Increase in ticagrelor use over time is associated with lower rates of ischemic stroke following myocardial infarction.

OBJECTIVES: To evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI). METHODS: Data for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n = 23,447) were treated with clopidogrel, while those in the later cohort (n = 24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke. RESULTS: Of 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p = 0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke. CONCLUSIONS: The introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

Increased Use of Ticagrelor After Myocardial Infarction Is Not Associated With Intracranial Hemorrhage.

Background and Purpose- Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction. Methods- Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH. Results- The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49-0.69]) versus 0.52% (97 cases [95% CI, 0.43-0.61]) during the second period ( P=0.83). In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH. Conclusions- The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.

Long-term, telephone-based follow-up after stroke and TIA improves risk factors: 36-month results from the randomized controlled NAILED stroke risk factor trial.

BACKGROUND: Strategies are needed to improve adherence to the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level recommendations after stroke and transient ischemic attack (TIA). We investigated whether nurse-led, telephone-based follow-up that included medication titration was more efficient than usual care in improving BP and LDL-C levels 36 months after discharge following stroke or TIA. METHODS: All patients admitted for stroke or TIA at Östersund hospital that could participate in the telephone-based follow-up were considered eligible. Participants were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C were measured one month after discharge and yearly thereafter. Intervention group patients who did not meet the target values received additional follow-up, including lifestyle counselling and medication titration, to reach their treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was the systolic BP level 36 months after discharge. RESULTS: Out of 871 randomized patients, 660 completed the 36-month follow-up. The mean systolic and diastolic BP values in the intervention group were 128.1 mmHg (95% CI 125.8-130.5) and 75.3 mmHg (95% CI 73.8-76.9), respectively. This was 6.1 mmHg (95% CI 3.6-8.6, p < 0.001) and 3.4 mmHg (95% CI 1.8-5.1, p < 0.001) lower than in the control group. The mean LDL-C level was 2.2 mmol/L in the intervention group, which was 0.3 mmol/L (95% CI 0.2-0.5, p < 0.001) lower than in controls. A larger proportion of the intervention group reached the treatment goal for BP (systolic: 79.4% vs. 55.3%, p < 0.001; diastolic: 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C (69.3% vs. 48.9%, p < 0.001). CONCLUSIONS: Compared with usual care, a nurse-led telephone-based intervention that included medication titration after stroke or TIA improved BP and LDL-C levels and increased the proportion of patients that reached the treatment target 36 months after discharge. TRIAL REGISTRATION: ISRCTN Registry ISRCTN23868518 (retrospectively registered, June 19, 2012).

One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010: An Observational Study.

BACKGROUND AND PURPOSE: Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. METHODS: Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. RESULTS: Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age >75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with ß-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. CONCLUSIONS: The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment.

Pre-hospital delay in patients with first time myocardial infarction: an observational study in a northern Swedish population.

BACKGROUND: In myocardial infarction (MI), pre-hospital delay is associated with increased mortality and decreased possibility of revascularisation. We assessed pre-hospital delay in patients with first time MI in a northern Swedish population and identified determinants of a pre-hospital delay ≥ 2 h. METHODS: A total of 89 women (mean age 72.6 years) and 176 men (mean age 65.8 years) from a secondary prevention study were enrolled in an observational study after first time MI between November 2009 and March 2012. Total pre-hospital delay was defined as the time from the onset of symptoms suggestive of MI to admission to the hospital. Decision time was defined as the time from the onset of symptoms until the call to Emergency Medical Services (EMS). The time of symptom onset was assessed during the episode of care, and the time of call to EMS and admission to the hospital was based on recorded data. The first medical contact was determined from a mailed questionnaire. Determinants associated with pre-hospital delay ≥ 2 h were identified by multivariable logistic regression. RESULTS: The median total pre-hospital delay was 5.1 h (IQR 18.1), decision time 3.1 h (IQR 10.4), and transport time 1.2 h (IQR 1.0). The first medical contact was to primary care in 52.3 % of cases (22.3 % as a visit to a general practitioner and 30 % by telephone counselling), 37.3 % called the EMS, and 10.4 % self-referred to the hospital. Determinants of a pre-hospital delay ≥ 2 h were a visit to a general practitioner (OR 10.77, 95 % CI 2.39-48.59), call to primary care telephone counselling (OR 3.82, 95 % CI 1.68-8.68), chest pain as the predominant presenting symptom (OR 0.24, 95 % CI 0.08-0.77), and distance from the hospital (OR 1.03, 95 % CI 1.02-1.04). Among patients with primary care as the first medical contact, 67.0 % had a decision time ≥ 2 h, compared to 44.7 % of patients who called EMS or self-referred (p = 0.002). CONCLUSIONS: Pre-hospital delay in patients with first time MI is prolonged considerably, particularly when primary care is the first medical contact. Actions to shorten decision time and increase the use of EMS are still necessary.

Implementation of a new guideline in cardiovascular secondary preventive care: subanalysis of a randomized controlled trial.

BACKGROUND: Cardiovascular secondary preventive recommendations are often not reached. We investigated whether a nurse-led telephone-based follow-up could improve the implementation of a new guideline within a year after its release. METHODS: In February 2013, a new secondary preventive guideline for diabetic patients was released in the county of Jämtland, Sweden. It included a changed of the low-density lipoprotein cholesterol (LDL-C) target value from <2.5 mmol/L to <1.8 mmol/L. In the Nurse-Based Age-Independent Intervention to Limit Evolution of Disease (NAILED) trial, patients with an acute coronary syndrome, stroke, or transient ischemic attack were randomized to secondary preventive care with nurse-based telephone follow-up (intervention) or usual care (control). Patient data were obtained from the NAILED trial to study the implementation of the new LDL-C guideline by comparing telephone follow-up with usual care. The Mann-Whitney U-test was used for continuous variables, and Person's χ (2) test was used for categorical variables to assess between-group differences. RESULTS: Out of the 1267 patients that entered the study period, 101 intervention and 100 control patients with diabetes fulfilled the inclusion criteria and completed the study period. Before the guideline change, 96 % of the intervention patients and 70 % of the control patients reached the target LDL-C value (p < 0.001). After the guideline change, the corresponding respective proportions were 65 % and 36 % (p < 0.001). The main reason that intervention patients did not achieve the target LDL-C value was that they received full-dose treatment; for control patients, the main reason was that medication was not adjusted, for an unknown reason. CONCLUSIONS: One year after a change in the cardiovascular secondary preventive guideline, nurse-based telephone follow-up performed better than usual care to implement the new recommendation. TRIAL REGISTRATION: ISRCTN registry; ISRCTN96595458 (date of registration 10 July 2011) and ISRCTN23868518 (date of registration 13 May 2012).

Low use of statins for secondary prevention in primary care: a survey in a northern Swedish population.

BACKGROUND: Cholesterol-lowering therapy with statins is recommended in established cardiovascular disease (CVD) and should be considered for patients at high cardiovascular risk. We surveyed statin treatment before first-time myocardial infarction in clinical practice compared to current guidelines, in patients with and without known CVD in primary care clinics with general practitioners (GPs) on short-term contracts vs. permanent staff GPs. METHODS: A total of 931 patients (345 women) in northern Sweden were enrolled in the study between November 2009 and December 2014 and stratified by prior CVD, comprising angina pectoris, revascularisation, ischaemic stroke or transitory ischaemic attack, or peripheral artery disease. Primary care clinics were classified by the proportion of GP salaries that were paid to GPs working on short-term contracts: low (0-9 %), medium (10-39 %), or high (≥40 %). We used logistic regression to identify determinants of statin treatment. RESULTS: Among patients with prior CVD, only 34.5 % received statin treatment before myocardial infarction. The probability of statin treatment decreased with age (≥70 years OR 0.30; 95 % CI 0.13-0.66) and female gender (OR 0.39; 95 % CI 0.20-0.78) but increased in patients with diabetes (OR 3.52; 95 % CI 1.75-7.08). Among patients with prior CVD, the type of primary care clinic was not predictive of statin treatment. In the entire study cohort, 17.3 % of patients were treated with statins; women < 70 years old were more likely to receive statin treatment than women ≥70 years old (OR 3.24; 95 % CI 1.64-6.38), and men ≥70 years old were twice as likely to be treated with statins than women of the same age (OR 2.22; 95 % CI 1.31-3.76) after adjusting for diabetes and CVD. Overall, patients from clinics with predominantly permanent staff GPs received statin therapy less frequently than those with GPs on short-term contracts. CONCLUSIONS: In patients with prior CVD we found considerable under-treatment with statins, especially among women and the elderly. Methodologies for case findings, recall, and follow-up need to be improved and implemented to reach the goals for CVD prevention in clinical practice.

Cardiovascular secondary prevention in high-risk patients: a randomized controlled trial sub-study.

BACKGROUND: Enhanced cardiovascular secondary preventive follow-up is needed to improve adherence to recommended low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) levels. Patients with diabetes mellitus (DM) or chronic kidney disease (CKD) have a high risk of recurrent events. Secondary prevention is therefore essential in these patients. METHODS: Patients with acute coronary syndrome, stroke, or transient ischemic attack were randomized to nurse-based telephone follow-up (intervention) or usual care (control). LDL-C and BP were measured at 1 month (baseline) and 12 months post-discharge. Intervention patients with above-target values at baseline received medication titration to achieve treatment goals. Values measured for control patients were given to the patient's general practitioner for assessment. RESULTS: The final analyses included 225 intervention and 215 control patients with DM or CKD. Among patients with above-target baseline values, the following 12-month values were recorded for intervention and control patients, respectively: LDL-C, 2.2 versus 3.0 mmol/L (p < 0.001); and median systolic BP (SBP), 140 versus 145 mmHg (p = 0.26). Among patients with above-target values at baseline, 52.3 % of intervention patients reached target LDL-C values at 12 months versus 21.3 % of control patients (absolute difference of 30.9 %, 95 % CI 16.1 to 43.8 %), and there was a non-significant trend of more intervention patients reaching target SBP (49.4 % versus 36.8 %; absolute difference of 12.6 %, 95 % CI -1.7 to 26.2 %). CONCLUSIONS: Cardiovascular secondary prevention with nurse-based telephone follow-up was more effective than usual care in improving LDL-C levels 12 months after discharge for patients with DM or CKD. TRIAL REGISTRATION: ISRCTN registry; ISRCTN96595458 (date of registration 10 July 2011) and ISRCTN23868518 (date of registration 13 May 2012).

The Prevalence of COPD in Individuals with Acute Coronary Syndrome: A Spirometry-Based Screening Study.

BACKGROUND: The prevalence of COPD among individuals with acute coronary syndrome (ACS) is estimated at 5% to 18%, and COPD appears to be a predictor of poor outcome. Diagnosis of COPD has mostly been based on medical records without spirometry. As COPD is largely undiagnosed and misdiagnosed, the prevalence and clinical significance of COPD in the ACS population has not been reliably assessed. The present study aimed to estimate the prevalence of COPD in patients with ACS and evaluate the accuracy of medical record-based COPD diagnoses. METHODS: This was a single-centre spirometry screening study for COPD in patients admitted for ACS in the county of Jämtland, Sweden. Patient medical records were reviewed to register previous medical history. Spirometry was performed prior to discharge or at the first follow-up outpatient visit after discharge. COPD was defined as a post-bronchodilator FEV1/FVC of <0.7 or below lower limit of normal. RESULTS: Of 743 eligible patients, 407 performed spirometry. Five percent had COPD according to medical records; 11% and 5% fulfilled spirometric criteria of COPD according to FEV1/FVC of < 0.7 (p = 0.002) and below lower limit of normal definitions, respectively. "COPD according to medical history" had a sensitivity of 23%, specificity of 98%, positive predictive value of 53%, and negative predictive value of 91% compared with spirometric COPD FEV1/FVC of < 0.7 CONCLUSIONS: In patients with ACS, COPD is underdiagnosed and misdiagnosed. We raise concerns regarding the validity of medical record-based COPD in evaluating the biological and clinical association between COPD and coronary disease. CLINICAL TRIAL REGISTRATION: ISRCTN number 05697808 (www. controlled-trials.com).

Incidence, trends, and predictors of ischemic stroke 30 days after an acute myocardial infarction.

BACKGROUND AND PURPOSE: Ischemic stroke is a known complication of acute myocardial infarction (AMI). Treatment of AMI has undergone great changes in recent years. We aimed to investigate whether changes in treatment corresponded to a lower incidence of ischemic stroke and which factors predicted ischemic stroke after AMI. METHODS: Data were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients with their first registered AMI between 1998 and 2008 were included. To identify ischemic strokes, we used the Swedish national patient register. To study a potential trend in the incidence of ischemic stroke after AMI over time, we divided the patient population into 5 time periods. Event-free survival was studied by Kaplan-Meier analysis. Cox proportional hazards regression model was used to identify stroke predictors. RESULTS: Of 173,233 patients with AMI, 3571 (2.1%) developed ischemic stroke within 30 days. The incidence of ischemic stroke was significantly lower during the years 2007 to 2008 compared with 1998 to 2000, with respective rates of 2.0% and 2.2% (P=0.02). Independent predictors of an increased risk of stroke were age, female sex, prior stroke, diabetes mellitus, atrial fibrillation, clinical signs of heart failure in hospital, ST-segment-elevation myocardial infarction, coronary artery bypass grafting, and angiotensin-converting enzyme inhibitor treatment at discharge. Percutaneous coronary intervention, fibrinolysis, acetylsalicylic acid, statins, and P2Y12 inhibitors were predictors of reduced risk of stroke. CONCLUSIONS: The incidence of ischemic stroke within 30 days of an AMI has decreased during the period 1998 to 2008. This decrease is associated with increased use of acetylsalicylic acid, P2Y12 inhibitors, statins, and percutaneous coronary intervention.

Incidence, trends, and predictors of ischemic stroke 1 year after an acute myocardial infarction.

BACKGROUND AND PURPOSE: Ischemic stroke after acute myocardial infarction is an important complication. It is unknown whether the risk has changed because the treatment of acute myocardial infarction has improved during the past decade. There is also conflicting data about predictors of stroke risk. METHODS: To obtain the 1-year incidence of stroke after acute myocardial infarction, the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions database for the years 1998 to 2008 was merged with the Swedish National Patient Register (NPR). The time trend was studied by dividing the entire time period into 5 separate periods. Independent predictors were identified using a multivariable Cox proportional hazards regression model. RESULTS: Between 1998 and 2008, 7185 of 173 233 patients with acute myocardial infarction had an ischemic stroke within 1 year (4.1%). There was a 20% relative risk reduction during the study period (1998-2000 versus 2007-2008) relative risk 0.80 (95% confidence interval, 0.75-0.86; P<0.001. Independent predictors of stroke were age, female sex, ST-segment-elevation myocardial infarction, previous stroke, previous diabetes mellitus, heart failure at admission, angiotensin-converting enzyme inhibitor treatment and atrial fibrillation. Reperfusion treatment with fibrinolysis and percutaneous coronary intervention and treatment with aspirin, P2Y12-inhibitors, and statins predicted a reduced risk of stroke. CONCLUSIONS: The risk of ischemic stroke within a year after myocardial infarction is substantial but has clearly been reduced during the studied time period. The major predictive factors found to correlate well with previous investigations. Reperfusion treatment, thrombocyte aggregation inhibition, and lipid lowering are the main contributors to the observed risk reduction.

The risk of ischemic stroke after an acute myocardial infarction in patients with decreased renal function.

BACKGROUND: Data on the incidence, trends over time and predictors of ischemic stroke after an acute myocardial infarction (AMI) are sparse for patients with chronic kidney disease (CKD). METHODS: Data for unselected AMI patients were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) between 2003 and 2010. Patients with and without CKD were compared. Multiple logistic regression was performed to identify predictors of ischemic stroke during the hospitalization for AMI, Kaplan-Meier analysis was used to analyze the 1-year postdischarge ischemic stroke trends over time and Cox regression analysis was used to identify predictors. RESULTS: Of 118,434 AMI patients, 40,679 had CKD. The CKD patients had more extensive previous cardiovascular disease and received less reperfusion and secondary preventive therapies than the patients without CKD. An inhospital ischemic stroke occurred in 2.3 and 1.2% of CKD and non-CKD patients, respectively. The incidence of ischemic stroke during hospitalization for AMI was stable during the study period. The occurrence of ischemic stroke after hospital discharge decreased between 2003-2004 and 2009-2010 from 4.1 to 2.5% in CKD patients and from 2.0 to 1.3% in non-CKD patients, respectively. Percutaneous coronary intervention (PCI) and statins were independently associated with a reduced risk of stroke after discharge from hospital. CONCLUSIONS: Ischemic stroke is a more common complication after an AMI in CKD patients than in non-CKD patients, but the risk has decreased in recent years. The increased use of PCI and statins may have contributed to this reduction.

Diagnostic characteristics and prognoses of primary-care patients referred for clinical exercise testing: a prospective observational study.

BACKGROUND: Evaluation of angina symptoms in primary care often includes clinical exercise testing. We sought to identify clinical characteristics that predicted the outcome of exercise testing and to describe the occurrence of cardiovascular events during follow-up. METHODS: This study followed patients referred to exercise testing for suspected coronary disease by general practitioners in the County of Jämtland, Sweden (enrolment, 25 months from February 2010). Patient characteristics were registered by pre-test questionnaire. Exercise tests were performed with a bicycle ergometer, a 12-lead electrocardiogram, and validated scales for scoring angina symptoms. Exercise tests were classified as positive (ST-segment depression >1 mm and chest pain indicative of angina), non-conclusive (ST depression or chest pain), or negative. Odds ratios (ORs) for exercise-test outcome were calculated with a bivariate logistic model adjusted for age, sex, systolic blood pressure, and previous cardiovascular events. Cardiovascular events (unstable angina, myocardial infarctions, decisions on revascularization, cardiovascular death, and recurrent angina in primary care) were recorded within six months. A probability cut-off of 10% was used to detect cardiovascular events in relation to the predicted test outcome. RESULTS: We enrolled 865 patients (mean age 63.5 years, 50.6% men); 6.4% of patients had a positive test, 75.5% were negative, 16.4% were non-conclusive, and 1.7% were not assessable. Positive or non-conclusive test results were predicted by exertional chest pain (OR 2.46, 95% confidence interval (CI) 1.69-3.59), a pathologic ST-T segment on resting electrocardiogram (OR 2.29, 95% CI 1.44-3.63), angina according to the patient (OR 1.70, 95% CI 1.13-2.55), and medication for dyslipidaemia (OR 1.51, 95% CI 1.02-2.23). During follow-up, cardiovascular events occurred in 8% of all patients and 4% were referred to revascularization. Cardiovascular events occurred in 52.7%, 18.3%, and 2% of patients with positive, non-conclusive, or negative tests, respectively. The model predicted 67/69 patients with a cardiovascular event. CONCLUSIONS: Clinical characteristics can be used to predict exercise test outcome. Primary care patients with a negative exercise test have a very low risk of cardiovascular events, within six months. A predictive model based on clinical characteristics can be used to refine the identification of low-risk patients.

Use of exercise tests in primary care: importance for referral decisions and possible bias in the decision process; a prospective observational study.

BACKGROUND: The utility of clinical exercise tests depends on their support of treatment decisions. We sought to assess the utility of exercise tests for the selection of primary-care patients for referral to cardiologic care, and to determine whether referral decisions were biased by gender or socioeconomic status. We also evaluated referral rates and cardiovascular events in patients with positive exercise tests. METHODS: We designed a prospective observational study of 438 men and 427 women from 28 Swedish primary-care clinics who were examined with exercise testing for suspected coronary disease. All participants were followed-up with respect to cardiologist referrals and cardiovascular events (hospitalisation for unstable angina, myocardial infarction, and cardiovascular death) within six months and revascularisation within 250 days. Variables associated with referral were identified by multivariable logistic regression. Socioeconomic status was determined by educational level and employment. RESULTS: Positive/inconclusive exercise tests and exertional chest pain predicted referral in men and women. Of 865 participants, patients with positive, inconclusive, or negative exercise tests were referred to cardiologists in 67.3%, 26.1%, and 3.5% of cases, respectively. Overall, there was no significant difference in referral rates related to gender or socioeconomic level. Self-employed women were referred more frequently compared to other women (odds ratio (OR) 3.62, 95% confidence interval (CI) 1.19-10.99). Among non-manual employees, women were referred to cardiologic examination less frequently than men (OR 0.40, 95% CI 0.16-1.00; p = 0.049; ORs adjusted for age, exertional chest pain, and exercise test result). In patients with positive exercise tests, the referral rate decreased continuously with age (OR 0.48, 95% CI 0.23-0.97; adjusted for cardiovascular co-morbidity). Cardiovascular events occurred in 22.2% (4/18) of non-referred patients with positive exercise tests; 56% (10/18) of these patients were not considered for cardiologic care, with continuity problems in primary care as one possible contributing cause. CONCLUSIONS: Exercise tests are important for selecting patients for referral to cardiologic care. Interactions related to gender and socioeconomic status affected referral rates. In patients with positive exercise tests, referral rates decreased with age. An increased awareness of possible bias regarding age, gender, and socioeconomic status, which may influence medical decisions, is therefore necessary.

Orthostatic hypotension in stroke/TIA patients: Association with new events and the effect of the NAILED intervention.

BACKGROUND: Fear of orthostatic hypotension (OH) and a reported association with an increased risk of cardiovascular (CV) events may limit antihypertensive treatment after stroke/TIA. In the NAILED trial, systematic titration of antihypertensive treatment resulted in lower blood pressure (BP) and reduced the incidence of stroke. Our aim was to assess the association between OH and CV events or death in a stroke/TIA population and the association between group allocation in the NAILED trial and risk of OH during follow-up. METHODS AND FINDINGS: This post-hoc analysis included all patients with complete BP measurement at baseline in the NAILED trial (n = 814). OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mmHg 1 minute after standing from a seated position. The association between OH and a composite of stroke, myocardial infarction, or death was assessed using an adjusted Cox regression model with OH as a time-varying variable. The association between group allocation (intervention vs. control) and OH was assessed using logistic regression. During a mean follow-up of 4.8 years, 35.3% of patients had OH at some point. OH was not significantly associated with the composite outcome (HR: 1.11, 95% CI: 0.80-1.54). Allocation to the intervention group in the NAILED trial was not associated with OH during follow-up (OR: 0.84, 95% CI: 0.62-1.13). CONCLUSIONS: OH was not associated with an increased risk of CV events or death in this stroke/TIA population. Systematic titration of antihypertensive treatment did not increase the prevalence of OH compared to usual care. Thus, OH did not reduce the gains of antihypertensive treatment.

Mortality after ischemic stroke in patients with acute myocardial infarction: predictors and trends over time in Sweden.

BACKGROUND AND PURPOSE: Acute myocardial infarction (AMI) increases the risk of ischemic stroke, and mortality among these patients is high. Here, we aimed to estimate the 1-year mortality reliably after AMI complicated by ischemic stroke. We also aimed to identify trends over time for mortality during 1998-2008, as well as factors that predicted increased or decreased mortality. METHODS: Data for 173 233 unselected patients with AMI were collected from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions registry for 1998-2008. Specifically, we analyzed 1-year follow-up and mortality data for patients with AMI with and without ischemic stroke. Kaplan-Meyer analysis was used to analyze mortality trends over time, and Cox regression analysis was used to identify uni- and multivariate predictors of mortality. RESULTS: The 1-year mortality was 36.5% for AMI complicated by ischemic stroke and 18.3% for AMI without stroke. Mortality decreased over time in patients with and without ischemic stroke. The absolute decreases in mortality were 9.4% and 7.5%, respectively. Reperfusion and secondary preventive therapies were associated with a decreased mortality rate. CONCLUSIONS: Mortality after AMI complicated by an ischemic stroke is very high but decreased from 1998 to 2008. The increased use of evidence-based therapies explains the improved prognosis.

Incidence and predictors of cardiovascular outcomes after acute coronary syndrome in a population-based cohort study.

There is limited data on long-term outcomes after hospitalization for ACS. We aimed to estimate the rate of recurrent cardiovascular events in the long-term, in a population-based, unselected cohort of ACS patients. We included 1379 patients with ACS hospitalized at Östersund hospital 2010-2014 and followed them from the day after discharge to 31 December 2017. The primary endpoint was the unadjusted rate of the composite of CV death, AMI and ischemic stroke. Risk factors for the primary endpoint were assessed in a multivariable Cox proportional hazards regression model. During a median follow-up of 4.7 years, the unadjusted rate of the primary endpoint was 10.3% at 1 year and 28.6% at the end of follow-up. Predictors of increased risk for subsequent events were congestive heart failure, diabetes mellitus, angina pectoris, prior revascularization with PCI or CABG and treatment with diuretics at discharge. Lipid-lowering therapy at discharge and revascularization with PCI or CABG were associated with a lower risk of recurrent events. The risk of recurrent cardiovascular was high at 1 year and continued to be so during the following almost 3 years of median follow-up. Established predictors of cardiovascular risk were confirmed.

Long-term risk of major adverse cardiovascular events following ischemic stroke or TIA.

Data are scarce on long-term outcomes after ischemic stroke (IS) or transient ischemic attack (TIA). In this prospective cohort study, we examined the cumulative incidence of major adverse cardiovascular events (MACE) after IS and TIA using a competing risk model and factors associated with new events using a Cox-proportional hazard regression model. All patients discharged alive from Östersund Hospital with IS or TIA between 2010 and 2013 (n = 1535) were followed until 31 December 2017. The primary endpoint was a composite of IS, type 1 acute myocardial infarction (AMI), and cardiovascular (CV) death. Secondary endpoints were the individual components of the primary endpoint, in all patients and separated in IS and TIA subgroups. The cumulative incidence of MACE (median follow-up: 4.4 years) was 12.8% (95% CI: 11.2-14.6) within 1 year after discharge and 35.6% (95% CI: 31.8-39.4) by the end of follow-up. The risk of MACE and CV death was significantly increased in IS compared to TIA (p-values < 0.05), but not the risk of IS or type 1 AMI. Age, kidney failure, prior IS, prior AMI, congestive heart failure, atrial fibrillation, and impaired functional status, were associated with an increased risk of MACE. The risk of recurring events after IS and TIA is high. IS patients have a higher risk of MACE and CV death than TIA patients.

Cardiovascular complications following cesarean section and vaginal delivery: a national population-based study.

INTRODUCTION: Rates of cesarean section are rising in both developed and developing countries and while pregnancy and cesarean section are established as risk factors for thromboembolism and stroke, large population-based investigations focusing on all types of cardiovascular complication after delivery is missing. The aim was to analyze the risk of severe cardiovascular complications in the post-partum period following delivery by cesarean section. We also had a control group of vaginal deliveries and a reference group with nulliparas. MATERIALS AND METHODS: This Swedish population-based study used three national registers between 2005 and 2017 and comprised a total of 1 165 684 individuals. Unselected register data was cross-linked and cardiovascular adverse events were identified by ICD diagnosis codes. 140 128 women (209 391 deliveries) were included in the cesarean group and 614 355 women (973 429 deliveries) in the vaginal control group. The reference group comprised 411 201 age-matched nulliparous women. The primary analysis was the risk of severe cardiovascular complications within 42 days of cesarean section or vaginal delivery. The secondary analysis evaluated risk factors for cardiovascular complications. RESULTS: In the cesarean section group, 410 (0.20%) had a serious cardiovascular event within 42 days after delivery, and in the vaginal control group the number was 857 (0.09%). The risk of having an adverse cardiovascular event was significantly greater in the cesarean group (OR 2.23, CI 1.98 to 2.51) for all types of cardiovascular events. Risk factors were high BMI, preeclampsia, greater maternal age, tobacco use and acute cesarean delivery. CONCLUSIONS: The absolute numbers on severe maternal morbidity after delivery are low. However, since almost half of the world's population are affected and the frequency of elective cesarean section continues to rise, a doubling of the risk for a severe cardiovascular event within 42 days of delivery is important to consider globally.

Nurse-led, telephone-based follow-up after acute coronary syndrome yields improved risk factors after 36 months: the randomized controlled NAILED-ACS trial.

We investigated whether a nurse-led, telephone-based follow-up including medical titration was superior to usual care in improving blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) values 36 months after acute coronary syndrome (ACS). We screened all patients admitted with ACS at Östersund hospital, Sweden, between January 1, 2010, and December 31, 2014, for inclusion based on ability to participate in a telephone-based follow-up. Participants were randomly allocated to usual care or an intervention group that received counselling and medical titration to target BP < 140/< 90 mmHg and LDL-C < 2.5/< 1.8 mmol/L. The primary outcome was LDL-C at 36 months. Of 962 patients, 797 (83%) were available for analysis after 36 months. Compared to controls, the intervention group had a mean systolic BP (SBP) 4.1 mmHg lower (95% confidence interval [CI] 1.9-6.5), mean diastolic BP (DBP) 2.9 mmHg lower (95% CI 1.5-4.5), and mean LDL-C 0.28 mmol/L lower (95% CI 0.135-0.42). All P < 0.001. A significantly greater proportion of patients reached treatment targets with the intervention. After 36 months of follow-up, compared to usual care, the nurse-led, telephone-based intervention led to significantly lower SBP, DBP, and LDL-C and to a larger proportion of patients meeting target values.Trial registration: ISRCTN registry. Trial number ISRCTN96595458. Retrospectively registered.