Spectrum of radionuclide perfusion study abnormalities in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo (stress) cardiomyopathy (TCM) is characterized by transient apical left ventricular dysfunction precipitated by emotional or physical stress. Its presentation makes it difficult to differentiate from an acute coronary syndrome. A suggestive echocardiogram plus normal coronary angiography most often are used for diagnosis. Radionuclide perfusion study (RPS) findings in TCM, including by positron emission tomography (PET), have been poorly characterized. METHODS AND RESULTS: Intermountain Healthcare electronic medical records were searched from 2009 to 2019 for patients with a discharge diagnosis of TCM, stress CM, or takotsubo syndrome. 16 TCM patients with an RPS, including by PET in 8, were identified: 13 (81%) were women; age averaged 72 years (50-89 years); 14 had an identified stressor. TCM diagnosis was definite in 11 and probable/possible in 5. RPS was abnormal in 11, with 9 showing an apical perfusion deficit, whereas angiography in 14 showed normal coronaries in 12 and non-obstructive disease in 2. Echo ejection fraction averaged 41% (29%-60%); an apical wall motion abnormality was present in 14 (88%). Troponin elevations were noted in 14/15. The presenting ECG was abnormal is 14, frequently showing ST-T-wave abnormalities. 13 patients were discharged on a beta-blocker. Follow-up echo (in 12) showed recovered ejection fraction in 9 and recovered apical wall motion in 11. CONCLUSIONS: Despite having normal or non-obstructive epicardial coronary arteries on angiography, TCM patients frequently present with apical wall motion abnormalities and matching RPS perfusion defects. These findings suggest microvascular abnormalities, whose pathophysiology, temporal course, and clinical implications should be the subject of further investigation.

Comparison of Three Atherosclerotic Cardiovascular Disease Risk Scores With and Without Coronary Calcium for Predicting Revascularization and Major Adverse Coronary Events in Symptomatic Patients Undergoing Positron Emission Tomography-Stress Testing.

Atherosclerotic cardiovascular disease (ASCVD) is the most important cause of morbidity and mortality nationally and internationally. Improving ASCVD risk prediction is a high clinical priority. We sought to determine which of 3 ASCVD risk scores best predicts the need for revascularization and incident major adverse coronary events (MACE) in symptomatic patients at low-to-intermediate primary ASCVD risk referred for regadenoson-stress positron emission tomography (PET). Risk scores included the standard ASCVD pooled cohort equation (PCE), the multiethnic study of atherosclerosis (MESA) risk equation, and the coronary artery calcium score (CACS), obtained by PET. All qualifying patients in our institution at primary ASCVD risk referred for PET-stress tests in whom PCE, MESA, and CAC scores could be calculated were studied. CACS categories were: 0, 1 to 10, 11 to 299, 300 to 999, and 1000+. MESA and PCE scores were divided into quartiles. Logistic regression modeling was used to predict clinical/PET-driven early revascularization (within 90 days) and 1-year MACE (death, myocardial infarction, or any-time revascularization). A total of 981 patients (54% men, age 67 ± 10 years) qualified and were studied. Scores including CAC (MESA, CACS) performed better than PCE for predicting overall 1-year MACE (MESA p <0.001, CACS p = 0.012 vs PCE), which was driven by early revascularization. In conclusion, in a large population of patients at primary ASCVD risk referred for PET-stress testing, risk scores including CAC (CACS, MESA), which better predicted early revascularization and 1-year MACE, may be particularly useful in primary coronary risk assessment when considering whom to refer for PET-stress testing.

Health Promotion and Preventive Care Intervention for Older Community-Dwelling People: Long-Term Effects of a Randomised Controlled Trial (RCT) within the LUCAS Cohort.

OBJECTIVES: An RCT of a health promotion and preventive care intervention was done in 2001-2002. Here, long-term analyses based on 12 years of follow-up of survival and of change in functional competence between intervention and control group are presented. Positive 1-year results (significantly higher use of preventive services and better health behaviour) were presented earlier. DESIGN: Parallel group randomised controlled trial (RCT) with 878 participants in the intervention and 1,702 participants in the control group. SETTING: The study took place in Hamburg, Germany and made use of health care structures and professionals of a geriatrics centre. PARTICIPANTS: Study participants were initially community-dwelling, aged 60 years and older and without B-ADL-restrictions, cognitive impairment, or need of nursing care, with sufficient command of the German language. INTERVENTIONS: Health promotion and preventive care interventions relied on an extensive health questionnaire and the subsequent offer to participate in multi-topic personal reinforcement performed in small group sessions or at preventive home visits. MEASUREMENTS: Primary outcome: Survival time; in some analyses, adjustments were made for gender, age and self-perceived health. Secondary outcome: Functional competence (LUCAS Functional Ability Index) based on responses to self-administered questionnaires at 1-year follow-up and 12 years after 1-year follow-up (2013/2014). RESULTS: Mean time under observation was 10.3 years. 38.3% (987/2,580) of the participants died; intervention group (IG): 35.7% (313/878), control group (CG): 39.6% (674/1,702); HR=0.89; p=0.09. Functional competence at 1-year follow-up: IG: ROBUST 67.4% (391/580), FRAIL 11.9% (69/580) vs. CG: ROBUST 62.9% (861/1,368), FRAIL 14.8% (203/1,368); p=0.12. 12-years after 1-year follow-up: IG: ROBUST 50.0% (160/320), FRAIL 30.9% (99/320) vs. CG: ROBUST 48.9% (307/628), FRAIL 34.1% (214/628); p=0.56. CONCLUSIONS: Insignificant but consistent effects on survival and the dynamics of functional competence suggest effectivity of the complex intervention. We plan to take a closer look at the effect of each reinforcement separately.

[Acceptance of preventive home visits among frail elderly persons : Participants an non-participants in a Follow-up after 2 and 4 years within the LUCAS longitudinal study]. / Akzeptanz des präventiven Hausbesuchs bei älteren Personen mit Frailty : Teilnehmende und Nichtteilnehmende im Zwei- und Vierjahres-Follow-up im Rahmen der LUCAS-Langzeitstudie.

BACKGROUND: The objective of preventive home visits (PHV) is to support independent living of elderly people. The target group is a matter of discussion and acceptance so far seems to have been low. The target group favored in studies were persons with functional impairments living independently; therefore, acceptance of this offer by frail persons and characteristics of participants and non-participants were studied. MATERIAL AND METHODS: All participants classified as frail in the longitudinal urban cohort ageing study (LUCAS; BMBF Fkz 01ET0708-13/01, ET1002A-D/01EL1407) were randomized (RCT) in 2007/2008 into an intervention group (174 persons) and a control group (379 persons). Participants in the intervention group were offered the option of a PHV. Sociodemographic and health-related characteristics were compared between the participants with a PHV, non-participants and controls at baseline and after 2 and 4 years. Non-participants who refused the offer of the PHV were asked about their reasons. RESULTS: There were 64 persons (36.8 %) in the intervention group classified as frail who accepted the offer of a PHV. Of these, significantly more lived alone, tended to be female with a higher educational level and with less need of care. After 2 years significantly more persons in the group without PHV had died and after 4 years more participants with PHV reported a depressive mood. There were no other significant differences between the groups. Half of the reasons not to accept the PHV that were reported by the non-participants were because of health-related or psychological problems and one third because of lack of interest or need for PHV. CONCLUSION: The offer of PHV to frail elderly persons with an unlimited age was associated with a relatively high acceptance. The high number of refusals by non-participants with functional impairments is remarkable and needs further investigation.

Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks.

PURPOSE OF REVIEW: Statins significantly reduce cardiovascular morbidity and mortality in patients with and without coronary heart disease. Recently, much debate has focused on use of statins for primary prevention following a class-wide safety label change by the US Food and Drug Administration amidst concerns of worsened hyperglycemia. Here, we review the evidence for statins in primary prevention and offer guidance for their appropriate use. RECENT FINDINGS: Two meta-analyses published since 2012 unequivocally support statins for primary prevention. Data from the Cholesterol Treatment Trialists' Collaborators demonstrated a 9% [relative risk (RR) 0.91, 95% confidence interval (CI) 0.85-0.97] reduction in all-cause mortality and a 25% (RR 0.75, 95% CI 0.70-0.80) reduction in major vascular events per 1.0 mmol/l reduction in low-density lipoprotein cholesterol, even among low-risk patients. A 2013 Cochrane review corroborated these findings including a 14% (OR 0.86, 95% CI 0.79-0.94) reduction in all-cause mortality and a 25% (RR 0.75, 95% CI 0.70-0.81) reduction in cardiovascular disease events with statin therapy despite an 18% (RR 1.18, 95% CI 1.01-1.39) increase in incident diabetes. SUMMARY: Statins effectively lower atherogenic lipoproteins and result in clinically significant reductions in cardiovascular morbidity and mortality. When well tolerated, the cardiovascular benefits of statins for primary prevention generally far outweigh the reported harms.

Landmark lipid-lowering trials in the primary prevention of cardiovascular disease.

Although atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality in the world, the long disease latency affords ample opportunity for preventive care. Indeed, lifelong exposure to atherogenic apoliprotein B-containing lipoproteins has consistently been shown to increase the cumulative risk of suffering a CVD event, including myocardial infarction, stroke, and symptomatic peripheral arterial disease. Over the past 25 years, lipid-lowering therapies have been developed that are proven to not only lower cholesterol, but also to decrease adverse CVD events and CVD mortality. This review will highlight several key clinical trials encompassing several classes of lipid-lowering medications that have provided clinicians with an evidence-based framework for managing their patients' cardiovascular risk.

Impact of fitness versus obesity on routinely measured cardiometabolic risk in young, healthy adults.

Obesity demonstrates a direct relation with cardiovascular risk and all-cause mortality, while cardiorespiratory fitness demonstrates an inverse relation. In clinical practice, several cardiometabolic (CM) risk factors are commonly measured to gauge cardiovascular risk, but the interaction between fitness and obesity with regard to CM risk has not been fully explored. In this study, 2,634 Brazilian adults referred for employer-sponsored heath exams were assessed. Obesity was defined as body mass index >30 kg/m(2) or waist circumference >102 cm in men or >88 cm in women when body mass index was 25 to 30 kg/m(2). Fitness was quantified by stage achieved on an Ellestad treadmill stress test, with those completing stage 4 considered fit. Hepatic steatosis was determined by ultrasound. CM risk factors were compared after stratifying patients into 4 groups: fit and normal weight, fit and obese, unfit and normal weight, and unfit and obese. Approximately 22% of patients were obese; 12% were unfit. Fitness and obesity were moderately correlated (ρ = 0.38 to 0.50). The sample included 6.5% unfit and normal-weight subjects and 16% fit and obese subjects. In overweight and obese patients, fitness was negatively associated with CM risk (p <0.01 for all values). In fit patients, increasing body mass index was positively associated with CM risk (p <0.01 for all values). In instances of discordance between fitness and obesity, obesity was the stronger determinant of CM risk. In conclusion, fitness and obesity are independently associated with CM risk. The effects of fitness and obesity are additive, but obesity is more strongly associated with CM risk when fitness and obesity are discordant. These findings underscore the need for weight loss in obese patients and suggest an unmeasured benefit of fitness.

[Resources and risks in old age: the LUCAS-I marker set for a classification of elderly people as fit, pre-frail and frail. First results on validity from the Longitudinal Urban Cohort Ageing Study (LUCAS), Hamburg]. / Ressourcen und Risiken im Alter: Die LUCAS-I Marker zur Klassifizierung älterer Menschen als FIT, pre-FRAIL und FRAIL. Validierung und erste Ergebnisse aus der Longitudinalen Urbanen Cohorten-Alters-Studie (LUCAS).

BACKGROUND: There is a need for a simple self-administered instrument to assess frailty in community-dwelling seniors. METHODS: We present a new marker set to assess the functional state of seniors. Contrary to current literature, we focus not only on risks, but also include resources. The questions relate to facts (ways to do things), rather than on subjective information (e.g. exhaustion). It was developed in the context of the Longitudinal Urban Cohort Ageing Study (LUCAS) in Hamburg, Germany. RESULTS: The classification based on these questions proposes operational definitions of the terms fit, pre-frail and frail and is predictive for need for nursing care as well as mortality. A wealth of results establishes the validity of the categorisation compared to other health questions. One of the classification questions concerns cycling. For areas where cycling is not suitable, we propose to replace this question with one about independently walking 500 m. However, the cycling question appears to indicate frailty earlier. CONCLUSION: The self-administered questionnaire provides a simple, cost-effective way to screen seniors for early signs of declining function in order to start preventive action.

[Health and competence: detection and decoding using comprehensive assessments in the Longitudinal Urban Cohort Ageing Study (LUCAS)]. / Grauzonen von Gesundheit und Handlungsfähigkeit: Erfassung und Aufschlüsselung durch erweiterte Assessments in der Longitudinalen Urbanen Cohorten-Alters-Studie (LUCAS).

PURPOSE: The goal of this work was to characterise and distinguish persons without (fit), with earliest signs (pre-frail) or accelerated functional decline (frail) during self-referral (geriatric centre) or preventive home visits. METHODS: After screening independently living older people in an urban longitudinal cohort (n = 1,995) using a self-administered questionnaire, they were functionally classified as fit, pre-frail or frail. In 10% randomly selected samples of these cohort parts a comprehensive extended gerontological-geriatric assessment (EGGA) was administered. RESULTS: Fit, pre-frail and frail samples are significantly different regarding comorbidity, medication, mobility, fall risk, instrumental activities of daily living and use of social support but not nutrition. The best indicator to discriminate fit versus frail was exhaustion (mobility tiredness). CONCLUSION: Competence is essential regarding health in old age. Identification of resources and risks by comprehensive assessment is useful before planning interventions to prevent frailty or its progression.

Evidence-based use of statins for primary prevention of cardiovascular disease.

Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, are widely available, inexpensive, and represent a potent therapy for treating elevated cholesterol. Current national guidelines put forth by the Adult Treatment Panel III recommend statins as part of a comprehensive primary prevention strategy for patients with elevated low-density lipoprotein cholesterol at increased risk for developing coronary heart disease within 10 years. Lack of a clear-cut mortality benefit in primary prevention has caused some to question the use of statins for patients without known coronary heart disease. On review of the literature, we conclude that current data support only a modest mortality benefit for statin primary prevention when assessed in the short term (<5 years). Of note, statin primary prevention results in a significant decrease in cardiovascular morbidity over the short and long term and a trend toward increased reduction in mortality over the long term. When appraised together, these data provide compelling evidence to support the use of statins for primary prevention in patients with risk factors for developing coronary heart disease over the next 10 years.

The LUCAS* consortium: objectives of interdisciplinary research on selected aspects of ageing and health care for older people in an urban community.

BACKGROUND: Decline in functional competence is a major determinant of older persons' needs, the development of dependency, use of care, clinical outcome and mortality. The interactions between rising life expectancy and changes in morbidity and disability warrant interdisciplinary research on functional disability, health promotion and prevention. The LUCAS (Longitudinal Urban Cohort Ageing Study) research consortium was established to study particular aspects of functional competence, its changes with ageing, to detect preclinical signs of functional decline, and to address questions on how to maintain functional competence and to prevent adverse outcome. The questions originate from problems encountered in practical health care provision in different settings, i.e. community, hospital and nursing home. METHODS: The subprojects apply a longitudinal cohort follow-up study, an embedded randomised controlled intervention, cross-sectional comparative, and prospective intervention studies. CONCLUSION: The results will provide instruments to screen for preclinical signs of functional decline and concrete recommendations to sustain independence and prevent adverse outcomes in older age in daily practice.

[The Longitudinal Urban Cohort Ageing Study (LUCAS)]. / Die Longitudinal-Urban-Cohort-Ageing-Studie (LUCAS).

BACKGROUND: The interactions between rising life expectancy, morbidity and development of disability warrant interdisciplinary research on functional disability, health promotion and prevention as well as healthcare provision for older people. Therefore, the interdisciplinary LUCAS (Longitudinal Urban Cohort Ageing Study) research consortium of university and non-university institutions was established and is coordinated by the research department of the Albertinen-Haus at the University of Hamburg. The aim is to study particular aspects of functional competence, the changes with ageing, to detect pre-clinical signs of functional decline and to address questions on how to maintain functional competence and to prevent adverse outcomes. The research questions have their origin in problems of practical healthcare provision in the different settings of communities, hospitals and nursing homes. The articles of LUCAS subprojects report selected results from the first project phase (2007-2010) which was funded by the German Federal Ministry of Education and Research (BMBF) (Research program"Health in the elderly").). METHODS: The LUCAS subprojects 1-7 applied a true cohort study design with embedded randomized controlled intervention studies and cross-sectional studies for comparative purposes and to prepare intervention studies to be performed in the second project phase. CONCLUSIONS: Results from the first project phase provided new instruments to screen and to assess functional competence in older people (population-based screening). In the second project phase these will be evaluated according to practicability and usefulness. Furthermore, parts of the results will be used by the health reporting system in Hamburg and for intervention studies performed by LUCAS subprojects during the second project phase (LUCAS II).

On Graphically Checking Goodness-of-fit of Binary Logistic Regression Models.

OBJECTIVES: This paper is concerned with checking goodness-of-fit of binary logistic regression models. For the practitioners of data analysis, the broad classes of procedures for checking goodness-of-fit available in the literature are described. The challenges of model checking in the context of binary logistic regression are reviewed. As a viable solution, a simple graphical procedure for checking goodness-of-fit is proposed. METHODS: The graphical procedure proposed relies on pieces of information available from any logistic analysis; the focus is on combining and presenting these in an informative way. RESULTS: The information gained using this approach is presented with three examples. In the discussion, the proposed method is put into context and compared with other graphical procedures for checking goodness-of-fit of binary logistic models available in the literature. CONCLUSION: A simple graphical method can significantly improve the understanding of any logistic regression analysis and help to prevent faulty conclusions.

Culture, risk factors and mortality: can Switzerland add missing pieces to the European puzzle?

BACKGROUND: The aim was to compare cause-specific mortality, self-rated health (SRH) and risk factors in the French and German part of Switzerland and to discuss to what extent variations between these regions reflect differences between France and Germany. METHODS: Data were used from the general population of German and French Switzerland with 2.8 million individuals aged 45-74 years, contributing 176 782 deaths between 1990 and 2000. Adjusted mortality risks were calculated from the Swiss National Cohort, a longitudinal census-based record linkage study. Results were contrasted with cross-sectional analyses of SRH and risk factors (Swiss Health Survey 1992/3) and with cross-sectional national and international mortality rates for 1980, 1990 and 2000. RESULTS: Despite similar all-cause mortality, there were substantial differences in cause-specific mortality between Swiss regions. Deaths from circulatory disease were more common in German Switzerland, while causes related to alcohol consumption were more prevalent in French Switzerland. Many but not all of the mortality differences between the two regions could be explained by variations in risk factors. Similar patterns were found between Germany and France. CONCLUSION: Characteristic mortality and behavioural differentials between the German- and the French-speaking parts of Switzerland could also be found between Germany and France. However, some of the international variations in mortality were not in line with the Swiss regional comparison nor with differences in risk factors. These could relate to peculiarities in assignment of cause of death. With its cultural diversity, Switzerland offers the opportunity to examine cultural determinants of mortality without bias due to different statistical systems or national health policies.

Multivariate modelling of responses to conditional items: New possibilities for latent class analysis.

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category 'missing by design', rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models.

Distinguishing phenotypes of childhood wheeze and cough using latent class analysis.

Airway disease in childhood comprises a heterogeneous group of disorders. Attempts to distinguish different phenotypes have generally considered few disease dimensions. The present study examines phenotypes of childhood wheeze and chronic cough, by fitting a statistical model to data representing multiple disease dimensions. From a population-based, longitudinal cohort study of 1,650 preschool children, 319 with parent-reported wheeze or chronic cough were included. Phenotypes were identified by latent class analysis using data on symptoms, skin-prick tests, lung function and airway responsiveness from two preschool surveys. These phenotypes were then compared with respect to outcome at school age. The model distinguished three phenotypes of wheeze and two phenotypes of chronic cough. Subsequent wheeze, chronic cough and inhaler use at school age differed clearly between the five phenotypes. The wheeze phenotypes shared features with previously described entities and partly reconciled discrepancies between existing sets of phenotype labels. This novel, multidimensional approach has the potential to identify clinically relevant phenotypes, not only in paediatric disorders but also in adult obstructive airway diseases, where phenotype definition is an equally important issue.

Pressure perturbation calorimetry of helical peptides.

Pressure perturbation calorimetry quantifies the temperature dependence of a solute's thermal expansion coefficient, providing information about solute-solvent interactions. We tested the idea that pressure perturbation calorimetry can provide information about solvent-accessible surface area by studying peptides with different secondary structures. The peptides comprised two host-guest series: one predominately an alpha-helix, the other predominately a polyproline II helix. In aqueous buffer, we find a correlation between the amount of secondary structure as assessed by circular dichroism spectropolarimetry and the pressure perturbation calorimetry data. We conclude that pressure perturbation calorimetry can provide information about the exposure of polar and nonpolar surface area. Data acquired in a buffered urea solution, however, are not as easily interpreted.

Education level inequalities and transportation injury mortality in the middle aged and elderly in European settings.

OBJECTIVE: To study the differential distribution of transportation injury mortality by educational level in nine European settings, among people older than 30 years, during the 1990s. METHODS: Deaths of men and women older than 30 years from transportation injuries were studied. Rate differences and rate ratios (RR) between high and low educational level rates were obtained. RESULTS: Among men, those of low educational level had higher death rates in all settings, a pattern that was maintained in the different settings; no inequalities were found among women. Among men, in all the settings, the RR was higher in the 30-49 age group (RR 1.46, 95% CI 1.32 to 1.61) than in the age groups 50-69 and > or = 70 years, a pattern that was maintained in the different settings. For women for all the settings together, no differences were found among educational levels in the three age groups. In the different settings, only three had a high RR in the youngest age group, Finland (RR 1.33, 95% CI 1.01 to 1.74), Belgium (RR 1.38; 95% CI 1.13 to 1.67), and Austria (RR 1.49, 95% CI 0.75 to 2.96). CONCLUSION: This study provides new evidence on the importance of socioeconomic inequalities in transportation injury mortality across Europe. This applies to men, but not to women. Greater attention should be placed on opportunities to select intervention strategies tailored to tackle socioeconomic inequalities in transportation injuries.