Statins as secondary preventives in patients with intracerebral hemorrhage.

BACKGROUND: Statins are important components of secondary stroke prevention, but there is a concern they may increase the risk of intracerebral hemorrhage. Although this risk may have been overestimated, there is still an open question whether statin therapy should be continued, or even initiated, in patients who have had a recent intracerebral hemorrhage. AIM: Our aim was to investigate the risk of statin use after an intracerebral hemorrhage with respect to recurrent intracerebral hemorrhage, stroke in general, and death. METHODS: This observational study was based on patients with a first intracerebral hemorrhage in 2004 through 2009. Clinical characteristics, index intracerebral hemorrhage, and recurrent intracerebral hemorrhages were identified by the Swedish Stroke Register; additional data on comorbidities and vital status were retrieved through record linkages to national registers. A propensity score for the likelihood of receiving statins at discharge was developed and used with other established risk factors in a multivariable analysis. RESULTS: Of 6082 intracerebral hemorrhage patients (mean age 69.6 years), 1097 (18%) were prescribed statins at discharge. During the follow-up (mean 3.1 years), 1434 (23.6%) deaths and 234 (3.8%) recurrent intracerebral hemorrhages were observed. Statin therapy was associated with a reduced risk of death (adjusted hazard ratio: 0.71; 95% confidence interval: 0.60-0.84) but not with the risk of recurrent intracerebral hemorrhage (adjusted hazard ratio: 0.82; 95% confidence interval: 0.55-1.22). CONCLUSIONS: This study provides some reassurance that statins may be safe to use, in at least some patients, after an intracerebral hemorrhage. In patients with intracerebral hemorrhage, statin use was associated with a reduced risk of death, without an increased risk of recurrent intracerebral hemorrhage.

Hypertension and cardiovascular diseases in Swedish persons with haemophilia - A longitudinal registry study.

INTRODUCTION: Data on the prevalence of hypertension and cardiovascular diseases (CVD) among persons with haemophilia (PWH) vary. Sweden has a long tradition of maintaining population-based data registries, and there is extensive follow-up of haemophilia patients due to the use of prophylaxis over decades. We evaluated the prevalence of these diseases among Swedish PWH compared to matched controls using a longitudinal study design. METHODS: Data were obtained from the National Patient Registry and linked to records of persons with haemophilia enrolled in the haemophilia centres. For each subject, five gender and age matched controls were identified. RESULTS: We identified 193 (19.7%) diagnoses of hypertension in PWH born in 1978 or earlier over ≥30 years compared with 550 (11.2%) among controls. The median ages and interquartile ranges were 60.0 (42.8, 69.9) and 57.2 (42.6, 70.6) years. The hazard rate (HR) for hypertension, PWH vs. controls, was 2.1, 95% CI: [1.8; 2.5], p < 0.001. The findings were similar in subgroup analyses of patients with non-severe and severe haemophilia with or without HIV and/or viral hepatitis. Angina pectoris was diagnosed in 69 (4.8%) of patients censored at age 75 compared with 311 (4.3%) in controls, and myocardial ischemia in 84 (5.9%) compared with 442 (6.2%). As a cause of death, the HR for myocardial ischemia, comparing PWH and controls, was 0.58, 95% CI: [0.42, 0.80], p = 0.001. CONCLUSION: Our data support an increased prevalence of hypertension among persons with haemophilia. The prevalence of CVD seems to be similar to that of controls, but with lower mortality.

Hereditary colorectal cancer diagnostics in southern Sweden: retrospective evaluation and future considerations with emphasis on Lynch syndrome.

Overlapping phenotypes between different hereditary colorectal cancer (CRC) syndromes together with a growing demand for cancer genetic testing and improved sequencing technology call for adjusted patient selection and adapted diagnostic routines. Here we present a retrospective evaluation of family history of cancer, laboratory diagnostic procedure, and outcome for 372 patients tested for Lynch syndrome (LS), i.e., the single most common hereditary cause of CRC. Based on number of affected family members and age at cancer diagnosis in families with genetically confirmed LS, we developed local patient selection criteria for a simplified one-step gene panel mutation screening strategy targeting also less common Mendelian CRC syndromes. Pros and cons of this strategy are discussed.

BRCAsearch: written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer.

PURPOSE: To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. METHODS: In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. RESULTS: During the period Feb 2, 2015-Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. CONCLUSIONS: Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.

Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls.

BACKGROUND: Little is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF). METHODS: From a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes. RESULTS: During follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.0 ± 3.1 years. CONCLUSIONS: In patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system.

BACKGROUND: Hypo- and hyperkalemia in clinical settings are insufficiently characterized and large-scale data from Europe lacking. We studied incidence and determinants of these abnormalities in a large Swedish healthcare system. METHODS: Observational study from the Stockholm CREAtinine Measurements project, including adult individuals from Stockholm accessing healthcare in 2009 (n=364,955). Over 3-years, we estimated the incidence of hypokalemia, defined as potassium<3.5mmol/L, hyperkalemia, defined as potassium>5mmol/L, and moderate/severe hyperkalemia, defined as potassium>5.5mmol/L. Kidney function was assessed by estimated glomerular filtration rate (eGFR). RESULTS: Of 364,955 participants, 69.4% had 1-2 potassium tests, 16.7% had 3-4 tests and the remaining 13.9% had >4potassiumtests/year. Hypokalemia occurred in 49,662 (13.6%) individuals, with 33% recurrence. Hyperkalemia occurred in 25,461 (7%) individuals, with 35.7% recurrence. Moderate/severe hyperkalemia occurred in 9059 (2.5%) with 28% recurrence. The frequency of potassium testing was an important determinant of dyskalemia risk. The incidence proportion of hyperkalemia was higher in the presence of diabetes, lower eGFR, myocardial infarction, heart failure (HF), or use of renin angiotensin-aldosterone system inhibitors (RAASi). In adjusted analyses, women and use of loop/thiazide diuretics were associated with lower hyperkalemia risk. Older age, lower eGFR, diabetes, HF and use of RAASi were associated with higher hyperkalemia risk. On the other hand, women, younger age, higher eGFR and baseline use of diuretics were associated with higher hypokalemia risk. CONCLUSION: Hypo- and hyperkalemia are common in healthcare. Optimal RAASi and diuretics use and careful potassium monitoring in the presence of certain comorbidities, especially lower eGFR, is advocated.

Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study.

BACKGROUND: Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. METHODS: This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. RESULTS: Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. CONCLUSIONS: A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated. TRIAL REGISTRATION: The present study is registered with ClinicalTrials.gov (ID: NCT00882336).

Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA2DS2-VASc score, age and sex - A Swedish nationwide observational study with 48 433 patients.

AIMS: There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA2DS2-VASc score of 1 point. METHODS: In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA2DS2-VASc score of 0, 1, 2 and ≥3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009. RESULTS: Patients with 1 point from the CHA2DS2-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men <65 years 1.11 (0.56-2.23) and women <65 years 2.13 (0.94-4.82), where HR <1 indicates protection with warfarin. In patients <65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 (0.21-0.73). Categories including age ≥65 years or ≥3 points showed a statistically significant protection from warfarin. CONCLUSIONS: Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA2DS2-VASc score is 1.

Association between enrolment in a heart failure quality registry and subsequent mortality-a nationwide cohort study.

AIMS: Heart failure (HF) quality registries report quality of care but it is unknown whether they improve outcomes. The aims were to assess predictors of enrolment in a HF registry, test the hypothesis that enrolment in a HF registry is associated with reduced mortality, and assess potential explanatory factors for this reduction in mortality, if present. METHODS AND RESULTS: We conducted a nationwide prospective cohort study of patients with new-onset HF registered in the Swedish National Patient Registry (NPR, a mandatory registry of ICD-code diagnoses) with or without concurrent registration in the Swedish Heart Failure Registry (SwedeHF, a voluntary quality reporting registry) 2006-2013. The association between demographics, co-morbidities and medications, and enrolment in the SwedeHF, was assessed using multivariable logistic regression. The association between enrolment in the SwedeHF and all-cause mortality was assessed using multivariable Cox regression, with adjustment for demographics, co-morbidities and medications. A total of 231 437 patients were included, of which 21 888 (9.5%) were in the SwedeHF [age (mean ± standard deviation) 74 ± 13 years; 41% women; 68% inpatients] and 209 549 (90.5%) were not (age 78 ± 12 years, 50% women; 79% inpatients). Selected variables independently associated with enrolment in the SwedeHF were male sex, younger age, higher education, absent co-morbidities and co-morbidity-related medications, and use of HF and cardiovascular medications. Over a median (interquartile range) follow-up of 874 (247-1667) days, there were 13.0 vs. 20.8 deaths per 100 patient-years (P < 0.001). The hazard ratio (95% confidence interval) for death for the SwedeHF yes vs. no was 0.65 (0.63-0.66) crude, and increased to 0.80 (0.78-0.81) after adding demographics, to 0.82 (0.80-0.84) after adding co-morbidities and co-morbidity-related medications, to 0.95 (0.93-0.97) after adding cardiovascular medications, and to 1.04 (1.02-1.07) after adding HF-specific medications. CONCLUSION: Heart failure patients of male sex, younger age, and higher education were more likely to be enrolled in a HF quality registry. Enrolment was associated with reduced all-cause mortality that was explained by demographic differences and better utilization of cardiovascular and HF medications.

Malignancies in Swedish persons with haemophilia: a longitudinal registry study.

The aim of the study was to investigate, over time, the incidence of and mortality due to malignant diseases among persons with haemophilia, compared to matched controls. Persons with haemophilia A or B were enrolled via registries at each haemophilia centre, as well as from the National Patient Registry, and were compared to five sex and age-matched controls per patient. Data from the national Cancer Registry were linked to the study participants. A total of 1431 persons with haemophilia and 7150 matched controls were enrolled. Between the years 1972 and 2008, 164 malignancies were reported. The most common type of cancer among patients was prostate cancer, followed by haematologic malignancies, including lymphoma and leukaemia, which were significantly more frequent in patients [n = 35 (2.4%) vs. n = 60 (0.8%); P < 0.001]. Malignancies in bladder and other urinary organs were also significantly different [n = 21 (1.5%) vs. n = 46 (0.6%); P < 0.01]. The overall incidence rate ratio of malignancies per 1000 person-years compared to the controls was 1.3 [95% confidence interval (CI) 1.1, 1.6]. In subgroup analysis, the corresponding incidence rate ratios per 1000 person-years for persons with severe haemophilia was 1.7 (95% CI 0.9, 3.1) and that for mild/moderate haemophilia 1.1 (95% CI 0.8, 1.5). Swedish persons with haemophilia had a significantly higher incidence of malignant diseases than controls. These were primarily haematologic malignancies and cancer in urinary organs, and the difference independent of any co-infections with HIV and/or viral hepatitis. The findings indicate the importance of further studies and close follow-up of malignancies in persons with haemophilia.

Suboptimal Control of Lipid Levels: Results from 29 Countries Participating in the Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS).

AIM: Five multicentre, cross-sectional Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS) were conducted in 29 countries across Asia, Western Europe, Eastern Europe, the Middle East, and Africa. The surveys assessed the current use and efficacy of lipid-lowering drugs (LLDs) worldwide and identified possible patient and physician characteristics associated with failure to attain low-density lipoprotein cholesterol (LDL-C) goals. The aim of this analysis was to consolidate the global results from these surveys. METHODS: The surveys involved patients aged ≥18 years who had been prescribed LLDs for at least 3 months without dose changes for at least 6 weeks. A single visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Cardiovascular risk profile and LDL-C goal attainment were assessed according to the 2004 updated US National Cholesterol Education Program Adult Treatment Panel III guidelines. RESULTS: In total, 35 121 patients (mean age: 60.4 years) were included, and 90.3% had been prescribed statin monotherapy. Overall, only 49.4% of patients reached their recommended LDL-C level. LDL-C goals were attained in 54.8% (5084/9273) and 22.8% (3287/14 429) of patients were at high and very high cardiovascular risk, respectively. Factors associated with an increased likelihood of LDL-C goal attainment were lower baseline cardiovascular risk; presence of diabetes mellitus, hypertension, or history of cardiovascular disease; and treatment with simvastatin, atorvastatin, or rosuvastatin (vs. all other LLDs). CONCLUSION: LDL-C goal attainment in patients taking LLDs is suboptimal worldwide, particularly in patients at high and very high cardiovascular risk.

Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: a nationwide cohort study of 9519 patients.

BACKGROUND: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition. METHODS: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls. RESULTS: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men. CONCLUSIONS: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men.

High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer.

The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6-9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1-7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment.

Warfarin-associated intracerebral hemorrhage after ischemic stroke.

BACKGROUND AND PURPOSE: The aim was to investigate the risk of intracerebral hemorrhage (ICH) in patients with ischemic stroke taking warfarin and whether this risk changed over time. METHODS: Between 2001 and 2008, the Swedish Stroke Register registered 12,790 patients with ischemic stroke discharged on warfarin. The patients was studied in two 4-year periods (inclusion 2001-2004: follow-up until 2005 and inclusion 2005-2008: follow-up until 2009) for which rates of subsequent ICH were calculated. Adjusted hazard ratios, comparing the second period with the first period, were estimated in Cox regression models. RESULTS: Of 6039 patients, 58 patients (1.0%) in the first period and 69 of 6751 patients (1.0%) in the second period had subsequent ICH. Annual rates of ICH ranged from 0.37% in the first period to 0.39% in the second period (adjusted hazard ratio, 1.04; 95% confidence interval, 0.73-1.48). CONCLUSIONS: In this nationwide study, the risk of warfarin-associated ICH among ischemic stroke patients was low and did not change during the 2000s.

All-cause mortality in 272,186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study.

AIMS: To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. METHODS AND RESULTS: A total of 272 186 patients (44% women) ≤ 85 years at the time of hospitalization with incidental AF 1995-2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories ≤ 65, 65-74, and 75-85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. CONCLUSION: Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.

Reduced risk of death with warfarin - results of an observational nationwide study of 20 442 patients with atrial fibrillation and ischaemic stroke.

BACKGROUND: Warfarin is demonstrated to be superior in efficacy over antiplatelet agents for the prevention of stroke, but the relationship between warfarin and mortality is less clear. Our aim was to investigate this relationship in a large cohort of unselected patients with atrial fibrillation and ischaemic stroke. METHODS: This observational study was based on patients who were discharged alive and registered in the Swedish Stroke Register in 2001 through 2005. Vital status was retrieved by linkage to the Swedish Cause of Death Register. We calculated a propensity score for the likelihood of warfarin prescription at discharge from hospital. The risk of death and 95% confidence intervals were estimated in Cox regression models. RESULTS: Out of the 20 442 patients with atrial fibrillation and ischaemic stroke (mean age = 79·5 years), 31% (n = 6399) were prescribed warfarin. After adjustment for the propensity score, warfarin was associated with a reduced risk of death (0·67; 95% confidence interval, 0·63-0·71). The crude rate (per 100 person-years) of fatal non-haemorrhagic stroke was lower in patients who received warfarin (1·60; 95% confidence interval, 1·34-1·89) compared to those who received antiplatelet (6·83; 95% confidence interval, 6·42-7·25). The rates (per 100 person-years) of fatal haemorrhagic stroke were 0·21 (95% confidence interval, 0·12-0·32) and 0·43 (95% confidence interval, 0·34-0·55) in patients prescribed warfarin and antiplatelet therapy, respectively. CONCLUSIONS: In addition to its established benefit for stroke prevention, warfarin therapy in patients with atrial fibrillation and ischaemic stroke was associated with a reduced risk of death, without an increased risk of fatal haemorrhagic stroke.

Hemorrhage after ischemic stroke - relation to age and previous hemorrhage in a nationwide cohort of 58,868 patients.

BACKGROUND: In randomized controlled trials of secondary prevention after stroke, the risk of hemorrhage varies between 1% and 5% per year in patients with antithrombotic therapy, i.e. anticoagulants and antiplatelets. AIM: To explore the rate and the risk of hemorrhage after stroke in a nationwide cohort. METHODS: We identified 58 868 first ever ischemic stroke patients in the Swedish Stroke Register during 2001 to 2005 (=index stroke) and followed them by record linkage to the National Patient Register. Rates of hemorrhage and hazard ratios, for comparisons of rates between subgroups, were calculated. RESULTS: Of the 58 586 ischemic stroke patients identified, 5527 (9·4%) had a history of hemorrhage. During follow-up (mean 2·0 years), 2876 patients endured a hemorrhage, giving an average hemorrhage rate of 2·6 (95% confidence interval 2·5-2·7) per 100 person-years. After index stroke, 11% of the patients were discharged with anticoagulants, and 79% with antiplatelets. Given the differences in baseline characteristics, the hemorrhage rates (per 100 person-years) were 2·5 (95% confidence interval 2·2-2·8), 2·4 (95% confidence interval 2·3-2·5), and 3·8 (95% confidence interval 3·5-4·2) in patients prescribed anticoagulants, antiplatelets, and no antithrombotics, respectively. There was an increased risk of hemorrhage in patients ≥75 years compared with those <75 years (hazard ratio = 1·61, 95% confidence interval 1·49-1·73) and in patients with previous hemorrhages compared with those without (hazard ratio = 1·82, 95% confidence interval 1·64-2·02). CONCLUSIONS: When antithrombotics were used in large-scale clinical practice, the observed rates of hemorrhage were similar with anticoagulant therapy but increased with antiplatelet therapy compared with rates reported in randomized controlled trials. Old age and previous hemorrhage were associated with an increased risk of hemorrhage after an ischemic stroke.

Comparison of cardiovascular risk factors and survival in patients with ischemic or hemorrhagic stroke.

BACKGROUND: Differences in risk factor profiles between patients with ischemic and hemorrhagic stroke may have an impact on subsequent mortality. AIM: To explore cardiovascular disease risk factors, including the CHADS(2) score, with survival after ischemic or hemorrhagic stroke. METHODS: Between 2001 and 2005, 87 111 (83%) ischemic stroke, 12 497 (12%) hemorrhagic stroke, and 5435 (5%) patients with unspecified stroke were identified in the Swedish Stroke Register. Data on gender, age, and cardiovascular disease risk factors were linked to the Swedish Hospital Discharge and Cause of Death Registers. Adjusted odds and hazard ratios and 95% confidence interval were calculated using logistic and Cox proportional hazard regression models. RESULTS: Hemorrhagic stroke patients were younger than ischemic stroke patients. All cardiovascular disease risk factors studied, alone or combined in the CHADS(2) score, were associated with higher odds ratios for ischemic stroke vs. hemorrhagic stroke. Higher CHADS(2) scores and all studied risk factors except hypertension were associated with higher odds ratio for death by ischemic stroke than hemorrhagic stroke. Ischemic stroke was associated with lower early mortality (within 30 days) vs. hemorrhagic stroke (hazard ratio = 0·28, confidence interval 0·27 to 0·29). CONCLUSIONS: Patients with hemorrhagic stroke had a higher risk of dying within the first 30 days after stroke, but the risk of death was similar in the two groups after one-month. Hypertension was the only cardiovascular disease risk factor associated with an increased mortality rate for hemorrhagic stroke as compared to ischemic stroke.

Bilateral prophylactic mastectomy in Swedish women at high risk of breast cancer: a national survey.

BACKGROUND/OBJECTIVE: This study attempted a national inventory of all bilateral prophylactic mastectomies performed in Sweden between 1995 and 2005 in high-risk women without a previous breast malignancy. The primary aim was to investigate the breast cancer incidence after surgery. Secondary aims were to describe the preoperative risk assessment, operation techniques, complications, histopathological findings, and regional differences. METHODS: Geneticists, oncologists and surgeons performing prophylactic breast surgery were asked to identify all women eligible for inclusion in their region. The medical records were reviewed in each region and the data were analyzed centrally. The BOADICEA risk assessment model was used to calculate the number of expected/prevented breast cancers during the follow-up period. RESULTS: A total of 223 women operated on in 8 hospitals were identified. During a mean follow-up of 6.6 years, no primary breast cancer was observed compared with 12 expected cases. However, 1 woman succumbed 9 years post mastectomy to widespread adenocarcinoma of uncertain origin. Median age at operation was 40 years. A total of 58% were BRCA1/2 mutation carriers. All but 3 women underwent breast reconstruction, 208 with implants and 12 with autologous tissue. Four small, unifocal, invasive cancers and 4 ductal carcinoma in situ were found in the mastectomy specimens. The incidence of nonbreast related complications was low (3%). Implant loss due to infection/necrosis occurred in 21 women (10%) but a majority received a new implant later. In total, 64% of the women underwent at least 1unanticipated secondary operation. CONCLUSIONS: Bilateral prophylactic mastectomy is safe and efficacious in reducing future breast cancer in asymptomatic women at high risk. Unanticipated reoperations are common. Given the small number of patients centralization seems justified.

First-ever atrial fibrillation documented after hemorrhagic or ischemic stroke: the role of the CHADS(2) score at the time of stroke.

BACKGROUND: The CHADS(2) score (C, congestive heart failure [CHF]; H, hypertension [HT]; A, age ≥75 y; D, diabetes mellitus; S(2) , prior stroke or transient ischemic attack) is used to assess the risk of ischemic stroke in patients with atrial fibrillation (AF). However, its role in patients without documented AF is not well explored. HYPOTHESIS: The goal of the current study was to explore if the incidence of hospitalization with first-ever AF after stroke increased with increasing CHADS(2) score. METHODS: We identified 57636 patients with nonfatal stroke and no documented AF in the Swedish Stroke Register (Riks-Stroke) during 2001-2004 and followed them for a mean of 2.2 years through record linkage to the Inpatient and Cause of Death registers. Cox regression hazard models were used to estimate the relative risk (RR) of new AF following stroke and its association with different CHADS(2) scores. RESULTS: Overall, 2769 patients were hospitalized with new AF (4.8%, 21.7 per 1000 person-years). The incidence increased from 9.6 per 1000 person-years in CHADS(2) score 0 to 42.7 in CHADS(2) score 6, conferring a RR of 4.2 (95% confidence interval [CI]: 2.5-6.8). For CHADS(2) scores 3-5, the RRs were approximately 3 (vs CHADS(2) score 0). Adjusted RRs were 1.9 (95% CI: 1.7-2.1) for CHF, 1.4 (95% CI: 1.3-1.5) for HT, 2.1 (95% CI: 2.0-2.3) for age ≥75 years, 0.9 (95% CI: 0.8-1.0) for diabetes, and 1.0 (95% CI: 0.91-1.07) for previous stroke. The risk of AF was higher in ischemic than in hemorrhagic stroke. CONCLUSIONS: In this retrospective register study, the incidence of AF following stroke was strongly influenced by higher CHADS(2) scores where age ≥75 years, CHF, and HT were the contributing CHADS(2) components.