Magnus Nakrem Lyngbakken

Effect of weight loss on subclinical myocardial injury: A clinical trial comparing gastric bypass surgery and intensive lifestyle intervention

Aims To investigate the effect of weight loss induced by bariatric surgery and intensive lifestyle intervention on levels of circulating high-sensitivity cardiac troponin I. Methods and Results We measured high-sensitivity cardiac troponin I concentrations pre- and 12 months post-intervention in 136 subjects with morbid obesity participating in a controlled clinical trial comparing the effect of intensive lifestyle intervention vs. Roux-en-Y gastric bypass. At baseline median (interquartile range) high-sensitivity cardiac troponin I levels were 2.40 (1.28–3.95) ng/L in the bariatric surgery group and 2.35 (1.38–4.40) ng/L in the intensive lifestyle intervention group (p = 0.736). The high-sensitivity cardiac troponin I concentration in a normal-weight control group was 0.90 (0.60–2.13) ng/L. During 12 months of follow-up, high-sensitivity cardiac troponin I decreased significantly more in the bariatric surgery group than in the intensive lifestyle intervention group (0.80 (0–1.80) vs. 0.15 (−0.50 to 1.00) ng/L; p = 0.002). In a multivariate logistic regression model, surgery emerged as a predictor of reduction in high-sensitivity cardiac troponin I levels (odds ratio 2.32; 95% confidence intervals 1.03–5.22; p = 0.041) independent of age, gender and other possible confounding baseline variables. In subsequent multivariate analyses, reductions in body weight and triglycerides emerged as possible mediators of reduction in circulating levels of high-sensitivity cardiac troponin I. Conclusion In patients with morbid obesity, bariatric surgery was associated with a significantly greater reduction in high-sensitivity cardiac troponin I, an index of subclinical myocardial injury, than intensive lifestyle intervention. The reduction appeared to be mediated by reductions in body weight and serum triglycerides. This suggests that weight loss following bariatric surgery may reduce cardiometabolic stress and subsequent risk of heart failure.

Impact of Smoking on Circulating Cardiac Troponin I Concentrations and Cardiovascular Events in the General PopulationClinical Perspective: The HUNT Study (Nord-Trøndelag Health Study)

Background: Both tobacco smoking and circulating cardiac troponin I (cTnI) levels are associated with the risk of acute myocardial infarction, heart failure, and cardiovascular death. However, whether cTnI levels differ according to smoking status and whether smoking modifies the prognostic relationship between cTnI and outcomes remain unclear. Methods: Using data from a large, population-based cohort, we assessed the association between smoking and cTnI and the impact of smoking on the associations between cTnI levels and the incidence of acute myocardial infarction, heart failure, and cardiovascular death. cTnI was measured with a high-sensitivity assay in 3824 never smokers, 2341 former smokers, and 2550 current smokers participating in the prospective observational HUNT Study (Nord-Trøndelag Health Study). All subjects were free from known prior cardiovascular disease and diabetes mellitus at baseline. Results: The age of the participants ranged from 19 to 94 years; 55.5% were women. Current smokers exhibited significantly lower levels of cTnI (median, 2.9 ng/L; interquartile range, 2.0–4.1 ng/L) than never smokers (3.2 ng/L; interquartile range, 2.2–4.7 ng/L; P<0.001) and former smokers (3.4 ng/L; interquartile range, 2.3–5.0 ng/L; P<0.001). This association remained significant after adjustment for potential confounders (B=−0.098; 95% confidence interval, −0.129 to −0.068). We observed an association between increasing concentrations of cTnI and clinical end points in the total study cohort (adjusted hazard ratio per log unit increase in cTnI, 1.41; 95% confidence interval, 1.29–1.54). This association was attenuated for current smokers (hazard ratio, 1.17; 95% confidence interval, 0.98–1.40) and was significantly weaker than in never/former smokers (P for interaction=0.003). Prognostic accuracy, as assessed by C statistics, was significantly lower in current smokers than in never smokers (P<0.001). In addition, cTnI provided no incremental prognostic information to the Framingham Cardiovascular Disease risk score in current smokers (P=0.08). Conclusions: Current smoking is associated with lower concentrations of cTnI, suggesting that substances in tobacco smoke may affect cardiomyocyte injury. The association between cTnI levels and cardiovascular end points is stronger in never/former smokers than in current smokers, compatible with the theory that the detrimental cardiovascular impact of current smoking is mediated via mechanisms other than subclinical myocardial injury.

Heart and Brain Interactions--the Akershus Cardiac Examination (ACE) 1950 Study Design.

Abstract> Objectives. The aim of the Akershus Cardiac Examination (ACE) 1950 Study is to investigate the development and progression of cardiovascular and cerebrovascular disease (CVD/CeVD) in an extensively characterized age cohort of middle-aged subjects with longitudinal long-term follow-up. Design. The ACE 1950 Study is a prospective, population-based, age-cohort study of all men and women born in 1950 in Akershus County, Norway. The study involves a comprehensive baseline examination, especially for CVD/CeVD, including advanced ultrasound imaging and biobanking (“deep phenotyping”). We expect to obtain an inclusion rate of > 60% from the total study population of 5,827 eligible subjects. Enrollment will be completed during 2015. Conclusions. The ACE 1950 Study will have potential to generate new and relevant insight into identification of subclinical disease progression. Extensive phenotyping will enable identification of novel disease markers and mechanisms for subclinical disease, which can prove important for future disease prevention.

Mid-regional pro-adrenomedullin in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study

BACKGROUND Mid-regional pro-adrenomedullin (MR-proADM) is a surrogate marker for adrenomedullin; a hormone that attenuates myocardial remodeling. Accordingly, we hypothesized that MR-proADM could provide diagnostic and prognostic information in patients with acute dyspnea. METHODS AND RESULTS We measured MR-proADM by a commercial ELISA on hospital admission in 311 patients with acute dyspnea and compared the utility of MR-proADM with N-terminal pro-B-type natriuretic peptide (NT-proBNP). Blood samples were also available after 24h (n=232) and before discharge (n=94). The principal diagnosis of the index hospitalization was determined by an adjudication committee. MR-proADM concentrations on hospital admission were higher in patients with acute heart failure (HF; n=143) vs. patients hospitalized with non-HF-related dyspnea (n=168): 1.31 (Q1-3 0.97-1.89) vs. 0.85 (0.59-1.15) nmol/L; p<0.001. The receiver-operating characteristics area under the curve (ROC-AUC) for MR-proADM to diagnose HF was 0.77 (95% CI 0.72-0.82) and 0.86 (0.82-0.90) for NT-proBNP. During a median follow-up of 816days, 66/143 patients (46%) with acute HF and 35/84 patients (42%) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) died; p=0.58 between groups. In multivariate Cox regression analyses, admission MR-proADM concentrations were associated with mortality in patients with acute HF (HR 5.90 [3.43-10.13], p<0.001), but not in patients with AECOPD. Admission MR-proADM concentrations also improved risk stratification in acute HF as assessed by the net reclassification index. MR-proADM concentrations decreased from admission to later time points. CONCLUSION Admission MR-proADM concentrations provide strong prognostic information in patients with acute HF, but modest diagnostic information in patients with acute dyspnea.

The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac surgical patients

BACKGROUND European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known. METHODS Preoperative (n=640) and postoperative (n=629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2). RESULTS Sixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho=0.58; p<0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134-1354) ng/L [NT-proBNP] and 39 (16-191) vs. 13 (8-32) ng/L [hs-TnT]; p<0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [lnNT-proBNP] 1.33 [95% CI 1.08-1.64]), p=0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14-0.64], p=0.003). Pre- and postoperative NT-proBNP concentrations were closely correlated (rho=0.80, p<0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurements CONCLUSION: NT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients.

Relative Prognostic Value of Cardiac Troponin I and C-Reactive Protein in the General Population (from the Nord-Trøndelag Health [HUNT] Study)

C-reactive protein and cardiac troponin I measured with high-sensitivity assays (high-sensitivity C-reactive protein [hs-CRP] and high-sensitivity troponin I [hs-TnI]) have been associated with risk of fatal and nonfatal cardiovascular events in the general population. The relative prognostic merits of hs-CRP and hs-TnI, and whether these markers of inflammation and subclinical myocardial injury provide incremental information to established cardiovascular risk prediction models, remain unclear. hs-CRP and hs-TnI were measured in 9,005 participants from the prospective observational Nord-Trøndelag Health (HUNT) study. All study subjects were free from known cardiovascular disease at baseline. During a median follow-up period of 13.9 years, 733 participants reached the composite end point of hospitalization for acute myocardial infarction or heart failure, or cardiovascular death. In adjusted models, increased hs-TnI concentrations (>10 ng/L for women and >12 ng/L for men) were associated with the incidence of the composite end point (hazard ratio 3.61, 95% confidence interval [CI] 2.89 to 4.51]), whereas the risk associated with increased hs-CRP concentrations (>3 mg/L for both genders) appeared to be weaker (HR 1.71, 95% CI 1.40 to 2.10). The addition of hs-TnI to established cardiovascular risk prediction models led to a net reclassification improvement of 0.35 (95% CI 0.27 to 0.42), superior to that of hs-CRP (0.21, 95% CI 0.13 to 0.28). The prognostic accuracy of hs-TnI, assessed by C-statistics, was significantly greater than that of hs-CRP (0.753, 95% CI 0.735 to 0.772, vs 0.644, 95% CI 0.625 to 0.663). In conclusion, in subjects from the general population without a history of cardiovascular disease, hs-TnI provides prognostic information superior to that provided by hs-CRP and may therefore be a preferred marker for targeted prevention.

Prevalence of Carotid Plaque in a 63‐ to 65‐Year‐Old Norwegian Cohort From the General Population: The ACE (Akershus Cardiac Examination) 1950 Study

Background New data on extracranial carotid atherosclerosis are needed, as improved ultrasound techniques may detect more atherosclerosis, the definition of plaque has changed over the years, and better cardiovascular risk control in the population may have changed patterns of carotid arterial wall disease and actual prevalence of established cardiovascular disease. We investigated the prevalence of atherosclerotic carotid plaques and carotid intima–media thickness (cIMT) and their relation to cardiovascular risk factors in a middle‐aged cohort from the general population. Methods and Results We performed carotid ultrasound in 3683 participants who were born in 1950 and included in a population‐based Norwegian study. Carotid plaque and cIMT were assessed according to the Mannheim Carotid Intima–Media Thickness and Plaque Consensus, and a carotid plaque score was used to calculate atherosclerotic burden. The participants were aged 63 to 65 years, and 49% were women. The prevalence of established cardiovascular disease was low (10%), but 62% had hypertension, 53% had hypercholesterolemia, 11% had diabetes mellitus, and 23% were obese. Mean cIMT was 0.73±0.11 mm, and atherosclerotic carotid plaques were present in 87% of the participants (median plaque score: 2; interquartile range: 3). Most of the cardiovascular risk factors, with the exception of diabetes mellitus, obesity and waist–hip ratio, were independently associated with the plaque score. In contrast, only sex, hypertension, obesity, current smoking, and cerebrovascular disease were associated with cIMT. Conclusions We found very high prevalence of carotid plaque in this middle‐aged population, and our data support a greater association between cardiovascular risk factors and plaque burden, compared with cIMT. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01555411.

Diagnostic and prognostic properties of procalcitonin in patients with acute dyspnea: Data from the ACE 2 Study

BACKGROUND Procalcitonin (PCT) concentrations increase during bacterial infections and could improve diagnosis of pneumonia and risk stratification in patients with acute dyspnea. METHODS PCT concentrations were measured <24 h of admission in 310 patients with acute dyspnea and compared to C-reactive protein (CRP) and white blood cells (WBC) in the total cohort and the subset of patients with concomitant acute heart failure (HF). RESULTS We diagnosed pneumonia in 16 out of 140 patients with acute HF (11%) and in 45 out of 170 patients with non-HF-related dyspnea (27%). PCT concentrations were higher in patients with pneumonia vs. patients without pneumonia, both among acute HF patients (median 2.79 [Q1-3 0.18-5.80] vs. 0.10 [0.07-0.14] ng/mL, p < .001) and non-HF patients (0.22 [Q1-3 0.13-0.77] vs. 0.07 [0.05-0.10] ng/mL, p < .001). CRP and WBC were also higher in patients with pneumonia in both groups, but among acute HF patients, only PCT concentrations were associated with pneumonia in multivariate analysis. In patients with acute HF, receiver-operating statistics area under the curve (ROC-AUC) to diagnose pneumonia was 0.90 (95% CI 0.81-0.98) for PCT, 0.84 (0.73-0.94) for CRP, and 0.72 (0.57-0.87) for WBC. The corresponding ROC-AUCs among patients with non-HF-related dyspnea were 0.88 (0.82-0.93), 0.94 (0.90-0.98), and 0.79 (0.72-0.87), respectively. During a median follow-up of 823 days (Q1-3 471-998) 114 patients died, and PCT and CRP, but not WBC concentrations were associated with all-cause mortality. CONCLUSION In acute HF patients, PCT concentrations were superior to CRP and WBC to diagnose concurrent pneumonia.

Prevalence of atrial fibrillation and cardiovascular risk factors in a 63–65 years old general population cohort: the Akershus Cardiac Examination (ACE) 1950 Study

Objectives To investigate the sex-specific prevalence of atrial fibrillation (AF), including subclinical AF found by screening in a general population aged 63–65 years. The prevalence of cardiovascular risk factors and their association with AF will also be investigated. Design Cross-sectional analysis of an observational, prospective, longitudinal, population-based cohort study. Setting General population in Akershus county, Norway. Participants Women and men born in 1950. We included 3706 of 5827 eligible individuals (63.6%); 48.8% were women. Methods All participants underwent extensive cardiovascular examinations, including 12-lead ECG. History of AF and other cardiovascular diseases were self-reported. Subsequent validation of all reported or detected AF diagnoses was performed. Results Mean age was 63.9±0.7 years. Prevalence of ECG-verified AF was 4.5% (women 2.4%, men 6.4%; p<0.001), including screen-detected AF in 0.3% (women 0.1%, men 0.6%; p<0.01). Hypertension was found in 62.0% (women 57.8%, men 66.0%; p<0.001). Overweight or obesity was found in 67.6% (women 59.8%, men 74.9%; p<0.001). By multivariate logistic regression, risk factors associated with AF were height (OR 1.67 per 10 cm; 95% CI 1.26 to 2.22; p<0.001), weight (OR 1.15 per 10 kg; 95% CI 1.01 to 1.30; p=0.03), hypertension (OR 2.49; 95% CI 1.61 to 3.86; p<0.001), heart failure (OR 3.51; 95% CI 1.71 to 7.24; p=0.001), reduced estimated glomerular filtration rate (OR 2.56; 95% CI 1.42 to 4.60; p<0.01) and at least one first-degree relative with AF (OR 2.32; 95% CI 1.63 to 3.31; p<0.001), whereas male sex was not significantly associated (OR 1.00; 95% CI 0.59 to 1.68; p=0.99). Conclusion In this cohort from the general population aged 63–65 years, we found a higher prevalence of known AF than previously reported below the age of 65 years. The additional yield of single time point screening for AF was low. Body size and comorbidity may explain most of the sex difference in AF prevalence at this age. Trial registration number NCT01555411; Results.

Kardialt troponin og kardiovaskulær risiko

I mitt doktorgradsarbeid har vi ved hjelp av høysensitive målemetoder undersøkt sammenhengen mellom nivåer av kardialt troponin I og risiko for hjertesvikt, hjerteinfarkt og kardiovaskulær død i den generelle befolkningen. Vi har også undersøkt effekten av bariatrisk kirurgi og vektnedgang på nivåer av kardialt troponin I hos pasienter med sykelig overvekt. Vi fant sterke sammenhenger mellom nivåer av kardialt troponin I og risiko for hjertesykdom og kardiovaskulær død. Disse sammenhengene var tilsynelatende sterkest for kvinner og ikke-røykere, og var uavhengige av tradisjonelle risikofaktorer som hypertensjon, overvekt og diabetes. Videre var drastisk vektnedgang hos pasienter med sykelig overvekt assosiert med en signifikant reduksjon i nivåer av kardialt troponin I.