Left atrial function in middle-aged men and women with and without paroxysmal atrial fibrillation: Data from the Akershus Cardiac Examination (ACE) 1950 study.

PURPOSE: To assess left atrial (LA) function in individuals with known paroxysmal atrial fibrillation (AF) compared with healthy and nonhealthy individuals without atrial fibrillation. METHODS: The Akershus Cardiac Examination 1950 Study included 3,706 individuals all born in 1950. LA strain assessment of reservoir (LASr), conduit (LAScd) and contractile (LASct) functions were performed in all participants by investigators blinded to clinical data. Participants with cardiovascular disease, obesity, diabetes, pulmonary or renal disease were defined as nonhealthy, and those without as healthy. Patients with paroxysmal AF were identified through medical history and ECG documentation. RESULTS: LA strain assessment was feasible in 3,229 (87%) of the participants (50% women). The healthy group (n = 758) had significantly higher LASr and LAScd than the nonhealthy (n = 2,376), but LASct was similar between the groups. Participants with paroxysmal AF had significantly lower values of all strain parameters than the other groups. Multivariable logistic regression showed a significantly reduced probability of having AF per standard deviation increase in LASr and LASct. A nonlinear restricted cubic spline model fitted better with the association of LASr with paroxysmal AF than the linear model, and LA strain values below the population mean associated with an increased probability of having AF, but for values above the population mean no such association was present. CONCLUSION: Compared to participants without AF, those with known paroxysmal AF had significantly lower values of all LA strain parameters during sinus rhythm. Lower values of LA strain were associated with a significantly increased probability of having AF.

Feasibility of Patient-Managed ECG Recordings to Detect the Time of Atrial Fibrillation Recurrence after Electrical Cardioversion: Results from the PRE-ELECTRIC Study.

BACKGROUND: Electrical cardioversion (ECV) is a common procedure to terminate persistent atrial fibrillation (AF). The recurrence rate is high, and the patients often fail to recognize AF recurrence. OBJECTIVES: The aim of the study was to evaluate the feasibility of patient-managed electrocardiography (ECG) to detect the time to AF recurrence after ECV. METHODS: PRE-ELECTRIC (predictors for recurrence of atrial fibrillation after electrical cardioversion) is a prospective, observational study. Patients ≥18 years of age scheduled for ECV of persistent AF at Bærum Hospital were eligible for inclusion in the study. Time to recurrence of AF was detected by thumb ECG, recorded twice daily and whenever experiencing symptoms. The observation period was 28 days. We defined adherence as the observed number of days with ECG recordings divided by the expected number of days with ECG recordings. Study personnel contacted the participants by phone to assess their awareness of AF recurrence after a recurrence was detected in the thumb ECG. RESULTS: The study enrolled 200 patients scheduled for ECV of persistent AF at Bærum Hospital between 2018 and 2022. The mean age was 66.2 ± 9.3 years, and 21.0% (42/200) were women. The most frequent comorbidities were hypertension (n = 94, 47.0%) and heart failure (n = 51, 25.5%). A total of 164 participants underwent ECV of AF. The procedure was initially successful in 90.9%, of which 50.3% had a recurrence of AF within 4 weeks. The median time to recurrence was 5 days. Among the cardioverted participants, 123 (75.0%) had no missing days of thumb ECG recording during the observation period, and 97.0% had ≤3 missing days. More than a third (37.3%) of the participants with AF recurrence were unaware of the recurrence at the time of contact. Women were older and more symptomatic than men but had similar outcomes after ECV. CONCLUSIONS: Recurrence of AF after ECV was common. Using patient-managed thumb ECG was a feasible method to detect AF recurrence following ECV. Further studies are needed to investigate whether patient-managed ECG after ECV can optimize AF treatment.

Troponin I levels in permanent atrial fibrillation-impact of rate control and exercise testing.

BACKGROUND: High-sensitivity troponin I (hs-TnI) and troponin T (hs-TnT) are moderately correlated and independently related to outcome in atrial fibrillation (AF). Rate controlling therapy has been shown to reduce hs-TnT, however the potential impact on hs-TnI levels, and whether this differs from the effects on hs-TnT, has not been investigated previously. METHODS: Sixty patients with stable, permanent AF without heart failure or known ischemic heart disease were included in a randomised crossover study (mean age 71 ± 9 years, 18 women). Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for three weeks, in a randomised sequence. At baseline and on the last day of each treatment period, hs-TnI was measured at rest and after a maximal exercise test and compared to hs-TnT. RESULTS: Hs-TnI and hs-TnT correlated moderately at baseline (rs = 0.582, p < 0.001). All drugs reduced both the resting and the peak exercise levels of hs-TnI compared with baseline (p < 0.001 for all). The decline in resting hs-TnI and hs-TnT values relative to baseline levels was similar for all drugs except for verapamil, which reduced hs-TnI more than hs-TnT (p = 0.017). Levels of hs-TnI increased significantly in response to exercise testing at baseline and at all treatment regimens (p < 0.001 for all). The relative exercise-induced increase in hs-TnI was significantly larger compared to hs-TnT at baseline (p < 0.001), on diltiazem (p < 0.001) and on verapamil (p = 0.001). CONCLUSIONS: In our population of stable, permanent AF patients, all four rate control drug regimens reduced hs-TnI significantly, both at rest and during exercise. The decline in hs-TnI and hs-TnT levels associated with beta-blocker and calcium channel blocker treatment was similar, except for a larger relative decrease in hs-TnI levels following verapamil treatment. TRIAL REGISTRATION: www.clinicaltrials.gov ( NCT00313157 ).

Circadian variation of variability and irregularity of heart rate in patients with permanent atrial fibrillation: relation to symptoms and rate control drugs.

The aim of the present study was to evaluate diurnal variations of the variability and irregularity of heart rate (HR) in patients with permanent atrial fibrillation (AF) with and without rate control drugs. Thirty-eight patients with permanent AF were part of an investigator-blind crossover study comparing diltiazem, verapamil, metoprolol, and carvedilol. We analyzed five Holter recordings per patient: at baseline (no rate control drug) and with each of the four drug regimens. HR, variability (SD; percentages of interval differences of successive RR intervals of >20, 50, and 80 ms; and root of the mean squared differences of successive RR intervals), and irregularity (approximate and sample entropy) parameters were computed in 20-min long nonoverlapping segments. Circadian rhythmicity was evaluated using cosinor analysis to each parameter series, which is characterized by the 24-h mean [midline statistic of rhythm (MESOR)] and excursion over the mean (amplitude). Arrhythmia-related symptoms were assessed by a questionnaire measuring symptom severity and frequency. HR and variability parameters showed a significant circadian variation in most patients, whereas only a small minority of the patients had circadian variations of irregularity parameters. Patients with circadian approximate entropy n at baseline had more severe symptoms (symptom severity: 9 ± 4 vs. 6 ± 5, P < 0.05, circadian vs. noncircadian variations). All drugs decreased the MESOR of HR and increased the MESOR of variability parameters. Only carvedilol and metoprolol decreased the normalized amplitude over 24 h of all parameters and HR. In conclusion, HR and RR variability parameters present a circadian variation in patients with permanent AF, whereas few patients demonstrated circadian fluctuations in irregularity parameters, suggesting different physiological mechanisms.

Rate-control drugs affect variability and irregularity measures of RR intervals in patients with permanent atrial fibrillation.

INTRODUCTION: Irregularity measures have been suggested as risk indicators in patients with atrial fibrillation (AF); however, it is not known to what extent they are affected by commonly used rate-control drugs. We aimed at evaluating the effect of metoprolol, carvedilol, diltiazem, and verapamil on the variability and irregularity of the ventricular response in patients with permanent AF. METHODS AND RESULTS: Sixty patients with permanent AF were part of an investigator-blind cross-over study, comparing 4 rate-control drugs (diltiazem, verapamil, metoprolol, and carvedilol). We analyzed five 20-minute segments per patient: baseline and the 4 drug regimens. On every segment, heart rate (HR) variability and irregularity of RR series were computed. The variability was assessed as standard deviation, pNN20, pNN50, pNN80, and rMSSD. The irregularity was assessed by regularity index, approximate (ApEn), and sample entropy. A significantly lower HR was obtained with all drugs, the HR was lowest using the calcium channel blockers. All drugs increased the variability of ventricular response in respect to baseline (as an example, rMSSD: baseline 171 ± 47 milliseconds, carvedilol 229 ± 58 milliseconds; P < 0.05 vs. baseline, metoprolol 226 ± 66 milliseconds; P < 0.05 vs. baseline, verapamil 228 ± 84; P < 0.05 vs. baseline, diltiazem 256 ± 87 milliseconds; P < 0.05 vs. baseline and all other drugs). Only ß-blockers significantly increased the irregularity of the RR series (as an example, ApEn: baseline 1.86 ± 0.13, carvedilol 1.92 ± 0.09; P < 0.05 vs. baseline, metoprolol 1.93 ± 0.08; P < 0.05 vs. baseline, verapamil 1.86 ± 0.22 ns, diltiazem 1.88 ± 0.16 ns). CONCLUSION: Modification of AV node conduction by rate-control drugs increase RR variability, while only ß-blockers affect irregularity.

Impact of atrial fibrillation on levels of high-sensitivity troponin I in a 75-year-old population.

PURPOSE: Atrial fibrillation (AF) has been associated with elevated levels of cardiac troponins; however, it is not clear if this association is independent of underlying cardiovascular disease. The aim of this study was to investigate the impact of AF on cardiac troponin I levels in a 75-year-old cohort from the general population, using a recently introduced, highly sensitive assay. METHODS: All 75-year-old citizens in Asker and Baerum counties were invited to participate in a prevalence study of AF. High-sensitive troponin I (hs-TnI) levels were measured (Abbott Diagnostics) in serum samples collected from 62 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. RESULTS: Hs-TnI was detectable in all subjects (median 7.3 ng/L [range 3.0-88.7]). Patients with AF had higher levels than subjects in sinus rhythm (8.3 ng/L [3.7-88.7] vs. 6.8 ng/L [3.0-77.5]; p = 0.011). Male gender (p = 0.002), hypertension (p = 0.001), coronary heart disease (p < 0.001), heart failure (p < 0.001), prior stroke or transient ischemic attack (p = 0.013) and serum creatinine (p < 0.001) were all associated with higher levels of hs-TnI in univariate analysis. Heart failure and coronary heart disease remained significantly associated with hs-TnI in multivariate analysis, whereas the relation between AF and hs-TnI was no longer statistically significant. CONCLUSION: All subjects had detectable levels of hs-TnI. AF patients had higher hs-TnI levels than subjects in sinus rhythm; however, this difference was not statistically significant after adjustment for heart failure and coronary heart disease.

Non-invasive assessment of the effect of beta blockers and calcium channel blockers on the AV node during permanent atrial fibrillation.

AIM: We aimed at assessing changes in AV nodal properties during administration of the beta blockers metoprolol and carvedilol, and the calcium channel blockers diltiazem and verapamil from electrocardiographic data. METHODS: Parameters accounting for the functional refractory periods of the slow and fast pathways (aRPs and aRPf) were estimated using atrial fibrillatory rate (AFR) and ventricular response assessed from 15-min ECG segments recorded at baseline and on drug treatment from sixty patients with permanent AF. RESULTS: The results showed that AFR and HR were significantly reduced for all drugs, and that aRPs and aRPf were significantly prolonged in both pathways. The prolongation in aRP was significantly larger for the calcium channel blockers than for the beta blockers. CONCLUSIONS: The changes observed in the AV node parameters are in line with the results of previous electrophysiological studies performed in patients during sinus rhythm, therefore supporting the clinical value of the method.

Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation.

AIMS: Rate control of atrial fibrillation (AF) has become a main treatment modality, but we need more knowledge regarding the different drugs used for this purpose. In this study, we aimed to compare the effect of four common rate-reducing drugs on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent AF. METHODS AND RESULTS: We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF and normal left ventricular function in a randomized, cross-over, investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered o.d. for 3 weeks. At baseline and on the last day of each treatment period, the patients underwent a maximal cardiopulmonary exercise test and blood samples were obtained at rest and at peak exercise. The exercise capacity (peak VO2) was significantly lower during treatment with metoprolol and carvedilol compared with baseline (no treatment) or treatment with diltiazem and verapamil (P < 0.001 for all). Compared with baseline, treatment with diltiazem and verapamil significantly reduced the NT-proBNP levels both at rest and at peak exercise, whereas treatment with metoprolol and carvedilol increased the levels (P < 0.05 for all). CONCLUSION: Rate-reducing treatment with diltiazem or verapamil preserved exercise capacity and reduced levels of NT-proBNP compared with baseline, whereas treatment with metoprolol or carvedilol reduced the exercise capacity and increased levels of NT-proBNP.

Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation.

AIMS: During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data, and to support our findings with simulated data based on results from an electrophysiological study. METHODS AND RESULTS: Sixty patients (age 71 ± 9 years, 42 men) with permanent AF were included in the RATe control in Atrial Fibrillation (RATAF) study. Two 15 min segments, during baseline and metoprolol administration, starting at 2 pm were analysed in this study. Atrial fibrillatory rate (AFR), heart rate (HR), and AV nodal parameters were assessed. The AV nodal parameters account for the probability of an impulse not taking the fast pathway, the absolute refractory periods of the slow and fast pathways (aRPs and aRPf), representing the functional refractory period, and their respective prolongation in refractory period. In addition, simulated RR series were generated that mimic metoprolol administration through prolonged AV conduction interval and AV node effective refractory period. During metoprolol administration, AFR and HR were significantly decreased and aRP was significantly prolonged in both pathways (aRPs: 337 ± 60 vs. 398 ± 79 ms, P < 0.01; aRPf: 430 ± 91 vs. 517 ± 100 ms, P < 0.01). Similar results were found for the simulated RR series, both aRPs and aRPf being prolonged with metoprolol (aRPs: 413 ± 33 vs. 437 ± 43 ms, P = 0.01; aRPf: 465 ± 40 vs. 502 ± 69 ms, P = 0.02). CONCLUSION: The AV nodal parameters reflect expected changes after metoprolol administration, i.e. a prolongation in functional refractory period. The simulations confirmed that aRPs and aRPf may serve as an estimate of the functional refractory period.

Diltiazem reduces levels of NT-proBNP and improves symptoms compared with metoprolol in patients with permanent atrial fibrillation.

AIMS: Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation (AF) after 6 months. METHODS AND RESULTS: Men and women with permanent AF and preserved left ventricular systolic function were randomized to receive either diltiazem 360 mg or metoprolol 100 mg once daily. The primary endpoint was the level of NT-proBNP after a 6-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71 ± 7 years, 28 women) were randomized. After 6-months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6-589.1, P < 0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity. CONCLUSION: Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent AF.

Impact of atrial fibrillation on inflammatory and fibrinolytic variables in the elderly.

PURPOSE: Atrial fibrillation (AF) is associated with inflammation and a prothrombotic state; however, it is still unclear whether this is independent of ageing and comorbidity. The objective of this study was to investigate the impact of AF on circulating levels of inflammatory and fibrinolytic markers in a 75-year-old general population. METHODS: All 75-year-old citizens in Asker and Baerum counties in Norway were invited to participate in a prevalence study of AF. Blood samples were collected from 63 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. C-reactive protein (CRP), tumour necrosis factor α (TNFα), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), P-selectin, CD40 ligand, tissue plasminogen activator antigen (tPA ag), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase inhibitor 1 (TIMP-1) activity were analyzed using commercially available assays. RESULTS: Subjects with AF had higher levels of IL-6 (median 3.07 pg/mL (interquartile range 2.11, 4.36) vs. 2.26 (1.70, 3.26); p = 0.002) and PAI-1 activity (12.9 U/mL (6.6, 17.1) vs. 9.0 (4.6, 14.0); p = 0.005). No difference was found for the other markers. The presence of AF was still significantly associated with higher levels of IL-6 and PAI-1 activity after adjusting for confounders (p = 0.028 and p = 0.007, respectively). CONCLUSION: AF was independently associated with higher levels of IL-6 and PAI-1 activity. Thus, there is evidence of a proinflammatory state and reduced fibrinolysis also in this stable, out-of-hospital group of 75-year-old AF patients.

Effects of training adaption in endurance athletes with atrial fibrillation: protocol for a multicentre randomised controlled trial.

Endurance athletes have a high prevalence of atrial fibrillation (AF), probably caused by exercise-induced cardiac remodelling. Athletes diagnosed with AF are often advised to reduce the intensity and amount of training but the efficacy of this intervention has not been investigated in endurance athletes with AF. Effects of detraining in endurance athletes with atrial fibrillation is a two-arm international multicentre randomised (1:1) controlled trial on the effects of a period of training adaption on AF burden in endurance athletes with paroxysmal AF. One-hundred-and-twenty endurance athletes diagnosed with paroxysmal AF are randomised to a 16-week period of intervention (training adaption) or a control group. We define training adaption as training with a heart rate (HR) not exceeding 75% of the individual maximum HR (HRmax), and total duration of weekly training not exceeding 80% of the self-reported average before the study. The control group is instructed to uphold training intensity including sessions with HR ≥85% of HRmax. AF burden is monitored with insertable cardiac monitors, and training intensity with HR chest-straps and connected sports watches. The primary endpoint, AF burden, will be calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. Secondary endpoints include number of AF episodes, adherence to training adaption, exercise capacity, AF symptoms and health-related quality of life, echocardiographic signs of cardiac remodelling and risk of cardiac arrhythmias related to upholding training intensity. Trial registration number: NCT04991337. Study protocol version: 4.7 (Date 9 March 2023).

Impact of Blood Pressure in the Early 40s on Left Atrial Volumes in the Mid-60s: Data From the ACE 1950 Study.

Background Echocardiographic measures of left atrial volumes are powerful predictors of cardiovascular events and important for assessing diastolic dysfunction. Despite this, there is limited knowledge of factors influencing left atrial remodeling. In particular, the impact of blood pressure in those in their early 40s on left atrial volumes later in life has not been sufficiently elucidated. Methods and Results We linked data from individuals born in 1950 who participated in the Age 40 Program, and the ACE (Akershus Cardiac Examination) 1950 Study. We divided the study population into quartiles of systolic blood pressure in their early 40s and assessed the proportion of individuals with an enlarged left atrium in their mid-60s. The associations between blood pressure and left atrial volumes were assessed in linear regression analyses. Of the 2591 individuals included in this study, 1302 (50.3%) were women, and the mean age in the Age 40 Program was 40.1±0.3 years. Systolic blood pressure was 128.1±13.6 mm Hg and diastolic blood pressure was 78.3±9.5 mm Hg. Mean age in the ACE 1950 Study was 64.0±0.6 years. The proportion of individuals with an enlarged left atrium increased across the quartiles of systolic blood pressure (P=0.001). Systolic blood pressure was independently associated with left atrial volumes; the end-systolic volume was 0.09 mL (95% CI, 0.04-0.14 mL) larger per 1-mm Hg higher systolic blood pressure. Conclusions Our findings suggest that increased blood pressure in those in their early 40s is relevant for left atrial remodeling later in life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01555411.

Abnormal atrial activation in young patients with lone atrial fibrillation.

AIMS: Patients with a history of atrial fibrillation (AF) have previously been shown to have altered atrial conduction, as seen non-invasively using signal-averaged P-wave analysis. However, little is known about the P-wave morphology in patients in the early phases of AF with structurally normal hearts. METHODS AND RESULTS: Thirty-six patients with lone AF were included before the age of 40 years (34±4 years, 34 men) and compared with age- and gender-matched control subjects. Standard 12-lead electrocardiogram (ECG) was recorded for at least 10 s. P-wave morphology and duration were estimated using signal-averaged P-wave analysis. Echocardiography was performed in association with the ECG recording. Heart rate (67±13 vs. 65±7 b.p.m., P=0.800) and PQ-interval (163±16 vs. 164±23 ms, P=0.629) were similar in AF cases and controls, as was P-wave duration (136±13 vs. 129±13 ms, P=0.107). The distribution of P-wave morphology differed between the AF cases and controls [33/58/0/8 vs. 75/25/0/0% (Type 1/Type 2/Type 3/atypical), P=0.001], with a larger proportion of patients with AF exhibiting signs of impaired interatrial conduction. CONCLUSION: A significant difference in P-wave morphology distribution was seen between patients with early-onset, lone paroxysmal AF and age- and gender-matched healthy control subjects. This finding indicates that alterations in atrial electrophysiology are common in the early stage of the arrhythmia, and since it occurs in young patients without co-morbidity may well be the cause rather than the consequence of AF.

Left ventricular mechanical dispersion in a general population: Data from the Akershus Cardiac Examination 1950 study.

AIMS: Increased left ventricular mechanical dispersion by 2D speckle tracking echocardiography predicts ventricular arrhythmias in ischaemic heart disease and heart failure. However, little is known about mechanical dispersion in the general population. We aimed to study mechanical dispersion in the general population and in diseases associated with increased risk of cardiovascular disease. METHODS AND RESULTS: The present cross-sectional study consists of 2529 subjects born in 1950 included in the Akershus Cardiac Examination (ACE) 1950 study. Global longitudinal strain (GLS) was assessed from 17 strain segments, and mechanical dispersion calculated as the standard deviation of contraction duration of all segments. The cohort was divided according to the median value of mechanical dispersion, and multivariable linear regression models were performed with mechanical dispersion as the dependent variable. The prevalence of coronary artery disease (CAD), hypertension, obesity, and diabetes (P < 0.01 for all) was significantly higher in subjects with supra-median mechanical dispersion. In a multivariable clinical model, CAD (B = 7.05), hypertension (B = 4.15; both P < 0.001), diabetes (B = 3.39), and obesity (B = 1.89; both P < 0.05) were independently associated with increasing mechanical dispersion. When echocardiographic indices were added to the multivariable model, CAD (B = 4.38; P < 0.01) and hypertension (B = 2.86; P < 0.001) remained significant in addition to peak early diastolic tissue velocity e' (B = -2.00), GLS (B = 1.68), and ejection fraction (B = 0.22; P < 0.001 for all). CONCLUSION: In a general middle-aged population, prevalent CAD and hypertension were associated with increasing mechanical dispersion, possibly indicating elevated risk of fatal arrhythmias and sudden cardiac death. Albeit weaker, systolic and diastolic dysfunction, were also associated with increasing mechanical dispersion.

Carotid Atherosclerosis is Associated with Middle Cerebral Artery Pulsatility Index.

BACKGROUND AND PURPOSE: Pulsatility index (PI) in the middle cerebral artery (MCA) is considered a measure of peripheral vascular resistance. Several established cardiovascular risk factors are common for both MCA PI and carotid atherosclerosis. Accordingly, in the present study we hypothesized an association between ultrasound-derived indices of carotid atherosclerosis and MCA PI. METHODS: All residents in Akershus County, born in 1950, were invited to a cardiovascular examination, The Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). A thorough ultrasound examination was performed to assess indices of atherosclerosis in the carotid arteries, and PI in the MCAs. In all, 3154 (85.1%) had adequate transcranial and carotid data. Associations between indices of carotid atherosclerosis and MCA PI were assessed by regression analyses adjusted for established cardiovascular risk factors. RESULTS: Mean age was 64 (standard deviation [SD]: .6) years, and 1,357 (43%) were women. Mean MCA PI was .97 (SD: .17). Participants in the upper quartile of MCA PI had higher pulse pressure, more frequently hypertension, diabetes mellitus, and a history of coronary artery disease. Both carotid plaque score (B .007 [95% CI: .003-.010]) and carotid intimamedia thickness (B .173 [95% CI: .120-.226]) were significantly associated with MCA PI in adjusted analysis. The model R2 was .055. CONCLUSION: In a population-based sample of middle-aged adults, ultrasound-derived indices of carotid atherosclerosis were independently associated with MCA PI. However, the overall explained variance of MCA PI was low, suggesting other factors than atherosclerosis and cardiovascular risk factors to play an important role for MCA PI.

Sex differences and higher upper normal limits for left atrial end-systolic volume in individuals in their mid-60s: data from the ACE 1950 Study.

AIMS: The current study aimed to describe normal values of left atrial (LA) volumes and LA emptying fraction (LAEF) in a large sample in their mid-60s from the general population and to explore sex differences. METHODS AND RESULTS: In the Akershus Cardiac Examination (ACE) 1950 Study, body surface area-indexed LA maximum (LAVimax) and minimum (LAVimin) volumes and LAEF were measured in 3489 individuals aged 63.9 ± 0.6 years from the general population. A healthy group of 832 individuals was defined. Data are presented as mean ± standard deviation (SD) and a normal range of mean ± 2 SD. T-tests were used for comparisons. In the healthy group, mean LAVimax was 25.5 ± 6.2 mL/m2 and the normal range was 13.1-37.9 mL/m2. Men had significantly larger body surface area-indexed volumes than women, but there was no difference in LAEF. The mean LAVimax for healthy men was 26.4 ± 6.5 mL/m2, for healthy women 24.9 ± 5.8 mL/m2 (P < 0.001) and the upper normal limits were 39.4 and 36.5 mL/m2, respectively. In the healthy group, 13.0% of all men and 5.4% of all women had LAVimax above the current upper normal limit of 34 mL/m2. CONCLUSION: A large proportion of healthy individuals, in particular men, had LAVimax >34 mL/m2. Our findings suggest that the recommended cut-off may be too low at the age of 65 years and above and that sex-specific cut-offs should be considered.

Impact of atrial fibrillation on NT-proBNP levels in a 75-year-old population.

OBJECTIVE: The objective of this study was to investigate the impact of atrial fibrillation (AF) on serum levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a 75-year-old population. METHODS: All 75-year-old citizens in Asker and Baerum counties in Norway were invited to participate in a prevalence study of AF. Blood samples for measurement of NT-proBNP were collected at rest from 61 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. NT-proBNP was measured in serum using the Elecsys proBNP sandwich immunoassay (Roche Diagnostics, Basel, Switzerland). RESULTS: Subjects with permanent AF had higher levels of NT-proBNP (median 1119 pg/mL (interquartile range 701, 1643)) than subjects with paroxysmal AF (257 pg/mL (169, 382)) and controls (95 pg/mL (60, 171)), p<0.001 for both.The presence of AF was still significantly associated with higher log NT-proBNP (B=0.61, p<0.001) after adjusting for the presence of heart failure, coronary heart disease and hypertension. CONCLUSION: In this stable, out-of-hospital population of 75-year-old subjects, AF was independently associated with increased levels of NT-proBNP. Permanent AF was associated with higher NT-proBNP levels than paroxysmal AF.

Blood pressure at age 40 predicts carotid atherosclerosis two decades later: data from the Akershus Cardiac Examination 1950 Study.

OBJECTIVE: We assessed the impact of a single time-point measurement of SBP, DBP and pulse pressure at the age of 40, on carotid plaque burden, echolucent plaques and carotid intima-media thickness late midlife. METHODS: Individuals participating in two separate studies, 23 years apart, defined our cohort (n = 2714). 'The Age 40 Program', a nationwide Norwegian cardiovascular screening survey, performed 1985-1999, assessed cardiovascular risk factors and lifestyle variables at age 40. 'The ACE 1950 Study', a population-based cohort study on individuals born in 1950, performed 2012-2015, included ultrasound examinations of the carotid arteries. Blood pressure (BP) determinants of carotid atherosclerosis were assessed by regression models adjusted for cardiovascular risk factors at age 40, and late midlife BP. RESULTS: The participants, 50.3% women, had a mean age of 40 (SD 0.3) years in the first study, and 64 (SD 0.6) years in the second. At age 40, mean SBP was 128 (SD 14) mmHg, mean DBP was 78 (SD 10) mmHg and mean pulse pressure was 50 (SD 9) mmHg. SBP and DBP at age 40 predicted carotid plaque burden in late midlife. Only DBP predicted echolucent plaques, and none of the BP components predicted carotid intima-media thickness. CONCLUSION: A single time-point measurement of SBP and DBP at age 40 is associated with carotid plaque burden late midlife, also after adjustment for other cardiovascular risk factors at age 40, and of late midlife BP. Our findings emphasize the strong association between BP and atherosclerosis.

Prevalence of abnormal glucose metabolism in atrial fibrillation: a case control study in 75-year old subjects.

BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing world wide and amongst factors that aggravate the risk is diabetes mellitus (DM), also in epidemic development.However, although DM is a potentially modifiable risk factor for AF, few, if any, studies have explored the prevalence of undiagnosed dysglycaemia among subjects with AF or if duration of AF are related to parameters of glycaemia or dysglycaemia prevalence. METHODS: In this case control study, amongst 75-year old subjects with and without AF, the prevalence of dysglycaemia, i.e., impaired fasting glycaemia, impaired glucose tolerance or DM, according to World Health Organisation criteria was assessed by a 75-g oral glucose tolerance test (OGTT). RESULTS: Prevalence of undiagnosed DM among the 108 subjects (male/female 73/35, BMI 25.4 +/- 3.2) without and the 46 (male/female 34/12, BMI 25.3 +/- 3.7) with AF (median AF duration five years) where 3.7% and 13.0%, respectively (p = 0.031, Odds ratio (OR) 3.86 (95% Confidence interval [CI]: 1.01, 16.25)) whereas the overall prevalence of dysglycaemia (prediabetes and DM) where similar (respectively 43.5% and 39.1%, p = 0.46, OR 0.83 [95% CI: 0.41, 1.69]). Patients with AF duration >or= 5 years had however a higher dysglycaemia prevalence (61.1% [DM 22.2%, prediabetes 38.9%]) as compared to AF duration < 5 years (25% [DM 7.1%, prediabetes 17.9%], p = 0.0014, OR 4.7 [95% CI: 1.30, 16.90]) or no AF (p = 0.17, OR 2.04 [95% CI: 0.73, 5.66]). There was also a significant correlation between the duration of AF and HbA1c (r = 0.408, p = 0.005) and fasting glucose levels (r = 0.353, p = 0.016). CONCLUSION: AF is associated with chronic hyperglycaemia amongst 75-year old subjects. Prediabetes and DM should be pro-actively assessed if AF duration >or= 5 years.