Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy.

Aims: Nationwide large-scale genetic and outcome studies in cohorts with hypertrophic cardiomyopathy (HCM) have not been previously published.

Methods And Results: We sequenced 59 cardiomyopathy-associated genes in 382 unrelated Finnish patients with HCM and found 24 pathogenic or likely pathogenic mutations in six genes in 38.2% of patients.

Permanent work disability in patients ≤50 years old after percutaneous coronary intervention and coronary artery bypass grafting (the CRAGS study).

Background: The aim of this study was to investigate the incidence of permanent working disability (PWD) in young patients after percutaneous or surgical coronary revascularization.

Methods And Results: The study included 1035 consecutive patients ≤50 years old who underwent coronary revascularization [910 and 125 patients in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) groups, respectively] between 2002 and 2012 at 4 Finnish hospitals. The median follow-up time was 41 months.

[Percutaneous treatment of coronary chronic total occlusions].

Chronic total occlusions (CTOs) are frequently detected on diagnostic coronary angiograms. For the selection of patients for CTO percutaneous coronary intervention, factors such as the level of symptoms, level of myocardial viability and extent of ischemia must be taken into account. Remarkable progress has been achieved in the success of complex CTO procedures during the past decade.

[Update on Current Care Guidelines. Current Care Guideline: Stable Coronary Artery Disease].

This guideline covers coronary heart disease symptoms, diagnosis and treatment. Stable coronary heart disease refers to a disease in, which patients have stable symptoms and evidence of ischemia or significant stenosis of coronary artery. Diagnosis is based on medical history and exercise test, which is the primary diagnostic test.

Predictors of permanent work disability among ≤50-year-old patients undergoing percutaneous coronary intervention.

Objectives: This study aimed to describe the incidence and periprocedural predictors of permanent work disability (PWD) pension among patients ≤50 years old who underwent percutaneous coronary intervention (PCI).

Methods: Patient records of 910 consecutive patients undergoing PCI at four Finnish hospitals in 2002-2012 were reviewed for baseline and procedural data and late adverse events. Data on permanent work disability (PWD) pension allocation were acquired from the Finnish Centre for Pensions, which governs the statutory pension security in Finland.

Prognosis and disease progression in patients under 50 years old undergoing PCI: the CRAGS (Coronary aRtery diseAse in younG adultS) study.

Objective: Young patients undergoing percutaneous coronary intervention (PCI) are generally considered at low procedural risk, but the potentially aggressive nature of coronary artery disease and long expectancy of life expose them to a high risk of recurrent coronary events. The extent and determinants of disease progression in this patient subset remain largely unknown. The aim of the present study was to evaluate general risk factors for late outcomes among patients ≤50 years old who underwent PCI.

A new common mutation in the cardiac beta-myosin heavy chain gene in Finnish patients with hypertrophic cardiomyopathy.

Background: In the nationwide FinHCM Study including 306 Finnish patients with hypertrophic cardiomyopathy (HCM), we have previously identified two founder mutations in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes, accounting for 18% of all cases. Objective. To screen additional mutations, previously identified in eastern Finnish cohorts with HCM, in the FinHCM Study population.

Comparison of 30-day and 5-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients aged≤50 years (the Coronary aRtery diseAse in younG adultS Study).

Data on the outcome of young patients after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are scarce. Data on 2,209 consecutive patients aged≤50 years who underwent CABG or PCI were retrospectively collected from 15 European institutions. PCI and CABG had similar 30-day mortality rates (0.

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects.

Background: High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt.

Methods: Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease.

Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.

Background: Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis.

Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population.

Background: Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland.

Objective: To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland.

Reduced systemic vascular resistance in healthy volunteers with presyncopal symptoms during a nitrate-stimulated tilt-table test.

What Is Already Known About This Subject: Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a nitroglycerin-stimulated tilt-table test.

What This Study Adds: A major decrease in systemic vascular resistance was documented in subjects with presyncope during 0.

Severe hypocalcemia simulating ST-elevation myocardial infarction.

ST-elevation myocardial infarction (STEMI) is an emergency situation in which immediate measures for myocardial reperfusion are needed. The diagnosis is based on the recognition of ST-segment elevation in the electrocardiogram (ECG). In case of coronary artery occlusion, ST-segment elevation is caused by an injury current from the ischemic myocardium.

Birthplace in area with high coronary heart disease mortality predicts the severity of coronary atherosclerosis among middle-aged Finnish men who had migrated to capital area: the Helsinki sudden death study.

Background: Reasons why eastern-born male Finns have higher coronary heart disease (CHD) mortality than do western-born men are still unsettled. Recently, eastern birthplace was found to be an independent predictor of pre-hospital sudden cardiac death (SCD) in the new low-mortality area of residence.

Aim: To investigate the association of birthplace with high CHD mortality attributes to more severe coronary atherosclerosis among men migrated to the low-mortality capital area.

Interactions of functional apolipoprotein E gene promoter polymorphisms with smoking on aortic atherosclerosis.

Background: Apolipoprotein E gene (APOE) interacts with environmental factors in defining risk for atherosclerosis. We studied whether the APOE epsilon2/epsilon3/epsilon4 genotype or APOE promoter polymorphisms -219G/T and +113G/C might interact with smoking on the development of fatty streaks. We also studied the previously unknown effects of +113G/C on transcriptional activity.

Interleukin 18 gene promoter polymorphism: a link between hypertension and pre-hospital sudden cardiac death: the Helsinki Sudden Death Study.

Aims: The interleukin 18 (IL-18) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with a lower risk of sudden cardiac death (SCD). We examined the process by which this polymorphism alters the risk of SCD and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors.

Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin.

Aims: To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance.

Methods: Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg(-1) min(-1)) or saline infusion, salbutamol (400 microg) or placebo inhalation, and sublingual nitroglycerin (0.

Ageing and cardiovascular responses to head-up tilt in healthy subjects.

Objective: Ageing is associated with increased postural blood pressure changes and attenuated cardiovascular reactivity. As the background of these changes remains uncertain, we examined arterial stiffness, cardiac function and vascular resistance in healthy subjects in supine position and during orthostatic challenge.

Methods: Haemodynamics of 179 normotensive subjects (109 female and 70 male, 21-59 years) were examined using continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic finger blood pressures.

ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.

Objective: Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8.

Methods: We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction.

Results: ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries.

[Coronary artery disease attack caused by cytotoxic chemotherapy].

Capesitabine is a orally administered cytotoxic drug metabolized to 5-fluorouracil and is widely used in large intestine cancer and breast cancer therapy. Its adverse effects against the heart have been considered to be rare. We describe four patients, who were diagnosed with an attack of coronary artery disease during capesitabine therapy on the basis of coronary spasm.

Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death.

Background: Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD).

Birthplace predicts risk for prehospital sudden cardiac death in middle-aged men who migrated to metropolitan area: The Helsinki Sudden Death Study.

Background: Eastern-born male Finns, irrespective of their place of residence, have high mortality from coronary heart disease (CHD), and half of such deaths are sudden.

Aim: To study whether eastern birthplace alone or combined with life-style factors predicts risk for prehospital sudden cardiac death (SCD) in the new (west) low-mortality area of residence.

Method: Prospective case-control autopsy study of all (700) out-of-hospital deaths of men aged 35-69 years in metropolitan Helsinki during 1981-82 and 1991-92.

COX-2 gene promoter polymorphism and coronary artery disease in middle-aged men: the Helsinki sudden death study.

Cyclooxygenase (COX) catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the -765G-->C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300) comprised of Finnish men who died suddenly.

Association analysis of allelic variants of USF1 in coronary atherosclerosis.

Objective: USF1 regulates the transcription of more than 40 cardiovascular related genes and is well established as a gene associated with familial combined hyperlipidemia, a condition increasing the risk for coronary heart disease. No detailed data, however, exists on the impact of this gene to the critical outcome at the tissue level: different types of atherosclerotic lesions.

Methods And Results: We analyzed the USF1 in 2 autopsy series of altogether 700 middle-aged men (the Helsinki Sudden Death Study) with quantitative morphometric measurements of coronary atherosclerosis.

Neuropeptide Y signal peptide Pro7 substitution protects against coronary artery atherosclerosis: the Helsinki Sudden Death Study.

Objective: Neuropeptide Y (NPY) has a single nucleotide polymorphism at T1128C, leading to change of Leucine7 to Proline7. The Leu7Pro substitution has been linked to cardiovascular disease, but it is unknown whether the Pro7 allele is associated with increased or decreased risk of coronary heart disease (CHD). The aim of the present study was to investigate the association of the Leu7Pro polymorphism with coronary atherosclerosis and its consequences.