Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based ...studies are lacking.
We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed.
In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%).
Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.
70-year legacy of the Framingham Heart Study Andersson, Charlotte; Johnson, Andrew D; Benjamin, Emelia J ...
Nature reviews cardiology,
11/2019, Letnik:
16, Številka:
11
Journal Article
Recenzirano
The Framingham Heart Study (FHS) was established in 1948 to improve understanding of the epidemiology of coronary heart disease (CHD) in the USA. In 1961, seminal work identified major risk factors ...for CHD (high blood pressure, high cholesterol levels and evidence on the electrocardiogram of left ventricular hypertrophy), which later formed the basis for multivariable 10-year and 30-year risk-prediction algorithms. The FHS cohorts now comprise three generations of participants (n ≈ 15,000) and two minority cohorts. The FHS cohorts are densely phenotyped, with recurring follow-up examinations and surveillance for cardiovascular and non-cardiovascular end points. Assessment of subclinical disease and physiological profiling of these cohorts (with the use of echocardiography, ambulatory electrocardiographic monitoring, exercise stress testing, cardiac CT, heart and brain MRI, serial vascular tonometry and accelerometry) have been performed repeatedly. Over the past decade, the FHS cohorts have undergone deep 'omics' profiling (including whole-genome sequencing, DNA methylation analysis, transcriptomics, high-throughput proteomics and metabolomics, and microbiome studies). The FHS is a rich, longitudinal, transgenerational and deeply phenotyped cohort study with a sustained focus on state-of-the-art epidemiological methods and technological advances to facilitate scientific discoveries.
Aim
Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this ...hypothesis.
Methods
Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case‐mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared.
Results
Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case‐mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities.
Conclusion
Management of very preterm infants exhibited significant regional variations in the Nordic countries.
BACKGROUND:The cumulative burden and importance of cardiovascular risk factors have changed over the past decades. Specifically, obesity rates have increased among younger people, whereas ...cardiovascular health has improved in the elderly. Little is known regarding how these changes have impacted the incidence and the mortality rates of heart failure. Therefore, we aimed to investigate the age-specific trends in the incidence and 1-year mortality rates following a first-time diagnosis of heart failure in Denmark between 1995 and 2012.
METHODS:We included all Danish individuals >18 years of age with a first-time in-hospital diagnosis of heart failure. Data were collected from 3 nationwide Danish registries. Annual incidence rates of heart failure and 1-year standardized mortality rates were calculated under the assumption of a Poisson distribution.
RESULTS:We identified 210 430 individuals with a first-time diagnosis of heart failure between 1995 and 2012; the annual incidence rates per 10 000 person-years declined among older individuals (rates in 1995 versus 2012164 versus 115 in individuals >74 years, 63 versus 35 in individuals 65–74 years, and 20 versus 17 in individuals 55–64 years; P<0.0001 for all) but increased among the younger (0.4 versus 0.7 in individuals 18–34 years, 1.3 versus 2.0 in individuals 35–44 years, and 5.0 versus 6.4 in individuals 45–54 years; P<0.0001 for all). The proportion of patients with incident heart failure ≤50 years of age doubled from 3% in 1995 to 6% in 2012 (P<0.0001). Sex- and age-adjusted incidence rate ratios for 2012 versus 1996 were 0.69 (95% confidence interval, 0.67–0.71; P<0.0001) among people >50 years of age, and 1.52 (95% confidence interval, 1.33–1.73; P<0.0001) among individuals ≤50 years of age; it remained essentially unchanged on additional adjustment for diabetes mellitus, ischemic heart disease, and hypertension. Standardized 1-year mortality rates declined for middle-aged patients with heart failure but remained constant for younger (<45 years) and elderly (≥65 years) patients. The prevalence of comorbidities (including diabetes mellitus, hypertension, and atrial fibrillation) increased, especially in younger patients with heart failure.
CONCLUSIONS:Over the past 2 decades, the incidence of heart failure in Denmark declined among older individuals (>50 years), but increased among younger (≤50 years) individuals. These observations may portend a rising burden of heart failure in the community.
Abstract
Background and Objectives
Male sex has been associated with severe coronavirus disease 2019 (COVID-19) infection. We examined the association between male sex and severe COVID-19 infection ...and if an increased risk remains after adjustment for age and comorbidities.
Methods
Nationwide register-based follow-up study of COVID-19 patients in Denmark until 16 May 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe COVID-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver, rheumatic, and chronic kidney disease (CKD).
Results
Of 4842 COVID-19 patients, 2281 (47.1%) were men. Median age was 57 25%–75% 43–73 for men versus 52 38–71 for women (P < .001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P < .001) as well as AF, stroke, and HF (all P = .01) were more often seen in men, and so was CKD (P = .03). Obesity diagnosis (P < .001) were more often seen in women. Other comorbidity differences were insignificant (P > .05). The fully adjusted average risk ratio was 1.63 95% CI, 1.44–1.84.
Conclusions
Men with COVID-19 infection have >50% higher risk of all-cause death, severe COVID-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.
Men with COVID-19 infection have a more than 50% higher risk of a 30-day composite outcome of all-cause death, severe COVID-19 infection, or ICU admission than women. This excess risk was not explained by age or underlying comorbid conditions.
Background Blood levels of high low-density lipoprotein cholesterol (LDL-C), high triglycerides (TG), and low high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of ...cardiovascular disease (CVD). The long-term comparative CVD risk associated with these 3 major lipid classes in various combinations is, however, unknown. Methods A total of 3,501 participants of the Framingham Offspring Study (mean age 51 ± 10 years, 56% women) without CVD at baseline were followed up for incident CVD between 1987 and 2011. Participants were grouped according to baseline lipid values into 8 distinct categories to compare the prognostic significance of values within an optimal range to Third Report of the National Cholesterol Educational Program–defined high LDL-C (>130 mg/dL), high TG (>150 mg/dL), and/or low HDL-C (<40 mg/dL) in various combinations using multivariable-adjusted Cox regression models. Results On follow-up (median 20.2 years), 724 (21%) had new-onset CVD. Adjusted for confounders and compared with the group with optimal lipid values, hazards ratios and population-attributable risks (PARs) were as follows: isolated low HDL-C, 1.93 (95% CI 1.37-2.71), PAR = 3.1%; isolated high LDL-C, 1.28 (1.03-1.59), PAR 6.4%; isolated high TG, 1.35 (0.91-1.98), PAR = 1.1% (not significant); low HDL-C and high LDL-C, 1.82 (1.33-2.49), PAR = 3.9%; low HDL-C and high TG, 1.74 (1.28-2.37), PAR = 3.9%; high LDL-C and high TG, 1.52 (1.12-2.07), PAR = 6.4%; and high LDL-C, high TG and low HDL-C 2.28 (1.73-3.02), PAR = 7.5%. Conclusions Aside from isolated hypertriglyceridemia, low levels of HDL-C, high levels of LDL-C, and high levels of TG in any combination were associated with increased risk of CVD.
Abstract Background The choice of either anatomical or functional noninvasive testing to evaluate suspected coronary artery disease might affect subsequent clinical management and outcomes. ...Objectives This study analyzed the association of initial noninvasive cardiac testing in outpatients with stable symptoms, with subsequent use of medications, invasive procedures, and clinical outcomes. Methods We studied patients enrolled in a Danish nationwide register who underwent initial noninvasive cardiac testing with either coronary computed tomography angiography (CTA) or functional testing (exercise electrocardiography or nuclear stress testing) from 2009 to 2015. Further use of noninvasive testing, invasive procedures, medications, and medical costs within 120 days were evaluated. Risks of long-term mortality and myocardial infarction (MI) were analyzed using adjusted Cox proportional hazard models. Results A total of 86,705 patients underwent either functional testing (n = 53,744, mean age 57.4 years, 49% males) or coronary CTA (n = 32,961, mean age 57.4 years, 45% males), and were followed for a median of 3.6 years. Compared with functional testing, there was significantly higher use of statins (15.9% vs. 9.1%), aspirin (12.7% vs. 8.5%), invasive coronary angiography (14.7% vs. 10.1%), and percutaneous coronary intervention (3.8% vs. 2.1%); all p < 0.001 after coronary CTA. The mean costs of subsequent testing, invasive procedures, and medications were higher after coronary CTA ($995 vs. $718; p < 0.001). Unadjusted rates of mortality (2.1% vs. 4.0%) and MI hospitalization (0.8% vs. 1.5%) were lower after coronary CTA than functional testing (both p < 0.001). After adjustment, coronary CTA was associated with a comparable all-cause mortality (hazard ratio: 0.96; 95% confidence interval: 0.88 to 1.05), and a lower risk of MI (hazard ratio: 0.71; 95% confidence interval: 0.61 to 0.82). Conclusions In stable patients undergoing initial evaluation for suspected coronary artery disease, coronary CTA was associated with greater use of statins, aspirin, and invasive procedures, and higher costs than functional testing. Coronary CTA was associated with a lower risk of MI, but a similar risk of all-cause mortality.
Summary Background Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We ...examined the risk of hospital admission for bleeding associated with different antithrombotic regimens. Methods By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. Findings During a mean follow-up of 476·5 days (SD 142·0), 1891 (4·6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2·6% for the aspirin group, 4·6% for clopidogrel, 4·3% for vitamin K antagonist, 3·7% for aspirin plus clopidogrel, 5·1% for aspirin plus vitamin K antagonist, 12·3% for clopidogrel plus vitamin K antagonist, and 12·0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 1·33 (95% CI 1·11–1·59) for clopidogrel, 1·23 (0·94–1·61) for vitamin K antagonist, 1·47 (1·28–1·69) for aspirin plus clopidogrel, 1·84 (1·51–2·23) for aspirin plus vitamin K antagonist, 3·52 (2·42–5·11) for clopidogrel plus vitamin K antagonist, and 4·05 (3·08–5·33) for triple therapy. Numbers needed to harm were 81·2 for aspirin plus clopidogrel, 45·4 for aspirin plus vitamin K antagonist, 15·2 for clopidogrel plus vitamin K antagonist, and 12·5 for triple therapy. 702 (37·9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18·4%) of 38 960 patients without non-fatal bleeding (HR 3·00, 2·75–3·27, p<0·0001). Interpretation In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. Funding Danish Heart Foundation and the Danish Medical Research Council.
Treatment of neuroendocrine tumors with 177Lu-octreotate results in prolonged survival and improved quality of life for the patient. However, the treatment is today limited by side effects on kidney ...and bone marrow, and complete tumor remission is rarely seen. A possible way to minimize dose-limiting toxicity and to optimize this treatment method is to use radioprotectors in conjunction with radiotherapy. A recombinant form of α1-microglobulin (rA1M) was recently shown to preserve kidney structure and function after 177Lu-octreotate injection in mice and was suggested as a radioprotector in peptide receptor radionuclide therapy. The aims of this work were to investigate the influence of rA1M on the in vivo biokinetics of 177Lu-octreotate, with a focus on tumor tissue, and to study the impact of rA1M on the therapeutic response in tumor tissue subjected to 177Lu-octreotate treatment. Methods: The biodistribution of 177Lu-octreotate was examined in BALB/c nude mice with GOT2 tumors 1–168 h after injection with either 177Lu-octreotate or coadministration of 177Lu-octreotate and rA1M. The effects of rA1M on the tumor response after 177Lu-octreotate treatment were studied in BALB/c nude mice with GOT1 tumors. Three groups of mice were administered rA1M, 177Lu-octreotate, or both. Another group served as untreated controls. Tumor volume was measured to follow the treatment effects. Results: No statistically significant difference in biodistribution of 177Lu was observed between the groups receiving 177Lu-octreotate or coinjection of 177Lu-octreotate and rA1M. The therapy study showed a decrease in mean tumor volume during the first 2 wk for both the 177Lu-octreotate group and the coadministration group, followed by tumor regrowth. No statistically significant difference between the groups was found. Conclusion: rA1M did not negatively impact absorbed dose to tumor or therapeutic response in combination with 177Lu-octreotate and may be a promising kidney protector during 177Lu-octreotate treatment of patients with neuroendocrine tumors.
Gene function can be described using various measures. We integrated association studies of three types of omics data to provide insights into the pathophysiology of subclinical coronary disease and ...myocardial infarction (MI). Using multivariable regression models, we associated: (1) single nucleotide polymorphism, (2) DNA methylation, and (3) gene expression with coronary artery calcification (CAC) scores and MI. Among 3106 participants of the Framingham Heart Study, 65 (2.1%) had prevalent MI and 60 (1.9%) had incident MI, median CAC value was 67.8 IQR 10.8, 274.9, and 1403 (45.2%) had CAC scores > 0 (prevalent CAC). Prevalent CAC was associated with AHRR (linked to smoking) and EXOC3 (affecting platelet function and promoting hemostasis). CAC score was associated with VWA1 (extracellular matrix protein associated with cartilage structure in endomysium). For prevalent MI we identified FYTTD1 (down-regulated in familial hypercholesterolemia) and PINK1 (linked to cardiac tissue homeostasis and ischemia-reperfusion injury). Incident MI was associated with IRX3 (enhancing browning of white adipose tissue) and STXBP3 (controlling trafficking of glucose transporter type 4 to plasma). Using an integrative trans-omics approach, we identified both putatively novel and known candidate genes associated with CAC and MI. Replication of findings is warranted.
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