Blood Pressure Level in Late Adolescence and Risk for Cardiovascular Events : A Cohort Study.

BACKGROUND: Not enough is known about the association between blood pressure (BP) in adolescence and future cardiovascular events. OBJECTIVE: To measure this association using the 2017 American College of Cardiology/American Heart Association guidelines for classifying BP elevation. DESIGN: Cohort study. SETTING: Sweden. PARTICIPANTS: Males in late adolescence who were conscripted into the military from 1969 to 1997. MEASUREMENTS: Baseline BP was measured at conscription. The primary outcome was a composite of cardiovascular death or first hospitalization for myocardial infarction, heart failure, ischemic stroke, or intracerebral hemorrhage. RESULTS: The study included 1 366 519 males with a mean age of 18.3 years. The baseline BP was classified as elevated (120 to 129/<80 mm Hg) for 28.8% of participants and hypertensive (≥130/80 mm Hg) for 53.7%. During a median follow-up of 35.9 years, 79 644 had a primary outcome. The adjusted hazard ratio was 1.10 for elevated BP (95% CI, 1.07 to 1.13), 1.15 for stage 1 isolated systolic hypertension (ISH) (CI, 1.11 to 1.18), 1.23 for stage 1 isolated diastolic hypertension (IDH) (CI, 1.18 to 1.28), 1.32 for stage 1 systolic-diastolic hypertension (SDH) (CI, 1.27 to 1.37), 1.31 for stage 2 ISH (CI, 1.28 to 1.35), 1.55 for stage 2 IDH (CI, 1.42 to 1.69), and 1.71 for stage 2 SDH (CI, 1.58 to 1.84). The cumulative risk for cardiovascular events also increased gradually across BP stages, ranging from 14.7% for normal BP to 24.3% for stage 2 SDH at age 68 years. LIMITATION: This was an observational study of Swedish men. CONCLUSION: Increasing BP levels in late adolescence are associated with gradually increasing risks for major cardiovascular events, beginning at a BP level of 120/80 mm Hg. PRIMARY FUNDING SOURCE: Västerbotten County Council, Swedish Society for Medical Research, and Heart Foundation of Northern Sweden.

Interventions in Adults With Repaired Coarctation of the Aorta.

Background Coarctation of the aorta coexists with other cardiac anomalies and has long-term complications, including recoarctation, which may require intervention after the primary coarctation repair. This study aims to clarify the prevalence of and risk factors for interventions related to the coarctation complex as well as late mortality in a large contemporary patient population. Methods and Results The Swedish National Register of Congenital Heart Disease was used, which comprised 683 adults with repaired coarctation of the aorta. Analysis was performed on freedom from intervention thereafter at the coarctation site, aortic valve, left ventricular outflow tract, or ascending aorta. One hundred ninety-six (29%) patients had at least 1 of these interventions. Estimated freedom from either of these interventions was 60% after 50 years. The risk of undergoing such an intervention was higher among men (hazard ratio, 1.6 [95% CI, 1.2-2.2]). Estimated freedom from another intervention at the coarctation site was 75% after 50 years. In women, there was an increase in interventions at the coarctation site after 45 years. Patients who underwent one of the previously mentioned interventions after the primary coarctation repair had poorer left ventricular function. Eighteen patients (3%) died during follow-up in the register. The standardized mortality ratio was 2.9 (95% CI, 1.7-4.3). Conclusions Interventions are common after coarctation repair. The risk for and time of interventions are affected by sex. Our results have implications for planning follow-up and giving appropriate medical advice to the growing population of adults with repaired coarctation of the aorta.

Detection of paroxysmal atrial fibrillation in 994 patients with a cerebrovascular event by intermittent 21-day ECG-monitoring and 7-day continuous Holter-recording.

Background: The detection of paroxysmal atrial fibrillation (AF) is of importance in stroke care. The method used is continuous electrocardiogram (ECG)-monitoring or multiple short ECG-recordings during an extended period. Their relative efficiency is a matter of discussion. In a retrospective cohort study on 994 patients with an ischemic stroke or transient ischemic attack (TIA), we have compared continuous 7-day monitoring to intermittent recording 60 sec three times daily with a handheld device during 3 weeks. We related the result to subsequent occurrence of AF as detected in 12-lead ECG recordings. Methods: The patients were identified in the local database of cardiovascular investigations. Their clinical profile and vital status during the follow-up were obtained from the Swedish Stroke Register and the Swedish general population registry. For comparison, we used an age- and sex-matched population with no known cerebrovascular event and a population with a cerebrovascular event that was not screened. Results: AF was detected in 7.1% by continuous screening and in 5.1% by intermittent screening (P = 0.3). During follow-up of 32 months, AF in 12-lead ECG was found in 7.0%. In the subgroup with positive screening, 46.3% had AF compared with 6.7% in the subgroup with negative screening (P < 0.0001). Conclusions: The two screening approaches had a similar yield of arrhythmia, in spite of the group with intermittent monitoring having a more favorable clinical profile. A positive screening was highly predictive of AF in ECG during the follow-up.

Prevalence, time-trends and clinical characteristics of hypertension in young adults: nationwide cross-sectional study of 1.7 million Swedish 18-year-olds, 1969-2010.

OBJECTIVE: The prevalence of hypertension in young adulthood, as well as the clinical characteristics associated with different hypertension subtypes, have been inconsistently described. Our aim was to assess the prevalence, time-trends and characteristics associated with isolated systolic hypertension (ISH), isolated diastolic hypertension and combined systodiastolic hypertension. METHODS: Serial cross-sectional analysis, using data from the Swedish conscription registry, including 1701 314 (99.2% male) individuals from 1969 to 2010. Risk factor associations were assessed through multivariable logistic regression. RESULTS: The prevalence of hypertension increased progressively during the study period, from 20.4% in 1969 to 29.3% in 2010, with ISH being the most common subtype (94.3%). ISH was associated with elevated resting heart rate (odds ratio 1.85, 95% confidence interval 1.84-1.86, per SD), increased exercise capacity (1.37, 1.36-1.39) and increased BMI (1.30, 1.29-1.31). Isolated diastolic hypertension and combined hypertension were also associated with elevated resting heart rate (1.37, 1.32-1.41 and 2.05, 1.99-2.11, respectively) and more strongly associated with increased BMI (1.36, 1.33-1.40 and 1.54, 1.51 - 1.58), but inversely associated with exercise capacity (0.79, 0.75-0.83 and 0.90, 0.86-0.95). CONCLUSION: The prevalence of hypertension in young adulthood has increased substantially over time, predominantly due to an increase in ISH. Risk factor patterns differed between ISH and other forms of hypertension, suggesting potentially different underlying mechanisms.

Phosphatidylethanol Levels, As a Marker of Alcohol Consumption, Are Associated With Risk of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Previous observational studies have shown a moderately increased risk of intracerebral hemorrhage (ICH) with high self-reported alcohol consumption. However, self-reported data tend to underestimate alcohol consumption. Phosphatidylethanol is a specific biomarker reflecting alcohol intake during the last month and correlates with the amount of alcohol consumed. The present study aimed to investigate the association between phosphatidylethanol levels and the risk of future ICH. METHODS: This population-based nested case-referent study was conducted within the Northern Sweden Health and Disease Cohort. At baseline, all participants underwent a health examination, including a questionnaire with questions about alcohol consumption. A blood sample was collected and stored at -80°C, and phosphatidylethanol 16:0/18:1 levels were measured in packed erythrocytes. Cases (n=97) were diagnosed with a first-ever ICH between 1985 and 2007. Two referents (n=180) were matched to each case. RESULTS: The mean age at baseline was 55 years, 39% of participants were women, and the mean time from blood sampling to ICH was 7.3 years. Only phosphatidylethanol and hypertension remained independently associated with ICH in a multivariable model. Participants with phosphatidylethanol >0.30 µmol/L had an increased risk of ICH compared with those with phosphatidylethanol <0.01 µmol/L (odds ratio, 4.64 [95% CI, 1.49-14.40]). CONCLUSIONS: High blood concentrations of phosphatidylethanol were associated with an increased risk of future ICH. This association was independent of hypertension and other risk factors for ICH. Our findings suggest that phosphatidylethanol, as a marker of alcohol consumption, may be used as a risk marker of future ICH.

STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage: Protocol for a randomised controlled trial.

BACKGROUND AND AIMS: Many patients with prior intracerebral haemorrhage have indications for antithrombotic treatment with antiplatelet or anticoagulant drugs for prevention of ischaemic events, but it is uncertain whether such treatment is beneficial after intracerebral haemorrhage. STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage will assess (i) the effects of long-term antithrombotic treatment on the risk of recurrent intracerebral haemorrhage and occlusive vascular events after intracerebral haemorrhage and (ii) whether imaging findings, like cerebral microbleeds, modify these effects. METHODS: STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is a multicentre, randomised controlled, open trial of starting versus avoiding antithrombotic treatment after non-traumatic intracerebral haemorrhage, in patients with an indication for antithrombotic treatment. Participants with vascular disease as an indication for antiplatelet treatment are randomly allocated to antiplatelet treatment or no antithrombotic treatment. Participants with atrial fibrillation as an indication for anticoagulant treatment are randomly allocated to anticoagulant treatment or no anticoagulant treatment. Cerebral CT or MRI is performed before randomisation. Duration of follow-up is at least two years. The primary outcome is recurrent intracerebral haemorrhage. Secondary outcomes include occlusive vascular events and death. Assessment of clinical outcomes is performed blinded to treatment allocation. Target recruitment is 500 participants.Trial status: Recruitment to STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is on-going. On 30 April 2020, 44 participants had been enrolled in 31 participating hospitals. An individual patient-data meta-analysis is planned with similar randomised trials.

Risk factors for subarachnoid haemorrhage: a nationwide cohort of 950 000 adults.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients.

BACKGROUND: Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients. METHODS: The medical records of all LTx ATTRm amyloidosis patients in the county of Västerbotten, Sweden, were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status. RESULTS: Sixty-three patients that had survived for 3 years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P < 0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P = 0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P = 0.029). CONCLUSIONS: AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However, the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.

Time trends and socioeconomic differences in blood pressure levels: The Northern Sweden MONICA study 1994-2014.

Background People with low socioeconomic status have higher blood pressure (BP), increasing their risk of myocardial infarction and stroke. We hypothesized that the gap in systolic (SBP) and diastolic (DBP) BP, according to educational level, has decreased over time but, that economical vulnerability would confer higher BP. Methods A total of 4564 women and 4363 men aged 25-74 years participated in five population-based surveys in the Northern Sweden MONICA study between 1994 and 2014 (participation rate 76.8-62.5%). Results SBP decreased by 10 mmHg in women and 4 mmHg in men, while DBP was unchanged. Treatment with antihypertensives increased in all but the youngest men. The prevalence of BP control in the population (<140/90 mmHg) increased and in 2014 reached 75% among women and 70% among men. The decrease in SBP was more pronounced in people without university education than in people with university education and DBP showed the same pattern, regardless of education. After adjustment for confounding factors, age, male sex, higher body mass index, and being born in a Nordic country were related to higher SBP and DBP. University education was related to lower SBP, while variables mirroring economic vulnerability were not associated with BP levels. Conclusions BP levels as well as the socioeconomic gap in BP has decreased in Sweden but people with a lower level of education still have higher SBP. Lacking economic resources is not associated with high BP.

Socioeconomic Status and the Risk of Stroke Recurrence: Persisting Gaps Observed in a Nationwide Swedish Study 2001 to 2012.

BACKGROUND AND PURPOSE: This nationwide observational study aimed to investigate how socioeconomic status is associated with risk of stroke recurrence and how possible associations change over time. METHODS: This study included 168 295 patients, previously independent in activities of daily living, with a first-ever stroke in the Swedish Stroke Register (Riksstroke) 2001 to 2012. Riksstroke was linked with Statistics Sweden as to add individual information on education and income. Subdistribution hazard regression was used to analyze time from 28 days after first stroke to stroke recurrence, accounting for the competing risk of other causes of death. RESULTS: Median time of follow-up was 3.0 years. During follow-up, 23 560 patients had a first recurrent stroke, and 53 867 died from other causes. The estimated cumulative incidence of stroke recurrence was 5.3% at 1 year, and 14.3% at 5 years. Corresponding incidence for other deaths were 10.3% and 30.2%. Higher education and income were associated with a reduced risk of stroke recurrence. After adjusting for confounding variables, university versus primary school education returned a hazard ratio of 0.902; 95% confidence interval, 0.864 to 0.942, and the highest versus the lowest income tertile a hazard ratio of 0.955; 95% confidence interval, 0.922 to 0.989. The risk of stroke recurrence decreased during the study period, but the inverse effect of socioeconomic status on risk of recurrence did not change significantly. CONCLUSIONS: Despite a declining risk of stroke recurrence over time, the differences in recurrence risk between different socioeconomic groups remained at a similar level in Sweden during 2001 to 2012.

Optimal Timing of Anticoagulant Treatment After Intracerebral Hemorrhage in Patients With Atrial Fibrillation.

BACKGROUND AND PURPOSE: This study aims to provide observational data on the relationship between the timing of antithrombotic treatment and the competing risks of severe thrombotic and hemorrhagic events in a cohort of Swedish patients with atrial fibrillation and intracerebral hemorrhage (ICH). METHODS: Patients with atrial fibrillation and a first-ever ICH were identified in the Swedish Stroke Register, Riksstroke, 2005 to 2012. Riksstroke was linked with other national registers to find information on treatment, comorbidity, and outcome. The optimal timing of treatment in patients with low and high thromboembolic risk was described through cumulative incidence functions separately for thrombotic and hemorrhagic events and for the combined end point vascular death or nonfatal stroke. RESULTS: The study included 2619 ICH survivors with atrial fibrillation with 5759 person-years of follow-up. Anticoagulant treatment was associated with a reduced risk of vascular death and nonfatal stroke in high-risk patients with no significantly increased risk of severe hemorrhage. The benefit seemed to be greatest when treatment was started 7 to 8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within 3 years was 17.0% when anticoagulant treatment was initiated 8 weeks after ICH and 28.6% without any antithrombotic treatment (95% confidence interval for difference, 1.4%-21.8%). For high-risk men, the corresponding risks were 14.3% versus 23.6% (95% confidence interval for difference, 0.4%-18.2%). CONCLUSIONS: This nationwide observational study suggests that anticoagulant treatment may be initiated 7 to 8 weeks after ICH in patients with atrial fibrillation to optimize the benefit from treatment and minimize risk.

Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation.

BACKGROUND AND PURPOSE: Patients who survive intracerebral hemorrhage (ICH) often have compelling indications for anticoagulant and antiplatelet medication. This nationwide observational study aimed to determine the extent and predictors of antithrombotic treatment after ICH in Sweden. METHODS: Patients with a first-ever ICH in the Swedish Stroke Register (Riksstroke) 2005 to 2012 who survived hospital discharge were included. Riksstroke data were individually linked with other national registers to determine comorbid conditions and dispensed prescriptions of antithrombotic agents. RESULTS: Among the 2777 patients with atrial fibrillation (AF), the proportion with a dispensed prescription of antithrombotic agents was 8.5% (anticoagulants) and 36.6% (antiplatelet agents) within 6 months and 11.1% (anticoagulants) and 43.6% (antiplatelet agents) within 1 year. Among the 11 268 patients without AF, the corresponding figures were 1.6% (anticoagulants) and 13.8% (antiplatelet agents) within 6 months and 2.0% (anticoagulants) and 17.5% (antiplatelet agents) within 1 year. In patients with AF, predictors of anticoagulant treatment were less severe ICH, younger age, previous anticoagulation, valvular disease, and previous ischemic stroke. High CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke [doubled], vascular disease, age, and sex category [female]) scores did not correlate with anticoagulant treatment. There was a positive correlation between high CHA2DS2-VASc and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol) scores (rs=0.590, P<0.001). CONCLUSIONS: In majority of patients who receive antithrombotic agents, treatment is initiated within 6 months of ICH. Still, many patients with compelling indications for antithrombotic treatment are not prescribed antithrombotic agents. Factors other than high risk of embolic stroke by CHA2DS2-VASc in ICH survivors with concurrent AF are used to guide the anticoagulant treatment decision in Swedish clinical practice.

Long-term risk and predictors of recurrent stroke beyond the acute phase.

BACKGROUND AND PURPOSE: Previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. This study set out to investigate the long-term risk and predictors of recurrent stroke in Northern Sweden 1995 to 2008. METHODS: In the population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence registry, stroke survivors of either ischemic stroke or intracerebral hemorrhage were followed for recurrent stroke or death. Cox regression was used to identify predictors of stroke recurrence. RESULTS: The study comprised 6700 patients and 26 597 person-years. During follow-up, 928 (13.9%) patients had a recurrent stroke. Comparison between the first time period (1995-1998) and the last (2004-2008) showed declined risk of stroke recurrence (hazard ratio, 0.64 [95% confidence interval, 0.52-0.78]). Previous myocardial infarction was less prevalent in the most recent cohort (P<0.001). Predictors of stroke recurrence were age (hazard ratio, 1.03 [95% confidence interval, 1.02-1.04]) and diabetes mellitus (hazard ratio, 1.34 [95% confidence interval, 1.15-1.57]). After an index intracerebral hemorrhage (n=815), a major part of recurrent events were ischemic (63%), and compared with the ischemic stroke group (n=5885), a tendency toward lower risk of recurrence was observed. CONCLUSIONS: Despite declining recurrence rates in this relatively young stroke population, almost one third are either dead or have experienced a second stroke in 5 years.

Heart complications in familial transthyretin amyloidosis: impact of age and gender.

Heart arrhythmia is common in Swedish patients with familial amyloidotic polyneuropathy (FAP), as well as cardiomyopathy. We investigated the relationship between Holter ECG and echocardiographic findings in 108 FAP patients, with particular focus on age and gender differences. Female patients were younger than male patients at symptom onset (p < 0.01). Only 4 of 39 patients with septal hypertrophy were females. Regression analysis showed that age of onset, gender and duration of disease were significantly related with intraventricular septum (IVS) thickness. Sixty-five patients (25 females) presented with abnormal 24-h ECG recordings. IVS thickness was not significantly related to conduction disturbances or the presence of ventricular arrhythmia (VA). However, IVS thickness and atrial dimension were both related to increased rate of supraventricular arrhythmia (SVA). Male gender was clearly associated with more pronounced septal thickness of the heart. Conduction disturbances were not related to IVS thickness, indicating that the distribution and extent of infiltration of the heart by amyloid are heterogeneous and related to gender and age of onset. These findings highlight the necessity of 24-h ECGs to detect conduction disturbances, due to their occurrence in the absence of echocardiographic evidence of amyloid deposition in the myocardium.