The association between GRACE score at admission for myocardial infarction and the incidence of sudden cardiac arrests in long-term follow-up - the MADDEC study.

Background. Sudden cardiac arrest (SCA), often also leading to sudden cardiac death (SCD), is a common complication in coronary artery disease. Despite the effort there is a lack of applicable prediction tools to identify those at high risk. We tested the association between the validated GRACE score and the incidence of SCA after myocardial infarction. Material and methods. A retrospective analysis of 1,985 patients treated for myocardial infarction (MI) between January 1st 2015 and December 31st 2018 and followed until the 31st of December of 2021. The main exposure variable was patients' GRACE score at the point of admission and main outcome variable was incident SCA after hospitalization. Their association was analyzed by subdistribution hazard (SDH) model analysis. The secondary endpoints included SCA in patients with no indication to implantable cardioverter-defibrillator (ICD) device and incident SCD. Results. A total of 1985 patients were treated for MI. Mean GRACE score at baseline was 118.7 (SD 32.0). During a median follow-up time of 5.3 years (IQR 3.8-6.1 years) 78 SCA events and 52 SCDs occurred. In unadjusted analyses one SD increase in GRACE score associated with over 50% higher risk of SCA (SDH 1.55, 95% CI 1.29-1.85, p < 0.0001) and over 40% higher risk for SCD (1.42, 1.12-1.79, p = 0.0033). The associations between SCA and GRACE remained statistically significant even with patients without indication for ICD device (1.57, 1.30-1.90, p < 0.0001) as well as when adjusting with patients LVEF and omitting the age from the GRACE score to better represent the severity of the cardiac event. The association of GRACE and SCD turned statistically insignificant when adjusting with LVEF. Conclusions. GRACE score measured at admission for MI associates with long-term risk for SCA.

What is already known about this subject?Nearly 50% of cardiac mortality is caused by sudden cardiac death, often due to sudden cardiac arrest.Despite the effort, there is a lack of applicable prediction tools to identify those at high risk.What does this study add?This study shows that GRACE score measured at the point of admission for myocardial infarction can be used to evaluate patients' risk for sudden cardiac arrest in a long-term follow-up.How might this impact on clinical practice?Based on our findings, the GRACE score at the point of admission could significantly affect the patients' need for an ICD device after hospitalization for MI and should be considered as a contributing factor when evaluating the patients' follow-up care.

Ventricular Arrhythmias and Hemodynamic Collapse During Acute Coronary Syndrome- Increased Risk for Sudden Cardiac Death?

AIM: In acute phase of acute coronary syndrome (ACS), ventricular tachycardia (VT) and/or ventricular fibrillation (VF) leading to resuscitation are not considered to be associated with increased long-term sudden cardiac death (SCD) because the cause - acute ischemia - is believed to be reversible.Aim of this study was to investigate whether ventricular arrhythmias leading to sudden cardiac arrest during ACS associate with the risk of incident SCD in patients with normal or mildly impaired left ventricular ejection fraction (LVEF). METHODS: This study is based on a retrospective analysis of all 8,062 consecutive ACS patients undergoing coronary angiography with baseline LVEF ≥40% between 2007-2018 (follow-up until December 31st, 2021). The primary outcome was SCD equivalent life-threatening ventricular arrhythmias (LTVA) composing of true SCDs, aborted SCDs by successful resuscitation or appropriate ICD therapy. The risk of sudden LTVA was estimated with multivariate subdistribution hazard model using other deaths as competing events. RESULTS: Two-hundred and thirteen (n=211, 2.6%) patients suffered acute phase VF/VT leading to resuscitation and survived to discharge and most happened before angiography (80.6%, N=170) and were VF (92.9%, N=196). During a median follow-up of 7.6 years, 3.9% (N=316) of all the patients had LTVA (10.0% in VF/VT group vs 3.8% in other patients). VF/VTs during ACS associated with an increased risk for future SCD (HR 3.07; 95% CI 1.94-4.85, p<0.001). Most LTVAs occurred in patients without ICDs. CONCLUSIONS: VF/VT in ACS associates with remarkably high long-term risk for SCD in patients with LVEF ≥40%.

This retrospective study comprising of over 8,000 patients without significant heart failure after acute coronary syndrome indicates that patients with potentially fatal ventricular arrhythmias during hospitalization for acute coronary syndrome are at 3-fold risk of sudden cardiac death or equivalent events in long-term when compared to those without ventricular arrhythmias Further study is required to confirm our findings and to assess whether electrophysiological examination or implantable cardioverter defibrillator therapy could be useful to prevent sudden cardiac death in these patients.

The incidence of atrial fibrillation, new oral anticoagulation, stroke, and significant bleeds in patients receiving a new dual-chamber pacemaker.

Background and objectives: Atrial fibrillation and flutter (AF/AFL) can be easily detected in patients who have a dual-chamber pacemaker (PM). This can result in a high detection rate of these arrhythmias especially if patients are monitored remotely and detection limits are sensitive. Materials and methods: A single-center retrospective registry analysis of 1,285 consecutive AF/AFL and anticoagulation naïve patients from a limited geographical area undergoing implantation of a new dual-chamber PM (between 2013 and 2019). Seven-year follow-up data for incident AF/AFL, initiation of new oral anticoagulation and for incident strokes and bleeds was obtained from an in-depth review of all relevant patient records including written medical records and death certificates detailing causes of death. Results: During the follow-up, mortality reached 22.2 % and cumulative incidence of AF/AFL, new anticoagulation, strokes, and bleeds were 52.6 %, 40.4 %, 4.7 % and 10.4 %. In 92.6 % of the cases, AF/AFL was discovered by PM. Remote monitoring was initiated in 67 % (n = 856). Risk factor adjusted mortality in this group was significantly lower when compared to patients in regular out-patient clinic controls (HR 0.45, 95 % CI 0.35-0.57). Despite of their better overall prognosis, the AF/AFL was discovered, and oral anticoagulation was initiated more often in remote monitoring group (HR 1.58, 95 % CI 1.23-1.79 for AF/AFL and HR 1.67, 95 % CI 1.33-2.09 for anticoagulation). There was no significant difference in the incidence of strokes or bleeds. Conclusions: The incidence of new AF/AFL is high in this population. Remote monitoring is associated with higher diagnostic yields of AF/AFL and initiated anticoagulation, but not with stroke and significant bleeds.

Psoas muscle quantified muscle status and long-term mortality after cardiovascular interventions.

RESULTS: In the meta-analysis, psoas muscle measurements were significantly associated with mortality among men (p < 0.05), with high heterogeneity in the associations across all cohorts. There was very little difference in the association between PMA and PMD and mortality (HR 0.83, 95% CI 0.69-0.99, p = 0.002; HR 0.85, 95% CI 0.77-0.94, p = 0.041 for one SD increase in PMA and PMD in the random effects model). Combining PMA and PMD into one composite variable by multiplying their values together showed the most robust association in terms of the magnitude of the effect size in men (HR, 0.77; 95% CI 0.73-0.87, p < 0.001). Indexing PMA to body size did not result in any significant differences in this association. Among women, psoas muscle measurements were not associated with long-term mortality in this meta-analysis. CONCLUSIONS: Different psoas muscle measurements were significantly and very similarly associated with mortality among men but not among women. No single measurement stands out, although combining PMA and PMD seems to be a slightly stronger estimate in terms of effect size and should be considered in further studies.

Significant sarcopenia affecting survival in patients undergoing heavy invasive operations may be preoperatively assessed using images of psoas muscle (PM) from routine computerized tomography but the optimal method for evaluation is unclear. A meta-analysis of individual participant data of over two thousand patients undergoing cardiovascular interventions shows that different PM measurements of surface area and density were significantly and very similarly associated with mortality among men but not among women. Combining PM area with PM density to one estimate of lean psoas muscle area seems to provide the strongest hazard estimate among men.

The Association Between Digoxin Use and Long-Term Mortality After Acute Coronary Syndrome.

Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have been conflicting. This study assessed the association between digoxin use and all-cause mortality using comprehensive health data of patients treated for acute coronary syndrome (ACS). This was a retrospective analysis of 8,388 consecutive ACS patients treated in Tays Heart Hospital between 2007 and 2017, with a follow-up until the end of 2018. The adjusted Cox regression model was used to analyze the association between digoxin treatment and all-cause mortality with and without the inverse probability of treatment weighting (IPTW) method. IPTW was applied to estimate the residual confounding by the treatment selection. Clinical phenotype data were collected from various sources, including a prospectively updated online database maintained by physicians. The median follow-up time was 6.0 years (interquartile range 3.5 to 9.0 years). During the follow-up, 30.8% (n = 2,580) of the patients died. Altogether, 4.0% (n = 333) of the patients were treated with digoxin during hospitalization. In the Cox regression model, digoxin associated with increased mortality (age- and sex-adjusted hazard ratio [HR] 1.76 [1.51 to 2.05], p <0.001 and in the full risk factor-adjusted HR 1.23 [1.04 to 1.45], p = 0.016). The IPTW Cox analysis average treatment effect HR was 1.71 (1.12 to 2.62, p = 0.013), standardized average treatment effect HR was 1.35 (0.96 to 1.90, p = 0.082), and treatment effect among the treated HR was 1.32 (1.09 to 1.59, p = 0.004). In conclusion, digoxin treatment during ACS associates with increased mortality, despite adjusting for other risk factors and after accounting for factors explaining the residual confounding by selection bias.

Risk Factors for Ischemic Stroke After Acute Coronary Syndrome.

Background Stroke incidence is elevated after acute coronary syndromes (ACS). The aim of this study was to characterize risk factors related to ischemic stroke (IS) after ACS. Methods and Results We conducted a retrospective registry study based on the data of 8049 consecutive patients treated for ACS between 2007 and 2018 in Tays Heart Hospital with a follow-up until December 31, 2020. Potential risk factors were identified by in-depth review of written hospital records and causes-of-death registry data maintained by Statistics Finland. The association between individual risk factors, early-onset IS (0-30 days after ACS, n=82), and late-onset IS (31 days to 14 years after ACS, n=419) were analyzed using logistic regression and subdistribution hazard analysis. In multivariable analysis, the most substantial risk factors for early- and late-onset IS were previous stroke, atrial fibrillation or flutter, and heart failure status depicted by the Killip classification. Left ventricular ejection fraction and coronary artery disease severity were significant risk factors for early-onset IS; age and peripheral artery disease were significant risk factors for late-onset IS. The risk of early-onset IS with ≥6 CHA2DS2-VASc score points (odds ratio, 6.63 [95% Cl, 3.63-12.09]; P<0.001) was notable compared with patients with 1 to 3 points as well as the risk of late-onset IS with ≥6 points (subdistribution hazard, 6.03 [95% Cl, 3.71-9.81]; P<0.001) in comparison with patients with 1 point. Conclusions Factors related to high thromboembolic risk also predict IS risk after ACS. CHA2DS2-VASc score and its individual components are strong predictors for both early- and late-onset IS.

Incidence of sudden cardiac arrest and sudden cardiac death after unstable angina pectoris and myocardial infarction.

BACKGROUND: Sudden cardiac arrests (SCA) and sudden cardiac deaths (SCD) are believed to account for a large proportion of deaths due to cardiovascular causes. The purpose of this study is to provide comprehensive information on the epidemiology of SCAs and SCDs after acute coronary syndrome. METHODS: The incidence of SCA (including SCDs) was studied retrospectively among 10,316 consecutive patients undergoing invasive evaluation for acute coronary syndrome (ACS) between 2007 and 2018 at Tays Heart Hospital (sole provider of specialized cardiac care for a catchment area of over 0.5 million residents). Baseline and follow-up information was collected by combining information from the hospital's electronic health records, death certificate data, and a full-disclosure review of written patient records and accounts of the circumstances leading to death. RESULTS: During 12 years of follow-up, the cumulative incidence of SCAs (including SCDs) was 9.8% (0.8% annually) and that of SCDs 5.4% (0.5% annually). Cumulative incidence of SCAs in patients with ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina pectoris were: 11.9%,10.2% and 5.7% at 12 years. SCAs accounted for 30.5% (n = 528/1,732) of all deaths due to cardiovascular causes. The vast majority of SCAs (95.6%) occurred in patients without implantable cardioverter defibrillator (ICD) devices or among patients with no recurrent hospitalizations for coronary artery disease (89.1%). CONCLUSIONS: SCAs accounted for less than a third of all deaths due to cardiovascular causes among patients with previous ACS. Incidence of SCA is highest among STEMI and NSTEMI patients. After the hospital discharge, most of SCAs happen to NSTEMI patients.

Incidence of stroke and mortality due to stroke after acute coronary syndrome.

OBJECTIVES: Stroke is a known complication after myocardial infarction (MI) and it is associated with increased mortality. We aimed to establish the true cumulative incidence of stroke and its subtypes and the associated mortality in a contemporary setting among patients treated for acute coronary syndrome (ACS). MATERIALS AND METHODS: A retrospective registry study based on the data of 8,049 consecutive patients treated for ACS in a sole provider of specialized cardiac and neurologic care for a catchment area of over 0.5 million residents between 2007 and 2018. Incident strokes and their subtypes were identified by in-depth review of written hospital records, hospital discharge registry data and causes of death registry data maintained by Statistics Finland up until December 31st 2020. RESULTS: During a median follow-up of 5.8 years (IQR 3.2-9.0) 570 ACS patients suffered a stroke. The cumulative incidences of stroke for first week, first month, first year and at thirteen years were: 0.8 %, 1.1 %, 2.2 % and 10.3 %. In long-term, patients with different ACS subtypes had similar cumulative incidence of strokes, although the incidence of in-hospital strokes was highest among myocardial infarction patients. Stroke mortality rate was 32.5 % (n=185/570). The majority (88.8 %) of strokes were ischemic with the proportion being most substantial for in-hospital strokes (95.6 %). CONCLUSIONS: The risk of stroke among patients treated for ACS and the related mortality are still notable in a contemporary setting. A distinctive majority of strokes following ACS were ischemic especially early on after ACS.

Interatrial block and P terminal force in the general population - Longitudinal changes, risk factors and prognosis.

BACKGROUND: Partial and advanced interatrial block (IAB) and P terminal force (PTF) in lead V1 are markers of atrial remodeling and risk factors for atrial fibrillation (AF). There is a lack of information about constancy and possible factors influencing the development of these P-wave abnormalities. METHODS: The study sample consisted of 6058 Finnish participants (mean age 52.16 ± 14.60 years, 45.0% male) from the general population with an ECG taken in a health examination, and from 3224 of these participants, who had a re-examination 11 years later. Risk factors for incident partial and advanced IAB and PTF were studied using binomial logistic regression analysis, and the prognostic significance of these ECG changes for new AF was studied using time-varying Cox regression analysis. RESULTS: The rate of reversal to normal of the studied ECG parameters were 47.4% for partial IAB, 40.0% for advanced IAB and 79.3% for PTF. Age, male sex, hypertension, higher BMI, higher LDL cholesterol, ECG left ventricular hypertrophy, use of beta blocker, and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist were independently associated with a risk to develop incident P-wave abnormality. Partial IAB was independently associated with increased AF risk (HR 1.28 [95% CI 1.04-1.58]), as was also advanced IAB (HR 1.72 [95% CI 1.07-2.75]). CONCLUSION: Traditional cardiovascular risk factors increase the risk of a new P-wave abnormality. Partial and advanced IAB are associated with increased AF risk. Surprisingly, P-wave abnormalities are often reversible during long-term follow-up in the general population.

Prehospital Adenosine Diphosphate Receptor Blocker Use, Culprit Artery Flow, and Mortality in STEMI: The MADDEC Study.

BACKGROUND AND OBJECTIVE: The newer adenosine diphosphate (ADP) receptor blockers ticagrelor and prasugrel are superior to clopidogrel in the long-term management of acute coronary syndrome (ACS). We evaluated the acute performance (prehospital loading) of these ADP receptor blockers in a primary percutaneous coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). METHODS: In a retrospective, single-center registry study, data on all STEMI patients admitted for their first primary PCI between January 2007 and April 2020 were analyzed (n = 3218). The three ADP receptor blockers were mainly used during consecutive periods (clopidogrel 2007-2010, prasugrel 2011-2014, and ticagrelor 2014-2020), and were compared with risk factor-adjusted multivariate logistic regression for acute 3- and 7-day mortality and culprit artery flow before and after PCI. RESULTS: Of the 3218 total patients, 47.6% (n = 1532) were treated with ticagrelor, 22.1% (n = 711) were treated with prasugrel, and 30.3% (n = 975) were treated with clopidogrel. The use of ticagrelor or prasugrel as opposed to clopidogrel was associated with better culprit artery flow before PCI (odds ratio [OR] 1.21 for moderate or good flow, 95% confidence interval [CI] 1.03-1.42, p = 0.022), as well as lower acute mortality (OR 0.66 for 3-day mortality, 95% CI 0.46-0.95, p = 0.025; and OR 0.71 for 7-day mortality, 95% CI 0.52-0.98, p = 0.039). The results in regard to acute mortality were highlighted among patients with short treatment delays (disappearing with longer treatment delays; p < 0.05 for interaction). CONCLUSIONS: The newer ADP receptor blockers are associated with lower mortality and better culprit artery flow at presentation when compared with clopidogrel. There are no significant differences between the two newer drugs. As the drugs were mainly used during three consecutive periods, unmeasured confounding related to the development of cardiac care and changes in the population may contribute to the results.

Cardiorespiratory fitness and heart rate recovery predict sudden cardiac death independent of ejection fraction.

OBJECTIVE: To evaluate whether cardiorespiratory fitness (CRF) and heart rate recovery (HRR) associate with the risk of sudden cardiac death (SCD) independently of left ventricular ejection fraction (LVEF). METHODS: The Finnish Cardiovascular Study is a prospective clinical study of patients referred to clinical exercise testing in 2001-2008 and follow-up until December 2013. Patients without pacemakers undergoing first maximal or submaximal exercise testing with cycle ergometer were included (n=3776). CRF in metabolic equivalents (METs) was estimated by achieving maximal work level. HRR was defined as the reduction in heart rate 1 min after maximal exertion. Adjudication of SCD was based on death certificates. LVEF was measured for clinical indications in 71.4% of the patients (n=2697). RESULTS: Population mean age was 55.7 years (SD 13.1; 61% men). 98 SCDs were recorded during a median follow-up of 9.1 years (6.9-10.7). Mean CRF and HRR were 7.7 (SD 2.9) METs and 25 (SD 12) beats/min/min. Both CRF and HRR were associated with the risk of SCD in the entire study population (HRCRF0.47 (0.37-0.59), p<0.001 and HRHRR0.57 (0.48-0.67), p<0.001 with HR estimates corresponding to one SD increase in the exposure variables) and with CRF, HRR and LVEF in the same model (HRCRF0.60 (0.45-0.79), p<0.001, HRHRR0.65 (0.51-0.82), p<0.001) or adjusting additionally for all significant risk factors for SCD (LVEF, sex, creatinine level, history of myocardial infarction and atrial fibrillation, corrected QT interval) (HRCRF0.69 (0.52-0.93), p<0.01, HRHRR0.74 (0.58-0.95) p=0.02). CONCLUSIONS: CRF and HRR are significantly associated with the risk of SCD regardless of LVEF.

A geospatial model to determine the spatial cost-efficiency of anticoagulation drug therapy: Patients' perspective.

Most atrial fibrillation (AF) patients need anticoagulation management to reduce the risk of thromboembolic events and stroke. Currently, two major drug therapies are available: warfarin and direct oral anticoagulant (DOAC). This study examined the spatial costs of these therapies and derived the least-cost market areas for both therapies in the study area. The concepts of spatial costs and the principles of forming market areas were used as theoretical starting points, and the patients' travel, time-loss, and medication cost parameters combined with geographical information systems methods were incorporated into the geospatial model. Results showed that for AF patients who live near the international normalized ratio (INR) monitoring sample collection point and have less than 15 annual INR monitoring visits, warfarin therapy resulted in the lowest cost regardless of patient's travel mode and their assumed working or retirement status. If the AF patient needs more frequent INR monitoring visits or lives farther from the nearest sample collection point, DOAC would be the least costly option. The modelled results reveal the variety and importance of patients' cost of time loss and travel costs when a physician selects the appropriate anticoagulation therapy.

Modeling patients' time, travel, and monitoring costs in anticoagulation management: societal savings achievable with the shift from warfarin to direct oral anticoagulants.

BACKGROUND: Anticoagulation therapy is used for atrial fibrillation (AF) patients for reducing the risk of cardioembolic complications such as stroke. The previously recommended anticoagulant, warfarin, has a narrow therapeutic window, and it requires regular laboratory monitoring, unlike direct oral anticoagulants (DOAC). From a societal perspective, it is important to measure time and travel costs associated with warfarin monitoring to better compare the total therapy costs of these two alternative forms of anticoagulation management. In this study we design a georeferenced cost model to investigate societal savings achievable with the shift from warfarin to DOACs in the study region of North Karelia in Eastern Finland. METHODS: Individual-level patient data of 6519 AF patients was obtained from the regional patient database. Patients' geocoded home addresses and other GIS data were used to perform a network analysis for the optimal routes for warfarin monitoring visits. These measures of revealed accessibility were then used in the cost model to measure monetary time and travel costs in addition to direct healthcare costs of anticoagulation management. RESULTS: The share of time and travel costs in warfarin monitoring is 26.6% of the total therapy costs in our study region. With current drug retail prices in Finland, the societal expense of anticoagulation management is only 2.6% higher with DOACs than in the baseline with warfarin. However, when 25% lower distributor's prices are used, the total societal cost decreases by 13.6% with DOACs. CONCLUSIONS: Our results indicate that patients' time and travel costs critically increase the societal cost of warfarin therapy; and despite the higher price of DOACs, they are already cost-efficient alternatives to warfarin in anticoagulation management. In the future, the cost of AF complications should be included in the cost comparison between warfarin and DOACs. Our modeling approach applies to different geographical regions and to different healthcare processes requiring patient monitoring.

Extensive phenotype data and machine learning in prediction of mortality in acute coronary syndrome - the MADDEC study.

Objective: Investigation of the clinical potential of extensive phenotype data and machine learning (ML) in the prediction of mortality in acute coronary syndrome (ACS). Methods: The value of ML and extensive clinical data was analyzed in a retrospective registry study of 9066 consecutive ACS patients (January 2007 to October 2017). Main outcome was six-month mortality. Prediction models were developed using two ML methods, logistic regression and extreme gradient boosting (xgboost). The models were fitted in training set of patients treated in 2007-2014 and 2017 (81%, n = 7344) and validated in a separate validation set of patients treated in 2015-2016 with full GRACE score data available for comparison of model accuracy (19%, n = 1722). Results: Overall, six-month mortality was 7.3% (n = 660). Several variables were found to be significantly associated with six-month mortality by both ML methods. The xgboost scored the best performance: AUC 0.890 (0.864-0.916). The AUC values for logistic regression and GRACE score were 0.867(0.837-0.897) and 0.822 (0.785-0.859), respectively. The AUC value of xgboost was better when compared to logistic regression (p = .012) and GRACE score (p < .00001). Conclusions: The use of extensive phenotype data and novel machine learning improves prediction of mortality in ACS over traditional GRACE score. KEY MESSAGES The collection of extensive cardiovascular phenotype data from electronic health records as well as from data recorded by physicians can be used highly effectively in prediction of mortality after acute coronary syndrome. Supervised machine learning methods such as logistic regression and extreme gradient boosting using extensive phenotype data significantly outperform conventional risk assessment by the current golden standard GRACE score. Integration of electronic health records and the use of supervised machine learning methods can be easily applied in a single centre level to model the risk of mortality.

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts.

INTRODUCTION: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. METHODS: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. RESULTS: Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. DISCUSSION: Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology.

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.

INTRODUCTION: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. METHODS: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. RESULTS: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. DISCUSSION: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.

The Finnish Prehospital Stroke Scale Detects Thrombectomy and Thrombolysis Candidates-A Propensity Score-Matched Study.

BACKGROUND: Prehospital stroke triage is challenged by endovascular treatment for large vessel occlusion (LVO) being available only in major stroke centers. Conjugate eye deviation (CED) is closely related to LVO, whereas common stroke signs (face-arm-leg-speech-visual) screen stroke. We hypothesized that combining CED with common stroke signs would yield a prehospital stroke scale for identifying both LVO and stroke in general. METHODS AND RESULTS: We retrospectively analyzed consecutive patients (n = 856) with prehospital Code Stroke (recanalization candidate). The National Institutes of Health Stroke Scale (NIHSS) and computed tomography were administered to patients on arrival. Computed tomography angiography was performed on patients with NIHSS score of 8 or greater and considered to benefit from endovascular treatment. With random forest analysis and deviance analysis of the general linear model we confirmed the superiority of the NIHSS "Best Gaze" over other NIHSS items in detecting LVO. Based on this and commonly used stroke signs we presented the Finnish Prehospital Stroke Scale (FPSS) including dichotomized face drooping, extremity weakness, speech difficulty, visual disturbance, and CED. FPSS detected LVO with a sensitivity of 54%, specificity of 91%, positive predictive value of 48%, negative predictive value of 93%, and likelihood ratio of 6.2. CONCLUSIONS: Based on CED and universally used stroke signs, FPSS recognizes stroke in general and additionally, LVO as a stroke subtype comparably to other scales intended to detect LVO only. As the FPSS items are dichotomized, it is likely to be easy for emergency medical services to implement.

High-sensitivity cardiac troponin I and NT-proBNP as predictors of incident dementia and Alzheimer's disease: the FINRISK Study.

Cardiac troponin and N-terminal pro-brain natriuretic peptide (NT-proBNP) are known to associate with incident dementia. The purpose of our study was to examine whether high-sensitivity cardiac troponin I (hs-TnI) and NT-proBNP are associated with incident dementia and Alzheimer's disease (AD) independently of each other. Our study was a part of the national population-based health examination survey, FINRISK 1997, with a total sample of 7114 subjects, including 407 incident dementia cases and 319 AD cases during the follow-up time of 18 years. Using multivariate Cox regression analyses, we calculated the hazard ratios (HR) for hs-TnI and NT-proBNP. Analyses were adjusted for the previously known dementia/AD risk factors, including the apoE genotype. NT-proBNP was independently associated with incident dementia (HR 1.32, 95% CI 1.17-1.49) and AD (HR 1.30, 95% CI 1.13-1.5). Hs-TnI was also associated with incident dementia (HR 1.12, 95% CI 1.02-1.23), but not independent of NT-proBNP (HR 1.10, 95% CI 0.99-1.21). Hs-TnI was not associated with incident AD. The results remained similar in cause-specific Cox regression models and among subjects over 40 years of age. NT-proBNP and hs-TnI improved the reclassification of dementia risk in 10 years follow-up, and hs-TNI also in 18 years of follow-up. Neither hs-TnI nor NT-proBNP was able to outperform each other in risk reclassification of dementia. Both cardiovascular biomarkers, NT-proBNP and hs-TnI, were associated with incident dementia independently of traditional dementia risk factors including the apoE genotype. NT-proBNP was also associated with AD. Both markers offered a better dementia risk reclassification compared with traditional risk factors.

Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer's disease: the National Finnish population study (FINRISK).

Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer's disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The follow-up time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely associated with incident AD risk when adjusted for competing risks of death, but the finding is unlikely to be of clinical relevance. Our study does not support the use of these risk markers to predict incident dementia or AD.

NT-proBNP and the risk of dementia: a prospective cohort study with 14 years of follow-up.

BACKGROUND: Memory disorders and Alzheimer's disease (AD) share the same risk factors with cardiovascular diseases. OBJECTIVE: We tested whether elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels would predict any incident dementia or AD. METHODS: The association between NT-proBNP and the risk of dementia was evaluated in a total of 7,158 subjects without previous memory disorders in a prospective study with a median follow-up of 13.8 years. RESULTS: A total of 220 new dementia cases occurred, of which 149 were AD. Baseline logNT-proBNP levels were associated significantly with the risk of dementia in the entire study population (HR 1.32, 95%CI 1.17-1.56, p = 0.001) per 1SD difference, adjusted for multiple cardiovascular risk factors. Integrated discrimination improvement (IDI) and continuous net-reclassification improvement (continuous NRI) were improved in the study population over 40 years of age: continuous NRI was 17.5% (95%CI 4.4-30.6%, p = 0.009) and IDI was 0.005 (95%CI 0.001-0.010, p = 0.021). Regarding AD, the HR for 1SD logNT-proBNP change was 1.23 (95%CI 1.01-1.49, p = 0.040) in the entire study population, but no IDI or continuous NRI improvement was seen. CONCLUSION: NT-proBNP is also an independent risk marker for dementia, and patient discrimination regarding dementia risk could be improved by using it.