokes, common coincident conditions and complications in 120 full PM reports was compared with the pathologists' opinions of cause of death given at the end of the reports. Intracranial haemorrhage and myocardial infarction were mentioned as frequently in the cause of death as in the full PM report. On the other hand, cerebral infarction, precerebral artery occlusion, severe cerebral atheroma, coronary artery occlusion, bronchopneumonia and pulmonary embolism were all under-cited in the causes of death. Whether a pathological condition mentioned in the full PM report also appeared in the cause of death varied with the decedent's age, the extent of the condition and type of stroke. Consideration should be given to using all the information in PM reports rather than just pathologists' opinions of cause of death given at the end of PM reports when studying the validity of clinicians' death certificates.