Serum Potassium Is Positively Associated With Stroke and Mortality in the Large, Population-Based Malmö Preventive Project Cohort.

BACKGROUND AND PURPOSE: Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years. METHODS: Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted. RESULTS: There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17-1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13-1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serum sodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects. CONCLUSIONS: Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.

Mild Hypokalemia and Supraventricular Ectopy Increases the Risk of Stroke in Community-Dwelling Subjects.

BACKGROUND AND PURPOSE: Stroke is independently associated with the common conditions of hypokalemia and supraventricular ectopy, and we hypothesize that the combination of excessive supraventricular ectopic activity and hypokalemia has a synergistic impact on the prognosis in terms of stroke in the general population. METHODS: Subjects (55-75 years old) from the Copenhagen Holter Study cohort (N=671) with no history of atrial fibrillation or stroke were studied-including baseline values of potassium and ambulatory 48-hour Holter monitoring. Excessive supraventricular ectopic activity is defined as ≥30 premature atrial complexes per hour or any episodes of runs of ≥20. Hypokalemia was defined as plasma-potassium ≤3.6 mmol/L. The primary end point was ischemic stroke. Cox models were used. RESULTS: Hypokalemia was mild (mean, 3.4 mmol/L; range, 2.7-3.6). Hypokalemic subjects were older (67.0±6.94 versus 64.0±6.66 years; P<0.0001) and more hypertensive (165.1±26.1 versus 154.6±23.5 mm Hg; P<0.0001). Median follow-up time was 14.4 years (Q1-Q3, 9.4-14.7 years). The incidence of stroke was significantly higher in the hypokalemic group (hazard ratio, 1.84; 95% confidence interval, 1.04-3.28) after covariate adjustments, as well as in a competing risk analysis with death (hazard ratio, 1.51; 95% confidence interval, 1.12-2.04). Excessive supraventricular ectopic activity was also associated with stroke (hazard ratio, 2.23; 95% confidence interval, 1.33-3.76). The combination of hypokalemia and excessive supraventricular ectopic activity increased the risk of events synergistically. Stroke rate was 93 per 1000 patient-year (P<0.0001) in this group (n=17) compared with 6.9 (n=480); 11 (n=81), and 13 (n=93) per 1000 patient-year in the groups without the combination. CONCLUSIONS: The combination of hypokalemia and excessive supraventricular ectopy carries a poor prognosis in terms of stroke.

Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study.

AIMS: The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. METHODS AND RESULTS: A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 ± 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. CONCLUSION: Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP.

Ambulatory cardiac arrhythmias in relation to mild hypokalaemia and prognosis in community dwelling middle-aged and elderly subjects.

AIMS: Severe hypokalaemia can aggravate arrhythmia tendency and prognosis, but less is known about risk of mild hypokalaemia, which is a frequent finding. We examined the associations between mild hypokalaemia and ambulatory cardiac arrhythmias and their prognosis. METHODS AND RESULTS: Subjects from the cohort of the 'Copenhagen Holter Study' (n = 671), with no history of manifest cardiovascular (CV) disease or stroke, were studied. All had laboratory tests and 48-h ambulatory electrocardiogram (ECG) recording. The median follow-up was 6.3 years. p-Potassium was inversely associated with frequency of premature ventricular complexes (PVCs) especially in combination with diuretic treatment (r = -0.22, P = 0.015). Hypokalaemia was not associated with supraventricular arrhythmias. Subjects at lowest quintile of p-potassium (mean 3.42, range 2.7-3.6 mmol/L) were defined as hypokalaemic. Cardiovascular mortality was higher in the hypokalaemic group (hazard ratio and 95% confidence intervals: 2.62 (1.11-6.18) after relevant adjustments). Hypokalaemia in combination with excessive PVC worsened the prognosis synergistically; event rates: 83 per 1000 patient-year in subjects with both abnormalities, 10 and 15 per 1000 patient-year in those with one abnormality, and 3 per 1000 patient-year in subjects with no abnormality. One variable combining hypokalaemia with excessive supraventricular arrhythmias gave similar results in univariate analysis, but not after multivariate adjustments. CONCLUSION: In middle-aged and elderly subjects with no manifest heart disease, mild hypokalaemia is associated with increased rate of ventricular but not supraventricular arrhythmias. Hypokalaemia interacts synergistically with increased ventricular ectopy to increase the risk of adverse events.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease.

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects served as controls. In univariate analysis CAD-subjects had higher median baseline NT-pro-BNP-levels (85.3 ng/L) compared with non-CAD-subjects (41.3 ng/L) and controls (40.1 ng/L), both p < 0.001, but the association disappeared in multivariate analysis adjusted for age and gender. NT-pro-BNP increased similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p < 0.0001. Median ΔcTnT (baseline to 20 h after exercise) was higher in CAD-subjects than non-CAD-subjects and controls (0.62 ng/L vs. 0.0 ng/L, p < 0.001). A linear relationship between ΔcTnT and 'percent of predicted maximal heart rate achieved' was found in subjects with ≥ 70% stenosis (n = 24, r = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP.

Infectious Aortitis: Could Early Radiology Improve Patient Outcome?

Aortitis is a rare condition and easily overlooked. It is defined as infectious or non-infectious inflammation of the aortic wall. This report describes two cases of aortitis, demonstrating the diagnostic difficulty and how diagnostic delay could have been reduced if early radiology had been performed. Due to the nature of aortitis, patient outcome can be improved considerably by timely diagnosis and treatment. LEARNING POINTS: Aortitis is rarely suspected due to its vague symptoms, but diagnosis is aided by computed tomography (CT) of the thorax and abdomen.A delay in aortitis diagnosis can be life threatening; however, early radiology can ensure timely diagnosis and considerably improve patient outcome.Aortitis should always be suspected in cases with immunosuppression and systemic Salmonella infection, and a CT of the thorax and abdomen should be performed.

2706 km cycling in 2 weeks: effects on cardiac function in 6 elderly male athletes.

OBJECTIVES: Physiological effects of exercise on trained and untrained individuals have been studied extensively. Typically, young or middle-aged individuals are examined before and after short periods of vigorous exertion. METHODS: We studied 6 elderly male athletes (61 ± 8 years (mean ± SD); baseline [Formula: see text]O2max 48 ± 5 ml·kg-1·min-1) with focus on cardiac function and biomarkers following 14 consecutive days of moderate intensity exercise. Cardiac dimensions, function, biomarkers, and other measures of cardiovascular health were examined at baseline and 2 and 28 h after the last day of cycling a total of 2706 km. RESULTS: Data collected after the cessation of exercise on the 14th day revealed significant increases in average size of the left atrium (3.5 ± 0.4 to 4.0 ± 0.3 cm; p = 0.02) and left ventricular end systolic volume (47 ± 2 to 52 ± 5 ml; p = 0.004), with no other significant changes in cardiac size or function. Small, transient increases in cardiac biomarkers (troponin T, creatine kinase myocardial band, and N-terminal pro-brain natriuretic peptide) (p < 0.01) were observed 2 h after completion of cycling but no changes in systolic (including strain-analyses) or diastolic cardiac function were observed at rest. [Formula: see text]O2max was significantly lower at the 28 h time point than at baseline (p < 0.02). Plasma concentrations of total- (p < 0.01) and low-density lipoprotein-cholesterol (p < 0.01) were markedly lower after exercise. Systolic blood pressure was unchanged, but diastolic pressure was significantly lower after exercise than at baseline. CONCLUSIONS: The results suggest that repeated moderate intensity exercise in elderly men was associated with a transient increase in cardiac biomarkers while cardiac function remained unaltered. A favorable reduction in blood lipids and diastolic blood pressure were seen for >28 h after the end of activity. An unexplained symptomless severe plasma hyponatremia developed in 3 of 6 subjects 28 h after the end of activity.

Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population-A Prospective Population Study.

BACKGROUND: Potassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population. METHODS: Participants (aged 48-76 years) from the general population study "Copenhagen City Heart Study" (n = 5916) were studied. Participants were divided into groups according to baseline values of plasma potassium (potassium): hypokalemia (<3.7 mmol/L, n = 758), normokalemia (3.7-4.5 mmol/L, n = 4973), and high potassium (>4.5 mmol/L, n = 185). Hypokalemia was further divided as potassium <3.4 mmol/L and 3.4-3.6 mmol/L. The primary endpoints were all-cause mortality and nonfatal validated ischemic stroke. The secondary endpoint was acute myocardial infarction (AMI). We adjusted for conventional risk factors, diuretics, and atrial fibrillation at baseline. RESULTS: Mean potassium in the hypokalemic group was 3.5 mmol/L (range, 2.6-3.6 mmol/L) and was associated (P < 0.05) with increased systolic blood pressure, higher CHA2DS2-VASc score, and increased use of diuretics as compared with normokalemia. Baseline atrial fibrillation was equally frequent across groups. Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was borderline associated with increased stroke risk in a multivariable Cox model (including adjustment for competing risk) as compared with normokalemia (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.00-1.98). The subgroup with potassium <3.4 mmol/L had higher stroke risk (HR 2.10; 95% CI, 1.19-3.73) and mortality risk (HR 1.32; 95% CI, 1.01-1.74) as compared with normokalemia. Hypokalemia was not associated with AMI, and no increased risk of mortality was seen with concomitant AMI and hypokalemia. No associations were seen with high potassium. CONCLUSION: In a general population mild hypokalemia is associated with increased stroke risk and, to a lesser degree, increased mortality risk.

Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men.

INTRODUCTION/PURPOSE: Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 ± 4 yr; V˙O2max, 48 ± 2 mL·kg·min) after repeated prolonged exercise). METHODS: A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. V˙O2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. RESULTS: The daily duration of exercise was 10 h and 31 ± 37 min, and the mean intensity was 53% ± 1% of V˙O2max. Body weight remained unchanged. V˙O2max and maximal fat oxidation rate decreased by 6% ± 2% (P = 0.04) and 32% ± 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 ± 77 µmol·L to 160 ± 38 µmol·L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and ß-hydroxy-acyl-CoA-dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. CONCLUSIONS: Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise.

Improvement of clinical quality indicators through reorganization of the acute care by establishing an emergency department-a register study based on data from national indicators.

BACKGROUND: The Emergency Departments (EDs) reorganization process in Denmark began in 2007 and includes creating a single entrance for all emergency patients, establishing triage, having a specialist in the front and introducing the use of electronic overview boards and electronic patient files. The aim of this study was to investigate the quality of acute care in a re-organized ED based on national indicator project data in a pre and post reorganizational setting. METHODS: Quasi experimental design was used to examine the effect of the health care quality in relation to the reorganization of an ED. Patients admitted at Nykøbing Falster Hospital in 2008 or 2012 were included in the study and data reports from the national databases (RKKP) regarding stroke, COPD, heart failure, bleeding and perforated ulcer or hip fracture were analysed. Holbæk Hospital works as a control hospital. Chi-square test was used for analysing significant differences from pre-and post intervention and Z-test to compare the experimental groups to the control group (HOL). P < 0.05 was considered statistically significant. RESULTS: We assessed 4584 patient cases from RKKP. A significant positive change was seen in all of the additional eight indicators related to stroke at NFS (P < 0.001); however, COPD indicators were unchanged in both hospitals. In NFS two of eight heart failure indicators were significantly improved after the reorganization (p < 0.01). In patients admitted with a bleeding ulcer 2 of 5 indicators were significantly improved after the reorganization in NFS and HOL (p < 0.01). Both compared hospitals showed significant improvements in the two indicators concerning hip fracture (p < 0.001). Significant reductions in the 30 day-mortality in patients admitted with stroke were seen when the pre- and the post-intervention data were compared for both NFS and HOL (p = 0.024). CONCLUSIONS: During the organisation of the new EDs, several of the indicators improved and the overall 30 days mortality decreased in the five diseases. The development of a common set of indicators for monitoring acute treatment at EDs in Denmark is recommended.

High-sensitivity C-reactive protein and exercise-induced changes in subjects suspected of coronary artery disease.

BACKGROUND: Inflammation plays a major role in the development of atherosclerosis. We wanted to investigate the effects of exercise on high-sensitivity (hs) C-reactive protein (CRP) in subjects who were suspected of having coronary artery disease (CAD). METHODS: Blood samples were obtained before, 5 minutes after, and 20 hours after an exercise test in 155 subjects who were suspected of CAD. Coronary anatomy was evaluated by computed tomography coronary angiography and/or coronary angiography. RESULTS: Median baseline hs-CRP was higher in subjects with ≥50% coronary artery lumen diameter stenosis (n=41), compared with non-CAD-subjects (n=114), 2.93 mg/L (interquartile range 1.03-5.06 mg/L) and 1.30 mg/L (interquartile range 0.76-2.74 mg/L), respectively, P=0.007. In multivariate analyses testing conventional risk factors, hs-CRP proved borderline significant, odds ratio =2.32, P=0.065. Adding baseline hs-CRP to the results of the exercise test did not improve the diagnostic evaluation. Baseline natural logarithm (Ln) hs-CRP was positively associated with body mass index and baseline Ln-transformed hs troponin T levels, and negatively associated with the daily life activity level. An increase in hs-CRP of 0.13 mg/L (interquartile range 0.05-0.24 mg/L) from baseline to 5 minutes after peak exercise was found (P<0.0001), but the increase was not associated with presence of CAD. From baseline to 20 hours after exercise, no increase in hs-CRP was found. CONCLUSION: In conclusion, hs-CRP was not independently associated with CAD. Hs-CRP increased immediately as a response to the exercise, and the increase was modest and not associated with CAD. The results indicate that exercise has potential to cause unwanted variations in hs-CRP and that exercise prior to hs-CRP measurements in subjects included in epidemiological studies, therefore, should be avoided.

[Extreme levels of hyperlipidaemia as a cause of acute pancreatitis]. / Ekstrem hyperlipidaemi ved akut pankreatitis.

Hypertriglyceridaemia is an uncommon cause of acute pancreatitis, accounting for 1-4% of cases. In the case of lipoprotein-lipase mutations, lipid levels may rise to extreme levels during acute pancreatitis. In this case a 29-year-old female was hospitalized several times due to acute pancreatitis. She presented with extreme lipid levels and difficulty in blood testing. While the correlation of acute pancreatitis and hyperlipidaemia is known, awareness of its association with defects in lipid metabolism could, in this case, have furthered diagnostic and prevented repeated hospitalizations.