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  • Tuohinen, Suvi Sirkku; Rankinen, Jani; Skyttä, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka; Nikus, Kjell (2018)
    Background: ST segment depression (STD) and T wave inversion (TWI) are typical electrocardiographic (ECG) findings in non-ST elevation myocardial infarction (NSTEMI). In ST elevation myocardial infarction, ST changes represent transmural ischemia. The pathophysiological mechanisms of the ECG changes in NSTEMI are unclear. Purpose: We studied the associations between ECG and the echocardiographic findings in NSTEMI patients. Methods: Twenty patients with acute NSTEMI were recruited during their hospital stay. A comprehensive echocardiography study was performed. The findings were compared with blinded ECG analyses. Results: Nine (45%) patients had STD, and 16 (85%) patients had TWI. In multivariable analysis, STD was independently associated with a lower global early diastolic strain rate (beta=-5.061, p=0.033). TWI was independently associated with lower circumferential strain (beta=0.132, p =0.032). Conclusions: The typical ECG changes in NSTEMI patients were associated with subtle echocardiographic changes. STD was related to changes in diastolic function, and TWI was associated with systolic deterioration. (C) 2017 Elsevier Inc. All rights reserved.
  • Itkonen, Matti K.; Tornio, Aleksi; Filppula, Anne M.; Neuvonen, Mikko; Neuvonen, Pertti J.; Niemi, Mikko; Backman, Janne T. (2018)
    The oxidation of montelukast is mainly mediated by cytochrome P450 (CYP) 2C8, but other mechanisms may contribute to its disposition. In healthy volunteers, we investigated the effects of two widely used P2Y(12) inhibitors on montelukast pharmacokinetics. Clopidogrel (300mg on day 1 and 75mg on day 2) increased the area under the plasma concentration-time curve (AUC) of montelukast 2.0-fold (90% confidence interval (CI) 1.72-2.28, P <0.001) and decreased the M6:montelukast AUC(0-7h) ratio to 45% of control (90% CI 40-50%, P <0.001). Prasugrel (60mg on day 1 and 10mg on day 2) had no clinically meaningful effect on montelukast pharmacokinetics. Our results imply that clopidogrel is at least a moderate inhibitor of CYP2C8, but prasugrel is not a clinically relevant CYP2C8 inhibitor. The different interaction potentials of clopidogrel and prasugrel are important to consider when antiplatelet therapy is planned for patients at risk for polypharmacy with CYP2C8 substrates.
  • Salo, Perttu P.; Vaara, Satu; Kettunen, Johannes; Pirinen, Matti; Sarin, Antti-Pekka; Huikuri, Heikki; Karhunen, Pekka J.; Eskola, Markku; Nikus, Kjell; Lokki, Marja-Liisa; Ripatti, Samuli; Havulinna, Aki S.; Salomaa, Veikko; Palotie, Aarno; Nieminen, Markku S.; Sinisalo, Juha; Perola, Markus (2015)
    Myocardial infarction (MI) is divided into either ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI), differing in a number of clinical characteristics. We sought to identify genetic variants conferring risk to NSTEMI or STEMI by conducting a genome-wide association study (GWAS) of MI stratified into NSTEMI and STEMI in a consecutive sample of 1,579 acute MI cases with 1,576 controls. Subsequently, we followed the results in an independent population-based sample of 562 cases and 566 controls, a partially independent prospective cohort (N = 16,627 with 163 incident NSTEMI cases), and examined the effect of disease-associated variants on gene expression in 513 healthy participants. Genetic variants on chromosome 1p13.3 near the damage-regulated autophagy modulator 2 gene DRAM2 associated with NSTEMI (rs656843; odds ratio 1.57, P = 3.11 x 10(-10)) in the case-control analysis with a consistent but not statistically significant effect in the prospective cohort (rs656843; hazard ratio 1.13, P = 0.43). These variants were not associated with STEMI (rs656843; odds ratio, 1.11, P = 0.20; hazard ratio 0.97, P = 0.87), appearing to have a pronounced effect on NSTEMI risk. A majority of the variants at 1p13.3 associated with NSTEMI were also associated with the expression level of DRAM2 in blood leukocytes of healthy controls (top-ranked variant rs325927, P = 1.50 x 10(-12)). The results suggest that genetic factors may in part influence whether coronary artery disease results in NSTEMI rather than STEMI.
  • Halava, Heli; Huupponen, Risto; Pentti, Jaana; Kivimaki, Mika; Vahtera, Jussi (2016)
    BACKGROUND: The discontinuation of statin medication is associated with an increased risk of cardiovascular and cerebrovascular events and, among high-risk patients, all-cause mortality, but the reasons for discontinuation among statin initiators in clinical practice are poorly understood. OBJECTIVE: To examine factors predicting the early discontinuation of statin therapy. METHODS: In this prospective cohort study, participants with baseline measurements before the initiation of statin treatment were linked to national registers and followed for the discontinuation of statins during the first year of treatment (no filled prescriptions after statin initiation within the subsequent 12 months). RESULTS: Of all the 9285 statin initiators, 12% (n = 1142) were discontinuers. Obesity, overweight, vascular comorbidities, and older age were independently associated with a reduced risk of discontinuation [odds ratios (OR) = 0.82 (95% confidence interval [CI], 0.69-0.99), 0.85 (95% CI, 0.73-0.98), 0.80 (95% CI, 0.68-0.93), and 0.82 (95% CI, 0.68-0.99), respectively]. In contrast, high-patient cost-sharing was associated with an increased odds (OR = 1.29; 95% CI, 1.03-1.62) for discontinuation. The only significant difference between the sexes (P = .002) was observed among the participants with risky alcohol use, which was associated with a decreased odds for discontinuation among the men (OR = 0.69; 95% CI, 0.49-0.98) and an increased odds among the women (OR = 1.28; 95% CI, 1.02-1.62). CONCLUSIONS: The discontinuation of statin therapy during the first year after initiation is common. Lowering out-of-pocket expenditures and focusing on low-risk patient groups and women with risky alcohol use could help maintain the continuation of medication. (C) 2016 National Lipid Association. This is an open access article under the CC BY license (
  • Hijazi, Ziad; Lindahl, Bertil; Oldgren, Jonas; Andersson, Ulrika; Lindback, Johan; Granger, Christopher B.; Alexander, John H.; Gersh, Bernard J.; Hanna, Michael; Harjola, Veli-Pekka; Hylek, Elaine M.; Lopes, Renato D.; Siegbahn, Agneta; Wallentin, Lars (2017)
    Background--Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate. Methods and Results--According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes. Conclusions--In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months. Clinical Trial Registration --URL: Unique identifier: NCT00412984.
  • Preiss, David; Campbell, Ross T.; Murray, Heather M.; Ford, Ian; Packard, Chris J.; Sattar, Naveed; Rahimi, Kazem; Colhoun, Helen M.; Waters, David D.; LaRosa, John C.; Amarenco, Pierre; Pedersen, Terje R.; Tikkanen, Matti J.; Koren, Michael J.; Poulter, Neil R.; Sever, Peter S.; Ridker, Paul M.; MacFadyen, Jean G.; Solomon, Scott D.; Davis, Barry R.; Simpson, Lara M.; Nakamura, Haruo; Mizuno, Kyoichi; Marfisi, Rosa M.; Marchioli, Roberto; Tognoni, Gianni; Athyros, Vasilios G.; Ray, Kausik K.; Gotto, Antonio M.; Clearfield, Michael B.; Downs, John R.; McMurray, John J. (2015)
    Aims The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. Methods and results We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first on-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring Conclusion In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.
  • Vihonen, Hanna; Tierala, Ilkka; Kuisma, Markku; Puolakka, Jyrki; Westerbacka, Jukka; Nurmi, Jouni (2014)
  • Kankaanpää, Meri; Raitakari, Maria; Muukkonen, Leila; Gustafsson, Siv; Heitto, Merja; Palomäki, Ari; Suojanen, Kimmo; Harjola, Veli-Pekka (2016)
    Background: To assess whether the use of point-of-care testing (POCT) and early assessment team (EAT) model shortens emergency department (ED) length of stay (LOS). Methods: This prospective, observational study with comparison between three study periods was performed in three phases in a metropolitan ED with 57,000 annual visits. Data were collected from adult ambulatory patients who were discharged home. Phase 1 served as a control (n = 1559 in one month). In phase 2, a comprehensive POCT panel including complete blood count, sodium, potassium, glucose, C-reactive protein, creatinine, alkaline phosphatase, alanine aminotransferase, bilirubin, amylase, and D-dimer was launched (n = 1442 in one month). In phase 3 (n = 3356 in subsequent two months), POCT approach continued. In addition, the working process was changed by establishing an EAT consisting of an emergency medicine resident and a nurse. The team operated from 12 noon to 10 p.m. was. The primary outcome was LOS (hh: mm) in the ED. Waiting times for patients requiring laboratory testing were analysed also, including time from admission to laboratory blood sampling (A2S interval), time from blood sampling to results ready (S2R interval) and time from results to discharge (R2D interval). Results: Median LOS of patients requiring laboratory tests in phase 1 was 3:51 (95 % confidence interval 03:38-04:04). During phase 2, introduction of POCT reduced median LOS by 29 min to 03: 22 (03:12-03:31, p = 0.000). In phase 3, the EAT model reduced median LOS further by 17 min to 03:05 (02: 59-03:12, p = 0.033). Altogether, the process was expedited by 46 min compared with the phase 1. Surprisingly, A2S interval was unaffected by the interventions among all patients needing laboratory testing. In comparison to phase 1, shortening of S2R interval was observed in phase 2 and 3, and that of R2D interval in all patients with laboratory assessments in phase 3. Discussion: The present study included adult ambulatory patients and is the first one to examine the impact of comprehensive POC test panel, first alone and then with additional process change. As a result, LOS was reduced significantly for patients needing laboratory tests. Considerable shortening in LOS came from introduction of POCT, and EAT process decreased the LOS further. We used a comprehensive POC test panel in order to maximise the patient population benefiting from the positive impacts of POC on laboratory turnaround time and length of stay. In EAT, diverse setups exist, and these differences affect the interpretation of results. The process changes in phase 3 were done by rearranging work shifts and no extra resources were added. Regarding to staffing the process improvement was thus cost neutral. Conclusions: The advantage of POCT alone compared with central laboratory seemed to lie in shorter waiting times for results and earlier discharge home. Moreover, POCT and EAT model shorten LOS additively compared with conventional processes. However, a longer time is seemingly needed to adopt a new working process in the ED, and to establish its full benefit.