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There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA2DS2-VASc score of 1 point. In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA2DS2-VASc score of 0, 1, 2 and ≥3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009. Patients with 1 point from the CHA2DS2-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men <65 years 1.11 (0.56-2.23) and women <65 years 2.13 (0.94-4.82), where HR <1 indicates protection with warfarin. In patients <65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 (0.21-0.73). Categories including age ≥65 years or ≥3 points showed a statistically significant protection from warfarin. Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA2DS2-VASc score is 1.

Brown bears (Ursus arctos) prepare for winter by overeating and increasing adipose stores, before hibernating for up to six months without eating, drinking, and with minimal movement. In spring, the bears exit the den without any damage to organs or physiology. Recent clinical research has shown that specific lipids and lipid profiles are of special interest for diseases such as diabetes type 1 and 2. Furthermore, rodent experiments show that lipids such as sulfatide protects rodents against diabetes. As free-ranging bears experience fat accumulation and month-long physical inactivity without developing diabetes, they could possibly be affected by similar protective measures. In this study, we investigated whether lipid profiles of brown bears are related to protection against hibernation-induced damage. We sampled plasma from 10 free-ranging Scandinavian brown bears during winter hibernation and repeated sampling during active state in the summer period. With quantitative shotgun lipidomics and liquid chromatography-mass spectrometry, we profiled 314 lipid species from 26 lipid classes. A principal component analysis revealed that active and hibernation samples could be distinguished from each other based on their lipid profiles. Six lipid classes were significantly altered when comparing plasma from active state and hibernation: Hexosylceramide, phosphatidylglycerol, and lysophosphatidylglycerol were higher during hibernation, while phosphatidylcholine ether, phosphatidylethanolamine ether, and phosphatidylinositol were lower. Additionally, sulfatide species with shorter chain lengths were lower, while longer chain length sulfatides were higher during hibernation. Lipids that are altered in bears are described by others as relevant for and associated with diabetes, which strengthens their position as potential effectors during hibernation. From this analysis, a range of lipids are suggested as potential protectors of bear physiology, and of potential importance in diabetes.

Brown bears ( Ursus arctos ) hibernate for 5–6 months during winter, but despite kidney insufficiency, dyslipidemia and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are associated with less atherosclerosis, CVD and mortality in uremia in humans and have anti-inflammatory and other potentially protective properties. PC but not MDA is exposed on different types of microorganisms. We determine anti-PC and anti-MDA in brown bears in summer and winter. Paired serum samples from 12 free ranging Swedish brown bears were collected during hibernation in winter and during active state in summer and analyzed for IgM, IgG, IgG1/2 and IgA anti-PC and anti-MDA by enzyme linked immunosorbent assay (ELISA). When determined as arbitrary units (median set at 100 for summer samples), significantly raised levels were observed in winter for anti-PC subclasses and isotypes, and for IgA anti-PC the difference was striking; 100 IQR (85.9–107.9) vs 782.3, IQR (422.8–1586.0; p < 0.001). In contrast, subclasses and isotypes of anti-MDA were significantly lower in winter except IgA anti-MDA, which was not detectable. Anti-PCs are significantly raised during hibernation in brown bears; especially IgA anti-PC was strikingly high. In contrast, anti-MDA titers was decreased during hibernation. Our observation may represent natural immunization with microorganisms during a vulnerable period and could have therapeutic implications for prevention of atherosclerosis.

A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain polyunsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.

AbstractObjectivesTo study circadian rhythm aspects, national holidays, and major sports events as triggers of myocardial infarction.DesignRetrospective observational study using the nationwide coronary care unit registry, SWEDEHEART.SettingSweden.Participants283 014 cases of myocardial infarction reported to SWEDEHEART between 1998 and 2013. Symptom onset date was documented for all cases, and time to the nearest minute for 88%.InterventionsMyocardial infarctions with symptom onset on Christmas/New Year, Easter, and Midsummer holiday were identified. Similarly, myocardial infarctions that occurred during a FIFA World Cup, UEFA European Championship, and winter and summer Olympic Games were identified. The two weeks before and after a holiday were set as a control period, and for sports events the control period was set to the same time one year before and after the tournament. Circadian and circaseptan analyses were performed with Sunday and 24:00 as the reference day and hour with which all other days and hours were compared. Incidence rate ratios were calculated using a count regression model.Main outcome measuresDaily count of myocardial infarction.ResultsChristmas and Midsummer holidays were associated with a higher risk of myocardial infarction (incidence rate ratio 1.15, 95% confidence interval 1.12 to 1.19, P<0.001, and 1.12, 1.07 to 1.18, P<0.001, respectively). The highest associated risk was observed for Christmas Eve (1.37, 1.29 to 1.46, P<0.001). No increased risk was observed during Easter holiday or sports events. A circaseptan and circadian variation in the risk of myocardial infarction was observed, with higher risk during early mornings and on Mondays. Results were more pronounced in patients aged over 75 and those with diabetes and a history of coronary artery disease.ConclusionsIn this nationwide real world study covering 16 years of hospital admissions for myocardial infarction with symptom onset documented to the nearest minute, Christmas, and Midsummer holidays were associated with higher risk of myocardial infarction, particularly in older and sicker patients, suggesting a role of external triggers in vulnerable individuals.

Long-term outcomes of percutaneous coronary intervention (PCI) for bifurcation lesions are underexplored. We investigated long-term PCI outcomes for proximal LAD bifurcation lesions involving D1. Using Swedish registries, we included all patients undergoing LAD-D1 bifurcation PCI with drug-eluting stents between 2010 and 2020. Patients were stratified into two groups: simple PCI and complex PCI. The simple PCI group included those with stents in the proximal LAD only, while complex PCI involved the kissing balloon technique or a 2-stent approach for the proximal LAD and D1. A multivariable Cox regression model was used to estimate event rates of major adverse clinical events (MACE), defined as all-cause death or a new myocardial infarction. Secondary outcomes included target segment revascularization or coronary artery by-pass graft surgery (CABG) and definite stent thrombosis. A total of 6,796 individuals were analyzed: 2,007 underwent complex PCI and 4,789 simple PCI. Baseline characteristics were comparable between groups. The complex PCI group was slightly younger, more often male, and more frequently taking statins. At 1-year, MACE rates were lower in the complex PCI group (6.2% vs 7.9%; adjusted HR 0.74, 95% CI 0.59-0.93, p = 0.010). The result was driven by lower all-cause mortality (3.6% vs. 5.0%; adjusted HR 0.73, 95% CI 0.54-0.98, p = 0.036). No significant differences in myocardial infarction, target segment revascularization, CABG, stent thrombosis, stroke, or bleeding were observed between groups, persisting at five years. Over a five-year period, complex PCI of LAD/D1 bifurcation lesions was associated with better outcome than simple PCI in a routine clinical setting.

Registry-based randomized controlled trials (RRCTs) are increasingly used, promising to address challenges associated with traditional randomized controlled trials. We identified strengths and limitations reported in planned and completed RRCTs to inform future RRCTs. We conducted an environmental scan of literature discussing conceptual or methodological strengths and limitations of using registries for trial design and conduct (n = 12), followed by an analysis of RRCT protocols (n = 13) and reports (n = 77) identified from a scoping review. Using framework analysis, we developed and refined a conceptual framework of RRCT-specific strengths and limitations. We mapped and interpreted strengths and limitations discussed by authors of RRCT articles using framework codes and quantified the frequencies at which these were mentioned. Our conceptual framework identified six main RRCT strengths and four main RRCT limitations. Considering implications for RRCT conduct and design, we formulated ten recommendations for registry designers, administrators, and trialists planning future RRCTs. Consideration and application of empirically underpinned recommendations for future registry design and trial conduct may help trialists utilize registries and RRCTs to their full potential.

ST-elevation myocardial infarction (STEMI) triggers a significant inflammatory response. Sweat may offer a novel, non-invasive medium for monitoring inflammation. In this prospective study, we characterized the inflammatory signatures in plasma and sweat collected from the skin surface of two patient groups: (1) 18 STEMI patients immediately following percutaneous coronary intervention (exposure) and (2) six patients who underwent outpatient angiography without subsequent intervention (control). Levels of 92 biomarkers were measured using a high-throughput proteomic assay and reassessed after 4–6 weeks in STEMI patients. Adjusting for patient group, sweat biomarkers did not show significant changes over time. In plasma, hepatocyte growth factor and interleukin-6 showed a significant decrease from the acute phase to follow-up, adjusted for patient group. STAM binding protein was significantly higher in the sweat of STEMI patients compared to controls, adjusted for time effects. While sweat was less sensitive than plasma for detecting biomarker levels in the setting of STEMI, its longitudinal analysis via wearable sensors holds promise for detecting specific markers. Trial registration : The trial is registered on www.clinicaltrials.gov with the trial registration number NCT05843006.

In this study, fractional flow reserve was used to identify patients with high-risk coronary stenoses, who received either PCI or medical therapy alone; patients with lower-risk lesions were entered in a registry. The PCI group had better outcomes than the medical-therapy group. The benefit of percutaneous coronary intervention (PCI) as an initial treatment strategy in patients with stable coronary artery disease remains controversial. 1 – 3 The potential result from revascularization depends on the extent and the degree of myocardial ischemia. 4 , 5 A fractional flow reserve (FFR) value of 0.80 or less (i.e., a drop in maximal blood flow of 20% or more caused by stenosis), as measured with the use of a coronary pressure wire during catheterization, indicates the potential of a stenosis to induce myocardial ischemia. 6 – 8 In such cases, robust clinical-outcome data favor FFR-guided revascularization, as compared with revascularization guided by . . .

The infrastructure of an established PCI registry was used to conduct a randomized trial comparing manual thrombus aspiration before PCI with PCI alone in patients with STEMI. There was no significant difference between the two groups in mortality at 30 days. One of the most important therapeutic challenges in the management of ST-segment elevation myocardial infarction (STEMI) is the establishment of normal coronary blood flow after percutaneous coronary intervention (PCI). Reduced flow is closely associated with reperfusion injury, 1 which can lead to arrhythmias, contractile dysfunction, microvascular impairment, and irreversible myocardial damage. 2 Reduced myocardial perfusion is also associated with heart failure and death. 3 , 4 Coronary-artery thrombus aspiration, a simple, rapidly performed, and relatively inexpensive adjunct to PCI, may improve blood flow and resolution of ST-segment elevation, 5 – 9 although this is not a universal finding. 10 – 12 Previous studies of thrombus aspiration have not . . .