Three-year outcomes related to coronary stenting; a registry-based real-life population study.

Objectives. Developments in medication and coronary interventions have improved coronary artery disease (CAD) treatment. We studied long-term outcomes in an observational, real-life population of CAD patients undergoing percutaneous coronary intervention (PCI) depending on the presentation and the stent type used. Design and results. Register included 789 consecutive patients undergoing PCI. Follow up period was three years with primary composite outcome (MACE) of all cause -mortality, myocardial infarction and target lesion revascularization. Mean age was 65 ± 11 and 69% were male. New-generation drug-eluting stents (DES-2) were associated with lower adjusted rates of MACE (HR 0.47; 95% CI 0.29-0.77) but not mortality (HR 0.50; 95% CI 0.22-1.14) in comparison to bare-metal stents. Patients with STEMI (14.4%) or NSTEMI (13.7%) had higher crude mortality rates than those with unstable (4.5%) or stable CAD (3.1%; p < .001). The association diminished after adjustments in NSTEMI (HR 2.01; 95% CI 0.88-4.58). Among smokers 45% quitted and 36% achieved recommended cholesterol levels. Conclusions. The overall prognosis was good. Irrespective of comorbidities, NSTEMI was not associated with worse outcome than stable CAD. DES-2 was associated with lower rates of MACE than BMS without affecting mortality rate. Patients succeeded better in smoking cessation than reaching recommended cholesterol levels.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

IRF4 Deficiency Leads to Altered BCR Signalling Revealed by Enhanced PI3K Pathway, Decreased SHIP Expression and Defected Cytoskeletal Responses.

The graded expression of transcription factor interferon regulatory factor 4 (IRF4) regulates B cell development and is critical for plasma cell differentiation. However, the mechanisms, by which IRF4 elicits its crucial tasks, are largely unknown. To characterize the molecular targets of IRF4 in B cells, we established an IRF4-deficient DT40 B cell line. We found that in the absence of IRF4, the expression of several molecules involved in BCR signalling was altered. For example, the expression of B cell adaptor for PI3K (BCAP) was upregulated, whereas the SHIP (SH2-containing Inositol 5?-Phosphatase) expression was downregulated. These molecular unbalances were accompanied by increased BCR-induced calcium signalling, attenuated B cell linker protein (BLNK) and ERK activity and enhanced activity of PI3K/protein kinase B (Akt) pathway. Further, the IRF4-deficient cells showed dramatically diminished cytoskeletal responses to anti-IgM cross-linking. Our results show that IRF4 has an important role in the regulation of BCR signalling and help to shed light on the molecular mechanisms of B cell development and germinal centre response.

Intracerebral hemorrhage at young age: long-term prognosis.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disorder associated with dismal outcomes. The long-term mortality and functional outcome of ICH in young patients was studied - areas so far poorly investigated. METHODS: A follow-up study was performed on a cohort of patients. Clinical and imaging data on ICH patients aged 16-49 were retrospectively obtained and linked with a nationwide cause-of-death register. The modified Rankin Scale (mRS) was evaluated for 30-day survivors at a visit 9.7 (7.0-12.0) years after ICH onset. Independent factors associated with mortality and unfavorable functional outcome (mRS 2-5) were sought by multivariate analysis. RESULTS: Amongst the 268 1-month survivors, 1-year survival was 98.1% [95% confidence interval (CI) 96.2%-100%], 5-year survival 93.2% (89.3%-97.1%) and 10-year survival 88.8% (84.9%-92.7%). After adjustment for age and intraventricular hematoma extension, male sex [odds ratio (OR) 3.36, 95% CI 1.28-8.80] and diabetes (OR 2.64, 1.01-6.89) were associated with increased mortality. Unfavorable functional outcome emerged in 49%. After adjustment for confounders, age (OR 1.09 per 1 year, 95% CI 1.03-1.15), initial stroke severity (1.17 per one National Institutes of Health Stroke Scale score point, 1.08-1.27) and intraventricular hemorrhage (3.26, 1.11-9.55) were associated with unfavorable functional outcome. CONCLUSIONS: Of every 10 survivors of acute phase ICH at a young age, one died within 10 years after onset, male sex and diabetes being associated with increased mortality. Half the survivors did not achieve a favorable functional outcome, which was predicted by increasing age, initial stroke severity and intraventricular hemorrhage.

Incidence, risk factors, etiology, severity and short-term outcome of non-traumatic intracerebral hemorrhage in young adults.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a common and severe form of stroke but is scarcely studied in young adults. Our aim was to study risk factors, clinical presentation and early mortality of ICH in the young and compare these features with older patients. METHODS: All consecutive patients aged between 16 and 49 diagnosed with a first-ever ICH at the Departments of Neurology or Neurosurgery of the Helsinki University Central Hospital between January 2000 and March 2010 (n = 336) were analyzed retrospectively. Comparisons were performed amongst demographic subgroups and with patients over 49 years of age enrolled between January 2005 and March 2010 (n = 921). RESULTS: In the young patients, median age was 42 years (interquartile range 34-47), 59.5% were male, and annual incidence was 4.9 (95% confidence interval 4.5-5.3) per 100 000. The most prevalent risk factors were hypertension (29.8%) and smoking (22.3%). Compared with older patients hypertensive microangiopathy was less common (25.0% vs. 34.3%, P = 0.002) and structural lesions more common (25.0% vs. 4.9%, P < 0.001) assumed etiologies of ICH. The cause remained elusive in 32.1% of all young patients and in 22.5% of those who underwent magnetic resonance imaging and any angiography (n = 89, P = 0.023). Three-month mortality rate was lower in young patients compared with older ones (17.0% vs. 32.7%, P < 0.001). Hematoma volumes were similar across all ages (P = 0.324) and independently predicted mortality in older patients but not in the young. CONCLUSIONS: Intracerebral hemorrhage (ICH) in the young appears less fatal and has a different spectrum of causes and factors associated with short-term mortality than for the elderly.

A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort.

Paragangliomas are rare neuroendocrine tumours arising from neural crest-derived tissue. In the head and neck region typical locations are the carotid bifurcation, vagal nerve or jugulotympanic region. Paragangliomas are normally benign, and malignant transformation is rare. During the past decade the understanding of the genetic and molecular aetiology has had an important clinical impact on the management of PGs. This is a retrospective review of all histologically verified paragangliomas diagnosed and managed at an academic tertiary care referral centre between 1990 and 2010. Data on age, sex, symptoms, tumour location, management and follow-up were recorded. There were 64 patients with 74 tumours. Thirty-six per cent of the tumours were located in the carotid body region, 48 % in the jugulotympanic region and 15 % in the vagal nerve. One tumour was located in the dorsal neck. Most (95 %) of the patients were treated primarily with surgery and with curative intent. Definitive radiation therapy was primarily given to two patients. Recurrent or residual tumours were treated with surgery in three patients and with radiation therapy in nine patients. The typical long-term post-operative sequel was vocal cord paralysis. Local recurrence was found in 6 % of patients. Symptoms and findings related to paragangliomas are variable and management should be individualized. Surgery remains the primary choice of the current treatment options, but often is challenging and warrants a multidisciplinary approach. We present an algorithm on the management of head and neck paragangliomas based on current knowledge.

Higher baseline international normalized ratio value correlates with higher mortality in intracerebral hemorrhage during warfarin use.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulation (OAC). Our aim was to investigate the impact of the international normalized ratio (INR) level on mortality in OAC-associated ICH compared with non-OAC-associated ICH. METHODS: A retrospective chart review of consecutive ICH patients treated at the Helsinki University Central Hospital from January 2005 to March 2010 (n = 1013) was performed. An ICH was considered to be OAC-associated if the patient was on warfarin at ICH onset. The association of INR with 3-month mortality was adjusted in a multivariable logistic regression model for factors influencing the crude odds ratios (ORs) in bivariable logistic regression by more than 5%. RESULTS: One in eight ICHs was OAC-associated (n = 132). Of these, 50% had therapeutic INR (2.0-3.0), 7% had INR <2.0 and 43% had high INR (>3.0) on admission. Patients on OAC were older (median 76 vs. 66 years; P < 0.001) with more severe symptoms (median National Institutes of Health Stroke Scale 14 vs. 10; P < 0.001) and larger hematomas (median 11.4 vs. 9.7 ml; P < 0.001) on admission than patients not on OAC. After adjustment for confounders, 3-month mortality in the whole cohort was associated with higher baseline INR (OR 1.06; CI 1.03-1.09 per 0.1 increment). Mortality was higher with both therapeutic (51% at 3 months; OR 3.59; CI 1.50-8.60) and high (61%; OR 5.26; CI 1.94-14.27) INR values compared with non-OAC-associated ICH (29%). CONCLUSIONS: Patients with OAC-associated ICH had more severe strokes and higher mortality compared with patients with ICH not related to OAC. Higher baseline INR was associated with increased 3-month mortality.

Microsurgical technique for previously coiled aneurysms.

Since the introduction of Guglielmi detachable coils to treat intracranial aneurysms in 1991, the number of patients undergoing endovascular coiling has continuously risen as well as the number of those residual and recurrent previously coiled aneurysms that necessitate a microsurgical occlusion. Between July 1995 and August 2009 we retrospectively analyzed 81 patients with 82 previously coiled aneurysms treated microsurgically at two Finnish Neurosurgical University Hospitals, Helsinki and Kuopio. Fifty-eight aneurysms (71%) were located at anterior circulation and 24 (29%) at posterior circulation. Fifteen patients were operated on within the first month (early surgery) after coiling, whereas 66 were treated later (late surgery). Complete or partial removal of coils during surgery may facilitate clipping, but is significantly (P<0.001) more difficult to accomplish in late surgery. Removal of coils may also increase the chance for poor outcome. Chance of poor outcome increased also with intraoperative aneurysm rupture, size of the aneurysm and posterior circulation location. Good clinical outcome, three months after surgery, was achieved in 71 patients (88%); four patients were severely disabled, and six patients died (three of them due to poor clinical condition). Complete microsurgical occlusion of the residual previously coiled aneurysm is a high-risk procedure in large and giant aneurysms, and these patients should be referred to a dedicated neurovascular center to minimize surgical complications. Bypass procedures may be the best option for demanding growing lesions, especially those in posterior circulation.

Management of dural arteriovenous fistulas - Helsinki and Kuopio experience.

Dural arteriovenous fistulas (DAVFs) are complex disorders, some of them with aggressive clinical behaviour. During past decades their treatment strategy has changed due to increased knowledge of their pathophysiology and natural history, and advances in treatment modalities. In asymptomatic cases or cases with mild symptoms in the absence of cortical venous drainage (CVD) no treatment is necessarily required, whereas aggressive DAVFs should be treated promptly by endovascular or microsurgical means.In our series of 323 patients with 333 fistulas, treated in two neurosurgical units in Finland since 1944, there were 265 true DAVFs and 68 Barrow type A caroticocavernous fistulas. Among the DAVFs there was a slight female predominance, 140 women (55%) and 115 men (45%), and the majority of the cases were located in the area of transverse and sigmoid sinuses. Mode of treatment in the early series was proximal ligation of feeding artery, and later craniotomy, endovascular treatment and radiosurgery, or combination of these treatments, with total occlusion rate being 53%.

Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumours.

AIMS: The polycomb factor BMI-1 has recently been implicated in tumorigenesis of the central nervous system in several experimental animal models. However, the significance of BMI-1 in human glioma has not been investigated. Here we describe expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a) and MDM2 in both high- and low-grade human glioma. METHODS: Tumour samples were collected from 305 adult patients treated for primary grades 2-4 gliomas between 1980 and 2006 in Finland and Germany. BMI-1, p16 and MDM2 expression was evaluated using immunohistochemistry in representative paraffin-embedded tumour tissue. The significance of observed immunoreactivity, age at onset, gender, histopathological findings and proliferative index was analysed in univariate and multivariate survival models. RESULTS: BMI-1 was expressed in all histologic types of diffuse gliomas. We found a significant correlation (P = 0.007) between the frequency of BMI-1 immunoreactive tumour cells and poor survival in World Health Organization grades II-III oligodendrogliomas and oligoastrocytomas (n = 62). The median survival of patients grouped by low, intermediate or high frequency of BMI-1 immunoreactive tumour cells was 191 months, 151 months and 68 months, respectively. This association was also significant in the Cox multivariate regression model. Nuclear p16 immunopositivity predicted better survival in astrocytomas and an inverse correlation between p16 expression and the Ki-67 mitotic index was also observed. CONCLUSIONS: BMI-1 is found in all histological types of gliomas and the relative protein expression of BMI-1 is a novel independent prognostic marker in oligodendroglial tumours.

Historical landmarks in vascular neurosurgery "On July 10th 2006, at the 70th Anniversary of the Department of Neurosurgery of Zürich Medical School".

Direct aneurysm surgery started more than 70 years ago. Introduction of cerebral angiography by Moniz in 20s and operating microscope by Yasargil in 60s were the real cornerstones in vascular neurosurgery. Since then the development of neuroanestesiology and further development of non-invasive imaging (MRA and CTA) together with the latest development of operating microscopes with intraoperative ICG angio have shifted vascular microneurosurgery to a different level to still compete with the 'non-invasiness' of endovascular therapy. There is an increasing demand to perform the already forgotten bypasses mastered only by few and with the high-flow techniques (e.g. ELANA) we can treat lesions that some time ago were considered impossible. Endovascular embolization to reduce the flow in AVM before surgery is very helpful in those cases that can not be treated by embolization or radiosurgery alone. We still need to find a way to detect aneurysms before they rupture and especially those thin-walled that are in an increased risk of rupture. Recent data on the pathobiology of the aneurysm wall may help us to better understanding of the growth mechanisms and it might be possible to develop more potent local or systemic pharmaceutical therapy to induce myo-intimal hyperplasia occluding the aneurysm and strengthening the wall to prevent rupture.

Biodegradation of inorganic drug delivery systems in subcutaneous conditions.

Despite extensive efforts to develop delivery systems for oral administration, subcutaneous (s.c.) injection remains the most common way to administer peptide drugs. To limit the number of frequent injections, sustained release systems that are easy to produce, suitable for various drugs, safe and biodegradable are urgently needed. Porous silicon (PSi) has been recognized to be one of the most promising materials for s.c. peptide delivery, but its biodegradation in s.c. tissue has not been studied in vivo, despite extensive in vitro research. In the present study, differently modified PSi microparticles were injected s.c. in mice, after which the morphology of the particles was thoroughly studied with transmission electron microscopy, micro-computed tomography and X-ray diffraction. Furthermore, histopathology of the s.c. tissue was analyzed to evaluate biocompatibility. To the best of our knowledge, this is the first systematic study which reveals the degradation behavior of various PSi materials in vivo. The PSi surface chemistry significantly affected the biodegradation rate of the s.c. injected microparticles. The most hydrophobic PSi microparticles with hydrocarbonized surface showed the lowest biodegradation rate while the hydrophilic microparticles, with oxide surface, degraded the fastest. The results from different empirical methods complemented each other to deduce the biodegradation mechanism of the inorganic delivery system, providing useful information for future development of s.c. carriers.

Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with Inflammation and Degenerative Changes of the Aneurysm Wall.

BACKGROUND AND PURPOSE: Saccular intracranial aneurysm is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with saccular intracranial aneurysm rupture. We investigated how saccular intracranial aneurysm hemodynamics is associated with wall remodeling and inflammation of the saccular intracranial aneurysm wall. MATERIALS AND METHODS: Tissue samples resected during a saccular intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT angiographies. RESULTS: More stable and less complex flows were associated with thick, hyperplastic saccular intracranial aneurysm walls, while slower flows with more diffuse inflow were associated with degenerated and decellularized saccular intracranial aneurysm walls. Wall degeneration (P = .041) and rupture were associated with increased inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate (P = .046) were associated with increased inflammation. Inflammation was also associated with lack of an intact endothelium (P = .034) and the presence of organized luminal thrombosis (P = .018), though overall organized thrombosis was associated with low minimum wall shear stress (P = .034) and not with the flow conditions associated with inflammation. CONCLUSIONS: Flow conditions in the saccular intracranial aneurysm are associated with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is related to high flow activity, including elevated wall shear stress. Endothelial injury may be a mechanism by which flow induces inflammation in the saccular intracranial aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular intracranial aneurysms at risk of developing inflammation, a potential biomarker for rupture.

Removal of cyanobacteria, cyanotoxins, heterotrophic bacteria and endotoxins at an operating surface water treatment plant.

The removal of cyanobacteria, hepatotoxins produced by them (microcystins), phytoplankton, heterotrophic bacteria and endotoxins were monitored at a surface water treatment plant with coagulation, clarification, sand filtration, ozonation, slow sand filtration and chlorination as the treatment process. Coagulation-sand filtration reduced microcystins by 1.2-2.4, and endotoxins by 0.72-2.01 log10 units. Ozonation effectively removed the residual microcystins. The treatment process reduced phytoplankton biomass by 2.2-4.6 and heterotrophic bacteria by 2.0-5.0 log10 units. In treated water, the concentration of microcystins never exceeded the WHO guide value (1 microg/L), but picoplankton and monad cells were often detected in high numbers. The heterotrophic bacterial isolates from the treated waters belonged to genera Sphingomonas, Pseudomonas, Bacillus, Herbaspirillum and Bosea.

Intracranial Suppurative Complications of Sinusitis.

BACKGROUND: Intracranial complications of paranasal sinusitis have become rare due to widespread and early use of antibiotics. Potentially life-threatening intracranial complications of sinusitis include subdural empyema, epidural and intracerebral abscess, meningitis, and sinus thrombosis. Patients with intracranial complication of sinusitis can present without neurological signs, which may delay diagnosis and correct treatment. AIMS: Our aim was to evaluate the diagnostics, treatment, and outcome of sinusitis-related intracranial infections at our tertiary referral hospital with a catchment area of 1.9 million people. MATERIALS AND METHODS: We retrospectively collected data on all patients diagnosed and treated with an intracranial infection at the Helsinki University Hospital, Helsinki, Finland, during a 10-year period between 2003 and 2013. RESULTS: Six patients were diagnosed to have a sinusitis-related intracranial infection. Four patients had an epidural abscess, one both an epidural abscess and a subdural empyema and one a subdural empyema. The most common presenting complaint was headache (100%) followed by fever (83%), vomiting (50%), nasal congestion (50%), forehead lump (34%), and neck stiffness (17%). All patients were managed surgically. Most (83%) patients recovered to premorbid state without neurological sequelae. One patient died intraoperatively. CONCLUSION: Patients with a sinusitis-related intracranial suppuration typically present with signs of raised intracranial pressure rather than signs of sinusitis. Most are likely to need neurosurgical intervention and evacuation of the abscess without delay.

Relationship of socioeconomic status to the incidence and prehospital, 28-day, and 1-year mortality rates of acute coronary events in the FINMONICA myocardial infarction register study.

BACKGROUND: Low socioeconomic status (SES) is associated with increased coronary heart disease mortality rates. There are, however, very little data on the relation of SES to the incidence, recurrence, and prognosis of myocardial infarction (MI) events. METHODS AND RESULTS: The FINMONICA MI Register recorded detailed information on all MI events among men and women aged 35 to 64 years in 3 areas of Finland during the period of 1983 to 1992. We carried out a record linkage of the MI register data with files of Statistics Finland to obtain information on indicators of SES, such as taxable income and education, for each individual who is registered. In the analyses, income was grouped into 3 categories (low, middle, and high), and education was grouped into 2 categories (basic and secondary or higher). Among men with their first MI event (n=6485), the adjusted incidence rate ratios were 1.67 (95% CI 1.57 to 1.78) and 1.84 (95% CI 1.73 to 1.95) in the low- and middle-income categories compared with the high-income category. For 28-day mortality rates, the corresponding rate ratios were 3.18 (95% CI 2.82 to 3.58) and 2.33 (95% CI 2.03 to 2.68). Significant differentials were observed for prehospital mortality rates, and they remained similar up to 1 year after the MI. Findings among the women were consistent with those among the men. CONCLUSIONS: The excess coronary heart disease mortality and morbidity rates among persons with low SES are considerable in Finland. To bring the mortality rates of low- and middle-SES groups down to the level of that of the high-SES group constitutes a major public health challenge.

Decline in out-of-hospital coronary heart disease deaths has contributed the main part to the overall decline in coronary heart disease mortality rates among persons 35 to 64 years of age in Finland: the FINAMI study.

BACKGROUND: Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance. METHODS AND RESULTS: We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, -7.3, -5.0%) among men and 7.0% (-10.0, -4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (-7.2, -3.2%), and among men without such history the decline was 2.9% (-4.4, -1.5%). Among women, the corresponding changes were -7.8% (-14.2, -1.5%) and -4.5% (-8.0, -1.0%). CONCLUSIONS: The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.

Effect of beta-blockade on heart rate variability in patients with coronary artery disease.

OBJECTIVES: This study assessed the effects of beta-blockade on heart rate variability in patients with coronary artery disease and determined whether the effects of metoprolol in a controlled-release formulation and atenolol differ with regard to electrocardiographic measures of cardiac autonomic control. BACKGROUND: Low heart rate variability is common in coronary artery disease and is associated with increased mortality. Beta-adrenergic blocking drugs may increase heart rate variability in healthy subjects, but there is limited knowledge of whether they are able to modify heart rate variability in patients with uncomplicated coronary artery disease. METHODS: In a randomly allocated, double-blind crossover study with three 2-week treatment periods, 200 mg of controlled-release metoprolol once a day, 100 mg of atenolol once a day or placebo once a day were administered in 18 male patients with stable coronary artery disease. The 24-h heart rate variability was measured in both the time and frequency domains. RESULTS: Beta-blockade induced a significant increase in heart rate variability, but no significant differences were found between atenolol and metoprolol. The average 24-h high frequency power increased by 64% after atenolol and by 62% after metoprolol. The root-mean-square successive difference of normal RR intervals increased by 70% after atenolol and by 62% after metoprolol, and the standard deviations of RR intervals increased by 20% and 16%, respectively. Beta-blockade had no significant effects on the amplitude of the circadian rhythm of heart rate variability, although both metoprolol and atenolol blunted the abrupt decrease of high frequency power after arousal. CONCLUSIONS: Beta-blockade by metoprolol and atenolol enhance the heart rate variability in patients with coronary artery disease. This may contribute to the protective effects of beta-blockade in ischemic heart disease.

Abnormalities in beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction.

OBJECTIVES: The purpose of this research was to study possible abnormalities in the beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction. BACKGROUND: Analysis of approximate entropy of time series data provides information on the complexity of both deterministic and random processes. It has been proposed that regularity or loss of complexity of RR interval dynamics may be related to pathologic states, but this hypothesis has not been well tested in cardiovascular disorders. METHODS: Approximate entropy and conventional time and frequency domain measures of RR interval variability were compared between 40 healthy subjects with no evidence of heart disease and 40 patients with coronary artery disease and a previous Q wave myocardial infarction. The groups were matched with respect to age, and cardiac medication was discontinued in the patients with coronary artery disease before the 24-h electrocardiographic recordings. RESULTS: Approximate entropy was significantly higher in the postinfarction patients (1.21 +/- 0.18 [mean +/- SD]) than in the healthy subjects (1.05 +/- 0.11, p < 0.001), whereas the standard deviation of RR intervals (63 +/- 19 vs. 86 +/- 23 ms, p < 0.001) and the very low, low and high frequency spectral components were lower (p < 0.01, p < 0.001, p < 0.05, respectively). Approximate entropy was not related to the time domain or the spectral components of heart rate variability and was more commonly abnormal in postinfarction patients (62.5%) than any linear measure (from 20% to 42.5%) when the 90% percentile of the values obtained for healthy subjects was defined as the normal range for each measure. CONCLUSIONS: Despite reduced linear measures of heart rate variability, the unpredictability or randomness of beat to beat heart rate dynamics is increased in patients with a previous myocardial infarction. Complexity analysis of RR interval dynamics may provide useful information on abnormalities in heart rate behavior that are not easily detected by the commonly used moment statistics.