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IntroductionBreathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear.MethodsThis population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.ResultsWe included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; pConclusionBreathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

Acute dyspnea with underlying congestion is a leading cause of emergency department (ED) visits with high rates of hospitalization. Adrenomedullin is a vasoactive neuropeptide hormone secreted by the endothelium that mediates vasodilation and maintains vascular integrity. Plasma levels of biologically active adrenomedullin (bio-ADM) predict septic shock and vasopressor need in critically ill patients and are associated with congestion in patients with acute heart failure (HF) but the prognostic value in unselected dyspneic patients at the ED is unknown. The purpose of this study is to test if bio-ADM predicts adverse outcomes when sampled in patients with acute dyspnea at presentation to the ED. In this single-center prospective observational study, we included 1402 patients from the ADYS (Acute DYSpnea at the Emergency Department) cohort in Malmö, Sweden. We fitted logistic regression models adjusted for sex, age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and C-reactive protein (CRP) to associate bio-ADM plasma levels to mortality, hospitalization, intravenous (IV) diuretic treatment and HF diagnosis. Using receiver operating characteristic (ROC) curve analysis we evaluated bio-ADM discrimination for these outcomes compared to a reference model (sex, age, NT-proBNP, creatinine, and CRP). Model performance was compared by performing a likelihood ratio test on the deviances of the models. Bio-ADM (per interquartile range from median) predicts both 90-day mortality [odds ratio (OR): 1.5, 95% confidence interval (CI) 1.2–2.0, p p χ2 9.8, p = 0.002) and hospitalization (added χ2 14.1, p = 0.0002), and is associated with IV diuretic treatment and HF diagnosis at discharge. Plasma levels of bio-ADM sampled at ED presentation in acutely dyspneic patients are independently associated with 90-day mortality, hospitalization and indicate the need for decongestive therapy.

Purpose: This study investigated whether living in immigrant dense urban districts (IDUDs) and low-income areas in the city of Malmo predicted 5-year mortality among patients admitted to the emergency department (ED) because of acute respiratory distress. Patients and methods: We randomly selected 184 patients with acute respiratory distress during 2007, visiting the ED at Skane University Hospital, Malmo. In 2007, Malmo had 36% first- and second-generation immigrants. The main exposure was defined as being resident in any of the five IDUDs of Malmo compared to being resident in the five districts of Malmo with the highest proportion of Sweden-born inhabitants (SDUDs). We recorded vital parameters; medical triage priority according to Adaptive Process Triage (ADAPT), ICD-10 diagnoses, and the mean annual income for the patient’s urban district. We examined 5-year mortality risk using Cox proportional hazards model. Results: After adjustment for age and gender, patients from IDUDs (n=100, 54%) had an HR (95% CI) of 1.65 (1.087-2.494; P=0.019) regarding mortality at 5-year follow-up. Patients in the lowest vs highest income quartile had an HR of 2.00 (1.06-3.79; P=0.032) regarding mortality at 5-year follow-up. Age, male gender, presence of cardiopulmonary disease, and ADAPT priority also independently predicted the 5-year mortality. The excess risk of 5-year mortality associated with living in IDUDs remained significant after adjustment for age, gender, ADAPT priority, presence of cardiopulmonary disease, and income with an HR of 1.79 (1.15-2.78; P=0.010). Conclusion: Living in an IDUD is a strong independent risk factor for 5-year mortality in patients with acute respiratory distress. The cause is unknown. Our study suggests a need for better structured follow-up of cardiopulmonary disease in such patients. (Less)

Body mass index, weight gain and activity-related breathlessness : the Swedish CArdioPulmonary bioImage Study

Purpose This study investigated whether living in immigrant dense urban districts (IDUDs) and low-income areas in the city of Malmö predicted 5-year mortality among patients admitted to the emergency department (ED) because of acute respiratory distress. Patients and methods We randomly selected 184 patients with acute respiratory distress during 2007, visiting the ED at Skåne University Hospital, Malmö. In 2007, Malmö had 36% first- and second-generation immigrants. The main exposure was defined as being resident in any of the five IDUDs of Malmö compared to being resident in the five districts of Malmö with the highest proportion of Sweden-born inhabitants (SDUDs). We recorded vital parameters; medical triage priority according to Adaptive Process Triage (ADAPT), ICD-10 diagnoses, and the mean annual income for the patient’s urban district. We examined 5-year mortality risk using Cox proportional hazards model. Results After adjustment for age and gender, patients from IDUDs (n=100, 54%) had an HR (95% CI) of 1.65 (1.087–2.494; P=0.019) regarding mortality at 5-year follow-up. Patients in the lowest vs highest income quartile had an HR of 2.00 (1.06–3.79; P=0.032) regarding mortality at 5-year follow-up. Age, male gender, presence of cardiopulmonary disease, and ADAPT priority also independently predicted the 5-year mortality. The excess risk of 5-year mortality associated with living in IDUDs remained significant after adjustment for age, gender, ADAPT priority, presence of cardiopulmonary disease, and income with an HR of 1.79 (1.15–2.78; P=0.010). Conclusion Living in an IDUD is a strong independent risk factor for 5-year mortality in patients with acute respiratory distress. The cause is unknown. Our study suggests a need for better structured follow-up of cardiopulmonary disease in such patients.

Objective/Purpose The objective was to identify inflammatory biomarkers that predict risk of 90-day mortality in patients with acute dyspnea. Method We analyzed 25 inflammatory biomarkers, in plasma, in 407 adult patients admitted to the emergency department (ED) with acute dyspnea and related them to risk of 90-day mortality using Cox proportional hazard models adjusted for age, sex, oxygen saturation, respiratory rate, C-reactive protein, and Medical Emergency Triage and Treatment System–Adult score. Results Fifty patients (12%) died within 90 day from admission. Two strong and independent biomarker signals were detected: The hazard ratio (95% confidence interval) for 90-day mortality per 1-SD increment of interleukin-8 (IL-8) was 2.20 (1.67-2.90) ( P = 2.5 × 10 −8 ) and for growth differentiation factor–15 (GDF-15) was 3.45 (2.18-5.45) ( P = 1.3 × 10 −7 ) A Biomarker Mortality Risk Score (BMRS) summing standardized and weighted values of IL-8 and GDF-15 revealed that of patients belonging to quartile 1 (Q1) of the BMRS, only 1 patient died, whereas 32 patients died among those belonging to quartile 4. Each 1-SD increment of the BMRS was associated with a hazard ratio of 3.79 (2.50-5.73) ( P = 2 × 10 −10 ) for 90-day mortality, and the point estimate was 13 times higher in Q4 as compared with Q1 of the BMRS ( P trend over quartiles=2 × 10 −6 ). Conclusion Interleukin-8 and GDF-15 are strongly and independently related to risk of 90-day mortality in unselected patients admitted to the ED because of acute dyspnea, suggesting that they may guide first-line physicians at the ED in risk assessment which in turn could lead to more accurate level of care and treatment intensity.

Rationale Patients with acute dyspnea are a large heterogeneous patient group where initial management is important for outcome. Objectives The objective of the study is to investigate if venous blood gas parameters predict 1-year risk of readmission or death in patients admitted to the emergency department due to acute dyspnea. Methods We studied 283 patients with acute dyspnea and followed them up for 1 year regarding incidence of readmission or death. Measurements and main results In venous blood obtained immediately upon admission levels of total carbon dioxide (TCO 2 ), base excess (BE), potential hydrogen (pH), and partial pressure of carbon dioxide (pCO 2 ) were measured. In Cox proportional hazards models, patients belonging to top and bottom quartiles of TCO 2 , BE, pH, and pCO 2 were compared to patients belonging to the 2 central quartiles and assessed for end point. After adjustment, top (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.08-2.04; P = .016) and bottom (HR, 1.54; 95% CI, 1.08-2.18; P = .017) quartiles of BE were associated with increased risk of readmission or death. The strongest predictor was top quartile of TCO 2 (HR, 1.68; 95% CI, 1.21-2.35; P = .002). In the combined analysis, top quartile of TCO 2 remained significantly related to the end point (HR, 1.59; 95% CI, 1.03-2.45; P = .035), whereas BE became nonsignificant. Comorbidities, for example, prevalent chronic obstructive pulmonary disease, did not explain the association. Neither pCO 2 nor pH predicted the end point. Conclusions A high value of TCO 2 appears to be an easily accessible marker for 1-year readmission or death in patients with acute dyspnea and may thus add clinically important information for risk stratification and follow-up strategies.

The close relationship between heart and kidney diseases was studied with respect to the ‘Shrunken pore syndrome’ that is characterized by a difference in renal filtration between cystatin C and creatinine. Patients were retrieved from the HeARt and brain failure inVESTigation trail (HARVEST) which is an ongoing study undertaken in individuals hospitalized for the diagnosis of heart failure. Ninety-five of 116 patients who underwent transthoracic echocardiograms (TTE) were eligible for this study. We used four different formulas for estimated glomerular filtration rate (eGFR); CKD-EPIcreatinine, CKD-EPIcystatin C, LMrev and CAPA. Presence of the syndrome was defined as eGFR cystatin C ≤ 60% of eGFR creatinine and absence of the syndrome as eGFR cystatin C >90% and

Objectives The aim of this pilot study was to investigate cause(s) of heart failure (HF). Setting The emergency department and medical wards at Malmo University Hospital. Method A cross sectional pilot study. Main outcome measures Comparison of compliance, comprehension and optimal treatment on a population basis between men and women, younger (a parts per thousand currency sign75 years) and elderly (> 75 years) patients, and patients in different New York Heart Association (NYHA) classes, in order to assess if exacerbation could have been caused by any of these factors. Results Of the 47 patients included, 60% reported high compliance, with significant differences between women and men, and between patients in NYHA class IV and patients in NYHA class III. Comprehension on self-care was poor. Only 30% weighed themselves regularly and 45% did not limit the amount of fluids. No more than 28% reported they would contact a health professional in the case of experiencing more symptoms. Suboptimal treatment was also found to be a great concern. The majority were treated with recommended agents, but had not achieved target dose as recommended in the guidelines. Conclusion This pilot study indicates suboptimal HF management of patients with HF prior to hospital admission due to HF exacerbation. A larger study is needed to assess the extent of the problem, and establish the need and nature of management improvement in different patient subgroups.

The pathophysiology of myocardial infarction (MI) may differ depending on whether it occurs early or late in life. We tested the hypothesis that risk factor pattern differs according to the age at MI.We performed a matched case-control study in the population-based Malmö Preventive Project (n = 33 346), where 3687 individuals developed MI during 22 ± 7 years of follow-up (=cases). The cases were divided into quartiles (Q1-Q4) according to age at event and were assigned two matched controls free from MI during follow-up. We used conditional logistic regression to assess relationship between risk factors at baseline and case status within quartiles of age at incident MI.The median (range) age (years) at incident MI in Q1 was 52.9 (37.0-57.1), Q2 60.8 (57.1-63.6), Q3 66.6 (63.6-69.7), and Q4 73.5 (69.7-84.0). The odds ratio (95% CI) for incident MI associated with 1 SD increase of baseline cholesterol decreased with age of MI and was 1.68 (1.50-1.87) for Q1, 1.43 (1.28-1.61) for Q2, 1.27 (1.14-1.42) for Q3, and 1.08 (0.98-1.19) for Q4. Similarly, family history of MI had a stronger relationship with MI in Q1 than with MI in Q4 of MI age, whereas smoking displayed a U-shaped relationship. Exposure to the remaining risk factors did not differentially affect MI occurring at different age spans.Exposure to cholesterol and family history of MI more strongly predicts onset of MI at younger ages, suggesting that MI in younger subjects is preceded by a different risk factor pattern than MI presenting in older subjects.

AimsGenetic predisposition for cardiovascular disease (CVD) is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors.Methods and resultsA total of 24,944 middle-aged subjects (62% females) from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309), ischemic stroke (N = 1253) and CVD-mortality (N = 1156). Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035) and CVD-mortality (P = 0.012). The hazard ratios (HR) per risk allele of rs4977574 were highest in never smokers (N = 9642) for CAD (HR = 1.26; 95% CI 1.13-1.40; PConclusionSmoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation.

OBJECTIVES: To evaluate the proportion of cardiovascular disease (CVD) incidence that is explained by genetic variation at chromosome 9p21 and to test whether such variation adds incremental information with regard to CVD prediction, beyond traditional risk factors. DESIGN, SETTING AND PARTICIPANTS: rs4977574 on chromosome 9p21 was genotyped in 24 777 subjects from the Malmo Diet and Cancer study who were free from CVD prior to the baseline examination. Association between genotype and incident CVD (n = 2668) during a median follow-up of 11.7 years was evaluated in multivariate Cox proportional hazard models. Analyses were performed in quartiles of baseline age, and linear trends in effect size across age groups were estimated in logistic regression models. RESULTS: In additive models, chromosome 9p21 significantly predicted CVD in the entire population (hazard ratio 1.17 per G allele, 95% confidence interval 1.11-1.23, P < 0.001). Effect estimates increased from the highest (Q4) to the lowest quartile (Q1) of baseline age, but this trend was not significant. The overall population attributable risk conferred by chromosome 9p21 in fully adjusted models was 13%, ranging from 17% in Q1 to 11% in Q4. Addition of chromosome 9p21 to traditional risk factors only marginally improved predictive accuracy. CONCLUSION: The high population attributable risk conferred by chromosome 9p21 suggests that future interventions interfering with downstream mechanisms of the genetic variation may affect CVD incidence over a broad range of ages. However, variation of chromosome 9p21 alone does not add clinically meaningful information in terms of CVD prediction beyond traditional risk factors at any age. (Less)

Context: The clinical utility and age dependant effects of the strongest single cardiovascular disease (CVD) susceptibility gene variant identified thus far (on chromosome 9p21) has not yet been evaluated in any large homogeneous prospective cohort study. We tested in a large prospective cohort

Background: Lack of consensus regarding use of an invasive strategy in the very elderly with coronary artery disease has repeatedly been demonstrated. This is in part due to the fear of complications and to the assumption that nothing can be done in most of these cases because of advanced disease. At the same time, the number of these patients is increasing in western societies. Methods: Data from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA) was analyzed in 54850 patients of age 80 years or older admitted between the years 2000–2005 with an acute coronary syndrome (ACS). To evaluate potential early hazard or benefit from revascularization performed within 14 days 1-year mortality was evaluated both in all patients and in 14-days survivals (n=47865). A multivariable Cox regression analysis was performed including 15 covariates. Results : Crude 1-year mortality in patients revascularized within 14 days of admission was 16.0% (857/5369) vs. 35.6% (17596/ 49481) in those revascularized later or not at all (p Conclusion: Also in patients older than 80 years with ACS revascularization is feasible and with the selection done by physicians associated with improved survival when comparing patients with similar comorbidity and risk factors.

Heart failure (HF) is characterized by myocardial dysfunction resulting in increased venous and capillary pressure, and extravascular fluid accumulation when the capacity of the lymphatic system is insufficient. Vascular endothelial growth factor D (VEGF-D) activates VEGF receptors 2 and 3 and is a