Browsing by Subject "ARTERY-DISEASE"

Sort by: Order: Results:

Now showing items 1-20 of 24
  • Schillemans, Tessa; Tragante, Vinicius; Maitusong, Buamina; Gigante, Bruna; Cresci, Sharon; Laguzzi, Federica; Vikstrom, Max; Richards, Mark; Pilbrow, Anna; Cameron, Vicky; Foco, Luisa; Doughty, Robert N.; Kuukasjarvi, Pekka; Allayee, Hooman; Hartiala, Jaana A.; Tang, W. H. Wilson; Lyytikainen, Leo-Pekka; Nikus, Kjell; Laurikka, Jari O.; Srinivasan, Sundararajan; Mordi, Ify R.; Trompet, Stella; Kraaijeveld, Adriaan; van Setten, Jessica; Gijsberts, Crystel M.; Maitland-van der Zee, Anke H.; Saely, Christoph H.; Gong, Yan; Johnson, Julie A.; Cooper-DeHoff, Rhonda M.; Pepine, Carl J.; Casu, Gavino; Leiherer, Andreas; Drexel, Heinz; Horne, Benjamin D.; van der Laan, Sander W.; Marziliano, Nicola; Hazen, Stanley L.; Sinisalo, Juha; Kahonen, Mika; Lehtimaki, Terho; Lang, Chim C.; Burkhardt, Ralph; Scholz, Markus; Jukema, J. Wouter; Eriksson, Niclas; Akerblom, Axel; James, Stefan; Held, Claes; Hagstrom, Emil; Spertus, John A.; Algra, Ale; de Faire, Ulf; Akesson, Agneta; Asselbergs, Folkert W.; Patel, Riyaz S.; Leander, Karin (2022)
    Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
  • Lee, Jiwoo; Kiiskinen, Tuomo; Mars, Nina; Jukarainen, Sakari; Ingelsson, Erik; Neale, Benjamin; Ripatti, Samuli; Natarajan, Pradeep; Ganna, Andrea (2021)
    Background: Acute coronary syndrome (ACS) is a clinically significant presentation of coronary heart disease. Genetic information has been proposed to improve prediction beyond well-established clinical risk factors. While polygenic scores (PS) can capture an individual's genetic risk for ACS, its prediction performance may vary in the context of diverse correlated clinical conditions. Here, we aimed to test whether clinical conditions impact the association between PS and ACS. Methods: We explored the association between 405 clinical conditions diagnosed before baseline and 9080 incident cases of ACS in 387 832 individuals from the UK Biobank. Results were replicated in 6430 incident cases of ACS in 177 876 individuals from FinnGen. Results: We identified 80 conventional (eg, stable angina pectoris and type 2 diabetes) and unconventional (eg, diaphragmatic hernia and inguinal hernia) associations with ACS. The association between PS and ACS was consistent in individuals with and without most clinical conditions. However, a diagnosis of stable angina pectoris yielded a differential association between PS and ACS. PS was associated with a significantly reduced (interaction P=2.87x10(-8)) risk for ACS in individuals with stable angina pectoris (hazard ratio, 1.163 [95% CI, 1.082-1.251]) compared with individuals without stable angina pectoris (hazard ratio, 1.531 [95% CI, 1.497-1.565]). These findings were replicated in FinnGen (interaction P=1.38x10(-6)). Conclusions: In summary, while most clinical conditions did not impact utility of PS for prediction of ACS, we found that PS was substantially less predictive of ACS in individuals with prevalent stable coronary heart disease. PS may be more appropriate for prediction of ACS in asymptomatic individuals than symptomatic individuals with clinical suspicion for coronary heart disease.
  • Lahtinen, Annukka M.; Noseworthy, Peter A.; Havulinna, Aki S.; Jula, Antti; Karhunen, Pekka J.; Kettunen, Johannes; Perola, Markus; Kontula, Kimmo; Newton-Cheh, Christopher; Salomaa, Veikko (2012)
  • Uusitalo, Valtteri; Kamperidis, Vasileios; de Graaf, Michiel A.; Maaniitty, Teemu; Stenstrom, Iida; Broersen, Alexander; Dijkstra, Jouke; Scholte, Arthur J.; Saraste, Antti; Bax, Jeroen J.; Knuuti, Juhani (2017)
    Background: We evaluated the prognostic value of an integrated atherosclerosis risk score combining the markers of coronary plaque burden, location and composition as assessed by computed tomography angiography (CTA). Methods: 922 consecutive patients underwent CTA for suspected coronary artery disease (CAD). Patients without atherosclerosis (n = 261) and in whom quantitative CTA analysis was not feasible due to image quality, step-artefacts or technical factors related to image acquisition or data storage (n = 153) were excluded. Thus, final study group consisted of 508 patients aged 63 9 years. Coronary plaque location, severity and composition for each coronary segment were identified using automated CTA quantification software and integrated in a single CTA score (0-42). Adverse events (AE) including death, myocardial infarction (MI) and unstable angina (UA) were obtained from the national healthcare statistics. Results: There were a total of 20 (4%) AE during a median follow-up of 3.6 years (9 deaths, 5 MI and 6 UA). The CTA risk score was divided into tertiles: 0-6.7, 6.8-14.8 and > 14.8, respectively. All MI (n = 5) and most of the other AE occurred in the highest risk score tertile (3 vs. 3 vs. 14, p = 0.002). After correction for age and gender, the CTA risk score remained independently associated with AE. Conclusions: Comprehensive CIA risk score integrating the location, burden and composition of coronary atherosclerosis predicts future cardiac events in patients with suspected CAD. (C) 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.
  • Gregson, John M.; Freitag, Daniel F.; Surendran, Praveen; Stitziel, Nathan O.; Chowdhury, Rajiv; Burgess, Stephen; Kaptoge, Stephen; Gao, Pei; Staley, James R.; Willeit, Peter; Nielsen, Sune F.; Caslake, Muriel; Trompet, Stella; Polfus, Linda M.; Kuulasmaa, Kari; Kontto, Jukka; Perola, Markus; Blankenberg, Stefan; Veronesi, Giovanni; Gianfagna, Francesco; Mannisto, Satu; Kimura, Akinori; Lin, Honghuang; Reilly, Dermot F.; Gorski, Mathias; Mijatovic, Vladan; Munroe, Patricia B.; Ehret, Georg B.; Thompson, Alex; Uria-Nickelsen, Maria; Malarstig, Anders; Dehghan, Abbas; Vogt, Thomas F.; Sasaoka, Taishi; Takeuchi, Fumihiko; Kato, Norihiro; Yamada, Yoshiji; Kee, Frank; Mueller-Nurasyid, Martina; Ferrieres, Jean; Arveiler, Dominique; Amouyel, Philippe; Salomaa, Veikko; Boerwinkle, Eric; Thompson, Simon G.; Ford, Ian; Jukema, J. Wouter; Sattar, Naveed; Packard, Chris J.; Majumder, Abdulla al Shafi; CKDGen Consortium; Int Consortium Blood Pressure; CHARGE Inflammation Working Grp; MICAD Exome Consortium; EPIC-CVD Consortium; CHD Exome Consortium (2017)
    Aims: Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA(2) enzyme activity is causally relevant to coronary heart disease. Methods: In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c. 109+2T> C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA(2). We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA(2) activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA(2)-lowering alleles. Results: Lp-PLA(2) activity was decreased by 64% (p = 2.4 x 10 (-25)) with carriage of any of the four loss-of-function variants, by 45% (p<10 (-300)) for every allele inherited at Val279Phe, and by 2.7% (p = 1.9 x 10 (-12)) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA(2) activity by 65% (p<10 (-300)). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA(2) activity were: 0.95 (0.88-1.03) with Val279Phe; 0.92 (0.74-1.16) with carriage of any loss-of-function variant; 1.01 (0.68-1.51) with Val379Ala; and 0.95 (0.89-1.02) with darapladib treatment. Conclusions: In a large-scale human genetic study, none of a series of Lp-PLA(2)-lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA(2) is unlikely to be a causal risk factor.
  • 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.
  • Liljestrand, John M.; Paju, Susanna; Pietiäinen, Milla; Buhlin, Kåre; Persson, G. Rutger; Nieminen, Markku S.; Sinisalo, Juha; Mäntylä, Päivi; Pussinen, Pirkko J. (2018)
  • PLATO Investigators; Franchi, Francesco; James, Stefan K.; Lakic, Tatevik Ghukasyan; Lassila, Riitta (2019)
    Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
  • Behrendt, Christian-Alexander; Bertges, Daniel; Eldrup, Nikolaj; Beck, Adam W.; Mani, Kevin; Venermo, Maarit; Szeberin, Zoltan; Menyhei, Gabor; Thomson, Ian; Heller, Georg; Wigger, Pius; Danielsson, Gudmundur; Galzerano, Giuseppe; Lopez, Cristina; Altreuther, Martin; Sigvant, Birgitta; Riess, Henrik C.; Sedrakyan, Art; Beiles, Barry; Bjorck, Martin; Boyle, Jonathan R.; Debus, E. Sebastian; Cronenwett, Jack (2018)
    Objective/Background: To achieve consensus on the minimum core data set for evaluation of peripheral arterial revascularisation outcomes and enable collaboration among international registries. Methods: A modified Delphi approach was used to achieve consensus among international vascular surgeons and registry members of the International Consortium of Vascular Registries (ICVR). Variables, including definitions, from registries covering open and endovascular surgery, representing 14 countries in ICVR, were collected and analysed to define a minimum core data set and to develop an optimum data set for registries. Up to three different levels of variable specification were suggested to allow inclusion of registries with simpler versus more complex data capture, while still allowing for data aggregation based on harmonised core definitions. Results: Among 31 invited experts, 25 completed five Delphi rounds via internet exchange and face to face discussions. In total, 187 different items from the various registry data forms were identified for potential inclusion in the recommended data set. Ultimately, 79 items were recommended for inclusion in minimum core data sets, including 65 items in the level 1 data set, and an additional 14 items in the more specific level 2 and 3 recommended data sets. Data elements were broadly divided into (i) patient characteristics; (ii) comorbidities; (iii) current medications; (iv) lesion treated; (v) procedure; (vi) bypass; (vii) endarterectomy (viii) catheter based intervention; (ix) complications; and (x) follow up. Conclusion: A modified Delphi study allowed 25 international vascular registry experts to achieve a consensus recommendation for a minimum core data set and an optimum data set for peripheral arterial revascularisation registries. Continued global harmonisation of registry infrastructure and definition of items will overcome limitations related to single country investigations and enhance the development of real world evidence. (C) 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.
  • Kerola, Anne M.; Semb, Anne Grete; Juonala, Markus; Palomäki, Antti; Rautava, Päivi; Kytö, Ville (2022)
    Background To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. Methods Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005-2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). Results Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74-2.17; p < 0.0001). Probabilities of cardiovascular death (sHR 1.81; p < 0.0001), recurrent MI (sHR 1.91; p < 0.0001), ischemic stroke (sHR 1.50; p = 0.0003), and heart failure hospitalization (sHR 1.98; p < 0.0001) were higher in patients with type 1 diabetes. Incidence of MACE was higher in diabetes patients than in controls in subgroups of men and women, patients aged < 60 and >= 60 years, revascularized and non-revascularized patients, and patients with and without atrial fibrillation, heart failure, or malignancy. Conclusions Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.
  • Kormi, Immi; Nieminen, Mikko T.; Havulinna, Aki S.; Zeller, Tanja; Blankenberg, Stefan; Tervahartiala, Taina; Sorsa, Timo; Salomaa, Veikko; Pussinen, Pirkko J. (2017)
    Background Extracellular matrix degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture leading to acute cardiovascular manifestations. Design and methods In this prospective cohort study, we investigated the prognostic value of circulating matrix metalloproteinase-8, tissue inhibitor of matrix metalloproteinase-1 concentrations, the ratio of matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 and, for comparison, myeloperoxidase and C-reactive protein concentrations for incident cardiovascular disease endpoints. The population-based FINRISK97 cohort comprised 7928 persons without cardiovascular disease at baseline. The baseline survey included a clinical examination and blood sampling. During a 13-year follow-up the endpoints were ascertained through national healthcare registers. The associations of measured biomarkers with the endpoints, including cardiovascular disease event, coronary artery disease, acute myocardial infarction, stroke and all-cause death, were analysed using Cox regression models. Discrimination and reclassification models were used to evaluate the clinical implications of the biomarkers. Results Serum tissue inhibitor of matrix metalloproteinase-1 and C-reactive protein concentrations were associated significantly with increased risk for all studied endpoints. Additionally, matrix metalloproteinase-8 concentration was associated with the risk for a coronary artery disease event, myocardial infarction and death, and myeloperoxidase concentration with the risk for cardiovascular disease events, stroke and death. The only significant association for the matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 ratio was observed with the risk for myocardial infarction. Adding tissue inhibitor of matrix metalloproteinase-1 to the established risk profile improved risk discrimination of myocardial infarction (p=0.039) and death (0.001). Both matrix metalloproteinase-8 (5.2%, p <0.001) and tissue inhibitor of matrix metalloproteinase-1 (12.9%, p <0.001) provided significant clinical net reclassification improvement for death. Conclusions Serum matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 can be considered as biomarkers of incident cardiovascular disease events and death.
  • Nuotio, Krista; Ijäs, Petra; Heikkilä, Hanna M.; Koskinen, Suvi M.; Saksi, Jani; Vikatmaa, Pirkka; Sorto, Pia; Mäkitie, Laura; Eriksson, Henrietta; Kasari, Sonja; Silvennoinen, Heli; Valanne, Leena; Mäyränpää, Mikko I.; Kovanen, Petri T.; Soinne, Lauri; Lindsberg, Perttu J. (2018)
    Introduction: Every fifth ischemic stroke is caused by thromboembolism originating from an atherosclerotic carotid artery plaque. While prevention is the most cost-effective stroke therapy, antiplatelet and cholesterol-lowering drugs have a ceiling effect in their efficacy. Therefore, discovery of novel pathophysiologic targets are needed to improve the primary and secondary prevention of stroke. This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.Materials and Methods: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses.Findings to date: We developed a morphological grading for macroscopic characteristics within CPs. The dominant macroscopic CP characteristics were: smoothness 62%, ulceration 61%, intraplaque hemorrhage 60%, atheromatous gruel 59%, luminal coral-type calcification 34%, abundant (44%) and moderate (39%) intramural calcification, and symptom-causing hot spot area 53%.Future plans: By combining clinically oriented and basic biomedical research, this large-scale study attempts to untangle the pathophysiological perplexities of human carotid atherosclerosis.Key MessagesThis article is a rationale and design of the HeCES2 study that is an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.The HeCES2 study strives to develop diagnostic algorithms including radiologic imaging to identify carotid atherosclerosis patients who warrant surgical treatment.In addition, the study aims at finding out new tools for clinical risk stratification as well as novel molecular targets for drug development.
  • Xu, Shishi; Scott, Charles A. B.; Coleman, Ruth L.; Tuomilehto, Jaakko; Holman, Rury R. (2021)
    Aims Robust diabetes risk estimates in Asian patients with impaired glucose tolerance (IGT) and coronary heart disease (CHD) are lacking. We developed a Chinese type 2 diabetes risk calculator using Acarbose Cardiovascular Evaluation (ACE) trial data. Methods There were 3105 placebo-treated ACE participants with requisite data for model development. Clinically relevant variables, and those showing nominal univariate association with new-onset diabetes (P <.10), were entered into BASIC (clinical variables only), EXTENDED (clinical variables plus routinely available laboratory results), and FULL (all candidate variables) logistic regression models. External validation was performed using the Luzhou prospective cohort of 1088 Chinese patients with IGT. Results Over median 5.0 years, 493 (15.9%) ACE participants developed diabetes. Lower age, higher body mass index, and use of corticosteroids or thiazide diuretics were associated with higher diabetes risk. C-statistics for the BASIC (using these variables), EXTENDED (adding male sex, fasting plasma glucose, 2-hour glucose, and HbA1c), and FULL models were 0.610, 0.757, and 0.761 respectively. The EXTENDED model predicted a lower 13.9% 5-year diabetes risk in the Luzhou cohort than observed (35.2%, 95% confidence interval 31.3%-39.5%, C-statistic 0.643). Conclusion A risk prediction model using routinely available clinical variables can be used to estimate diabetes risk in Chinese people with CHD and IGT.
  • Javanainen, Tuija; Sans-Rosello, Jordi; Harjola, Veli-Pekka; Nieminen, Markku S.; Lassus, Johan; Sionis, Alessandro; Varpula, Marjut; Jurkko, Raija (2019)
    Objectives The aim was to assess the extent of coronary artery disease and revascularization using baseline SYNTAX Score (bSS) and residual SYNTAX Score (rSS) in patients with cardiogenic shock (CS) secondary to ST-segment elevation myocardial infarction (STEMI). The prognostic impact of SYNTAX Score (SS) was evaluated and assessed for additive value over clinical risk scores. Background bSS and rSS have been proven to be useful in risk stratification in stable coronary artery disease as well as in acute coronary syndromes, but they have not been studied in STEMI related CS. Methods Patients from a multinational prospective study of CS were analyzed. The study population was divided into tertiles according to bSS. The Cox regression and receiver operating characteristic (ROC) curves were used to assess the predictive power of SS. Results Of the 61 studied patients, 85% were male and the mean age was 67 years. Median bSS was 22 (15-32) and rSS 7 (0-13). Ninety-day mortality was 43%. bSS had negative prognostic value in multivariable analysis (HR 1.06, 95% CI 1.01-1.10). However, additive value over clinical risk scores was limited. rSS was not associated with mortality, whereas post-percutaneous coronary intervention (PCI) TIMI flow 3 of infarct-related artery (IRA) predicted better survival. Conclusions In STEMI related CS, the added value of bSS and rSS over clinical assessment and risk scores is limited. Our results suggest that while immediate PCI in order to restore blood flow to the IRA is essential, deferring the treatment of residual lesions does not seem to be associated with worse prognosis.
  • Nordic Baltic Bifurcation Study; Kumsars, Indulis; Holm, Niels Ramsing; Niemelä, Matti; Kervinen, Kari; Eskola, Markku; Romppanen, Hannu; Laine, Mika; Pietila, Mikko; Hartikainen, Juha (2020)
    Background It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation. Methods The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates. Results A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment. Conclusion In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years.
  • 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: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
  • Wennstig, A. -K.; Garmo, H.; Wadsten, L.; Lagerqvist, B.; Fredriksson, I.; Holmberg, L.; Blomqvist, C.; Nilsson, G.; Sund, M. (2022)
    Purpose Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT. Methods A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence. Results A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21-1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22-2.10), 1.38 (95% CI 1.07-1.78), and 2.43 (95% CI 1.33-4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT. Conclusion Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.
  • Kim, Chee Hae; Koo, Bon-Kwon; Dehbi, Hakim-Moulay; Lee, Joo Myung; Doh, Joon-Hyung; Nam, Chang-Wook; Shin, Eun-Seok; Cook, Christopher M.; Al-Lamee, Rasha; Petraco, Ricardo; Sen, Sayan; Malik, Iqbal S.; Nijjer, Sukhjinder S.; Mejia-Renteria, Hernan; Alegria-Barrero, Eduardo; Alghamdi, Ali; Altman, John; Baptista, Sergio B.; Bhindi, Ravinay; Bojara, Waldemar; Brugaletta, Salvatore; Silva, Pedro Canas; Di Mario, Carlo; Erglis, Andrejs; Gerber, Robert T.; Going, Olaf; Haerle, Tobias; Hellig, Farrel; Indolfi, Ciro; Janssens, Luc; Jeremias, Allen; Kharbanda, Rajesh K.; Khashaba, Ahmed; Kikuta, Yuetsu; Krackhardt, Florian; Laine, Mika; Lehman, Sam J.; Matsuo, Hitoshi; Meuwissen, Martijin; Niccoli, Giampaolo; Piek, Jan J.; Ribichini, Flavo; Samady, Habib; Sapontis, James; Seto, Arnold H.; Sezer, Murat; Sharp, Andrew S. P.; Singh, Jasvindar; Takashima, Hiroaki; Talwar, Suneel; Tanaka, Nobuhiro; Tang, Kare; Van Belle, Eric; van Royen, Niels; Vinhas, Hugo; Vrints, Christiaan J.; Walters, Darren; Yokoi, Hiroyoshi; Samuels, Bruce; Buller, Christopher; Patel, Manesh R.; Serruys, Patrick W.; Escaned, Javier; Davies, Justin E. (2019)
    OBJECTIVES This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p <0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p <0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (C) 2019 by the American College of Cardiology Foundation.
  • FinnDiane Study Grp; Pongrac Barlovic, Drazenka; Harjutsalo, Valma; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik (2020)
    Aims/hypothesis Lipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes. Methods Individuals (n = 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria. Results During a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median [IQR] for eGFR change:
  • Palanca, Ana; Castelblanco, Esmeralda; Betriu, Angels; Perpinan, Hector; Soldevila, Berta; Manuel Valdivielso, Jose; Bermudez-Lopez, Marcelino; Puig-Jove, Carlos; Puig-Domingo, Manel; Groop, Per-Henrik; Fernandez, Elvira; Alonso, Nuria; Mauricio, Didac (2019)
    Background: Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes. Methods: We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis. Results: During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7. Conclusions: The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.