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To compare management and outcome of female and male non-ST-elevation acute coronary syndrome (ACS) patients.FINACS Studies are prospective registries of non-ST-elevation ACS patients conducted in 2001, 2003, and 2005 in nine hospitals.The studies enrolled 1,399 patients from which 39% were women. During hospitalisation women were treated less often than men with aspirin (odds ratio [OR]) for women 0.60, 95% confidence interval [CI] 0.41 to 0.88, p=0.03). Women underwent less often in-hospital coronary angiography than men (adjusted OR 0.71, 95% CI 0.55 to 0.93, p=0.01). Also in the subgroup of younger (75 years) high-risk patients, female sex was independent predictor for not performing in-hospital angiography (OR 0.64, 95% CI 0.42 to 0.97, p=0.04). Age-adjusted mortality at 6 months was similar between men and women.Compared to men women received less often aspirin. Women were referred less often to in-hospital coronary angiography. Under-use of in-hospital angiography was evident also in patients with high-risk features when guidelines recommend early invasive treatment.

Vikman S, Airaksinen KEJ, Tierala I, Peuhkurinen K, Majamaa-Voltti K, Niemela M, Tuunanen H, Nieminen MS, Niemela K (Tampere University Hospital, Tampere; University of Turku, Turku; University of Helsinki, Helsinki; University of Kuopio, Kuopio; and University of Oulu, Oulu; Finland). Improved adherence to practice guidelines yields better outcome in high-risk patients with acute coronary syndrome without ST elevation: findings from nationwide FINACS studies. J Intern Med 2004; 256: 316–323. Objectives. Treatment options for acute coronary syndrome (ACS) without ST elevation have evolved rapidly during the recent years, but the successful implementation of practice guidelines incorporating new treatments into practice has been challenging. In this study, we evaluate whether targeted educational intervention could improve adherence to treatment guidelines of ACS without ST elevation. Design, setting and subjects. A previous study, FINACS I, evaluated the treatment and outcome of 501 consecutive non-ST elevation ACS patients that were referred in early 2001 to nine hospitals, covering nearly half of the Finnish population. That study revealed poor adherence to ESC guidelines, so targeted educational intervention on optimal practice was arranged before the second study (FINACS II), which was performed in the same hospitals using the same protocol as FINACS I. FINACS II, undertaken in early 2003, evaluated 540 consecutive patients. Interventions. Targeted educational programmes on optimal practice. Main outcome measures. The use of evidence-based therapies in non-ST elevation ACS patients. In-hospital event-free (death, new myocardial infarction, refractory angina, readmission with unstable angina and transient cerebral ischaemia/stroke) survival, and event-free survival at 6 months. Results. Baseline characteristics and risk markers were similar in both studies, and no significant changes in resources were seen. In 2003, the in-hospital use of statins, ACE-inhibitors, clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonists increased significantly, and in-hospital angiography was performed more often, especially in high-risk patients (59% vs. 45%, P

Patients with the 3243AG mutation in mitochondrial DNA (mtDNA) have an increased risk for cardiovascular morbidity and mortality. The function of the autonomic nervous system has not been evaluated in these patients.Indices of 24-hour heart rate variability (HRV) and baroreflex sensitivity (BRS) were measured in 28 patients with 3243AG. The results were compared to controls matched with respect to age, sex, the presence of hypertension and diabetes mellitus and the use of cardiac medication. Conventional time and spectral domain indices and fractal correlation properties of HRV were analysed.In spectral analysis of HRV, the ultra-low and very-low-frequency spectral components were lower in the patients than the controls (P0.05 for both). Furthermore, the short-term fractal scaling exponent was lower in the patients with 3243AG compared to the controls (1.16 +/- 0.18 versus 1.28 +/- 0.13, P0.01). No significant associations were found between the HRV indices and the other characteristics of the patients with 3243AG, such as the presence of diabetes or left ventricular hypertrophy, left ventricular systolic function, the severity of the disease or the degree of 3243AG heteroplasmy.Patients with the 3243AG mutation in mtDNA have abnormalities in the spectral and fractal characteristics of HRV suggesting altered cardiac autonomic regulation. The abnormalities are not clearly associated with clinical manifestations related to 3243AG suggesting that mitochondrial dysfunction may affect the autonomic regulatory systems more directly.

We report the development of a time-resolved fluorometry-based immunoassay concept for the rapid measurement of three cardiac markers from whole blood, serum or plasma. Using a universal all-in-one (AIO) dry reagent concept, all the analyte specific reagents are built into a single microtire well, to which an identical assay protocol is applied. Addition of 5-20 microL sample (whole blood, serum or plasma) together with a universal buffer initiates the reaction, which is brought close to equilibrium in 15 min. After the wash step the Eu chelate-derived signal is measured directly from the dried surface. Application of this concept to the three cardiac markers illustrates its ability to provide rapid, highly sensitive and fully quantitative results over a large dynamic range with good reproducibility. Such a performance, especially when using whole blood specimens, is largely a consequence of the inherently fluorescent and stable Eu-chelate employed in the system. Correlation to commercial assays was excellent for all three analytes, as was between-sample matrix correlation using the AIO assays. The presented assay concept enabling a simple automation is particularly suited for point-of-care applications, where the performance characteristics are fully comparable to state-of-the-art central laboratory immunoassays.

SummaryMitochondrial diseases are characterized by considerable clinical variability and are most often caused by mutations in mtDNA. Because of the phenotypic variability, epidemiological studies of the frequency of these disorders have been difficult to perform. We studied the prevalence of the mtDNA mutation at nucleotide 3243 in an adult population of 245,201 individuals. This mutation is the most common molecular etiology of MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes), one of the clinical entities among the mitochondrial disorders. Patients with diabetes mellitus, sensorineural hearing impairment, epilepsy, occipital brain infarct, ophthalmoplegia, cerebral white-matter disease, basal-ganglia calcifications, hypertrophic cardiomyopathy, or ataxia were ascertained on the basis of defined clinical criteria and family-history data. A total of 615 patients were identified, and 480 samples were examined for the mutation. The mutation was found in 11 pedigrees, and its frequency was calculated to be ⩾16.3/100,000 in the adult population (95% confidence interval 11.3–21.4/100,000). The mutation had arisen in the population at least nine times, as determined by mtDNA haplotyping. Clinical evaluation of the probands revealed a syndrome that most frequently consisted of hearing impairment, cognitive decline, and short stature. The high prevalence of the common MELAS mutation in the adult population suggests that mitochondrial disorders constitute one of the largest diagnostic categories of neurogenetic diseases.

Background: Causes of death of patients with the 3243A>G mutation have been described in case reports or case series with a limited number of subjects. Methods: Eighty-two maternally related sibships of 11 families with 3243A>G were included in this survey. The lifespan of each subject in these families was compared with the life expectancy of the general population, adjusted with respect to year of birth and gender. Causes of death were determined among 3243A>G carriers and their first-degree maternal relatives. Results: We identified 123 deceased subjects in families with 3243A>G and found an excess mortality during the early years of life and young adulthood. The median age at death for 3243A>G carriers and their first-degree maternal relatives was significantly lower than that of the general population. Neurological and cardiovascular diseases made up one-third of the causes of death. Sudden and unexpected death was not uncommon in patients with cardiovascular diseases, diabetes and epilepsy. Conclusions: 3243A>G carriers and their first-degree maternal relatives died younger than was predicted by their life expectancy at birth. Neurological disease was the most common cause of death.

Objective: To follow the clinical course of patients with the mitochondrial DNA mutation 3243A>G for 3 years. Methods: Thirty-three adult patients with the 3243A>G mutation entered a 3-year follow-up study. They were clinically evaluated annually, audiometry was performed, and samples were drawn for the analysis of blood chemistry and mutation heteroplasmy in leukocytes. Holter recording was performed three times during the follow-up and echocardiography, neuropsychological assessment, and quantitative EEG and brain imaging conducted at entry and after 3 years. Results: The incidence of new neurologic events was low during the 3-year follow-up. Sensorineural hearing impairment (SNHI) progressed, left ventricular wall thickness increased, mean α frequency in the occipital and parietal regions decreased, and the severity of disease index (modified Rankin score) progressed significantly. The rate of SNHI progression correlated with mutation heteroplasmy in muscle. The increase in left ventricular wall thickness was seen almost exclusively in diabetic patients. Seven patients died during the follow-up, and they were generally more severely affected than those who survived. Conclusions: Significant changes in the severity of disease, sensorineural hearing impairment, left ventricular hypertrophy, and quantitative EEG were seen in adult patients with 3243A>G during the 3-year follow-up.

To evaluate how new treatment guidelines of acute coronary syndrome (ACS) without ST elevation have been implemented into clinical practice in Finland.A prospective survey on 501 consecutive patients (mean age 68 [range 27-96] years) admitted to nine hospitals in Finland with suspected ACS without persistent ST elevation between January and March 2001.The rate of death was 4.2% in hospital and 9.8% at 6 months. Six-month composite incidence of death, new myocardial infarction, refractory angina or readmission for unstable angina was 25.4%. The majority of patients had beta-blocker and aspirin both in hospital and at 6 months. Low molecular weight heparin was used in 76% of patients. Statins were used in 52% of patients in hospital and in 64% at 6 months. Glycoprotein (GP) IIb/IIIa receptor antagonists were used in 18% of all patients. The overall rate of coronary angiography was 40% in hospital and 54% at 6 months, but there was large interhospital variation. Overall, only 45% of very high-risk patients underwent angiography during initial hospitalization. Very high-risk patients had longer waiting times for angiography than low-risk patients (5.8 vs 4.5 days, p0.05).Traditional medication with aspirin and beta-blocker is widely used in ACS, whereas statins, GPIIb/IIIa receptor antagonists and invasive therapy are underused. Well-known risk factors were poor predictors of receiving in-hospital angiography. Implementation of new ESC guidelines into clinical practice needs further education and more resources.

Background: Cardiac troponin I (cTnI) is a sensitive marker of cardiac injury, but cTnI assays, like other immunoassays, are susceptible to interferences. We evaluated the presence of interfering substances by measuring the recovery of cTnI added to samples from volunteers and from patients with acute coronary syndromes (ACS).Methods: We added a ternary complex of human cardiac troponin (30–500 μg/L) or cTnI from serum to samples from healthy volunteers and ACS patients. We measured cTnI with a two-site sandwich time-resolved immunofluorometric assay using two antibodies against epitopes in the central stable part of cTnI. We also analyzed 108 heparin-plasma samples from 16 ACS patients with this assay, with an assay based on four antibodies, and with two commercial cTnI assays, AxSYM and ACS:180.Results: In samples from both healthy persons and ACS patients, recoveries for our assay were 1–167% (range). Recoveries were increased by addition of an antibody with an epitope in the N-terminal region of cTnI to the solid phase and an antibody with an epitope in the C-terminal region as a second detection antibody. In 2 of 16 patients with ACS, normal cTnI concentrations found when measured with the original assay demonstrated clinically abnormal (up to 10-fold higher) results with the additional N- and C-terminal antibodies in the early phase of infarction. Both commercial cTnI assays also demonstrated clinically misleading, falsely low cTnI concentrations.Conclusions: Some yet unidentified, variable component, present in the blood from healthy volunteers and ACS patients, interferes with the binding of antibodies against epitopes in the central part of cTnI used in two commercial assays. Our approach to supplement the mid-fragment cTnI antibodies with antibodies in the N- and C-terminal parts of the molecule in an experimental assay represents a step in resolving this interferent.

Pregnancy associated plasma protein A (PAPP-A) has recently been shown to be associated with acute coronary syndromes (ACS). The goal of this study was to investigate its release patterns in patients with ACS.PAPP-A concentrations in plasma samples serially collected after admissions from 15 patients with ACS were measured. The levels of PAPP-A were compared with a reference range determined from 80 normal subjects. The associations between PAPP-A and myoglobin (Mb), C-reactive protein (CRP), fatty-acid-binding protein (FABP) and creatine kinase MB (CK-MB) were determined.Various release patterns were observed with 2-10-fold changes of PAPP-A in the different patients. Increases in PAPP-A levels above the reference range could appear early at 2 h or late at 30 h after onset of chest pain. Only in 4 of the 15 cases were significantly elevated PAPP-A levels detected before 6 h after onset. Elevations early after admission showed rapid decline whereas later elevations were more persistent. No associations between PAPP-A and Mb, CRP, FABP and CK-MB were found. However, a weak but significant association to cardiac troponin I (cTn I) was found.PAPP-A is an additional marker for ACS, but does not seem to be a useful early marker for acute myocardial infarction (AMI). The possible clinical utility of PAPP-A calls for extensive studies of chest pain patients using serial sampling combined with short- and long-term outcome studies.

Background Tissues that depend on aerobic energy metabolism suffer most in diseases caused by mutations in mitochondrial DNA (mtDNA). Cardiac abnormalities have been described in many cases, but their frequency and clinical spectrum among patients with mtDNA mutations is unknown. Methods Thirty-nine patients with the 3243A>G mtDNA mutation were examined, methods used included clinical evaluation, electrocardiogram, Holter recording and echocardiography. Autopsy reports on 17 deceased subjects were also reviewed. The degree of 3243A>G mutation heteroplasmy was determined using an Apa I restriction fragment analysis. Better hearing level (BEHL0.5–4 kHz) was used as a measure of the clinical severity of disease. Results Left ventricular hypertrophy (LVH) was diagnosed in 19 patients (56%) by echocardiography and in six controls (15%) giving an odds ratio of 7.5 (95% confidence interval; 1.74–67). The dimensions of the left ventricle suggested a concentric hypertrophy. Left ventricular systolic or diastolic dysfunction was observed in 11 patients. Holter recording revealed frequent ventricular extrasystoles (>10/h) in five patients. Patients with LVH differed significantly from those without LVH in BEHL0.5–4 kHz, whereas the contribution of age or the degree of the mutant heteroplasmy in skeletal muscle to the risk of LVH was less remarkable. Conclusions Structural and functional abnormalities of the heart were common in patients with 3243A>G. The risk of LVH was related to the clinical severity of the phenotype, and to a lesser degree to age, suggesting that patients presenting with any symptoms from the mutation should also be evaluated for cardiac abnormalities.

Background: Large-scale mitochondrial DNA (mtDNA) deletions are associated with clinical conditions such as Kearns–Sayre syndrome and chronic progressive external ophthalmoplegia in adults and Pearson syndrome in children. Reported case series have suggested that deletions are not uncommon in the population, but their prevalence has not been documented. Methods: The authors ascertained patients with clinical features associated with mtDNA deletions in a defined adult population in northern Finland. Buccal epithelial samples were requested from each patient fulfilling the selection criteria, and full-length mtDNA was amplified using the long PCR method. Deletion breakpoints were identified using sequencing. Patients with deletions were examined clinically. Results: The authors identified four patients with single large-scale mtDNA deletions. The prevalence of deletions was calculated to be 1.6/100,000 in the adult population in the province of Northern Ostrobothnia (0.0 to 3.2; 95% CI). Analysis of incident cases from a neighboring province revealed two patients with deletions and yielded a similar population frequency. Conclusions: The frequency of large-scale mitochondrial DNA deletions is similar among populations, suggesting that there is a constant rate of new deletions.