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1.  Spontaneous intra-cerebral hemorrhage: A retrospective study of risk factors and outcome in a Turkish population 
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.
Results:
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).
Conclusion:
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.
doi:10.4103/0976-3147.118770
PMCID: PMC3821411  PMID: 24250158
Mortality; risk factors; spontaneous intra-cerebral hemorrhage; treatment
2.  Assessing the global burden of ischemic heart disease, part 2: analytic methods and estimates of the global epidemiology of ischemic heart disease in 2010 
Global heart  2012;7(4):331-342.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.gheart.2012.10.003
PMCID: PMC3595103  PMID: 23505617
3.  Cardiac Workup of Ischemic Stroke 
Current Cardiology Reviews  2010;6(3):175-183.
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.
doi:10.2174/157340310791658721
PMCID: PMC2994109  PMID: 21804776
Ambulatory electrocardiography; atrial fibrillation; cardiac workup; cardioembolic stroke; cryptogenic stroke; echocardiography; electrocardiography; stroke.
4.  Assessing the quality of evidence for verbal autopsy diagnosis of stroke in Vietnam 
Background:
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.
Results:
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.
Conclusion:
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.
doi:10.4103/0976-3147.102603
PMCID: PMC3505314  PMID: 23188975
Cause-of-death; stroke; validation; verbal autopsy
5.  Body mass index and cardiovascular mortality at different levels of blood pressure: a prospective study of Norwegian men and women. 
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.
PMCID: PMC1060795  PMID: 7629461
6.  Decreasing trends in cardiovascular mortality in Turkey between 1988 and 2008 
BMC Public Health  2013;13:896.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1471-2458-13-896
PMCID: PMC3850640  PMID: 24079269
Coronary heart disease mortality; Stroke mortality; Cardiovascular mortality; Trends; Turkey
7.  Is higher body temperature beneficial in ischemic stroke patients with normal admission CT angiography of the cerebral arteries? 
Background
Low body temperature is considered beneficial in ischemic stroke due to neuroprotective mechanisms, yet some studies suggest that higher temperatures may improve clot lysis and outcomes in stroke patients treated with tissue plasminogen activator (tPA). The effect of increased body temperature in stroke patients treated with tPA and with normal computed tomography angiography (CTA) on admission is unknown. We hypothesized a beneficial effect of higher body temperature in the absence of visible clots on CTA, possibly due to enhanced lysis of small, peripheral clots.
Methods
Patients with ischemic stroke admitted to our Stroke Unit between February 2006 and April 2013 were prospectively registered in a database (Bergen NORSTROKE Registry). Ischemic stroke patients treated with tPA with normal CTA of the cerebral arteries were included. Outcomes were assessed by the modified Rankin Scale (mRS) after 1 week. An excellent outcome was defined as mRS=0, and a favorable outcome as mRS=0–1.
Results
A total of 172 patients were included, of which 48 (27.9%) had an admission body temperature ≥37.0°C, and 124 (72.1%) had a body temperature <37.0°C. Body temperature ≥37.0°C was independently associated with excellent outcomes (odds ratio [OR]: 2.8; 95% confidence interval [CI]: 1.24–6.46; P=0.014) and favorable outcomes (OR: 2.8; 95% CI: 1.13–4.98; P=0.015) when adjusted for confounders.
Conclusion
We found an association between higher admission body temperature and improved outcome in tPA-treated stroke patients with normal admission CTA of the cerebral arteries. This may suggest a beneficial effect of higher body temperature on clot lysis in the absence of visible clots on CTA.
doi:10.2147/VHRM.S55423
PMCID: PMC3905091  PMID: 24482573
acute ischemic stroke; body temperature; thrombolysis; tissue plasminogen activator
8.  Agreement Between Nosologist and Cardiovascular Health Study Review of Deaths: Implications of Coding Differences 
Objectives
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).
Design
Observational study.
Setting
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).
Participants
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.
Measurements
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.
Results
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.
Conclusion
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.
doi:10.1111/j.1532-5415.2008.02056.x
PMCID: PMC2631612  PMID: 19016930
death certificates; mortality; vital statistics
9.  Dietary Glycemic Index, Glycemic Load, and Risk of Coronary Heart Disease, Stroke, and Stroke Mortality: A Systematic Review with Meta-Analysis 
PLoS ONE  2012;7(12):e52182.
Background
The relationship between dietary glycemic index, glycemic load and risk of coronary heart disease (CHD), stroke, and stroke-related mortality is inconsistent.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1371/journal.pone.0052182
PMCID: PMC3527433  PMID: 23284926
10.  Pathophysiology, treatment, and animal and cellular models of human ischemic stroke 
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.
doi:10.1186/1750-1326-6-11
PMCID: PMC3037909  PMID: 21266064
11.  Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people. 
BMJ : British Medical Journal  1995;310(6994):1563-1566.
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.
PMCID: PMC2549941  PMID: 7787644
12.  Relation of Serum α- and γ-Tocopherol Levels to Cardiovascular Disease-Related Mortality Among Japanese Men and Women 
Journal of Epidemiology  2012;22(5):402-410.
Background
There is limited evidence regarding the relationship between serum tocopherol levels and cardiovascular disease.
Methods
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.
Results
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.
Conclusions
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.
doi:10.2188/jea.JE20120002
PMCID: PMC3798634  PMID: 22672959
α-tocopherol; γ-tocopherol; vitamin E; prospective study; stroke; cardiovascular disease; nested case-control study
13.  Associations of Dietary Iron Intake With Mortality From Cardiovascular Disease: The JACC Study 
Journal of Epidemiology  2012;22(6):484-493.
Background
We investigated the relationship between dietary iron intake and mortality from cardiovascular disease (CVD) in a population-based sample of Japanese adults.
Methods
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.
Results
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.
Conclusions
Dietary intake of total iron was positively associated with mortality from stroke and total CVD in Japanese men.
doi:10.2188/jea.JE20120006
PMCID: PMC3798559  PMID: 22986645
dietary iron; mortality; stroke; coronary heart disease; cardiovascular disease; follow-up studies
14.  The dynamics of mortality in follow-up time after an acute myocardial infarction, lower extremity arterial disease and ischemic stroke 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2261-10-57
PMCID: PMC3003625  PMID: 21106115
15.  Multiple cause-of-death analysis of hypertension-related mortality in New York State. 
Public Health Reports  1987;102(3):329-335.
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.
PMCID: PMC1477851  PMID: 3108950
16.  Trends in ischemic heart disease and stroke death ratios in brazilian women and men 
Clinics  2010;65(11):1143-1147.
OBJECTIVE:
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.
METHOD:
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.
RESULTS:
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).
CONCLUSION:
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.
doi:10.1590/S1807-59322010001100016
PMCID: PMC2999711  PMID: 21243288
Brain Ischemia; Myocardial Ischemia; Mortality; São Paulo; Brazil
17.  Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial 
PLoS ONE  2008;3(5):e2158.
Background
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.
Methods
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.
Findings
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.
Interpretation
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.
Trial Registration
Controlled-Trials.com ISRCTN74386719
doi:10.1371/journal.pone.0002158
PMCID: PMC2373885  PMID: 18478129
18.  Changes in experimental stroke outcome across the lifespan 
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.
doi:10.1038/jcbfm.2009.5
PMCID: PMC2748430  PMID: 19223913
age; blood brain barrier; cerebral edema; inflammation; sex difference; focal cerebral ischemia
19.  The ethnic differences of stroke in Yakutia 
International Journal of Circumpolar Health  2013;72:10.3402/ijch.v72i0.21221.
Background
In Yakutia, the morbidity and mortality from stroke increased in the past 2 decades. Stroke share in the total mortality structure increased significantly. According to the autopsies, haemorrhagic stroke (HS) was more common in indigenous patients.
Objective
The aim of the study was to examine ethnic features of stroke patients of indigenous and non-indigenous ethnicity admitted to Regional Vascular Center (RVC), Yakutsk.
Design
The study used data from a hospital stroke registry, which took into account the cases of acute stroke in 2011. Stroke type and aetiology were determined by clinical examination, computed tomography and magnetic resonance imaging studies, cerebral angiography and ultrasound of cerebral vessels.
Results
A total of 1,108 patients were hospitalized (51.4% male, n=569) in 2011. The mean age was 60.5±12.9 years, male: 59.1±12.8, female: 61.9±13.05. Five hundred and ninety-two ischemic strokes (IS; 53.4%), 236 HS (21.3%), 280 transient ischemic attacks (TIA; 25.3%) were diagnosed. Patients who had a stroke were divided into 3 groups according to their ethnicity: native (n=411; 49.6%), Russians (n=347; 41.9%) and other nationalities (n=70; 8.5%). When comparing the incidence of HS in different ethnic groups, it was found that indigenous patients had more cases of HS than Russians (38% vs. 20.2%, p<0.05; adjusted odds ratio=2.42; 95% confidence interval: 1.72–3.41). Mean age of IS and HS indigenous patients had no significant differences compared with the average age of Russian ethnicity patients (p=0.69; p=0.201, respectively).
Conclusions
The data from this study suggest that among the patients who suffered from stroke in the indigenous population, the share of a haemorrhagic form washigher than those of non-indigenous Caucasians. At the same time, the average age of patients, both having IS and HS had no significant differences by ethnicity. Further studies are needed to establish the causes of ethnic differences of stroke in Yakutia.
doi:10.3402/ijch.v72i0.21221
PMCID: PMC3754494  PMID: 23986887
epidemiology; ischemic stroke; haemorrhagic stroke; incidence; ethnic differences
20.  Hemodynamic findings in patients with brain stroke 
Introduction
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.
Results
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.
Conclusions
The hemodynamic parameters correlate with long term prognosis in patients with ischemic brain stroke.
doi:10.5114/aoms.2012.28567
PMCID: PMC3361052  PMID: 22662014
ischaemic stroke; hemorrhagic; hemodynamics; impedance cardiography
21.  Fatty liver predicts the risk for cardiovascular events in middle-aged population: a population-based cohort study 
BMJ Open  2014;4(3):e004973.
Objective
We investigated if the differences in liver fat content would predict the development of non-fatal and fatal atherosclerotic endpoints (coronary heart disease and stroke).
Design, setting and participants
Our study group is a population-based, randomly recruited cohort (Oulu Project Elucidating Risk of Atherosclerosis, OPERA), initiated in 1991. The cohort consisted of 988 middle-aged Finnish participants.
Intervention
Total mortality and hospital events were followed up to 2009 based on the registry of the National Institute for Health and Welfare and the National death registry.
Main outcome measure
The severity of hepatic steatosis was measured by ultrasound and divided into three groups (0–2). Cox regression analysis was used in the statistical analysis.
Results
In the follow-up of years 1991–2009, 13.5% of the participants with non-fatty liver, 24.2% of participants having moderate liver fat content and 29.2% of the participants having severe fatty liver experienced a cardiovascular event during the follow-up time (p<0.001). Severe liver fat content predicted the risk for future risk of cardiovascular event even when adjusted for age, gender and study group (HR 1.92, CI 1.32 to 2.80, p<0.01). When further adjustments for smoking, alcohol consumption, low-density lipoprotein-cholesterol, body mass index and systolic blood pressure were conducted, the risk still remained statistically significant (HR 1.74, CI 1.16 to 2.63, p<0.01). Statistical significance disappeared with further adjustment for QUICKI.
Conclusions
Liver fat content increases the risk of future cardiovascular disease event in long-term follow-up but it is seems to be dependent on insulin sensitivity.
doi:10.1136/bmjopen-2014-004973
PMCID: PMC3963104  PMID: 24650811
22.  Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences 
Current Cardiology Reviews  2010;6(3):138-149.
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.
doi:10.2174/157340310791658785
PMCID: PMC2994106  PMID: 21804773
Coronary heart disease; ischemic stroke; epidemiology; risk factors.
23.  Relationship of National Institutes of Health Stroke Scale to 30-Day Mortality in Medicare Beneficiaries With Acute Ischemic Stroke 
Background
The National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied.
Methods and Results
We analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]).
Conclusions
The NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.)
doi:10.1161/JAHA.111.000034
PMCID: PMC3487316  PMID: 23130117
ischemic stroke; National Institutes of Health Stroke Scale; mortality; registries
24.  Validation of a model to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD: the rotterdam ischemic heart disease and stroke computer simulation (RISC) model 
BMC Medicine  2012;10:158.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1741-7015-10-158
PMCID: PMC3566939  PMID: 23217019
Cardiovascular disease prevention; Simulation modeling; Model validation
25.  Fatal pulmonary embolism in hospitalized patients: a large autopsy-based matched case-control study 
Clinics  2013;68(5):679-685.
OBJECTIVE:
Pulmonary embolism is an underdiagnosed major cause of death for hospitalized patients. The objective of this study was to identify the conditions associated with fatal pulmonary embolism in this population.
METHODS:
A total of 13,074 autopsy records were evaluated in a case-control study. Patients were matched by age, sex, and year of death, and factors potentially associated with fatal pulmonary embolism were analyzed using univariate and multivariate conditional logistic regression.
RESULTS:
Pulmonary embolism was considered fatal in 328 (2.5%) patients. In the multivariate analysis, conditions that were more common in patients who died of pulmonary embolism were atherosclerosis, congestive heart failure, and neurological surgery. Some conditions were negatively associated with fatal pulmonary embolism, including hemorrhagic stroke, aortic aneurism, cirrhosis, acquired immune deficiency syndrome, and pneumonia. In the control group, patients with hemorrhagic stroke and aortic aneurism had short hospital stays (8.5 and 8.8 days, respectively), and the hemorrhage itself was the main cause of death in most of them (90.6% and 68.4%, respectively), which may have prevented the development of pulmonary embolism. Cirrhotic patients in the control group also had short hospital stays (7 days), and 50% died from bleeding complications.
CONCLUSIONS:
In this large autopsy study, atherosclerosis, congestive heart failure, and neurological surgery were diagnoses associated with fatal pulmonary embolism.
doi:10.6061/clinics/2013(05)16
PMCID: PMC3654296  PMID: 23778403
Atherosclerosis; Heart Failure; Neurosurgery; Pulmonary Embolism; Venous Thromboembolism

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