Mika Lehto

Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation

OBJECTIVE To investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney disease and patients with IgA glomerulonephritis (IgAGN). RESEARCH DESIGN AND METHODS Serum LPS activity was determined with the Limulus Amoebocyte Lysate chromogenic end point assay in type 1 diabetic patients with a normal albumin excretion rate (n = 587), microalbuminuria (n = 144), macroalbuminuria (n = 173); patients with IgAGN (n = 98); and in nondiabetic control subjects (n = 345). The relationships of the LPS/HDL ratio and MetS-associated variables were evaluated with Pearson correlation. RESULTS The MetS was more prevalent in type 1 diabetic patients (48%) than in patients with IgAGN (15%). Diabetic patients with macroalbuminuria had a significantly higher serum LPS/HDL ratio than patients with IgAGN. In the normoalbuminuric type 1 diabetic group, patients in the highest LPS/HDL quartile were diagnosed as having the MetS three times more frequently than patients in the lowest quartile (69 vs. 22%; P < 0.001). High LPS activity was associated with higher serum triglyceride concentration, earlier onset of diabetes, increased diastolic blood pressure, and elevated urinary excretion of monocyte chemoattractant protein-1. CONCLUSIONS High serum LPS activity is strongly associated with the components of the MetS. Diabetic patients with kidney disease seem to be more susceptible to metabolic endotoxemia than patients with IgAGN. Bacterial endotoxins may thus play an important role in the development of the metabolic and vascular abnormalities commonly seen in obesity and diabetes-related diseases.

Persistent atrial fibrillation: a population based study of patients with their first cardioversion

BACKGROUND Electrical cardioversion is effective in terminating even long standing atrial fibrillation (AF), but the relapse risk of AF is high. Data on long-term success of cardioversion in real life clinical practice are scant. METHODS Restoration and maintenance of sinus rhythm as well as acceptance of permanent AF was studied in a population based cohort (catchment area with a population of 440,000) of patients with persistent AF after first elective cardioversion. RESULTS Of the 183 patients having their first electrical cardioversion during the 1-year study period, sinus rhythm was restored in 153 patients (84%). Only 39 of these (25%) maintained sinus rhythm for 1 year, even though 108 (71%) patients had anti-arrhythmic medication. Age, hypertension, coronary artery disease, heart failure and valvular disease, or absence of these known risk factors for AF were not associated with the outcome. The outcome was better if the cardioversion was performed earlier than the median delay (78 days) from the diagnosis of AF to cardioversion compared to longer delay (P=0.022 in multivariate modelling). The decision of acceptance of permanent AF was made in 74 cases (40%) during 1 year of follow-up. CONCLUSIONS Patients with persistent AF had a high tendency to remain in or relapse into AF, even though most patients had anti-arrhythmic medication after first cardioversion. Short history of arrhythmia was associated with better outcome. Acceptance of permanent AF was made in almost half of the cases during 1 year of follow-up.

Undetermined stroke with an embolic pattern—a common phenotype with high early recurrence risk

Abstract Introduction. Undetermined strokes with an embolic pattern (USEP) represent a common phenotype. We assessed their frequency and compared USEP with cardioembolic stroke with a known source and non-cardioembolic stroke etiology. Methods. Study patients were 540 consecutive ischemic stroke patients admitted to Helsinki University Hospital with primary end-point of recurrent stroke in a 21-month follow-up. Cox regression adjusting for CHA2DS2-VASc and anticoagulation estimated the risk of USEP on recurrent stroke. Results. A total of 229 (42.4%) patients had a non-cardioembolic stroke etiology, 184 (34.1%) had a cardioembolic stroke with a known source, and 127 (23.5%) were classified as USEP. USEP patients had less diabetes and prior TIA, with more severe symptoms than the non-cardioembolic stroke cases. They were younger, had fewer comorbidities, and less severe symptoms than the cardioembolic stroke patients. Cumulative risk of recurrent stroke was 10.0% (95% CI 4.1%–15.9%) for USEP, 5.0% (1.1%–8.9%) for cardioembolic strokes, and 5.0% (3.0%–7.0%) for non- cardioembolic strokes (P = 0.089). USEP associated with a higher risk of recurrent stroke compared to non-cardioembolic strokes (hazard ratio 2.36, 95% CI 1.02–5.47; P = 0.046) and cardioembolic stroke with a known source (1.83, 1.07–3.14; P = 0.028). Conclusions. Despite their younger age and more favorable risk factor profile compared with other phenotypes, USEP exhibited a high risk of stroke recurrence.

In-hospital cardiac complications after intracerebral hemorrhage

Background and purpose Data on cardiac complications and their precipitants after intracerebral hemorrhage are scarce. We examined the frequency and risk factors for serious in-hospital cardiac events in a large cohort of consecutive intracerebral hemorrhage patients. Methods A retrospective chart review of 1013 consecutive patients with nontraumatic intracerebral hemorrhage treated at the Helsinki University Central Hospital (2005–2010). We excluded patients with intraparenchymal hematoma related to sub-arachnoid hemorrhage or intracerebral hemorrhage because of fibrinolytic therapies for acute ischemic stroke or myocardial infarction. Serious in-hospital cardiac event was defined as any of in-hospital poststroke acute myocardial infarction, ventricular fibrillation or tachycardia, moderate to serious acute heart failure, or cardiac death. Results Among the 948 patients included, ≥1 serious in-hospital cardiac event occurred in 39 (4·1%) patients after a median delay of two-days from stroke onset (acute myocardial infarction in three patients, ventricular fibrillation or tachycardia in three patients, acute heart failure in 36 patients, and cardiac death in three patients). Hospital stay was longer in patients with serious in-hospital cardiac event than in those without (median 12, interquartile range 7–19 vs. 8, 3–14; P = 0·001), with no difference in in-hospital mortality (23·1% vs. 24·3%; P = 0·86). In multivariable logistic regression analysis adjusted for age, gender, and diabetes, atrial fibrillation during hospitalization (odds ratio 6·68 for new-onset atrial fibrillation, 95% confidence interval 2·11–21·18; 4·46 for old atrial fibrillation, 2·08–9·56), and history of myocardial infarction (3·20, 1·18–8·66) were independently associated with serious in-hospital cardiac events. Conclusions After intracerebral hemorrhage, 4% of patients suffer an acute serious cardiac complication. Those with history of myocardial infarction or in-hospital atrial fibrillation are at greater risk for such events.

Resting 12-lead electrocardiogram reveals high-risk sources of cardioembolism in young adult ischemic stroke.

BACKGROUND The diagnostic work-up to reveal etiology in a young ischemic stroke (IS) patient includes evaluation for high-risk source of cardioembolism (HRCE), since this subtype associates with high early recurrence rate and mortality. We investigated the association of ECG findings with a final etiologic subgroup of HRCE in a cohort of young patients with first-ever IS. METHODS The Helsinki Young Stroke Registry includes IS patients aged 15 to 49 years admitted between 1994 and 2007. Blinded to other clinical data, we analyzed a 12-lead resting ECG obtained 1-14 days after the onset of stroke symptoms in 690 patients. We then compared the ECG findings between a final diagnosis of HRCE (n=78) and other/undetermined causes (n=612). We used multivariate logistic regression to study the association between ECG parameters and HRCE. RESULTS Of our cohort (63% male), 35% showed ECG abnormality, the most common being T-wave inversion (16%), left ventricular hypertrophy (14%), prolonged P-wave (13%), and prolonged QTc (12%). 3% had atrial fibrillation (AF), and 4% P-terminal force (PTF). Of the continuous parameters, longer QRS-duration, QTc, and wider QRS-T-angle independently associated with HRCE. After AF, PTF had the strongest independent association with HRCE (odds ratio=44.32, 95% confidence interval=[10.51-186.83]), followed by a QRS-T angle >110° (8.29 [3.55-19.32]), T-wave inversion (5.06, 2.54-10.05), and prolonged QTc (3.02 [1.39-6.56]). CONCLUSION Routine ECG provides useful information for directing the work-up of a young IS patient. In addition to AF, PTF in particular showed a strong association with etiology of HRCE.

Reversal of Atrial Remodeling after Cardioversion of Persistent Atrial Fibrillation Measured with Magnetocardiography

Background: Atrial fibrillation (AF) causes electrical, functional, and structural changes in the atria. We examined electrophysiologic remodeling caused by AF and its reversal noninvasively by applying a new atrial signal analysis based on magnetocardiography (MCG).

Cardiovascular events after ischemic stroke in young adults A prospective follow-up study

Objectives: To study the long-term risk of recurrent cardiac, arterial, and venous events in young stroke patients, and whether these risks differed between etiologic subgroups. Methods: The study population comprised 970 patients aged 15–49 years from the Helsinki Young Stroke Registry (HYSR) who had an ischemic stroke in 1994–2007. We obtained follow-up data until 2012 from the Finnish Care Register and Statistics Finland. Cumulative 15-year risks were analyzed with life tables, whereas relative risks and corresponding confidence intervals (CI) were based on hazard ratios (HR) from Cox regression analyses. Results: There were 283 (29.2%) patients with a cardiovascular event during the median follow-up of 10.1 years (range 0.1–18.0). Cumulative 15-year risk for venous events was 3.9%. Cumulative 15-year incidence rate for composite vascular events was 34.0 (95% CI 30.1–38.2) per 1,000 person-years. When adjusted for age and sex, patients with an index stroke caused by high-risk sources of cardioembolism had the highest HR for any subsequent cardiovascular events (3.7; 95% CI 2.6–5.4), whereas the large-artery atherosclerosis group had the highest HR (2.7; 95% CI 1.6–4.6) for recurrent stroke compared with patients with stroke of undetermined etiology. Conclusions: The risk for future cardiovascular events after ischemic stroke in young adults remains high for years after the index stroke, in particular when the index stroke is caused by high-risk sources of cardioembolism or large-artery atherosclerosis.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients undergoing elective cardioversion

Aims Non-vitamin K antagonist oral anticoagulants (NOAC) have been shown to be safe and effective alternatives to warfarin for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF). The aim of this study was to investigate the complications and the use of NOACs in AF patients undergoing elective cardioversion. Methods and results This nationwide multicentre study included consecutive elective cardioversions in AF patients treated with NOACs between October 2011 and May 2016. Data on patient characteristics, antithrombotic treatment and acute (<30 days) complications were collected. One thousand twenty-one patients (mean age 64 years, 70% men) underwent 1291 elective cardioversions, of which 680 (52.7%) cardioversions were performed in patients using dabigatran, 431 (33.4%) rivaroxaban, and 159 (12.3%) apixaban. Mean CHA2DS2-VASc score was 1.8 (±1.5). A total of 3 thromboembolic events occurred after the cardioversion (0.2%): 1 patient receiving dabigatran experienced an ischaemic stroke on Day 2 and 1 rivaroxaban treated patient on Day 4. One patient receiving dabigatran experienced a transient ischaemic attack on Day 11. All 3 patients had used recommended doses of the NOAC. A total of 6 (0.5%) clinically relevant, but not serious bleeding events occurred. Only short duration of AF was associated with lower rate of AF recurrence. Conclusion Thrombotic and bleeding complications related to NOACs were uncommon (<0.5%) in real life AF patients undergoing elective cardioversion.

Quality of warfarin therapy and risk of stroke, bleeding, and mortality among patients with atrial fibrillation: results from the nationwide FinWAF Registry

The most important management strategy in atrial fibrillation (AF) patients is preventing stroke with oral anticoagulants. Warfarin is still used as a first‐line anticoagulant, although non‐vitamin K antagonist oral anticoagulants are currently recommended to manage AF. Using a large, unselected national sample of AF patients, we evaluated the relationships between quality of warfarin therapy and the risks of thromboembolism, bleeding complications, and mortality.

Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke

Background and Purpose— High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. Methods— The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. Results— Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7–13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P<0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP ≥160 mm Hg compared with those with SBP <160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05–4.55]; P<0.001) occurring earlier (13.9 years [13.0–14.6] versus 16.2 [15.8–16.6]; P<0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. Conclusions— In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes.